Gentamicin 3mg/kg/day IV q24h, MAY ADD **Cloxacillin 12g/day IV (2g q4h)
Alternative Regimen (Allergy / Resistance)
Antibiotic allergy:
*Vancomycin 15-20mg/kg (actual body weight) IV q8-12h; not to exceed 2g/dose
PLUS
Gentamicin 3mg/kg IV q24h
Remarks & Clinical Comments:
To adjust antibiotics based on culture and sensitivity. If culture negative, to refer Infectious Disease (ID) physician.
*Refer to Appendix 1 for vancomycin loading dose.
**Cloxacillin: For patients with suspected Staphylococcus aureus infections (such as IVDU or patients with prosthesis) and acute presentation.
Refer to Appendix 3 for antibiotic allergy.
(commonest cause) Enteroviruses Adenovirus Influenza Coronaviruses HIV etc.
Preferred Regimen
Treatment mainly supportive.
Remarks & Clinical Comments:
Among the viruses implicated are enteroviruses including Coxsackie & EV71. For severe HFMD with cardiopulmonary failure stage, use of IVIG may be considered if not used during CNS involvement or autonomic nervous system dysregulation stage.
Immunomodulation may be considered in SARS-CoV-2 infection
*Vancomycin 15-20mg/kg (actual body weight) IV q8-12h; not to exceed 2g/dose
PLUS
Gentamicin 3mg/kg IV q24h
PLUS
**Cefepime 2g IV q8h
PLUS
***Rifampicin 300-450mg PO/IV q12h
Remarks & Clinical Comments:
*Refer to Appendix 1 for vancomycin loading dose.
**Cefepime is indicated if local epidemiology suggests for Gram-negative rod infections (such as Pseudomonas).
***Rifampicin is only recommended for PVE and it should be started 3-5 days later than vancomycin and gentamicin.
Benzylpenicillin 3MU IV q4-6h for 4 weeks (native valves) or 6 weeks (prosthetic valves)
Alternative Regimen (Allergy / Resistance)
Ampicillin 2g IV q4h for 4 weeks (native valves) or 6 weeks (prosthetic valves)
OR
Ceftriaxone 2g IV q24h for 4 weeks (native valves) or 6 weeks (prosthetic valves) (for non-severe hypersensitivity to penicillin)
OR
*Vancomycin 15-20mg/kg (actual body weight) IV q8-12h; not to exceed 2g/dose, for 4 weeks (native valves) or 6 weeks (prosthetic valves) (for severe hypersensitivity to penicillin e.g., anaphylaxis, DRESS etc.)
Remarks & Clinical Comments:
For penicillin-susceptible Viridans streptococci, monotherapy with benzylpenicilin, ampicillin or ceftriaxone is adequate.
4 weeks for NVE and 6 weeks for PVE.
*Refer to Appendix 1 for vancomycin loading dose.
Refer to Appendix 3 for antibiotic allergy.
Benzylpenicillin 4MU IV q4h (total 24 MU/24h) or 24MU IV continuously for 4 weeks (native valves) or 6 weeks (prosthetic valves)
PLUS
*Gentamicin 3mg/kg IV q24h for 2 weeks (native valves and prosthetic valves)
Alternative Regimen (Allergy / Resistance)
Ceftriaxone 2g IV q24h for 4 weeks (native valves) or 6 weeks (prosthetic valves) (for non-severe hypersensitivity to penicillin)
PLUS
*Gentamicin 3mg/kg IV q24h for 2 weeks (native valves and prosthetic valves)
OR
Prosthetic Valve:
**Vancomycin 15-20mg/kg (actual body weight) IV q8-12h; not to exceed 2g/dose, for 6 weeks (for severe hypersensitivity to penicillin)
PLUS
*Gentamicin 3mg/kg IV q24h for 2 weeks
Native Valve:
**Vancomycin 15-20mg/kg (actual body weight) IV q8-12h; not to exceed 2g/dose, for 4 weeks (for severe hypersensitivity to penicillin)
Remarks & Clinical Comments:
*Gentamicin: aim for pre-dose (trough) serum level of < 1 mcg/ml.
**Refer to Appendix 1 for vancomycin loading dose.
Refer to Appendix 3 for antibiotic allergy.
1.4.1 Native and Prosthetic Valves Enterococcal Endocarditis
1.4 Enterococcus
Sensitive to ampicillin and gentamicin
Preferred Regimen
Ampicillin 2g IV q4h
PLUS
*Gentamicin 1mg/kg IV q8h
Remarks & Clinical Comments:
Duration of therapy:
● Symptoms < 3 months and native valve: (4 weeks ampicillin, 2 weeks gentamicin).
● Symptoms > 3 months or prosthetic valves: 6 weeks therapy (6 weeks ampicillin and 2 weeks gentamicin).
*Gentamicin: In order to maximise synergistic effect, administer gentamicin at the same time or temporally close to ampicillin.
Consult ID specialist for enterococcal endocarditis with high level resistance to gentamicin.
1.4.2 Enterococcus - Sensitive to ampicillin and gentamicin
1.4 Enterococcus
Renal impairment or elderly patients
Preferred Regimen
Ampicillin 2g IV q4h for 6 weeks
PLUS
Ceftriaxone 2g IV q12h for 6 weeks
Remarks & Clinical Comments:
This combination is not active against Enterococcus faecium.
Ceftriaxone should not be used alone for enterococcus infection, as they are intrinsically resistant.
1.4.3 Enterococcus - High level resistance to gentamicin
1.4 Enterococcus
Sensitive to ampicillin and vancomycin
Preferred Regimen
Ampicillin 2g IV q4h for 6 weeks
PLUS
Ceftriaxone 2g IV q12h for 6 weeks
Remarks & Clinical Comments:
This combination is not active against Enterococcus faecium.
Ceftriaxone should not be used alone for enterococcus infection, as they are intrinsically resistant.
Left sided endocarditis or complicated right sided endocarditis:
Cloxacillin 2g IV q4h for 4 to 6 weeks
*Right sided endocarditis (tricuspid valve) in uncomplicated endocarditis:
Cloxacillin 2g IV in q4h for 2 to 4 weeks
Alternative Regimen (Allergy / Resistance)
Antibiotic allergy:
Severe hypersensitivity to penicillin:
**Vancomycin 15-20mg/kg (actual body weight) IV q8-12h; not to exceed 2g/dose, for 4 to 6 weeks
For non-severe hypersensitivity:
Cefazolin 2g IV q8h for 4 to 6 weeks
Remarks & Clinical Comments:
*2 weeks’ regime is sufficient for right sided IE provided the patient fulfils all the following criteria (uncomplicated IE):
● MSSA
● Absence of associated prosthetic valve or left sided valve infection
● Good response to treatment
● Absence of metastatic sites of infection or empyema
● Absence of cardiac and extracardiac complications
● Vegetation < 10 mm
●Absence of severe immuno-suppression (< 200 CD4 cells/ml) with or without Acquired Immune Deficiency Syndrome (AIDS)
**Refer to Appendix 1 for vancomycin loading dose.
Regimen for β-lactam allergic patients, replace cloxacillin with the following:
Severe hypersensitivity to penicillin:
**Vancomycin 15-20mg/kg (actual body weight) IV q8-12h; not to exceed 2g/dose, for at least 6 weeks
PLUS
Gentamicin 1mg/kg IM/IV q8h for 2 weeks
PLUS
*Rifampicn 300-450mg PO q12h for ≥ 6 weeks
For non-severe hypersensitivity:
Cefazolin 2g IV q8h for at least 6 weeks
PLUS
Gentamicin 1mg/kg IM/IV q8h for 2 weeks
PLUS
*Rifampicn 300-450mg PO q12h for ≥ 6 weeks
Remarks & Clinical Comments:
*Rifampicin: To avoid the development of resistance, it should be started after 3-5 days of effective initial cloxacillin therapy and/or once the bacteraemia has been cleared.
**Refer to Appendix 1 for vancomycin loading dose.
*Vancomycin 15-20mg/kg (actual body weight) IV q8-12h; not to exceed 2g/dose, for 4 to 6 weeks
Alternative Regimen (Allergy / Resistance)
**Daptomycin 10mg/kg IV q24h for 4 to 6 weeks
Remarks & Clinical Comments:
*Refer to Appendix 1 for vancomycin loading dose.
**Daptomycin: Daptomycin might be more effective in IE caused by MRSA with higher MIC (above 1 mg/L) to vancomycin based on case-control studies. However, risk for MIC creep against daptomycin may be present in those exposed to vancomycin.
*Vancomycin 15-20mg/kg (actual body weight) IV q8-12h; not to exceed 2g/dose, for ≥ 6 weeks
PLUS
Gentamicin 1mg/kg IV q8h for 2 weeks
PLUS
**Rifampicin 300-450mg PO q12h for ≥ 6 weeks*
Remarks & Clinical Comments:
**Refer to Appendix 1 for vancomycin loading dose.
**Rifampicin: To avoid the development of resistance, it should be started after 3-5 days of effective initial vancomycin therapy and/or once the bacteraemia has been cleared.
1.7.1 Candida Endocarditis (native and prosthetic valve)
1.7 Therapy for Candida Endocarditis (Native and Prosthetic valve)
Preferred Regimen
Initial therapy:
Amphotericin B deoxycholate 0.6-1mg/ kg IV q24h for at least 6 weeks after surgery
OR
Liposomal amphotericin B 3-5mg/kg IV q24h for at least 6 weeks after surgery
MAY ADD
*Flucytosine 25mg/kg PO q6h for at least 6 weeks after surgery
Step down therapy:
Fluconazole 400-800mg (6-12mg/kg) PO q24h for susceptible microorganism in stable patients with negative blood cultures (clearance of Candida from blood stream)
Alternative Regimen (Allergy / Resistance)
Initial therapy:
High dose of echinocandins are recommended. Options include:
● IV caspofungin 150mg daily OR
● IV micafungin 150mg daily OR
● IV anidulafungin 200mg daily
Remarks & Clinical Comments:
Valve replacement surgery is mandatory.
Continue therapy for 6 weeks after surgical replacement or longer in patient with perivalvular abscess.
If prosthetic valve cannot be replaced, lifelong suppressive therapy with fluconazole 400mg (6mg/kg) daily is recommended.
The duration of therapy will depend on patient response and surgical intervention.
Patients with Candida IE should be referred to ID physician.
*Flucytosine: For synergistic effect. Causes dose-related marrow toxicity. Avoid using in patients with renal failure.
Footnotes for antibiotic treatment of endocarditis:
Vancomycin: aim for AUC24/MIC of 400–600 (preferred, if stable renal functions), or serum trough level of 15–20mg/L (10–14 µmol/L) for both adults and paediatrics. Vancomycin dose should be adjusted in patients with renal impairment. Refer to Appendix 2 (Antibiotic Dosage in Adult with Impaired Renal Function) for dosing of adult patients with renal impairment, obese patients and monitoring recommendations.
Gentamicin for gram positive synergy dosing: use adjusted body weight for obese patients. Monitor gentamicin levels at least weekly. For conventional dosing (1mg/kg/dose q8h), aim for gentamicin peak level (taken 30 mins after completion of a 30-minute infusion OR one hour after bolus injection) of 6–10 µmol/L (3-5 mcg/mL) and trough level (within 30 mins before the next dose) of < 2 µmol/L (< 1 mcg/mL). For gentamicin 3mg/kg q24h dosing, monitor trough levels only. Refer to Appendix 1 (Clinical Pharmacokinetic Guidelines (Aminoglycosides & Vancomycin).
There should be a high tendency for stopping gentamicin in patients with deteriorating renal function or other signs of toxicity.
If there is high level of gentamicin resistance, ampicillin or vancomycin will need to be continued for ≥ 6 weeks. Referral to an ID physician is recommended if high level gentamicin resistance is present.
Rifampicin should always be used in combination with another effective antistaphylococcal drug (ideally two active agents, i.e. cloxacillin) to minimize risk of resistance. Rifampicin increases hepatic clearance of warfarin and other drugs.
In selected patients of native valve endocarditis with a stable clinical course, it may be possible to switch from IV to oral antibiotics after careful assessment by both cardiologist and ID physician. If feasible, outpatient parenteral antimicrobial therapy (OPAT) can also be considered in this subset of patients.
2.1 Non- tunneled central venous catheter (subclavian, internal jugular, femoral)
Peripherally inserted central catheter
Preferred Regimen
Cloxacillin 2g IV q4-6 h
OR
Cefazolin 2g IV q8h
MAY ADD
Ceftazidime 2g IV q8h
(For gram negative coverage if critically ill, OR patients with femoral lines)
Alternative Regimen (Allergy / Resistance)
If patient has risk factor for MRSA :
*Vancomycin 15-20mg/kg (actual body weight) IV q8-12h; not to exceed 2g/dose
For patients with history of colonization or infected with ESBL and severely/critically ill patients:
Meropenem 2g IV q8h
OR
Imipenem 1g IV q8h
Remarks & Clinical Comments:
BOTH peripheral blood C&S and cultures from the central line must be obtained if CRBSI is suspected.
Change antibiotic to targeted therapy once cultures available.
Antibiotic of choice depends on local epidemiology of CRBSI and guided by antibiogram results.
Catheter removal is recommended.
Duration of antibiotics depends on organisms, catheter removal, and presence of complications. Suggest ID consultation.
**Refer to Appendix 1 for vancomycin loading dose.
Staphylococcus aureus Haemophilus influenza Salmonella spp. M. tuberculosis Non-infectious causes (especially post cardiac surgery) are becoming more common.
Preferred Regimen
*Empiric for purulent pericarditis:
Cloxacillin 200mg/kg/day IV in 4-6 divided doses (max. 12g/day)
PLUS
Cefotaxime 200-300mg/kg/day IV in 4 divided doses (max. 12g/day)
Alternative Regimen (Allergy / Resistance)
Antibiotic allergy:
Cefazolin 100mg/kg/day IV in 3 divided doses (max. 6g/day)
Remarks & Clinical Comments:
Need pericardial fluid to differentiate between different etiologic agent & C&S to adjust antibiotic. Consider surgical drainage for tamponade, pre-tamponade & ineffective conservative management.
Duration of therapy: 4 weeks.
Refer to Appendix 3 for antibiotic allergy.
*Cover with IV Vancomycin in settings with high prevalence of MRSA
2.2 Tunnel type indwelling venous catheters and ports (Broviac, Hickman)
Haemodialysis catheter
Preferred Regimen
Cloxacillin 2g IV q4-6h
OR
Cefazolin 2g IV q8h
PLUS
Ceftazidime 2g IV q8h
Alternative Regimen (Allergy / Resistance)
If patient has risk factor for MRSA:
*Vancomycin 15-20mg/kg (actual body weight) IV q8-12h; not to exceed 2g/dose
PLUS
Ceftazidime 2g IV q8h
Remarks & Clinical Comments:
Adjust dose according to renal function.
Catheter removal is recommended in the following:
● Septic shock
● Septic phlebitis
● Endocarditis, or metastatic infections
● Persistent positive culture > 72 hours
● Pathogens: S.aureus, P.aeruginosa, fungi, mycobacteria
● Tunnel infections
● Port abscess
Duration of antibiotics depends on organisms, catheter removal, and presence of complications. Suggest ID consultation.
*Refer to Appendix 1 for vancomycin loading dose.
Vancomycin 60mg/kg/day IV in 2- 3 divided doses (max. 2g/day unless unable to achieve therapeutic level)
PLUS
Gentamicin 1mg/kg/dose IV q8h
MAY ADD
*Rifampicin 20mg/kg/day IV/PO in 3 divided doses (max. 900mg/day)
Remarks & Clinical Comments:
*Rifampicin IS ONLY for prosthetic valve AND added after 3-5 days later than vancomycin & gentamicin.
If non-HACEK Gram-negative organism like pseudomonas is suspected epidemiologically, add cefepime 50mg/kg/dose IV q8h until cultures are known.
Once cultures are available, adjust accordingly.
Strains fully susceptible to penicillin (MIC < 0.125 mg/l):
Benzylpenicillin 200,000-300,000 units/kg/day IV in 4-6 divided doses (up to 12-18 million units/day)
Strains with MIC > 0.125 to 2 µg/ml:
Benzylpenicillin 200,000-300,000 units/kg/day IV in 4-6 divided doses (up to 12-18 million units/day)
PLUS
Gentamicin 1mg/kg/dose IV q8h for 2 weeks (add to first line regimen of penicillin/ceftriaxone)
Do not use ampicillin.
Alternative Regimen (Allergy / Resistance)
Strains fully susceptible to penicillin (MIC < 0.125 mg/l):
Ampicillin 300mg/kg/day IV in 4-6 divided doses (max. 12g/day)
OR
Ceftriaxone 100mg/kg/day IV in 1-2 divided doses (max. 4g/day)
OR
Antibiotic allergy
*Vancomycin 40mg/kg/day IV in
2-3 divided doses (max. 2g/ day)
Strains with MIC > 0.125 to 2 µg/ml:
Beta-lactam allergy
Vancomycin
PLUS
Gentamicin
Remarks & Clinical Comments:
Duration:
4 weeks for native valve
6 weeks for prosthetic valve
Vancomycin dose adjusted for trough concentration of 10-15 mg/L.
Refer to Appendix 3 for antibiotic allergy.
*Vancomycin therapy is recommended only for patients with immediate type penicillin hypersensitivity.
For this strain (MIC > 0.125):
Antibiotic of choice is either penicillin with gentamicin OR ceftriaxone with gentamicin.
Ampicillin 200-300mg/kg/day IV in 4-6 divided doses (max. 12g/day) for *4-6 weeks
PLUS
Gentamicin 1mg/kg/dose IV q8h for *2-6 weeks
Sensitive to penicillin & vancomycin but high-level resistance to gentamicin (MIC>500 mg/l):
Ampicillin 300mg/kg/day IV in 4-6 divided doses (max. 12g/day)
PLUS
Ceftriaxone 100mg/kg/day IV in 1-2 divided doses (max. 4g/day)
Duration: 6 weeks
Resistant to penicillin but susceptible to vancomycin & gentamicin:
**Vancomycin 40mg/kg/day IV in 3 divided doses (max. 2g/ day)
PLUS
Gentamicin 1mg/kg/dose IV q8h
Duration: 6 weeks
Alternative Regimen (Allergy / Resistance)
Penicillin-sensitive (MIC ≤ 8 mg/l):
Ampicillin 200-300mg/kg/day IV in 4-6 equally divided doses (max. 12g/day)
PLUS
Ceftriaxone 100mg/kg/day IV in 1-2 divided doses (max. 4g/day)
Remarks & Clinical Comments:
*Duration:
If symptoms less than 3 months & native valve: ampicillin for 4 weeks & gentamicin for 2 weeks.
If symptoms more than 3 months: ampicillin & gentamicin for 6 weeks.
Ampicillin plus ceftriaxone is preferred for individuals with renal impairment (CrCl ≤50ml/min) ONLY.
Do not use ceftriaxone alone since enterococcus is intrinsically resistant to this drug. This combination is NOT ACTIVE against E. faecium.
**Maximum dose of vancomycin: 2g/day unless not able to achieve therapeutic range. Aim for serum trough of 10-20mg/L.
Cloxacillin 200-300mg/kg/day IV in 4-6 divided doses (max. 12g/day) for 4-6 weeks
Methicillin-sensitive (right-sided):
Cloxacillin 200-300mg/kg/day IV in 4-6 divided doses (max. 12g/day) for 4 weeks
Methicillin-resistant (left & right):
Vancomycin 60mg/kg/day IV in 2-3 divided doses (max. 2g/day) for 4-6 weeks
Methicillin-sensitive (prosthetic valve):
Cloxacillin 200-300mg/kg/day in 4-6 divided doses (max. 12g/day) for ≥ 6 weeks
PLUS
Gentamicin 1mg/kg/dose IV q8h for 2 weeks
PLUS
*Rifampicin 20mg/kg/day PO in 3 divided doses (max. 900mg/day) for ≥ 6 weeks
Methicillin-resistant (prosthetic valve):
Vancomycin 60mg/kg/day in 2-3 divided doses (max. 2g/day) for ≥ 6 weeks
PLUS
Gentamicin 1mg/kg/dose IV q8h for 2 weeks
PLUS
*Rifampicin 20mg/kg/day PO in 3 divided doses (max. 900mg/day) ≥ 6 weeks
Alternative Regimen (Allergy / Resistance)
Methicillin-sensitive (left-sided or right-sided):
Antibiotic allergy
Cefazolin 100mg/kg/day IV in 3 divided doses (max. 6g/day) for 4-6 weeks
OR
Vancomycin 60mg/kg/day IV in
2-3 divided doses (max. 2g/day) for 4-6 weeks.
Methicillin-resistant (left & right):
*Daptomycin 10 mg/kg IV daily for 4-6 weeks
Remarks & Clinical Comments:
If allergy to penicillin but not immediate type hypersensitivity, use cefazolin. Refer to Appendix 3 for antibiotic allergy.
Methicillin-sensitive (right sided): May shorten duration to 2 weeks if good response, no metastatic sites, no cardiac or extracardiac complications with size of vegetation less than 20mm.
*Daptomycin: Registered in Malaysia however not in FUKKM.
Daptomycin is superior to vancomycin for MRSA bacteremia with MIC >1 mg/L.
*Rifampicin has better penetration but to protect against development of resistance, use only after 3-5 days of cloxacillin AND/OR bacteremia has been cleared.
MRSA (prosthetic valve): vancomycin & rifampicin for 6 weeks or more.
Ampicillin/sulbactam 300mg/kg/day IV in 4-6 divided doses (max. 8g/day ampicillin component) for 4-6 weeks
PLUS
Gentamicin 1mg/kg/dose IV q8h for 4-6 weeks
Remarks & Clinical Comments:
Culture-negative endocarditis (CNE) is diagnosed when a child has clinical & echocardiogram evidence of IE but persistent negative cultures.
This is in individuals with no prior antimicrobial use.
If fungi or fastidious organism is suspected, kindly ask microbiologist to prolong incubation.
Patients with culture-negative endocarditis should be treated in consultation with an ID specialist.
Cefotaxime 200-300mg/kg/day IV in 4 divided doses (max. 2g/dose)
OR
Ceftriaxone 100mg/kg/day IV in 2 divided doses
(max. 2g/dose; 4g/day)
Remarks & Clinical Comments:
For children below 3 months of age:
Cefotaxime is the preferred third generation cephalosporin since less drug-drug interactions (in terms of interaction with calcium-containing infusion & bilirubin displacement).
Given the commonality of GBS in this age group, adding IV C Penicillin (Benzylpenicillin) to Cefotaxime while awaiting culture results can be considered.
Once organism is known, please refer below to adjust antibiotics and duration.
Common organisms: Streptococcus pneumoniae Neisseria meningitidis Haemophilus influenzae Other organisms: Listeria monocytogenes
Preferred Regimen
Ceftriaxone 2g IV q12h
PLUS
Ampicillin 2g IV q4h
(if suspecting listeriosis, please see comments)
Alternative Regimen (Allergy / Resistance)
Cefotaxime 2g IV q6h
PLUS
Ampicillin 2g IV q4h
(if suspecting listeriosis, please see comments)
*If allergic to Cephalosporin, consider meropenem 2g IV q8h
Remarks & Clinical Comments:
Antibiotics should not be delayed if lumbar puncture is delayed by radiological investigation.
If no organism is isolated from CSF C&S but LP is suggestive of bacterial meningitis and the patient is responding, continue antibiotics for 10-14 days.
Dexamethasone 10mg IV q6h is recommended 15 to 20 minutes before or at the time of first dose of antibiotics. Continue for 4 days if the Gram stain and/or cultures are consistent with S. pneumoniae. Discontinue if not Streptococcus pneumonia or if bacterial meningitis is subsequently thought not to be present.
Incidence of listeriosis increases in people > 50 years of age, immunosuppressed and pregnancy. Consider empirical cover with IV ampicillin especially if the course of disease is indolent or there is epidemiological risk (refer section 1.4 - Listeriosis).
Duration: 10-14 days
Penicillin-sensitive strains (MIC to Penicillin ≤ 0.06 mcg/ml):
Benzylpenicillin 4MU IV q4h
Penicillin resistant strains (MIC to Penicillin ≥ 0.12 mcg/ml):
Ceftriaxone 2g IV q12h
Penicillin resistant and Cephalosporin intermediate strains (MIC to Cephalosporin ≥ 1 and < 2 mcg/ml):
*Vancomycin 25-30mg/kg loading dose then 15-20mg/kg IV q8-12h; not to exceed 2g per dose
PLUS
Ceftriaxone 2g IV q12h
OR
Cefotaxime 2g IV q4h
Refer ID physician if patient not responding with above treatment
Penicillin resistant and cephalosporin resistant strains (MIC to Cephalosporin ≥ 2 mcg/ml):
Refer ID physician
Alternative Regimen (Allergy / Resistance)
Penicillin resistant strain
(MIC to Penicillin ≥ 0.12 mcg/ml)
Cefotaxime 2g IV q6h
Remarks & Clinical Comments:
All attempts should be made to ascertain the MIC of isolated pneumococcus. Ceftriaxone or cefotaxime should be de-escalated to benzylpenicillin once the MIC result has been confirmed.
Duration: 10-14 days
*Refer to Appendix 1 for vancomycin loading dose.
Benzylpenicillin 300,000-400,000 units/kg/day; max. 12 million units/day) IV in 4-6 divided doses
OR
Ceftriaxone 100mg/kg/day IV in 2 divided doses (max. 2g/dose; 4g/day)
Remarks & Clinical Comments:
Duration: 7 days
Prophylaxis for all household contacts & health care workers involved in unprotected contact during intubation & suctioning of airway/mouth-to-mouth resuscitation.
Ceftriaxone 250mg IM as single dose (especially in pregnancy and lactating mothers)
OR
Azithromycin 500mg PO as single dose
Remarks & Clinical Comments:
Close contacts are defined as those individuals who have had contact for > 8 hours and within 1 meter of the index case. Individuals who were in contact with oropharyngeal secretions of the index case in the last 7 days before onset of symptoms up to 24 hours after appropriate antibiotics should also receive chemoprophylaxis.
For index case who received only benzylpenicillin as therapy, chemoprophylaxis should also be given upon discharge to eliminate nasopharyngeal carriage.
Benzylpenicillin 4MU IV q4h, MAY ADD *Gentamicin 5mg/kg/day IV in 3 divided doses
Alternative Regimen (Allergy / Resistance)
Trimethoprim/sulfamethoxazole 10 to 20mg/kg/day [based on the TMP component] IV/PO q6-12h
OR
Meropenem 2g IV q8h
Remarks & Clinical Comments:
Duration of treatment is 3 weeks depending on clinical response. May be longer in an immunocompromised host.
*Current evidence supporting combination therapy with gentamicin is weak but it can be considered for severe infections for synergistic effect.
Common organisms: Streptococci Staphylococcus Gram-negative bacilli Anaerobes
Preferred Regimen
Oral/Sinus/Hematogenous source:
Ceftriaxone 2g IV q12h
OR
Cefotaxime 2g IV q4-6h
PLUS
Metronidazole 500mg IV q8h
Otogenic source:
Ceftazidime 2g IV q8h
OR
Ceftriaxone 2g IV q12h
PLUS
Metronidazole 500mg IV q8h
Remarks & Clinical Comments:
Duration to be determined by clinical response (usually 4-8 weeks with IV therapy for 2 weeks minimum depending on whether surgical drainage done, clinical and radiological response).
De-escalate antibiotics based on culture result and sensitivity.
Common organisms: Streptococci Staphylococcus Gram-negative bacilli
Preferred Regimen
Cloxacillin 2g IV q6h
PLUS
Ceftriaxone 2g IV q12h
OR
Cefotaxime 2g IV q4-6h
Remarks & Clinical Comments:
Source control is strongly recommended.
It is important to attempt to obtain specimen to guide antimicrobial therapy.
Continue therapy for at least 6 weeks, with a minimum of 2 weeks IV therapy. Duration to be determined by clinical response, whether surgical drainage done, clinical and radiological response.
Add on Vancomycin if suspecting MRSA infection or patient is deteriorating.
Use Ideal Body Weight in obese class 1 and 2 patients (BMI 30-39.9kg/m2).
Use Adjusted Body Weight for class 3 obesity patients (BMI>40kg/m2).
Duration: 14-21 days
IV Acyclovir 60mg/kg/day IV in 3 divided doses for minimum 21 days followed by oral suppressive therapy, PO aciclovir 300 mg/m2/dose, 3 times per day for 6 months
Remarks & Clinical Comments:
IV duration: 21 days minimum.
Dosing exceeding 500mg/m2 can be associated with acute kidney injury.
Amphotericin B deoxycholate 0.7-1.0mg/kg/day IV q24h
PLUS
5-Flucytosine 100mg/kg/day PO q6h
Consolidation Therapy:
Fluconazole 400-800mg PO q24h
Maintenance Therapy:
Fluconazole 200mg PO q24h
Alternative Regimen (Allergy / Resistance)
Induction Therapy:
Amphotericin B deoxycholate 0.7-1.0mg/kg/day IV q24h
PLUS
Fluconazole 800-1200mg PO q24h
OR
Fluconazole 1200mg PO q24h
PLUS
5-Flucytosine 100mg/kg/day PO q6h
Consolidation Therapy:
Fluconazole 800mg PO q24h
Maintenance Therapy:
Fluconazole 200mg PO q24h
Remarks & Clinical Comments:
Lipid formulations of amphotericin may be used in cases of severe nephrotoxicity.
Repeat lumbar puncture at end of 2 weeks of induction therapy.
Duration of induction therapy:
4-6 weeks (consider 6 weeks if patient has neurological complications and positive CSF culture at 2 weeks).
Duration of consolidation phase:
8 weeks
Use fluconazole 800mg/day if induction phase is less than 4 weeks/ induction phase did not use flucytosine or amphotericin B.
Duration of maintenance Phase:
12 months (longer therapy may be needed to achieve eradication).
Prompt baseline lumbar puncture is strongly encouraged. If pressures are elevated, regular LP is recommended. Consider insertion of EVD/ VP shunting if persistent high CSF pressures. Use of mannitol/ steroids and acetazolamide are not recommended in managing pressures.
In non-HIV/non-transplant patients, consider intermittent LP to look for relapse of cryptococcal infection during consolidation/ maintenance phase (relapse/persistent rate).
2.3 Healthcare-associated Ventriculitis and Meningitis
Empirical treatment should be decided by the primary team based on local antibiogram and CSF gram stain result.
Preferred Regimen
If C&S is not available:
Ceftazidime 2g IV q8h
MAY ADD
*Vancomycin 25-30mg/kg loading dose then 15-20mg/kg IV q8-12h; not to exceed 2g per dose
Alternative Regimen (Allergy / Resistance)
Meropenem 2g IV q8h
MAY ADD
*Vancomycin 25-30mg/kg loading dose then 15-20mg/kg IV q8-12h; not to exceed 2g per dose
Remarks & Clinical Comments:
De-escalate antibiotics to targeted therapy when the culture results are available.
*Vancomycin trough level should be 10-14µmol/L or 15-20mcg/L
*Refer to Appendix 1 for vancomycin loading dose.
LATEST UPDATES! (Jan '26)
ANTIBIOTICS ALLERGY EVALUATION PROTOCOL
1. BACKGROUND2. EVALUATION OF PENICILLIN ALLERGY3. ALGORITHM FOR PATIENTS SUSPECTED OF PENICILLIN/CEPHALOSPORIN ALLERGY4. FOLLOW-UP DOCUMENTATION
The estimated true incidence of penicillin hypersensitivity worldwide is low; up to 90% of patients who reported penicillins allergy could be delabeled safely after formal testing.
Cross-reactivity between truly penicillin allergic patients with third and fourth generation cephalosporins and/or carbapenem is very low (Figures 1 and 2 and, Table 1). It is mainly determined by the R side chain.
Alterations in antibiotic prescribing due to reported penicillins allergy has been shown to result in poorer clinical outcomes, increased incidence of serious antibiotic-resistant infections, prolonged hospitalisation, and increased healthcare burden.
Careful drug allergy history paired with the PEN-FAST risk assessment (Table 2) should be performed, to decide if formal testing is needed; delabeling of allergy will result in more judicious use of narrow spectrum beta-lactam (BL) antibiotics when clinically indicated and improve patient safety.
Figure 1: β-lactams antibiotics structure (adapted from Blumenthal KG et.al, 2019)
Figure 2: Comparison of R1 & R2 structural similarities between B-lactams drugs.
Drugs that have identical R1 or R2 are listed as R1 (red cell) or R2 (gold cell). If ONLY the ring or branch chain moiety of the R1 structure is identical, it is listed as R1’ or R’’, respectively. Drugs that have similar R1 or R2 structures are listed as r1 or r2. If ONLY the ring or branch chain moiety of R1 structure is similar, it is listed as r1’ or r1’’, respectively. Blank cells imply NO R1 or R2 structural similarities. (Zagursky & Pichichero, 20183)
Table 1: β-lactam cross reactivity in penicillins allergic patients.
Table 2: PEN-FAST Penicillin Allergy Clinical Decision Rule Criteria and Interpretation
The PEN-FAST clinical decision rule for patients reporting a penicillin allergy uses 3 clinical criteria of time from penicillin allergy episode, phenotype, and treatment required. A total score is calculated using PEN-FAST score in the upper panel, and interpretation for risk strategy is provided in the lower panel.
a Includes unknown. b Forms of severe delayed reactions include potential Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, and acute generalized exanthematous pustulosis. Patients with a severe delayed rash with mucosal involvement should be considered to have a severe cutaneous adverse reaction. Acute interstitial nephritis, drug induced liver injury, serum sickness and isolated drug fever were excluded phenotypes from the derivation and validation cohorts.
2. EVALUATION OF PENICILLIN ALLERGY
Obtain a detailed history of the drug allergic reaction (Refer Section 2.1).
Conduct risk assessment of the patient using the PEN-FAST Clinical Decision Tool; proceed with either test-dose challenge (score <3) or refer if score more than 3.
Send bloods for in vitro tests; refer for skin and provocation testing to centers specialized in drug allergy testing for moderate and high-risk patients.
Refer to Table 3 for list of medications needed on-site when performing the test dose challenge for low-risk patients at the point-of-care.
2.1 Important Clinical Questions to Clarify a Beta-lactam Adverse Reaction History*
When did the reaction occur?
Which medication was prescribed, and what was the route of administration?
What was the indication for the medication?
How many courses of this medication or a related medication have been administered?
How many doses were received prior to onset of reaction?
How soon after the most recent dose did the reaction occur?
Were there any concurrent medications administered?
What was the nature of the reaction? Specifically ask about:
Raised, erythematous, pruritic rash with each lesion typically lasting <24 h? (hives/urticaria)
Swelling of the tongue, mouth, lips, or eyes (angioedema)
Respiratory or haemodynamic changes with skin manifestations (anaphylaxis)
Lesions or ulcers involving the mouth, lips, or eyes; skin desquamation (SJS, TEN, and other severe type IV reactions)
Organ involvement such as haematologic, renal, or hepatic (cytopenias, Acute Interstitial Nephritis (AIN), transaminitis)
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome, and other severe type IV reactions
Joint pain (serum-sickness like reaction)
Rashes that were not hives, were mild, or delayed in onset (mild type IV reaction or morbilliform rash)
Nausea, vomiting, diarrhea, minor laboratory abnormalities or local injection reactions
Was the medication stopped?
Was medical attention sought in an emergency room or from a community physician?
How was the reaction managed?
Were there symptoms of unexplained fever, arthritis/arthralgia, lymphadenopathy, skin exfoliation or mucous membrane involvement?
How long did symptoms last?
Were any symptoms consistent with severe cutaneous adverse reaction (SCAR – SJS/TEN, DRESS, AGEP, Exfoliative dermatitis)?
Has the same medication been taken subsequently? If yes, was there a reaction?
Has any recurrent signs and symptoms occurred with subsequent same drug exposure?
Are there other tolerated antimicrobial agents?
*Adapted from Jeimy S et al. Practical guide for evaluation and management of beta-lactam allergy: position statement from the Canadian Society of allergy and clinical immunology. 2020.Allergy Asthma Clin Immunol;1695.
Risk assessment before referring for testing, using the PEN-FAST Clinical Decision Tool for possible point-of-care testing:
Risk assessment should be performed using the recently published and validated PEN-FAST clinical decision tool - a predictive screening tool for true penicillin allergy to identify low risk penicillin allergy patients that do not require referral for formal allergy testing.
PEN-FAST is a validated clinical decision-making tool with a high negative predictive value for patients >12 years old. It is a point-of-care screening tool that identifies adult patients with low risk of penicillins allergy and therefore, do not require formal allergy testing when the total score is <3 (Table 2)13; therefore, a drug provocation test (DPT) by the treating physician is recommended.
All routes of administration are possible for a DPT (oral, subcutaneous, intramuscular or intravenous). Nevertheless, the oral route is preferred as the risk of a severe reaction with the oral route is low. The cumulative dose should be documented and may be 10-20% more than the therapeutic dose. For patients with a PEN-FAST score of <3 (interpreted as very low risk and low risk), a test dose challenge is recommended.
Test dose challenge:
Giving 1/10 of the normal concentration intravenous medication or ¼ of the oral dosage being given followed by a 20-minute observation. If no objective symptom(s) is/are observed, a full dose x 1 (or the remaining 9/10) is given followed by a 2-hour observation period (Table 3).
*There is NO MERIT in drug skin testing referrals for SCREENING purposes (i.e. testing without prior history of exposure and subsequent reaction to the drug)
Table 3: Test dose challenge and medications to have on-site
Bloods should be sent for mast cell tryptase level during (up to 4 hours) a suspected acute anaphylaxis.
This should be repeated 24 hours later for baseline measurements. For normal acute tryptase level, the equation 1.2 x baseline tryptase + 2 should be used to interpret results.
In vitro quantification may be sent for specific IgE to penicilloyl G and penicilloyl V to the Allergy lab, Institute for Medical Research (IMR). The specific IgE:total IgE of > 0.002 has been shown to have high predictability of true penicillin allergy.
3. ALGORITHM FOR PATIENTS SUSPECTED OF PENICILLIN/CEPHALOSPORIN ALLERGY
Figure 3: Penicillin allergy risk stratification, and relative contraindication to re-administration.
1. Type 1 or IgE-mediated reaction:symptoms within 2 hours after first dose, duration < 24 hours. 2. Type II, III, IV: symptoms >2 hours after drug administration. [Adapted and modified from Jeimy S et al. Practical guide for evaluation and management of beta-lactam allergy: position statement from the Canadian Society of allergy and clinical immunology. 2020.Allergy Asthma Clin Immunol;1695].
4. FOLLOW-UP DOCUMENTATION
If provocation is not tolerated, document the BL(s) intolerance in the patient records
If provocation is tolerated, delabel and/or document the BL(s) tolerance in the patient records
An allergy card/passport/medic alert should be issued for future avoidance of the allergic BL(s)
S. epidermidis, S. aureus, Corynebacterium sp., Enteric Gram-negative bacilli
Preferred Regimen
Cefazolin 30 mg/kg IV; max. 2g
Recommended re-dosing interval from initiation of pre -operative dose: every 4 hours
Alternative Regimen (Allergy / Resistance)
If known to have MRSA/MRSE colonisation, use vancomycin 15mg/kg IV
Remarks & Clinical Comments:
Antibiotic allergy:
Clindamycin 10mg/kg IV; max 900mg
Recommended re-dosing interval from initiation of pre-operative dose: every 6 hours
Refer to Appendix 3 for antibiotic allergy.
1. Prophylactic Regimens for High-risk Dental Procedures in High-risk Patients
Preferred Regimen
Amoxicillin 2g PO single dose 30 to 60 minutes before procedure
OR
Ampicillin 2g IV single dose 30 to 60 minutes before procedure
Alternative Regimen (Allergy / Resistance)
*Antibiotic allergy:
For non-severe hypersensitivity to penicillin:
Cephalexin 2g PO
OR
Cefazolin 1g IV single dose 30 to 60 minutes before procedure
For severe hypersensitivity to penicillin:
Doxycycline 100mg PO
OR
Azithromycin 500mg PO single dose 30 to 60 minutes before procedure
Remarks & Clinical Comments:
See above for antibiotic prophylaxis in patients undergoing invasive surgical procedure to treat an established infection.
*Refer to Appendix 3 for antibiotic allergy.
Examples: Aortic dissection Thoracic endovascular aortic repair (TEVAR) Valve repair or replacement Left ventricular assist device (LVAD) placement
Preferred Regimen
Cefazolin 2g IV followed by 2g IV q8h
If MRSA colonized:
Cefazolin 2g IV STAT
PLUS
Vancomycin 15-20mg/kg IV STAT
Followed by:
Cefazolin 2g IV q8h
PLUS
Vancomycin 15mg/kg IV q12h
Alternative Regimen (Allergy / Resistance)
Severe penicillin allergy:
Vancomycin 15-20mg/kg IV STAT followed by 15mg/kg IV q12h
Remarks & Clinical Comments:
IV vancomycin dose of 20mg/kg pre-operatively may be preferred to achieve sufficient tissue concentrations at the time of surgery.
At onset of bypass: May consider additional 1-2g of IV cefazolin via cardiopulmonary bypass circuit.
1. With carditis & residual heart disease (persistent valvular disease): 10 years since the last episode of ARF or 40 years of age whichever is longer. Consider lifelong prophylaxis.
2. With carditis but no residual heart disease (no valvular disease): 10 years since the last episode of ARF or 21 years of age whichever is longer.
3. Without carditis: 5 years since last ARF or until 21 years of age whichever is longer.
Alternative Regimen (Allergy / Resistance)
Phenoxymethylpenicillin (Penicillin V) 250 mg PO q12h
Antibiotic allergy:
Erythromycin ethylsuccinate 15-20mg/kg/dose PO q12h (max. 800mg/dose)
Amoxicillin 50mg/kg PO (max. 2g) 30-60 minutes before procedure
OR
Ampicillin 50mg/kg IV (max. 2g) 30-60 minutes before procedure
Alternative Regimen (Allergy / Resistance)
Antibiotic allergy:
Clindamycin 20mg/kg IV/PO (max. 900mg) 30-60 minutes before procedure
Another alternative:
Cefazolin 50mg/kg IV (max. 2g) (cephalosporin should not be used in children with anaphylaxis, angioedema or urticaria)
Remarks & Clinical Comments:
IE prophylaxis is recommended for patients with the highest risk cardiac conditions undergoing procedures likely to result in bacteremia with a microorganism that has the potential ability to cause bacterial endocarditis.
Prophylaxis is always required for:
1. Dental procedures that involve
Extraction
Periodontal procedure including surgery
Subgingival scaling
Root planning
Re-planting avulsed teeth
Other surgical procedure e.g.: implant placement & apicectomy
2. Incision & drainage of local abscess in the brain, skin, subcutaneous tissue (boils & carbuncle, eye (dacryocystitis), epidural, lung, orbital area, per rectal area, liver (pyogenic liver), tooth & surgical procedure through infected skin.
3. Percutaneous endoscopic gastrotomy.
Prophylaxis is required in some circumstances. Please refer to Ministry of Health CPG for Prevention, Diagnosis & Management of Infective Endocarditis (2017).
Maintenance of optimal oral hygiene may reduce the incidence of bacteremia from daily activities and is more important than prophylactic antibiotics for a dental procedure to reduce the risk of IE.
Refer to Appendix 3 for antibiotic allergy.
Clean contaminated Surgery (Examples: Gastroduodenal procedures, early appendicitis, closure of stoma)
Preferred Regimen
Cefazolin 30mg/kg IV; max. 2g
Recommended re-dosing interval from initiation of pre -operative dose: every 4 hours
Alternative Regimen (Allergy / Resistance)
Ampicillin/sulbactam 50mg/kg (of ampicillin component) IV
Recommended re-dosing interval from initiation of pre -operative dose: every 2 hours
Remarks & Clinical Comments:
Antibiotic allergy:
Clindamycin 10mg/kg IV; max 900mg
Recommended re-dosing interval from initiation of pre -operative dose: every 6 hours
AND
Gentamicin 2.5 mg/kg IV
Refer to Appendix 3 for antibiotic allergy.
Benzathine Penicillin 1.2MU IM every 4 weeks (*consider every 3 weeks for high-risk group)
OR
Phenoxymethylpenicillin (Penicillin V) 250mg PO q12h
Alternative Regimen (Allergy / Resistance)
Antibiotic allergy:
Erythromycin ethylsuccinate 800mg PO q12h
Remarks & Clinical Comments:
Refer to Appendix 3 for antibiotic allergy.
*High risk group:
Breakthrough ARF despite complete adherence to a 28-day regimen, OR
Severe RHD, or a history of heart valve surgery
At risk for infection caused by Pneumococcus, Meningococcus, Haemophilus sp.
Preferred Regimen
Phenoxymethylpenicillin (Penicillin V)
125mg PO q12h for ≤5 years old
250mg PO q12h for >5 years old
Duration of chemoprophylaxis:
Minimum 1 – 3 years post splenectomy
Life-long prophylaxis for those with other cause of asplenia, previous episode of sepsis and remain immunocompromised.
Alternative Regimen (Allergy / Resistance)
Amoxicillin 20mg/kg/day (250 – 500mg PO q12h; 500mg daily if poor compliance i.e., adult dose)
Antibiotic allergy:
Erythromycin ethylsuccinate 15-20mg/kg/dose PO q12h (max. 800mg/dose)
Remarks & Clinical Comments:
Risk of sepsis is lifelong but especially high in the first 2 years after splenectomy.
Important adjunct:
Immunisation against Pneumococcus, Haemophilus, Meningococcus at least 14 days prior to splenectomy (if not possible then as soon as possible, 14 days or more after surgery).
Pneumococcal conjugate vaccine is preferred for better immunogenicity
Yearly influenza vaccine is also recommended.
Not all pneumococcal isolates are sensitive to these antibiotics. Limitation stressed to parents so that all febrile illness in this group of children are taken seriously since initial signs & symptoms of fulminant septicaemia can be subtle.
Refer to Appendix 3 for antibiotic allergy.
Reference:
Bratzler DW, Dellinger EP, Olsen KM et al. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J Health-Syst Pharm.2013; 70:195-283
Surgical antibiotic prophylaxis not recommended.
References:
Chung et al., National surgical antibiotic prophylaxis guideline in Singapore. Ann Acad Med Singap. 2022 Nov; 51(11):695-711.
Biliary tract (Cholecystectomy, Choledochal cysts excision, On Table Cholangiogram)
Preferred Regimen
Cefazolin 30mg/kg IV; max. 2g
Recommended re-dosing interval from initiation of pre -operative dose: every 4 hours
OR
Ampicillin/sulbactam 50mg/kg (of ampicillin component) IV
Recommended re-dosing interval from initiation of pre -operative dose: every 2 hours
Alternative Regimen (Allergy / Resistance)
Ceftriaxone 50-75mg/kg IV; max. 2g
OR
Cefotaxime 50mg/kg; max. 1g
Recommended re-dosing interval from initiation of pre -operative dose: every 3 hours
PLUS
Metronidazole 15 mg/kg IV
(For neonates less than 1200g, to give 7.5 mg/kg)
Remarks & Clinical Comments:
Antibiotic allergy:
Clindamycin 10mg/kg IV; max 900mg
Recommended re-dosing interval from initiation of pre -operative dose: every 6 hours
PLUS
Gentamicin 2.5 mg/kg IV
Refer to Appendix 3 for antibiotic allergy.
Chloroquine dose: 5mg/kg base (8.3mg/kg salt) orally, once weekly, up to maximum adult dose of 300mg base (begin 1-2 weeks before travelling and take weekly through-out and 4 weeks after leaving area)
For chloroquine-resistant area:
Mefloquine∞: weekly dose by weight in kg (tablet with 250 mg base, 274 mg salt)
≤ 9 kg – 5mg/kg weekly
>9-19 kg – 1/4 adult tablet weekly
>19-30 kg – ½ adult tablet weekly
>30-45 kg – ¾ adult tablet weekly
>45 kg – 1 adult tablet weekly
Start 2-3 weeks before, continue weekly during exposure and for 4 weeks thereafter.
Age >8 years old:
Doxycycline 2.2mg/kg once daily up to 100mg/day. Take 1-2 days before, during and 4 weeks after travelling.
Alternative Regimen (Allergy / Resistance)
Atovaquone-proguanil (Malarone®)*
Paediatric dose:
5-8 kg – ½ paediatric tablet daily
9-10 kg – ¾ paediatric tablet daily
11-20 kg – 1 paediatric tablet daily
21-30 kg – 2 paediatric tablets daily
31-40 kg – 3 paediatric tablets daily
> 40 kg – 1 adult tablet daily
Start prophylactic treatment with Malarone® 1 or 2 days before entering a malaria-endemic area and continue daily during the stay and for 7 days after return.
Remarks & Clinical Comments:
∞ Mefloquine: Not recommended if there are cardiac conduction abnormalities, seizures or psychiatric disorders. E.g.: depression, psychosis.
(Black box warning: Neuropsychiatric reactions may persist even after discontinuation).
If using Mefloquine: Start 2-3 weeks before, continue weekly during exposure and 4 weeks thereafter.
* Atovaquone/proguanil is another drug used in malaria prophylaxis in children (for chloroquine-resistance) BUT not yet registered in Blue Book (available commercially in Malaysia).
*To carefully assess risk and benefit of starting antimalarial prophylaxis to any children to prevent development of drug resistance.
Recommended re-dosing interval from initiation of pre -operative dose: every 4 hours
Alternative Regimen (Allergy / Resistance)
Cefuroxime 50mg/kg IV; max. 1.5g
If known to have MRSA/MRSE colonisation, use vancomycin 15mg/kg IV
Remarks & Clinical Comments:
Antibiotic allergy:
Clindamycin 10mg/kg; max. 900 mg
Recommended re-dosing interval from initiation of pre -operative dose: every 6 hours
Refer to Appendix 3 for antibiotic allergy.
Chemoprophylaxis is indicated for:
1.ALL household contacts in the following circumstances (household contact is defined as a person who resides with the index patient or who spent ≥ 4 hours with the index patient for at least five of the seven days before the day of hospital admission of the index case):
Household with at least one contact <4 years old who is unimmunised or incompletely immunised.
Household with a contact who is an immunocompromised child, regardless of that child's Hib immunisation status.
Household with a child younger than 12 months who has not completed the primary Hib series.
2.Nursery Contact
For ALL attendees in childcare & preschool (regardless of age or vaccination status) when unimmunised or incomplete immunised children attend the facility and two or more cases of Hib invasive disease have occurred within 60 days.
3. Index case
Prior to discharge if did not receive at least ONE dose of cefotaxime/ ceftriaxone and infants younger than 2 years.
For contacts < 2 years old who are not immunised: complete immunisation.
Gentamicin 5mg/kg IV; MAY ADD Clindamycin 600-900mg IV
Remarks & Clinical Comments:
The determinant of antibiotic duration is the surgical findings of perforation.
If appendectomy shows no perforation, antibiotics are for prophylaxis only (single dose) and should not be continued postoperatively. Otherwise, antibiotics should be continued to treat perforated appendicitis (see section on Gastrointestinal & Hepatobiliary Infections .
Clindamycin resistance has been increasing in Bacteroides species.
Metronidazole may be preferred if the procedure transverses the lower gastrointestinal tract.
15-20mg/kg/dose (max. 600mg/dose) PO q12h for 2 days
Remarks & Clinical Comments:
Tailor antibiotic prophylaxis based on sensitivity of the index case.
Chemoprophylaxis is provided to close contact at HIGH RISK which include:
All household especially children younger than 2 years old.
Childcare or preschool contact at any time during 7 days before onset of illness.
Direct exposure to index patient’s secretion through kissing or through sharing toothbrushes or eating utensils at any time during 7 days before onset of illness.
Frequently slept in same place as index patient during 7 days before onset of illness.
Healthcare staff
Routine prophylaxis is not recommended unless there is intimate exposure to respiratory secretion during mouth-to-mouth resuscitation, unprotected contact during intubation/suctioning at any time 7 days before onset of illness or within 24 hours of initiation of effective antimicrobial therapy.
Give chemoprophylaxis to index case prior to discharge if treated with regimens other than cefotaxime or ceftriaxone. Chemoprophylaxis is ideally initiated within 24 hours after index patient is identified; prophylaxis is not indicated more than 2 weeks after exposure.
Benzylpenicillin 5 million units IV loading, then 2.5-3.0 million units IV q6h till delivery
Alternative Regimen (Allergy / Resistance)
Ampicillin 2g IV loading, then 1g IV q6h till delivery
Antibiotic allergy:
Low risk anaphylaxis
Cefazolin 2g IV loading then 1g IV q8h till delivery
High risk anaphylaxis
Clindamycin 900mg IV q8h till delivery
OR
Vancomycin 1g IV loading, then q12h till delivery (if clindamycin resistant)
Remarks & Clinical Comments:
Treat during labour if previously delivered infant with invasive GBS, GBS bacteriuria or antenatal screening swabs positive OR if GBS status is not known AND any of the following:
Preterm <37 weeks
PROM >18 hours
Intrapartum temperature >38ºC
Refer to Appendix 3 for antibiotic allergy.
*To be used only in conjunction with Mechanical Bowel Preparation (MBP) (if given):
Neomycin sulfate 1g PO
PLUS
Erythromycin base 1g PO
OR
Neomycin sulfate 1g PO
PLUS
Metronidazole 1g PO
Alternative Regimen (Allergy / Resistance)
Cefoperazone 2g IV
OR
Ceftriaxone 2g IV
PLUS
Metronidazole 500mg IV
Severe penicillin allergy:
Gentamicin 5mg/kg IV;
MAY ADD Metronidazole 500mg IV OR Clindamycin 600-900mg IV
Remarks & Clinical Comments:
Single dose
Clindamycin resistance has been increasing in Bacteroides species.
Metronidazole may be preferred if the procedure transverses the lower gastrointestinal tract.
*3 doses in conjunction with MBP over 10 hours the day before surgery (between 1pm – 11pm). The need for MBP + PO prophylaxis to be decided by individual institution.
<1 month old till 5 months old: 10mg/kg/day PO in a single dose q24h for 5 days
6 months & older:
10mg/kg/day PO in a single dose on Day 1, (max. 500mg) then 5mg/kg/dose (max. 250mg) on Day 2-Day 5.
OR
Clarithromycin
< 1 month: not recommended
≥ 1 month till 12 years: 15mg/kg/day PO q12h (max. 1g/day)
≥ 12 years till adult: 1g per day PO q12h for 7 days
Alternative Regimen (Allergy / Resistance)
*Erythromycin
<1 months: not preferred. Use only if azithromycin is not available.
≥ 1 month till adult:
Erythromycin ethylsuccinate:
40-50mg/kg/day PO in 2 divided doses for 14 days (max. 2g/day)
Trimethoprim/sulfamethoxazole
2 months & older:
8mg (TMP)/kg/day PO in 2 divided doses for 14 days. (max. 320mg TMP/day)
Remarks & Clinical Comments:
Drug of choice for PEP and treatment is a macrolide. Azithromycin is the preferred macrolide.
*Association between orally administered azithromycin and erythromycin with infantile hypertrophic pyloric stenosis (especially in infant <6 weeks) has been reported but azithromycin remains the drug of choice in very young infants because the risk of developing severe disease outweighs the potential risk.
Antimicrobial prophylaxis is recommended for:
1. ALL household contacts of the index cases & other close contacts, including children in childcare, regardless of immunisation status.
2. When considering borderline degree of exposure for a non-household contact, PEP should be administered if contact personally is at high risk∞ or lives in a household with person at high risk of severe disease (E.g.: young infant, pregnant women, person who has contact with infants).
3. Close contacts who are unimmunised or under immunised should have pertussis immunisation initiated or continued using age-appropriate products according to the recommended schedule as soon as possible (this include off-label Tdap in children 7-9 years old who did not complete DTaP series.)
∞High risk:
Infant, women at third trimester of pregnancy and people with pre-existing health conditions that may be exacerbated by pertussis infection (not limited to immunocompromised individuals & those with moderate to severe asthma).
Potential interventions for people without evidence of immunity exposed to varicella (chicken pox) following significant exposure*:
1. Varicella vaccine:
Within 3-5 days of exposure for susceptible healthy adult/child 12 months old or older (followed by a second dose at age-appropriate interval)
2. When indicated & available, Varicella zoster immune globulin (VZIG)**:
VZIG dose as per product information; weight-based as soon as possible after exposure up to 10 days after
AND
Acyclovir 20mg/kg/dose PO q6h (max. 3200mg/day) beginning 7-10 days after exposure & continue for 7 days to prevent breakthrough VZV after VZIG or IVIG if no contraindications.
3. When VZIG not available:
****IVIG (400mg/kg) IV once
AND
Acyclovir 20mg/kg/dose PO q6h (max. 3200mg/day) beginning 7-10 days after exposure & continue for 7 days to prevent breakthrough VZV after VZIG or IVIG if no contraindications.
Remarks & Clinical Comments:
*Exposure is significant if:
1.Household: Residing in the same household
2.Playmate: Face-to-face indoor play ≥1 hour
3.Hospital: In same 2 to 4-bed room or adjacent beds in a large ward, face-to-face contact with an infectious staff member or patient, or visit by a person deemed contagious
4.Newborn infant
**For patients who are at high risk for severe infection & complications*** & significant exposure* (and have contraindications to vaccine).
***Susceptible hosts include:
1.Immunocompromised children
2.Pregnant women, newborns of mothers with Varicella shortly before or after delivery (i.e.: 5 days before or within 2 days after delivery)
3.Premature infants born at ≥28 weeks of gestation who are exposed during their hospitalization & whose mothers do not have evidence of immunity
4.Premature infants born at <28 weeks of gestation or birth weight ≤1000 g regardless of their mothers' immunity.
****Patients receiving monthly high dose IVIG (≥400 mg/kg) are likely to be protected & probably do not require VZIG if the most recent dose of IVIG was administered ≤3 weeks before exposure.
Single Dose
It is reasonable to give single dose prophylaxis for patients undergoing laparoscopic cholecystectomy although evidence showed that antibiotic not required in low risk patients. This is because some of these risk factors cannot be determined before surgery.
5.2 Spinal Procedure with or without Instrumentation/Hip Surgery/ Implantation of Internal Fixation Devices (e.g.: nails, screws, plates, wires)
Preferred Regimen
Cefazolin 30mg/kg IV; max. 2g
Recommended re-dosing interval from initiation of pre -operative dose: q4h
Remarks & Clinical Comments:
Antibiotic allergy:
Clindamycin 10mg/kg; max. 900 mg
Recommended re-dosing interval from initiation of pre -operative dose: q6h
Refer to Appendix 3 for antibiotic allergy.
At risk for Pneumococcus, Meningococcus & Haemophilus infection
Preferred Regimen
Phenoxymethylpenicillin (Penicillin V) 250mg PO q12h
Alternative Regimen (Allergy / Resistance)
Amoxicillin 250mg PO q24h
Severe penicillin allergy:
Cephalexin 250mg PO q12h
OR
Azithromycin 250mg PO q24h
Remarks & Clinical Comments:
Duration of chemoprophylaxis:
At least 1 year following splenectomy.
Risk of sepsis remains lifelong and is highest in immunocompromised patients.
Duration of chemoprophylaxis should be individualized based on patient’s risk factors:
Severely immunosuppressed patient
Patient with hematological malignancy
Patient who has survived severe sepsis
Post-splenectomy counselling with regards to need for repeated vaccinations and appropriate health-seeking behavior in the event of fever.
Pamphlet
Post splenectomy card
At risk for Pneumococcus, Meningococcus & Haemophilus infection
Preferred Regimen
Initial - Single dose only
Pneumococcal PCV13 0.5ml IM/SC stat,
followed by PPV23 0.5ml IM/SC stat (8 weeks interval)
*Meningococcal A,C,Y,W 135 0.5ml IM stat
Haemophilus influenzae Type B conjugate 0.5ml IM/SC stat
*Co-administration of meningococcal ACYW135 (MenACWY-D) with PCV13 may result in immune blunting, hence should be administered at least 4 weeks apart.
Revaccination - Every 5 years
**Pneumococcal PPV23 0.5ml IM/SC stat
Meningococcal A,C,Y,W 135 0.5ml IM stat
Remarks & Clinical Comments:
Elective splenectomy:
Administer vaccines at least 2 weeks before procedure
Emergency splenectomy:
Give vaccine at least 7 days postoperatively or on the day of discharge, whichever comes first
It is safe to give all the initial vaccinations at the same time using different administration sites.
**A third dose is recommended at the age of 60 years OR a minimum of 5 years after the second dose, whichever is later. You can have a maximum of 3 doses of Pneumovax 23(23vPPV) as an adult (> 18 years). If you have your spleen removed after 60 years of age, only a single booster dose is recommended (i.e. the third and final dose is not given).
Single dose
Duration: Up to 24 hours
For patients with recent biliary interventions/stenting, there is a higher incidence of bacteria with ESBL-producers.
Antibiotic should be tailored to in-house antibiogram or recent bile/blood culture from the patients
Uninfected operative wounds in which no inflammation is encountered No viscus is entered during the procedures E.g.: Elective craniotomy, spinal procedures
Preferred Regimen
Cefazolin 2g IV
Alternative Regimen (Allergy / Resistance)
Cefuroxime 1.5g IV
Severe penicillin allergy:
*Vancomycin 15-20mg/kg IV
OR
Clindamycin 600mg-900mg IV
Remarks & Clinical Comments:
Single dose
*Situation where the use of vancomycin is appropriate:
In patients previously colonized with MRSA
Those who are allergic to penicillins or cephalosporins
In hospitals in which MRSA or MRCoNS are frequent causes of postoperative wound infection
Rapid IV administration of vancomycin may cause vancomycin infusion reaction AND/OR hypotension.
Recommended re-dosing interval from initiation of pre -operative dose: every 4 hours
Alternative Regimen (Allergy / Resistance)
Ampicillin/sulbactam 50mg/kg (of Ampicillin component; max.2g/dose) IV
Recommended re-dosing interval from initiation of pre-operative dose: every 2 hours
OR
Cefuroxime 50mg/kg IV; (max. 1.5g/dose)
Recommended re-dosing interval from initiation of pre -operative dose: every 4 hours
Remarks & Clinical Comments:
Antibiotic allergy:
Clindamycin 10mg/kg IV (max. 900mg)
Recommended re-dosing interval from initiation of pre-operative dose: every 6 hours
Refer to Appendix 3 for antibiotic allergy.
6.2 Clean Wounds with Foreign Body or Instrumentation
CSF shunting procedures Implantation of cranial or spinal implants
Preferred Regimen
Cefazolin 2g IV
Alternative Regimen (Allergy / Resistance)
Cefuroxime 1.5g IV
Severe penicillin allergy:
*Vancomycin 15-20mg/kg IV
OR
Clindamycin 600mg-900mg IV
Remarks & Clinical Comments:
Single dose
*Situation where the use of vancomycin is appropriate:
In patients previously colonized with MRSA
Those who are allergic to penicillins or cephalosporins
In hospitals in which MRSA or MRCoNS are frequent causes of postoperative wound infection
Rapid IV administration of vancomycin may cause Vancomycin infusion reaction AND/OR hypotension.
Procedures that breach air cells or nasal or oral cavity: Transphenoidal Transoral Trauma or surgery that causes a breach in air sinuses
Preferred Regimen
Cefuroxime 1.5g IV
PLUS
Metronidazole 500mg IV
Alternative Regimen (Allergy / Resistance)
Amoxicillin/Clavulanate 1.2g IV
Severe penicillin allergy:
*Vancomycin 15-20mg/kg IV
PLUS
Gentamicin 5mg/kg IV
PLUS
Metronidazole 500mg IV
Remarks & Clinical Comments:
Single dose
Consider escalation to ceftriaxone 2g IV if there is dura breach or CSF leak.
*Situation where the use of vancomycin is appropriate:
In patients previously colonized with MRSA
Those who are allergic to penicillins or cephalosporins
In hospitals in which MRSA or MRCoNS are frequent causes of postoperative wound infection
Rapid IV administration of vancomycin may cause Vancomycin infusion reaction AND/OR hypotension.
Recommended re-dosing interval from initiation of pre -operative dose: every 4 hours
Remarks & Clinical Comments:
Antibiotic allergy:
Clindamycin 10mg/kg IV; max. 900mg
Recommended re-dosing interval from initiation of pre -operative dose: every 6 hours
Refer to Appendix 3 for antibiotic allergy.
7.2 Normal Vaginal Delivery - Operative Vaginal Deliveries
Preferred Regimen
Cefazolin 2g IV
PLUS
Metronidazole 500mg IV
Alternative Regimen (Allergy / Resistance)
Cefuroxime 1.5g IV
PLUS
Metronidazole 500mg IV
OR
Ampicillin/Sulbactam 3g IV
OR
Amoxicillin/Clavulanate 1.2g IV
Severe penicillin allergy:
Clindamycin 600-900mg IV
Remarks & Clinical Comments:
Single dose after delivery
Please refer to Obstetrics & Gynaecology Infections section for:
Group B Streptococcus (GBS)
Preterm premature rupture of membranes (PPROM) prophylaxis
Recommended re-dosing interval from initiation of pre -operative dose: every 4 hours
Remarks & Clinical Comments:
Antibiotic allergy:
Clindamycin 10mg/kg; max. 900mg
Recommended re-dosing interval from initiation of pre -operative dose: every 6 hours
Refer to Appendix 3 for antibiotic allergy.
Recommended re-dosing interval from initiation of pre -operative dose: every 4 hours
Remarks & Clinical Comments:
Antibiotic allergy:
Clindamycin 10mg/kg; max. 900mg
Recommended re-dosing interval from initiation of pre -operative dose: every 6 hours
Refer to Appendix 3 for antibiotic allergy.
Single dose
Continuation of antimicrobial prophylaxis (max up to 2 days) may be considered for patients with major risk factors for surgical infections. E.g.:
Obesity
Complicated cesarean
Immunocompromised
Risk of infection is very low, antibiotic prophylaxis generally not necessary unless high risk (associated with risk of post-operative PID/endometritis). E.g.:
Dilated fallopian tubes
History of pelvic inflammatory disease (PID)
Tubal damage
Abnormal tubal architecture (associated with risk of post-operative PID/ endometritis)
If evidence of endometritis/ infection found at point of procedure, treat accordingly.
Consider sexually transmitted infections (STI) screening in high-risk populations and advise to complete treatment prior procedure.
Risk of infection is very low, antibiotic prophylaxis generally not necessary unless high risk (associated with risk of post-operative PID/endometritis). E.g.:
Dilated fallopian tubes,
History of pelvic inflammatory disease (PID)
Tubal damage
Abnormal tubal architecture
If evidence of endometritis/ infection found at point of procedure, treat accordingly.
References:
Chung et al., National surgical antibiotic prophylaxis guideline in Singapore. Ann Acad Med Singap. 2022 Nov; 51(11):695-711.
American Congress of Obstetrics & Gynecologist (ACOG) 2018
Prevention and Management of Third & Fourth Degree Tears, NHS Wales, Feb 2019
Heisterberg, L., Petersen, K., Sørensen, S. S., & Nielsen, D. (1986). A comparison of metronidazole and ampicillin prophylaxis to women with a history of pelvic inflammatory disease undergoing first-trimester abortion. International Journal of Gynecology & Obstetrics, 24(5), 343–346. doi:10.1016/0020-7292(86)90152-9
Non-cardiac including lobectomy, pneumonectomy, segmentectomy, lung biopsy & thoracotomy
Preferred Regimen
Cefazolin 30mg/kg IV (max. 12g/day)
Recommended re-dosing interval from initiation of pre -operative dose: every 4 hours
Alternative Regimen (Allergy / Resistance)
Ampicillin/sulbactam 50mg/kg (of Ampicillin component; max. 2g/dose) IV
Recommended re-dosing interval from initiation of pre -operative dose: every 2 hours
Remarks & Clinical Comments:
Antibiotic allergy:
Clindamycin 10mg/kg IV (max. 3.6g/day)
Recommended re-dosing interval from initiation of pre-operative dose: every 6 hours
Refer to Appendix 3 for antibiotic allergy.
9.2 Clean without entry into urinary tract/clean with entry into urinary tract (e.g.: hypospadias surgery)
Preferred Regimen
Cefazolin 30mg/kg IV; max. 2g
Recommended re-dosing interval from initiation of pre -operative dose: q4h
Alternative Regimen (Allergy / Resistance)
Amoxicillin/clavulanate 30mg/kg IV; max 1.2g
Recommended re-dosing interval from initiation of pre -operative dose: q4h
Remarks & Clinical Comments:
UTI should be treated before procedure when possible.
Medical literature does not support continuing antimicrobial prophylaxis until urinary catheter have been removed.
Insertion of dental implants and use of graft material High degree of difficulty / long duration
Preferred Regimen
Benzylpenicillin 2MU IV
Alternative Regimen (Allergy / Resistance)
Oral (PO) prophylaxis options
Amoxicillin 2g PO
OR
Amoxicillin/Clavulanate 1.25g PO
OR
Cephalexin 2g PO
PLUS
Metronidazole 400mg PO
Intravenous (IV) prophylaxis options
Ampicillin 2gm IV
OR
Amoxicillin/clavulanate 1.2gm IV
OR
Cefazolin 2g IV
PLUS
Metronidazole 500mg IV
Severe penicillin allergy:
Clindamycin 600-900mg PO/IV
Remarks & Clinical Comments:
Single dose
*Additional of metronidazole only if choice of prophylaxis is cephalosporin.
In patients with cardiac conditions with increased risk of Infective Endocarditis, chemoprophylaxis is indicated. Please refer to Chemoprophylaxis Non-Surgical section.
Orthognathic surgery Excision / enucleation of large benign tumours / cysts All oral cancer surgery Open reduction and internal fixation of facial bone fractures
Preferred Regimen
Benzylpenicillin 2MU IV
Alternative Regimen (Allergy / Resistance)
Amoxicillin/clavulanate 1.2g IV
OR
Cefuroxime 1.5g IV
PLUS
Metronidazole 500mg IV
Remarks & Clinical Comments:
Single dose
For oral & maxillofacial fractures, antibiotics is recommended for the immediate post trauma period and should be discontinued once open reduction and internal fixation is completed.
Additional of metronidazole only if choice of prophylaxis is cephalosporin
In patients with cardiac conditions with increased risk of Infective Endocarditis, chemoprophylaxis is indicated. Please refer to Chemoprophylaxis Non-Surgical section.
Clindamycin 600-900mg IV; MAY ADD *Gentamicin 5mg/kg IV
Remarks & Clinical Comments:
Single dose
Duration: Up to 24 hours
Prolonged course of oral antibiotics has not been shown to reduce post-operative infections and may increase risk of complications.
*Addition of gentamicin may be appropriate when there is an increase likelihood of gram-negative contamination of surgical site.
Clindamycin 600-900mg IV; MAY ADD *Gentamicin 5mg/kg IV
Remarks & Clinical Comments:
Single dose
Duration: Up to 24 hours
*Addition of gentamicin may be appropriate when there is an increase likelihood of gram-negative contamination of surgical site.
Surgical antibiotic prophylaxis not recommended. Infection rates are very low, especially when nasal packing/splint use ≤ 48 hours.
Complex septorhinoplasty:
Cefazolin 2g IV
PLUS
Metronidazole 500mg IV
Alternative Regimen (Allergy / Resistance)
Complex septorhinoplasty:
Amoxicillin/Clavulanate 1.2g IV
Severe penicillin allergy:
Clindamycin 600-900mg IV; MAY ADD *Gentamicin 5mg/kg IV
Remarks & Clinical Comments:
Single dose
Complex septorhinoplasty:
Duration: Up to 24 hours
*Addition of gentamicin may be appropriate when there is an increase likelihood of gram-negative contamination of surgical site.
Clindamycin 600-900mg IV; MAY ADD *Gentamicin 5mg/kg IV
Remarks & Clinical Comments:
Single Dose
*Addition of gentamicin may be appropriate when there is an increase likelihood of gram-negative contamination of surgical site.
Post-operative antibiotics should not be given if there is no mucous seen intra-operatively.
12.3 Cleft reconstruction and other cleft-related surgeries
Preferred Regimen
Amoxicillin/clavulanate 1.2gm IV q8h
Alternative Regimen (Allergy / Resistance)
Ampicillin/sulbactam 3g IV q8h
Remarks & Clinical Comments:
Duration: 3-5 days
There is no consensus on the use of post-operative prophylaxis antibiotics. However, studies have shown that postoperative pre-emptive antibiotics may reduce postoperative complications such as palatal fistula.
There is no consensus on the use of antibiotic prophylaxis.
The choice of antibiotic will depend on the most recent organism isolated from previous tissue culture and sensitivity obtained from the recipient site.
As suggested by SICPRE guidelines, prophylaxis should be prolonged up to 72 hours for:
Microsurgical transplantation
Major skin cancer surgery
Large flap harvest
Duration: Up to 24 hour
However, as suggested by SICPRE guidelines, prophylaxis can be prolonged up to 72 hours in case of high risk index such as:
Microsurgical transplantation
Major skin cancer surgery
Large flap harvest
Amoxicillin/clavulanate 1.2g IV followed by 1.2g IV q8h
Severe penicillin allergy
Clindamycin 600-900mg IV STAT followed by 600mg IV q8h
OR
Vancomycin 15-20mg/kg IV STAT followed by 15mg/kg IV q12h
Remarks & Clinical Comments:
Duration: Up to 24 hour
Unless a drain is present, antibiotics should be discontinued within 24 hours of the completion of the procedure. If a drain is present, the role of antibiotics is less clear and should be left to physician judgment.
Reference:
Antibiotic Expert Groups. Therapeutic guidelines: antibiotics. Version 15. Melbourne: Therapeutic Guidelines Limited; 2014.
National Surgical Antibiotic Prophylaxis Guideline Singapore 2022
Piccillo EM, Farsar CJ, Holmes DM. Prophylactic Antibiotics After Cleft Lip and Palate Reconstruction: A Review From a Global Health Perspective. Cureus. 2023 Mar 19;15(3):e36371. doi: 10.7759/cureus.36371. PMID: 37090369; PMCID: PMC10113116.
Homsy P.,Romo I. et al. Antibiotic Prophylaxis in clean and clean-contaminated plastic surgery: A Critical Review, Volume 83, P233-245. Published April 23, 2023.DOI: http://doi.org/10.1016/j.bjps.2023.04.071
Borrelli MR, Sinha V, Landin ML, Chicco M, Echlin K, Agha RA, Ross AM. A systematic review and meta-analysis of antibiotic prophylaxis in skin graft surgery: A protocol. Int J Surg Protoc. 2019 Feb 28;14:14-18. doi: 10.1016/j.isjp.2019.02.001. PMID: 31851735; PMCID: PMC6913549.
Brambullo T, Biffoli B, Scortecci L, Messana F, Vindigni V, Bassetto F. Antibiotic Prophylaxis in Plastic Surgery: From Systematic Review to Operative Algorithm. World J Plast Surg. 2022 Jul;11(2):24-36. doi: 10.52547/wjps.11.2.24. PMID: 36117892; PMCID: PMC9446112.
Alderman A, Gutowski K, Ahuja A, Gray D, Post Mastectomy Expander Implant Breast Reconstruction Guideline Work Group. ASPS Clnical Practice Guideline Summary on Breast Reconstruction with expanders and implants. Plastic Reconstr Surg. 2014; 134(4):648e-655e. doi:10.1097/PRS.0000000000000541
Gupta, R., Sinnett, D., Carpenter, R., Preece, P. E., & Royle, G. T. (2000). Antibiotic prophylaxis for post-operative wound infection in clean elective breast surgery. European Journal of Surgical Oncology (EJSO), 26(4), 363–366. doi:10.1053/ejso.1999.0899
Fosfomycin trometamol 3g PO 3 hours before procedure, followed by 3g PO 24 hours after procedure
Remarks & Clinical Comments:
Single dose
Rectal wash out (rectal povidone-iodine preparation) to further decrease infection risk.
Consider pre-operative rectal swab followed by targeted antibiotic prophylaxis
Prophylaxis may be recommended in *high risk cases:
Cefuroxime 500mg PO
Remarks & Clinical Comments:
Single dose
*High-risk cases:
Immunocompromised patients
Debilitated patients on long term catheters
Patient with prosthesis/ heart valves**
Diabetics
Transplant recipients
**Follow the recommendations outlined in the Non-Surgical Chemoprophylaxis section: Prophylactic Regimens for High-Risk Dental Procedures in High-Risk Patients.
Surgical antibiotic prophylaxis not recommended
LAPAROSCOPIC SURGERY
Recommendation as per open surgery, depending on the type of procedure performed i.e. clean or clean– contaminated.
Reference:
Urological Infections - European Association of Urology Guidelines March 2023
Chung et al., National surgical antibiotic prophylaxis guideline in Singapore. Ann Acad Med Singap. 2022 Nov; 51(11):695-711.
Matthew Coates et al. Prophylactic Cefazolin Dosing in Obesity—a Systematic Review. https://doi.org/10.1007/s11695-022-06196-5
*Dosages of Proton Pump Inhibitors:
Omeprazole 20mg PO q12h
Pantoprazole 40mg PO q12h
Lansoprazole 30mg PO q12h
Esomeprazole 20mg PO q12h
Rabeprazole 20mg PO q12h
Dexlansoprazole 30mg PO q12h
First line therapy recommended in areas with < 15-20% clarithromycin resistance.
Consider second line treatment if clarithromycin resistance exceeds more than 15%.
Duration of therapy: 14 days
Meta-analysis of RCTs found 14 days duration of therapy showed greater eradication rate.
Refer to Appendix 3 for antibiotic allergy.
Most are mild infections which resolve spontaneously without antibiotics.
Mild or uncomplicated
Adequate fluid replacement. No antibiotics required.
Severe illness
(hospitalisation, invasive/other complications or immunocompromised patients*)
Ceftriaxone 75-100 mg/kg/day IV q24h (max. 2g/day) for 5 days (origin of infections: Asia)
Alternative Regimen (Allergy / Resistance)
Mild or uncomplicated
Ampicillin 100mg/kg/day PO in 4 divided doses (max. 2g/day) for 5-7 days for hospitalized children
Severe illness
**Ciprofloxacin 20-30mg/kg/day IV in 2 divided doses (max. 1.5g/day) for 3 days
OR
***Azithromycin 10mg/kg/dose IV q24h (max. 500mg/dose).
Total course: 3 days
Remarks & Clinical Comments:
Resistance patterns towards amoxicillin, trimethoprim sulfamethoxazole, ciprofloxacin & azithromycin are on the rise. Adjust antibiotic once culture & sensitivity (C&S) results are available.
*For immunocompromised host - treat longer (7-10 days).
**Reserve fluoroquinolone only for isolate where there is no other antibiotic option available due to its many side effects.
***Alternative dosage regimen: Azithromycin 10mg/kg/dose IV q24h Day 1 (max. 500mg/dose) followed by 5mg/kg/dose IV q24h Day 2-5 (max. 250mg/dose). Total course: 5 days
Common organisms: Salmonella typhi S. paratyphi A & B
Preferred Regimen
Empirical treatment
Ceftriaxone 75-100mg/kg/day IV q24h (max. 2g/day) for 7-14 days
Mild or uncomplicated
*Ciprofloxacin 30-40mg/kg/day PO in 2 divided doses (max. 1.5g/day) for 5-7 days
Severe infection or suspected resistant organism
Ceftriaxone 80-100mg/kg/day IV q24h (max. 2g/day) for 7-14 days
Chronic carrier state (> 1 year)
Ampicillin 100mg/kg/day PO in 4 divided doses (max. 2g/day) for 6 weeks
OR
Amoxicillin 100mg/kg/day PO in 2 divided doses (max. 4g/day) for 6 weeks
OR
Trimethoprim/sulfamethoxazole
8mg (TMP)/kg/day PO in two divided doses (max. 320mg TMP/day) for 6 weeks.
Alternative Regimen (Allergy / Resistance)
Mild or uncomplicated
Azithromycin 20mg/kg/dose PO q24h (max. 1g/dose)
OR
Ampicillin 100mg/kg/day PO in 4 divided doses (max. 2g/day)
Severe infection or suspected resistant organism
*Ciprofloxacin 30-40mg/kg/day IV in 2 divided doses (max. 0.8-1.2g/day) for 7-10 days
Chronic carrier state (> 1 year)
*Ciprofloxacin 20-30mg/kg/day PO in 2 divided doses (max. 1.5g/day) for 4 weeks
OR
Ampicillin 200-300mg/kg/day IV maximum in 4-6 divided doses (max. 12g/day).
(If oral therapy not tolerated & strain is susceptible)
Remarks & Clinical Comments:
Adjust antibiotic once C&S results are known.
Duration of antibiotics: 7 days (uncomplicated) to 10 days (for severe disease) or 14 days (if using ampicillin) if patient is clinically improving and without a fever for 48 hours.
Choice of antibiotics & duration depends on disease, C&S results & whether oral route is preferred.
*Fluoroquinolones need to be used with caution in children due to possible arthropathy & rapid development of resistance. There is now increasing data of other side effects e.g: hypoglycaemia & neuropsychiatric d/o.
Ampicillin & trimethoprim/ sulfamethaxazole may be considered for susceptible strain. More strains now becoming sensitive to these agents except for certain countries
Azithromycin 20mg/kg/day PO in a single dose (max. 1g)
OR
Erythromycin ethylsuccinate 12.5mg/kg/dose PO q6h (max. 400mg/dose) for 3 days
OR
*Doxycycline 4.4mg/kg/day PO in a single dose (max. 200mg) for children > 8 years old
Remarks & Clinical Comments:
Oral or IV rehydration is the cornerstone of treatment. Prompt initiation of antibiotic therapy reduces the volume and duration of diarrhoea. Antibiotics should be considered for people who are moderately to severely ill. Antibiotic choice depends on age and pattern of resistance.
Monitor antibiotic sensitivity pattern at the beginning of and during the outbreak as it can change.
*Avoid using doxycycline for young children as they can cause staining of the teeth. Use of doxycycline should be considered in an epidemic caused by susceptible isolate.
Fluoroquinolones are not approved for children younger than 18 years old for this indication.
Most community-acquired watery diarrhoea are self-limiting and viral in origin (norovirus, rotavirus, and adenovirus), therefore antibiotics should be discouraged. Rehydration and electrolyte replacement are the main treatment for acute infectious diarrhoea.
Antibiotics may be considered in the following conditions after blood and stool cultures collection:
Immunocompetent hosts with fever and bloody diarrhoea
Suspected to have enteric fever (Refer to chapter on Typhoid)
Ill immunocompromised hosts
Duration:
Immunocompetent: 5-7 days
Immunocompromised: 14 days
If bacteremia or with foci of infection, treatment has to be individualized.
*Antibiotic is usually not indicated, except in the following conditions:
Severe illness or septic shock
Presence of prostheses, valvular heart disease or severe atherosclerosis
Malignancy
Immunocompromised hosts
*Trimethoprim/sulfamethoxazole 160/800mg PO q12h for 3 days
Remarks & Clinical Comments:
*Moderate disease in individual such as food handler, residents of nursing home/ institutions, immunocompromised patients should be treated with antibiotic.
Duration of antibiotic in immunocompromised patients is 7-10 days.
Common organisms: Gram-positive Gram-negative organisms Anaerobes
Preferred Regimen
Primary/spontaneous bacterial peritonitis
Cefotaxime 200mg-300mg/kg IV in 4 divided doses (max. 2g/dose)
Secondary peritonitis (secondary to perforated viscus)
Cefotaxime 200mg-300mg/kg IV in 4 divided doses (max. 2g/dose)
PLUS
Metronidazole 15mg/kg/dose loading dose followed by 7.5mg/kg/dose IV q8h (max. 750mg/dose)
Secondary (nosocomial) peritonitis
Piperacillin/tazobactam IV 300-400mg/kg/day in 3-4 divided doses (max. 16g/day)
If culture proven ESBL:
Imipenem/cilastatin 60-100mg/kg/day IV in 4 divided doses (max. 4g/day)
OR
Meropenem 60-120mg/kg/day IV in 3 divided doses (max. 6g/day)
Alternative Regimen (Allergy / Resistance)
Ampicillin 200mg/kg/day IV in 4 divided doses (max. 2g/day)
PLUS
Gentamicin 5mg/kg/day IV OD
PLUS
Metronidazole 7.5mg/kg/dose IV q8h (max. 750mg/dose) for 7-14 days
OR
Amoxicillin-clavulanate
Age ≥ 3 months and weight ≥ 4kg: 75-90mg/kg/day (amoxicillin dose) IV in 3 divided doses
Age < 3 months or < 4kg: 50mg/kg/day (amoxicillin dose) IV in 2 divided doses
Remarks & Clinical Comments:
May omit metronidazole in primary peritonitis.
In immunocompetent patient with mild to moderate peritonitis and source control, suggest 5 days of therapy.
*If ileus is present, consider rectal instillation of vancomycin (enema): Vancomycin 500mg (in 100 mL normal saline) q6h via enema or by nasogastric tube
Duration: 10 days (may extend to 14 days if recovery is delayed)
6.2 In Cirrhosis with Upper Gastrointestinal Hemorrhage
Common organisms: Enterobacterales (eg: E. coli, K. pneumoniae, and Streptococcus spp.)
Preferred Regimen
Cefotaxime 2g IV q8h for 7 days
OR
Ceftriaxone 2g IV q24h for 7 days
Alternative Regimen (Allergy / Resistance)
Ciprofloxacin 400mg IV q12h
Remarks & Clinical Comments:
Antibiotics should be used judiciously for this indication in view of emergence of resistance.
Primary SBP prophylaxis in high risk patients:
RCTs’ demonstrate decreased in mortality and incidence of SBP with selective intestinal decontamination.
However, in most studies the efficacy to prevent death decreases over time due to the emergence of MDRO.
Ideally, antibiotics for SBP prophylaxis should have low systemic bioavailability.
For patients who may benefit from SBP prophylaxis, it is best to discuss with gastroenterologists or refer to a centre of specialisation.
Patient with recurrent SBP:
To discuss with gastroenterologists or refer to a centre of specialisation for the role of and option for secondary SBP prophylaxis.
Cefotaxime 200mg -300mg/kg IV in 4 divided doses (max. 2g/dose)
OR
Ceftriaxone 100 mg/kg/day IV in 1-2 divided doses (max. 2g/dose; 4g/day)
PLUS
Metronidazole 22.5-40 mg/kg/day IV in 3 divided doses (max. 750mg/dose)
Alternative Regimen (Allergy / Resistance)
Piperacillin/tazobactam 300-400mg/kg/day (of piperacillin component) in 3-4 divided doses IV (max. 16g/day)
OR
Ampicillin/sulbactam 200-300mg/kg/day (of ampicillin component) IV in 4-6 equally divided doses
Remarks & Clinical Comments:
Acute cholangitis
Gram-positive & Gram-negative organisms, anaerobes
Duration ∽ 7 days. Outcome is similar with less than 7 days to those with longer duration > 7 days in patients treated with percutaneous cholecystectomy. Source control is needed in cases of treatment failure.
Duration: 2 - 6 weeks
Shorter duration when there is adequate drainage with fever resolution.
To convert IV to oral when there is clinical improvement. The duration of oral antibiotic depends on the complete resolution of the abscess clinically and radiologically.
To consider drainage if abscess size is ≥ 5cm or impending rupture.
*Piperacillin/tazobactam: if given as q8h, to be given as extended infusion (over 3 – 4 hours).
**May add metronidazole in patients with risk factors of anaerobic liver abscess:
Acute and chronic inflammatory bowel disease with or without perforation
Malignancy of gastrointestinal tract
Surgery of the gastrointestinal tract or pelvic organs
Metronidazole has excellent bioavailability: consider IV to PO switch (refer to Appendix 6 ).
Reserve carbapenem for patients with history of biliary instrumentation suspecting multi-resistant gram negative organism.
Luminal agent: To eradicate intestinal colonization after amoebicidal treatment
**Paromomycin 25-35mg/kg/day PO q8h for 7 days
Remarks & Clinical Comments:
*May consider IV to PO switch when there is satisfactory clinical improvement.
Dose: Metronidazole 800mg PO q8h
Drainage of amoebic liver abscess is not usually required but is necessary if:
The patient does not respond to antibiotic therapy.
The abscess is > 5 cm in diameter.
The abscess is in the left lobe of the liver.
The diagnosis remains in doubt.
** Requires DG’s approval.
Common pathogens: Klebsiella spp Escherichia coli Enterococci
Preferred Regimen
Non-sepsis:
Amoxicillin/clavulanate 1.2g q6h
OR
Ampicillin/sulbactam 1.5-3g IV q6h
Sepsis/organ failure or complicated cholecystitis (E.g.: abscess or perforation):
*Piperacillin/tazobactam 4.5g IV q6-8h
Alternative Regimen (Allergy / Resistance)
Non-sepsis:
Third generation cephalosporins:
Cefoperazone 1-2g IV q12h
OR
Cefotaxime 2g IV q8h
OR
Ceftriaxone 2g q24h
Remarks & Clinical Comments:
Duration : 4 -7days
However, for mild to moderate acute cholecystitis, antibiotics may be ceased within 24h post-cholecystectomy, in the absence of gallbladder necrosis, pericholecystic abscess or biliary peritonitis.
Reserve carbapenems for patients who are at high risk of antimicrobial resistance or history of biliary instrumentation.
*Piperacillin/tazobactam: if given as q8h, to be given as extended infusion (over 3 – 4 hours).
Community acquired Common pathogens: Klebsiella spp Escherichia coli Enterococci Appropriate source control to drain infected foci and restoration of anatomic and physiological function is recommended for all patients, as antibiotics will not penetrate the biliary system in the presence of obstruction.
Preferred Regimen
Non-sepsis:
Amoxicillin/clavulanate 1.2g q6h
OR
Ampicillin/sulbactam 1.5-3g IV q6h
Sepsis/organ failure or complicated cholangitis (E.g.: abscess or perforation) and Hospital acquired infection:
*Piperacillin/tazobactam 4.5g IV q6-8h
Alternative Regimen (Allergy / Resistance)
Non-sepsis:
Third generation cephalosporins:
Cefoperazone 1-2g IV q12h
OR
Cefotaxime 2g IV q8h
OR
Ceftriaxone 2g q24h
MAY ADD
**Metronidazole 500mg IV q8h
Remarks & Clinical Comments:
Duration: 4- 7 days
Treatment may be reduced to 3 days post-biliary drainage with fever resolution.
Reserve carbapenems for patients who are at high risk of antimicrobial resistance or history of biliary instrumentation.
*Piperacillin/tazobactam: to be given as extended infusion over 3-4 hours.
**Metronidazole is required if biliary enteric anastomosis is present.
Uncomplicated acute diverticulitis with any of the following:
Systemic signs of infection
Elderly
Presence of significant comorbidities E.g.: diabetes, significant cardiac disease (IHD, cardiac failure) chronic liver disease or end stage renal disease
Immunocompromised state
Amoxicillin/clavulanate 1.2g q6h
OR
Ampicillin/sulbactam 1.5-3g IV q6h
Alternative Regimen (Allergy / Resistance)
Cefuroxime 1.5g IV q8h
PLUS
Metronidazole 500mg IV q8h
Remarks & Clinical Comments:
Uncomplicated acute diverticulitis in non-septic immunocompetent host:
Antibiotics is usually not required
Uncomplicated diverticulitis is defined as acute diverticulitis without perforation or abscess.
Require close clinical monitoring and re-evaluation for antibiotics if symptoms progress.
May convert to oral antibiotics if clinically improving.
Duration: 7-10 days (IV and oral)
*Piperacillin/tazobactam: If given as q8h, to be given as extended infusion (over 3-4 hours).
Reserve carbapenem for patients who are at high risk of antimicrobial resistance.
Uncomplicated acute appendicitis can be managed by two approaches: a) Non operative management (NOM) with antibiotics alone. b) Appendectomy (for patients who are not suitable for NOM approach or those who do not respond to antibiotics).
Preferred Regimen
Non operative management (NOM):
Amoxicillin/clavulanate 1.2g IV q6h
OR
Ampicillin/sulbactam 1.5-3g IV q6h
Alternative Regimen (Allergy / Resistance)
Cefuroxime 1.5g IV q8h
PLUS
Metronidazole 500mg IV q8h
Remarks & Clinical Comments:
Non-operative management approach:
May convert to oral antibiotics if clinically improving.
Duration: 7-10 days (IV and oral) with close clinical monitoring and re-evaluation for surgery if symptoms do not resolve.
Appendectomy done:
Antibiotic treatment can be stopped once surgery is performed; provided adequate control of the source of infection is achieved and symptoms have resolved.
Duration: 4-7 days (if adequate source control, no delay in surgical intervention and patient has rapid clinical recovery).
*Piperacillin/tazobactam: If given as q8h, to be given as extended infusion (over 3-4 hours).
Reserve carbapenem for patients who are at high risk of antimicrobial resistance and adverse outcomes.
Moderate to severe (E.g.: deep seated, sepsis/organ failure, immunocompromised):
Ceftriaxone 2g IV q24h
OR
Cefoperazone 1-2g IV q12h
PLUS
Metronidazole 500mg IV q8h
Remarks & Clinical Comments:
Drainage procedure is mandatory.
Duration: 4-7 days (advice to stop antibiotics once adequate source control, no delay in surgical intervention and patient has rapid clinical recovery).
Mild to moderate:
Self-limiting, often do not require antibiotics. Prophylactic antibiotics have not been shown to reduce mortality, rates of pancreatic or peripancreatic infection or need for surgery.
If infective biliary calculi in origin, refer to severe pancreatitis.
Short course of antibiotics until surgically obtained cultures are available.
Modify antibiotics according to culture and sensitivity.
Reserve carbapenem for patients at high risk of resistant pathogens.
Duration depends on adequate source control.
*Piperacillin/tazobactam: if given as q8h, to be given as extended infusion (over 3 – 4 hours).
Pain at intravenous catheter sites (tunneled or untunnelled)
Unexplained diarrhoea
Remarks & Clinical Comments:
Any infection in the immunocompromised host is life-threatening and needs immediate attention. Febrile neutropenia is defined as single temperature: ≥ 38.3°C orally or ≥ 38.0°Cover 1 hour; and neutropenia: < 500 neutrophils/mcL or < 1000 neutrophils/mcL and a predicted decline to ≤ 500 neutrophils/mcL over the next 48 hours.
Cultures may be positive in less than 40% of cases. Patients have impaired inflammatory responses and hence may have no localizing signs. The usual sign is fever > 38°C or hypothermia. The common portals of infection include the oral cavity, gastrointestinal tract, perianal region, lungs and IV lines.
Patients may not always mount a temperature response due to the severity of their illness. If a patient is unwell on assessment with a history of receiving systemic anticancer therapies, neutropenic sepsis should be suspected.
Other signs/symptoms that may suggest infection in neutropenic patients (any one of the following):
PaediatricB5INFECTIONS IN IMMUNOCOMPROMISED PATIENTS
1. FEBRILE NEUTROPENIA
1.1 First line
Fever >38°C, neutrophil<500mm³ Common organisms: Enterobacteriaceae (Klebsiella sp., E. coli etc.) Pseudomonas Aerobic Gram-positive (Staphylococci, Streptococci)
Preferred Regimen
Cefepime 50mg/kg/dose IV in q8h (max. 6g/day)
Alternative Regimen (Allergy / Resistance)
Piperacillin/tazobactam 300 - 400 mg/kg/day IV in 4 divided doses (max. 16g/day of piperacillin component)
Remarks & Clinical Comments:
Use monotherapy with an anti-pseudomonal β–lactam agents.
Meta-analysis has shown that there is no clinical advantage with β-lactam and aminoglycoside combination therapy.
Also need to look at local epidemiological data.
6. The oncology or haematology team responsible for the patient should be made aware as soon as possible that the patient has been admitted for suspected neutropenic sepsis.
1.1.2 Low Risk (Outpatient)
1.1 Suggested Empirical Antibiotic Therapy in Adult Febrile Neutropenic Patients
Suitable low risk patients include: no evidence of dehydration or hypotension no evidence of pneumonia no COAD able to access prompt medical attention if deteriorates Outpatient oral antibiotics may be considered after careful risk assessment and consultation with a hemato-oncologist.
Preferred Regimen
Amoxicillin/clavulanate 625mg PO q8h
MAY ADD
*Ciprofloxacin 500mg PO q12h
Remarks & Clinical Comments:
Treat until patient recovers.
Can consider stopping the antibiotic after reassessing the patient following 2 days afebrile at the discretion of the treating hemato-oncologists – if the patient has stable vital signs, no evidence of ongoing infection, are educated about their condition and stay near to hospital facilities.
*Add ciprofloxacin if patient is previously colonized by Pseudomonas aeruginosa.
6. The oncology or haematology team responsible for the patient should be made aware as soon as possible that the patient has been admitted for suspected neutropenic sepsis.
1.1.3 High Risk (Inpatient)
1.1 Suggested Empirical Antibiotic Therapy in Adult Febrile Neutropenic Patients
Risk assessment for complication of severe infection should be done during triage. Patient is deemed high risk if there is: prolonged and profound neutropenia with ANC < 0.1x109/L hypotension pneumonia new onset abdominal pain or neurological signs The administration of the first dose of empirical antibiotic with anti-pseudomonal coverage should be done as soon as possible following triage (within the first hour) after taking blood cultures. The suggested antibiotics are listed below. Consider IV to PO antibiotic switch in a clinically stable patient who has no gastrointestinal absorption issue.
Preferred Regimen
First line therapy:
*Piperacillin/tazobactam 4.5g IV q6h
MAY ADD
**Amikacin 15mg/kg IV q24h
Alternative Regimen (Allergy / Resistance)
Cefepime 2g IV q8h
MAY ADD
**Amikacin 15mg/kg IV q24h
MAY ADD
***Metronidazole 500mg IV q8h
Remarks & Clinical Comments:
*Piperacillin/tazobactam: if given as q8h, to be given as extended infusion (over 3-4 hours).
**Amikacin may be added in patient with severe sepsis for broader gram negative coverage. It can be discontinued if microbiological cultures showed isolated organisms sensitive to piperacillin/tazobactam or cefepime and patient is clinically stable.
***Metronidazole may be added in the presence of:
severe mucositis
intra-abdominal infections
peri-anal abscesses
colitis
6. The oncology or haematology team responsible for the patient should be made aware as soon as possible that the patient has been admitted for suspected neutropenic sepsis.
1.1.3 High Risk (Inpatient)
1.1 Suggested Empirical Antibiotic Therapy in Adult Febrile Neutropenic Patients
Risk assessment for complication of severe infection should be done during triage. Patient is deemed high risk if there is: prolonged and profound neutropenia with ANC < 0.1x109/L hypotension pneumonia new onset abdominal pain or neurological signs The administration of the first dose of empirical antibiotic with anti-pseudomonal coverage should be done as soon as possible following triage (within the first hour) after taking blood cultures. The suggested antibiotics are listed below. Consider IV to PO antibiotic switch in a clinically stable patient who has no gastrointestinal absorption issue.
Preferred Regimen
Severe sepsis or
Second line therapy for persistent fever of 4 - 7 days and deterioration of signs:
Meropenem 1g IV q8h
MAY ADD
*Vancomycin 15-20mg/kg (actual body weight) IV q8-12h; not to exceed 2g/dose
Alternative Regimen (Allergy / Resistance)
Imipenem 500mg q6h or 1g IV q8h (in severe sepsis)
MAY ADD
*Vancomycin 15-20mg/kg (actual body weight) IV q8-12h; not to exceed 2g/dose
Remarks & Clinical Comments:
*Refer to Appendix 1 for vancomycin loading dose.
*Vancomycin is not a routine in the initial antibiotic regime. Consider add vancomycin for these patients:
colonized with MRSA
suspected to have catheter-related infection, skin and soft-tissue infection
in septic shock
Stop vancomycin after 48 hours if no evidence of gram positive cocci.
Linezolid is an alternative in those patients with no clinical response to vancomycin and in those with suspected or confirmed VRE, VISA or VRSA.
PaediatricB5INFECTIONS IN IMMUNOCOMPROMISED PATIENTS
1. FEBRILE NEUTROPENIA
1.2 Second line:
Persistent fever > 72 hours* Common organisms: Enterobacteriaceae (Klebsiella sp, E. coli etc.) Pseudomonas Aerobic Gram-positive (Staphylococci, Streptococci) Enterococci Other resistant organisms *DO NOT MODIFY INITIAL COVERAGE BASED SOLELY ON PERSISTENCE OF FEVER.
Preferred Regimen
Meropenem 60-120mg/kg/day IV in 3 divided doses (max. 6g/day)
MAY ADD
Vancomycin 60 mg/kg/day in 3-4 divided doses (max. 2g/day)
Remarks & Clinical Comments:
Escalate to second line if patient is unstable, to cover resistant gram negative, gram positive and anaerobes.
Consider adding vancomycin in suspected catheter-related infections, positive blood culture for gram positive cocci, hypotensive patients and patients who are known to be colonised with MRSA.
In patients responding to initial empiric antibiotic therapy, discontinue double coverage (empirical vancomycin, if initiated) or double gram negative after 24-72 hours if there is no specific microbiologic indication to continue combination therapy.
PaediatricB5INFECTIONS IN IMMUNOCOMPROMISED PATIENTS
1. FEBRILE NEUTROPENIA
1.3 Third line
Fever > 4-7 days with no identified source of fever Bacterial: Candida sp. Aspergillus sp., Fusarium sp. Viral: Respiratory viruses are the most common, HSV, VZV
Preferred Regimen
Imipenem/cilastatin 60-100 mg/kg/day IV in 4 divided doses (max. 4g/day)
PLUS
Amphotericin B 0.5mg/kg/dose IV q24h & gradually escalate by (0.25- 1mg/kg/dose) q24h
(max. 1.5mg/kg/day)
OR
Lipid formulation of amphotericin B 3-5mg/kg/day
Alternative Regimen (Allergy / Resistance)
Imipenem/cilastatin 60-100 mg/kg/day IV in 4 divided doses (max. 4g/day)
PLUS
Caspofungin 70mg/m2/dose IV q24h at Day 1, then 50mg/m2/dose IV q24h (max. 70mg/dose for loading and maintenance dose)
Remarks & Clinical Comments:
1/3 of febrile neutropenic patients with persistent fever >1 week have systemic fungal infections.
Initiate antifungal in patients at high risk of invasive fungal disease with prolonged (≥ 96 hours) febrile neutropenia unresponsive to broad spectrum antibacterial agents.
Amphotericin based antifungal is considered broader spectrum than echinocandin (E.g.: caspofungin).
6. The oncology or haematology team responsible for the patient should be made aware as soon as possible that the patient has been admitted for suspected neutropenic sepsis.
1.4 Antifungal Therapy
Preferred Regimen
Micafungin 100mg IV q24H
Alternative Regimen (Allergy / Resistance)
Anidulafungin 200mg IV single dose, then 100mg IV q24h
OR
Caspofungin 70mg IV single dose, then 50mg IV q24h
Remarks & Clinical Comments:
It should be initiated earlier in the presence of:
severe mucositis
oral thrush
dysphagia
suspicious skin infiltrates or pulmonary infiltrates
fundal exudates
prolonged steroid use more than 2 weeks
IV amphotericin B remains the empirical therapy of choice for invasive fungal infections. For patients who are intolerant, refractory or those with toxicity to conventional amphotericin B, the lipid formulations of amphotericin B, voriconazole and echinocandins are alternatives for empirical therapy based on local availability and costs.
Voriconazole is an alternative to amphotericin B for pre-emptive and directed therapy for invasive aspergillosis.
In candidiasis, echinocandins, azoles and amphotericin B are antifungals of choice.
Daily Dose of Antifungal Agent
Amphotericin B lipid complex (ABLC): 5mg/kg q24h
Amphotericin B deoxycholate (conventional): 0.7-1.0mg/kg q24h
Liposomal amphotericin B: 3-5mg/kg q24h
Anidulafungin: 200mg loading dose, followed by 100mg q24h
Caspofungin: 70mg loading dose, followed by 50mg q24h
Micafungin: 100mg q24h
Fluconazole: 12mg/kg/day for 1 day, then 6mg/kg q24h
Itraconazole: 200mg q8h for 3 days, followed by 200mg q12h
Posaconazole: (Tablet) 300mg q12h for 1 day, followed by 300mg q24h
Voriconazole: 6mg/kg q12h for 2 doses, followed by 3-4 mg/kg q12h
a) For patients on fluconazole or no antifungal prophylaxis, if
New clinical signs or symptoms suggestive of invasive fungal infections (IFI)*
Fever persists ≥ 7days with no identified fever source
*If sinus and/or chest CT scan findings not suggestive of fungal infection, it is less likely to be aspergillus or mold infections.
6. The oncology or haematology team responsible for the patient should be made aware as soon as possible that the patient has been admitted for suspected neutropenic sepsis.
1.4 Antifungal Therapy
b) If signs and symptoms suggestive of invasive fungal infections (IFI)* AND sinus ± chest CT suggestive of fungal infection.
Trimethoprim/ sulfamethoxazole 15-20mg/kg/day [TMP component] IV/PO in 3-4 divided doses
Alternative Regimen (Allergy / Resistance)
For mild to moderate cases:
(PO2 70-80mmHg)
Clindamycin 600mg IV/PO q8h
PLUS
Primaquine 30mg (base) PO q24h
OR
Dapsone 100mg PO q24h
PLUS
Trimethoprim 15mg/kg/day PO in 3-4 divided doses
For severe cases:
(PO2 < 70mmHg)
Pentamidine 4mg/kg/day IV
(in 1 pint D5% or NS run over 1-2 hours)
OR
Clindamycin 600mg IV q6h or 900mg IV q8h
PLUS
Primaquine 30mg (base) PO q24h
Remarks & Clinical Comments:
Comment
Duration: 21 days
Patients with severe disease should receive adjunctive corticosteroids as soon as possible (within 72 hours of starting PCP treatment):
Prednisolone dose:
40mg PO q12h for 5 days, then
40mg PO q24h for 5 days, then
20mg PO q24h for 11 days
(Total duration is 21 days)
Trimethoprim/sulfamethoxazole & clindamycin has excellent bioavailability, may consider IV to PO switch after clinical improvement.
Patients given dapsone or primaquine should be tested for G6PD deficiency.
Indications: CD4 count < 200 cells/μL CD4 count 200-250 cells/μL if ART cannot be initiated
Preferred Regimen
Trimethoprim/sulfamethoxazole (80/400mg) 1–2 tablets PO q24h
Alternative Regimen (Allergy / Resistance)
*Dapsone 100mg PO q24h
OR
Aerosolized Pentamidine 300mg monthly via ultrasonic nebulizer
Remarks & Clinical Comments:
Comment
Discontinuation:
Can consider when CD4 100-200 cells/μL if HIV RNA is suppressed for 3-6 months with ART.
Restarting prophylaxis:
CD4 count falls to < 200 cells/μL or PCP occurs at a CD4 > 200 cells/μL (lifelong prophylaxis should be considered).
Patients receiving Sulfadiazine/ Pyrimethamine or Sulfadoxine/ Pyrimethamine for treatment or suppression of toxoplasmosis do not require additional prophylaxis for PCP.
*Requires DG’s approval.
2. OPPORTUNISTIC INFECTION (OI) IN PATIENTS WITH HUMAN IMMUNODEFICIENCY VIRUS (HIV)
2.2.1 Acute Infection
2.2 Toxoplasma gondii Encephalitis
Up to 97% patients are Toxo IgG +ve
Preferred Regimen
Trimethoprim/sulfamethoxazole 10mg/kg/day (TMP component) IV/PO in 2 divided doses
OR
*Pyrimethamine 200mg PO loading dose followed by Pyrimethamine:
50mg PO q24h (if BW ≤ 60kg)
75mg PO q24h (if BW > 60kg)
PLUS
Folinic acid 10-25mg IV q24h OR 15mg PO q24h
PLUS
*Sulfadiazine 1g PO q6h
Alternative Regimen (Allergy / Resistance)
*Pyrimethamine 200mg PO loading dose followed by Pyrimethamine:
50mg PO q24h (if BW ≤ 60kg)
75mg PO q24h (if BW > 60kg)
PLUS
Folinic acid 10-25mg IV q24h OR
15mg PO q24h
PLUS
Clindamycin 600mg IV/PO q6h
Remarks & Clinical Comments:
Duration: At least 6 weeks
Longer duration if clinical and radiologic disease is extensive or response is incomplete in 6 weeks.
Adjunctive corticosteroids
(E.g.: dexamethasone) should be administered when clinically indicated to treat mass effect associated with focal lesions or associated oedema but should be discontinued as soon as clinically feasible.
To use trimethoprim/sulfamethoxazole if pyrimethamine not available.
In the case of sulfa allergy and pyrimethamine is not available, sulfa desensitization should be attempted in those without a history of severe reaction (E.g.: Stevens-Johnson syndrome).
If clindamycin is used, additional therapy must be added for primary prophylaxis for PCP.
*Requires DG’s approval.
2. OPPORTUNISTIC INFECTION (OI) IN PATIENTS WITH HUMAN IMMUNODEFICIENCY VIRUS (HIV)
2.3.1 Oropharyngeal (oral thrush)
2.3 Mucocutaneous Candidiasis
Preferred Regimen
Fluconazole 100mg PO q24h
OR
Nystatin suspension 500,000 units PO 4 times daily
Alternative Regimen (Allergy / Resistance)
*Itraconazole 200mg PO q24h
Remarks & Clinical Comments:
Duration: 7-14 days
Chronic suppressive therapy is usually not recommended.
*Itraconazole: Absorption depends on gut acidity. Take capsule with a full meal. Oral solution should be taken on an empty stomach. Avoid PPIs and H2 blockers.
2. OPPORTUNISTIC INFECTION (OI) IN PATIENTS WITH HUMAN IMMUNODEFICIENCY VIRUS (HIV)
2.3.2 Oesophageal
2.3 Mucocutaneous Candidiasis
Preferred Regimen
Fluconazole 200-400mg PO/IV q24h
Alternative Regimen (Allergy / Resistance)
*Itraconazole 200mg PO q24h
Remarks & Clinical Comments:
Duration: 14-21 days
Infection with other pathogens (E.g.: CMV, HSV that causes esophagitis) can result in symptoms that mimic esophageal candidiasis, a diagnostic and therapeutic trial of antifungal therapy is usually warranted before endoscopy.
Endoscopy is required with unusual presentations or lack of response to azole within several days.
2. OPPORTUNISTIC INFECTION (OI) IN PATIENTS WITH HUMAN IMMUNODEFICIENCY VIRUS (HIV)
2.4.2 Consolidation Therapy
2.4 Cryptococcal Meningitis or Meningoencephalitis (Cryptococcus neoformans)
Continued after successful induction therapy; defined as substantial clinical improvement and negative CSF culture after repeat LP.
Preferred Regimen
*Fluconazole 400mg - 800mg PO/IV q24h
**Use actual body weight for weight-based dose calculations: 6 mg/kg once daily (maximum dose [not well established]: 800mg to 1600mg).
Alternative Regimen (Allergy / Resistance)
Itraconazole 200mg PO q12h
Remarks & Clinical Comments:
Duration: 8 weeks
*The dose can then be reduced to 400mg/day to complete the 8-week consolidation phase if all of the following criteria are met:
(i) The patient received induction therapy with amphotericin B plus flucytosine for 2 weeks.
(ii) CSF cultures obtained after 2 weeks of induction therapy are negative.
(iii) ART has been started.
**Consider weight-based dosing for Class 1, 2, or 3 obesity (BMI ≥30 kg/m2) patients.
2. OPPORTUNISTIC INFECTION (OI) IN PATIENTS WITH HUMAN IMMUNODEFICIENCY VIRUS (HIV)
2.4.3 Maintenance Therapy
2.4 Cryptococcal Meningitis or Meningoencephalitis (Cryptococcus neoformans)
Continued after consolidation therapy
Preferred Regimen
Fluconazole 200mg PO q24h
Alternative Regimen (Allergy / Resistance)
Itraconazole 200mg PO q24h for patients intolerant or failed fluconazole (however, less effective and higher relapse rate)
Remarks & Clinical Comments:
Discontinuation:
Completed initial (induction, consolidation) therapy
AND
At least 1 year on maintenance therapy
AND
Remains asymptomatic from cryptococcal infection
AND
CD4 count ≥ 100 cells/µL and suppressed HIV RNA in response to effective ART for ≥ 6 months
2. OPPORTUNISTIC INFECTION (OI) IN PATIENTS WITH HUMAN IMMUNODEFICIENCY VIRUS (HIV)
2.5.1 Mild-moderate pulmonary infection or extra-pulmonary non-CNS disease OR Asymptomatic with positive lung/blood culture or positive antigen test (no CNS disease)
Discontinuation of maintenance:
At least 1 year of treatment
AND
CD4 count ≥ 100 cells/µL and suppressed HIV RNA in response to effective ART for ≥ 6 months.
In the case of treatment failure, all patients initially treated with fluconazole should have their therapy changed to amphotericin B until clinical response is achieved.
*Itraconazole:
Absorption depends on gut acidity. Take capsule with a full meal. Oral solution should be taken on an empty stomach.
**Consider weight-based dosing for Class 1, 2, or 3 obesity (BMI ≥30 kg/m2) patients.
2. OPPORTUNISTIC INFECTION (OI) IN PATIENTS WITH HUMAN IMMUNODEFICIENCY VIRUS (HIV)
2.6.3 Mild Disseminated Disease
2.6 Histoplasmosis (Histoplasma capsulatum)
Blood culture positive but patient is asymptomatic.
Preferred Regimen
Induction & maintenance therapy:
*Itraconazole 200mg PO q8h for 3 days, then 200mg PO q12h
Alternative Regimen (Allergy / Resistance)
For patients intolerant to itraconazole:
Fluconazole 800mg PO q24h
OR
Voriconazole 400mg PO q12h on Day 1, then 200mg PO q12h
Remarks & Clinical Comments:
Duration: At least 12 months
*Itraconazole: Absorption depends on gut acidity. Take capsule with a full meal. Oral solution should be taken on an empty stomach. Avoid PPIs and H2 blockers.
Indication: Severe disseminated or CNS infection after completion of at least 12 months of treatment. Relapsed despite appropriate initial therapy.
Preferred Regimen
*Itraconazole 200mg PO q24h
Alternative Regimen (Allergy / Resistance)
Fluconazole 400mg PO q24h
Remarks & Clinical Comments:
Discontinuation:
Received azole for > 1 year
AND
Negative fungal blood cultures
AND
CD4 count > 150 cells/μL for ≥ 6 months on ART
Restarting secondary prophylaxis:
CD4 count < 150 cells/μL
*Itraconazole: Absorption depends on gut acidity. Take capsule with a full meal. Oral solution should be taken on an empty stomach. Avoid PPIs and H2 blockers.
Liposomal amphotericin B 3-5mg/kg/day IV for 2 weeks
Must be followed by consolidation therapy.
Consolidation therapy:
**Itraconazole 200mg PO q12h for 10 weeks
Must be followed by maintenance therapy.
Alternative Regimen (Allergy / Resistance)
Induction therapy:
Voriconazole 6mg/kg IV q12h on Day 1, then 4mg/kg IV q12h for at least 3 days
OR
Voriconazole 600mg PO q12h on Day 1, then 400mg q12h for 2 weeks if IV therapy not available
Must be followed by consolidation therapy.
Consolidation therapy:
**Itraconazole 200mg PO q12h for 10 weeks
Must be followed by maintenance therapy.
Remarks & Clinical Comments:
All triazole antifungals have the potential to interact with certain ARV agents and other anti-infective agents.
**Itraconazole: Absorption depends on gut acidity. Take capsule with a full meal. Oral solution should be taken on an empty stomach. Avoid PPIs and H2 blockers.
Therapeutic drug monitoring is recommended for azoles therapy.
**Itraconazole 200mg PO q12h for at least 8-12 weeks
Loading dose: 200mg q8h for 3 days and then reduce to q12 therapy
Must be followed by maintenance therapy.
Alternative Regimen (Allergy / Resistance)
Voriconazole 400mg PO q12h on Day 1 followed by 200mg q12h for 12 weeks.
Must be followed by maintenance therapy.
Remarks & Clinical Comments:
All triazole antifungals have the potential to interact with certain ARV agents and other anti-infective agents.
**Itraconazole: Absorption depends on gut acidity. Take capsule with a full meal. Oral solution should be taken on an empty stomach. Avoid PPIs and H2 blockers.
Therapeutic drug monitoring is recommended for azoles therapy.
2. OPPORTUNISTIC INFECTION (OI) IN PATIENTS WITH HUMAN IMMUNODEFICIENCY VIRUS (HIV)
2.9.1 Treatment
2.9 Mycobacterium avium Complex (MAC) Disease
Preferred Regimen
Clarithromycin 500mg PO q12h
PLUS
Ethambutol 15mg/kg PO q24h
PLUS
***Rifampicin 10mg/kg PO q24h
**MAY ADD
4th drug:
Amikacin 10-15mg/kg IV q24h
OR
Streptomycin 15mg/kg IM q24h
OR
Levofloxacin 500mg PO q24h
OR
Ciprofloxacin 500-750mg PO q12h
OR
Moxifloxacin 400mg PO q24h
Alternative Regimen (Allergy / Resistance)
*Azithromycin 500mg PO q24h
PLUS
Ethambutol 15mg/kg PO q24h
PLUS
***Rifampicin 10mg/kg PO q24h
**MAY ADD
4th drug:
Amikacin 10-15mg/kg IV q24h
OR
Streptomycin 15mg/kg IM q24h
OR
Levofloxacin 500mg PO q24h
OR
Ciprofloxacin 500-750mg PO q12h
OR
Moxifloxacin 400mg PO q24h
Remarks & Clinical Comments:
Duration: At least 12 months
*Azithromycin: use if drug interaction or intolerance precludes the use of clarithromycin.
**Addition of 4th drug should be considered for patients with disseminated disease, require IV/IM.
***Concomitant tuberculosis needs to be ruled out if monotherapy rifampicin is used.
Treatment of choice shall be tailored according to culture and susceptibility testing results.
Discontinuation:
Consider if patient is on ART and viral load is suppressed, CD4 > 100 cells/μL > 6 months, asymptomatic of MAC, and has completed > 12 months of therapy.
Ganciclovir 5mg/kg IV q12h, may consider switch to valganciclovir 900mg PO q12h once patient tolerate orally (In CMV oesophagitis and colitis only).
Followed by maintenance therapy.
Alternative Regimen (Allergy / Resistance)
*Foscarnet 60mg/kg IV q8h or 90mg/kg IV q12h
Followed by maintenance therapy.
Remarks & Clinical Comments:
Duration: 21-42 days or until signs and symptoms have been resolved.
Immune recovery is essential for successful treatment. Start ART within 2 weeks if possible.
*For patients with treatment limiting toxicities to ganciclovir or with ganciclovir resistant. Requires DG’s approval.
Discontinuation:
Consider if patient is on ART and viral load well suppressed, CD4 > 100 cells/μL > 3 months and after 3-6 months of CMV treatment.
Maintenance therapy is generally not necessary; ART offers best hope for prevention of relapses.
2. OPPORTUNISTIC INFECTION (OI) IN PATIENTS WITH HUMAN IMMUNODEFICIENCY VIRUS (HIV)
2.13.1 Salmonellosis
2.13 Bacterial Enteric Infections
Salmonella non-typhi
Preferred Regimen
Ciprofloxacin 500-750mg PO or 400mg IV q12h
OR
Ceftriaxone 2g IV q24h
Alternative Regimen (Allergy / Resistance)
Ampicillin 2g IV q4-6h
OR
Trimethoprim/sulfamethoxazole (80/400mg) 2 tablets PO or 2 ampoules IV q12h
Remarks & Clinical Comments:
Susceptibility profile may help guide final choice.
Duration:
CD4 ≥ 200: 7-14 days.
CD4 ≥ 200 and with bacteraemia: 14 days is appropriate provided documented clearance of bacteraemia.
CD4 < 200 and with bacteraemia: 6 weeks.
Longer course with debridement and drainage needed for persistent bacteraemia or metastatic disease.
Ciprofloxacin 500-750mg PO q12h or 400mg IV q8-12h or levofloxacin 500-750mg IV/PO q24h
PLUS
Rifampicin 600mg PO q24h
Alternative Regimen (Allergy / Resistance)
Azithromycin 500mg STAT and then 250mg IV/PO q24h
OR
Ciprofloxacin 500-750mg PO q12h or 400mg IV q8-12h or levofloxacin 500-750mg IV/PO q24h
OR
Rifampicin 600mg PO q24h
PLUS
Imipenem/Cilastatin 500mg IV q6h
OR
Vancomycin 15-20mg/kg (actual body weight) IV q8-12H; not to exceed 2g/dose
Remarks & Clinical Comments:
Duration:
Immunocompromised – at least 2 months
Duration will depend on the extent of the diseases.
Adjust antibiotics according to susceptibility data.
Use at least two or more susceptible agents.
Concomitant tuberculosis needs to be ruled out with use of rifampicin monotherapy.
For CNS involvement, to consider antibiotics with good CNS penetration.
Duration: Until CD4 > 200 cells/μL
Choice to be based on susceptibility test.
Concomitant tuberculosis needs to be ruled out with use of rifampicin monotherapy.
2. OPPORTUNISTIC INFECTION (OI) IN PATIENTS WITH HUMAN IMMUNODEFICIENCY VIRUS (HIV)
2.16.1 Initial Therapy
2.16 Isospora belli Infection
Preferred Regimen
Trimethoprim/sulfamethoxazole 160/800mg IV/PO q6h
Alternative Regimen (Allergy / Resistance)
*Pyrimethamine 50-75mg PO q24h
PLUS
Folinic acid 15mg PO q24h
OR
Ciprofloxacin 500mg PO q12h
Remarks & Clinical Comments:
Duration: 10 days
For patients whose symptoms persist after 10 days, the treatment duration can be extended to 3-4 weeks.
*Requires DG’s approval.
Discontinuation:
CD4 count > 200 cells/μL for ≥ 6 months on ART.
2. OPPORTUNISTIC INFECTION (OI) IN PATIENTS WITH HUMAN IMMUNODEFICIENCY VIRUS (HIV)
2.16.2 Secondary Prophylaxis
2.16 Isospora belli Infection
Preferred Regimen
Trimethoprim/sulfamethoxazole 160/800mg PO q24h
Alternative Regimen (Allergy / Resistance)
*Pyrimethamine 25mg PO q24h
PLUS
Folinic acid 15mg PO q24h (if sulfa-intolerant)
OR
Ciprofloxacin 500mg PO three times a week
Remarks & Clinical Comments:
Duration: 10 days
For patients whose symptoms persist after 10 days, the treatment duration can be extended to 3-4 weeks.
*Requires DG’s approval.
Discontinuation:
CD4 count > 200 cells/μL for ≥ 6 months on ART.
2. OPPORTUNISTIC INFECTION (OI) IN PATIENTS WITH HUMAN IMMUNODEFICIENCY VIRUS (HIV)
2.20.1 Bacillary Angiomatosis, Peliosis Hepatis, Bacteraemia, and Osteomyelitis
2.20 Bartonellosis
Preferred Regimen
Doxycycline 100mg PO q12h
OR
Erythromycin 500mg PO/IV q6h
Alternative Regimen (Allergy / Resistance)
Azithromycin 500mg PO q24h
OR
Clarithromycin 500mg PO q12h
Remarks & Clinical Comments:
Duration: At least 3 months
If relapse occurs after initial (> 3 month) course of therapy, long-term suppression with doxycycline or a macrolide is recommended as long as CD4 <200 cells/μL.
2. OPPORTUNISTIC INFECTION (OI) IN PATIENTS WITH HUMAN IMMUNODEFICIENCY VIRUS (HIV)
2.20.2 Other Severe Infections (or CNS involvement)
2.20 Bartonellosis
Preferred Regimen
Doxycycline 100mg PO/IV q12h
OR
Erythromycin 500mg PO/IV q6h
MAY ADD
Rifampicin 300mg PO/IV q12h
Remarks & Clinical Comments:
Duration: At least 3 months
If relapse occurs after initial (> 3 month) course of therapy, long-term suppression with doxycycline or a macrolide is recommended as long as CD4 <200 cells/μL.
If cephalosporin allergy and low risk for gonorrhoea:
Levofloxacin 500mg PO q24h for 14 days
PLUS
Metronidazole 400mg PO q12h for 14 days
Remarks & Clinical Comments:
Sexual partner(s) within 60 days should be examined, investigated and treated epidemiologically for chlamydia and gonorrhoea, regardless of PID aetiology or pathogen isolated.
Abstain from sex until the patient and partner(s) have completed treatment and symptoms are resolved.
Duration: 14 days
Tubo-ovarian abscess: Surgical intervention for source control may be required.
May need to consider tuberculosis if not responding to standard treatment.
*Patients with clinical improvement after 24-48 hours can be transitioned to oral therapy to complete the 14 days of treatment.
Common organisms: Klebsiella E. coli Clostridia Coagulase-negative Staphylococci Enterococci Bacteroides
Preferred Regimen
Stage 1
Ampicillin 100mg/kg/dose IV
≤ 1 week of age: q12h
>1 week of age: q8h
PLUS
Gentamicin 5mg/kg/dose IV
< 30 weeks of CGA: q48h
30-34 weeks of CGA: q36h
≥ 35 weeks CGA: q24h
OR
Amikacin 15mg/kg/dose IV
< 30 weeks of CGA: q48h
30-34 weeks of CGA: q36h
≥35 weeks of CGA: q24h
PLUS
Metronidazole
Loading dose: 15mg/kg/dose IV
Maintenance dose:
≤ 34 weeks of age: 7.5mg/kg/dose IV q12h
35-40 weeks of age: 7.5mg/kg/dose IV q8h
> 40 weeks of age: 10mg/kg/dose IV q8h
Stage 2 / Stage 3
Cefotaxime 50mg/kg/dose IV
≤ 1 week of age: q12h
> 1 week of age: q8h
PLUS
Metronidazole
Loading dose:15mg/kg/dose IV
Maintenance dose:
≤ 34 weeks of age: 7.5mg/kg/dose IV q12h
35-40 weeks of age: 7.5mg/kg/dose IV q8h
>40 weeks of age: 10mg/kg/dose IV q8h
Duration: 10-14 days
Alternative Regimen (Allergy / Resistance)
ONLY consider IV Piperacillin/tazobactam after recent exposure to first line antibiotics.
Piperacillin/tazobactam IV
PMA ≤30 weeks: 100mg/kg/dose q8h
PMA >30 weeks: 80mg/kg/dose q6h
Remarks & Clinical Comments:
There is insufficient evidence regarding the duration of antibiotic treatment for NEC. This suggested regimen for NEC is empirical. Once culture is known, decisions regarding choice of antibiotics are best guided by culture results.
Use vancomycin if CoNS/MRSA is suspected (substitute Ampicillin with Vancomycin).
Common organisms: Group B Streptococcus (GBS) Listeria Streptococcus sp. E. coli Haemophilus influenza Klebsiella sp. etc.
Preferred Regimen
Benzylpenicillin (Penicillin G) 100,000 units/kg/dose IV
GA ≤ 34 weeks:
PNA ≤ 7 days: q12h
PNA >7 days: q8h
GA > 34 weeks:
PNA ≤ 7 days: q8h
PNA >7 days: q6h
OR
Ampicillin 200-300mg/kg/day IV
≤ 1 week of age: in 3 divided doses
> 1 week of age: in 4 divided doses
PLUS
Gentamicin 5mg/kg/dose IV
< 30 weeks of CGA: q48h
30-34 weeks of CGA: q36h
≥ 35 weeks CGA: q24h
Remarks & Clinical Comments:
Consider stopping antibiotics at 36-48 hours if negative blood culture, initial clinical suspicion not strong and reassuring baby’s condition with low CRP.
If positive blood culture or strong clinical suspicion of sepsis but negative culture, may give 7 days of antibiotics.
Consider antibiotics for more than 7 days if baby not fully recovered and based on pathogen identified on blood culture.
In this empiric therapy - meningitis is not a consideration.
Once cultures are known, adjust antibiotics accordingly.
Common organisms: Methicillin-sensitive/resistant S. aureus (MSSA/MRSA) Coagulase- negative Staphylococci (CoNS) Gram-negative rods (Depending on local epidemiological data)
Preferred Regimen
First line
Cloxacillin 50mg/kg/dose IV
≤ 1 week of age: q12h
> 1 week of age: q8h
PLUS
Gentamicin 5mg/kg/dose IV
< 30 weeks of CGA: q48h
30-34 weeks of CGA: q36h
≥ 35 weeks of CGA: q24h
Second line
Piperacillin/tazobactam IV
PMA ≤ 30 weeks: 100mg/kg/dose q8h
PMA > 30 weeks: 80mg/kg/dose q6h
< 30 weeks
0-28 days: 100mg/kg q12h
> 28 days: 100mg/kg q8h
30-36 weeks
0-14 days: 100mg/kg q12h
> 14 days: 100mg/kg q8h
37-44 weeks
0-7 days:100mg/kg q12h
> 7 days: 100mg/kg q8h
≥ 45 weeks: 100mg/kg q8h
Alternative Regimen (Allergy / Resistance)
First line
Amikacin 15mg/kg/dose IV
< 30 weeks of CGA: q48h
30-34 weeks of CGA: q36h
≥ 35 weeks of CGA: q24h
Second line
Cefepime IV
Term and Prem younger than 28 days of life: 30mg/kg/dose q12h
Term and Prem greater than 28 days of life: 50mg/kg/dose q12h
Remarks & Clinical Comments:
For late onset sepsis, the most common organisms are predominantly Gram-positive cocci, namely Staphylococci, especially CONS, in premature neonates and also neonates with central catheters.
Piperacillin/tazobactam is a good second line option in pneumonia and intra-abdominal sepsis (non–CONS sepsis with good coverage against Gram-positive, Gram-negative & anaerobes).
There is possibility of Gram-negative rods with inducible β-lactamases and ESBL producing organism such as Klebsiella, Serratia and E. coli in some NICU in Malaysia hence need to look at local epidemiology before deciding on suitable second line.
Cefepime is the preferred agent when there are Gram-negative bacteria with extended spectrum cephalosporin resistance due to AmpC-β-lactamases (also termed Class C or Group 1).
Duration: If positive blood culture or strong clinical suspicion of sepsis but negative culture, may give 7 days of antibiotics.
Consider antibiotics for more than 7 days if baby not fully recovered, based on site of infection & pathogen identified on blood culture.
Benzylpenicillin (Penicillin G) 50,000 units/kg/dose IV
For first 7 days of life: q12h
Thereafter: q8h
Duration: 10 days*
If diagnosed with congenital syphilis after one month of age
Benzylpenicillin (Penicillin G) 200,000-300,000 units/kg/day IV in 4-6 divided doses for 10-14 days.
In infants considered less likely to have syphilis and normal CSF examination including normal physical examination & long bone radiograph
Benzathine penicillin 50,000 units/kg/dose IM in a single dose can be given.
Alternative Regimen (Allergy / Resistance)
Procaine penicillin 50,000 units/kg/dose IM in a single daily dose for 10 days.*
Remarks & Clinical Comments:
Only severe cases are clinically apparent at birth.
Refer to algorithm for diagnosing & evaluation.
Re-evaluate & possibly re-treat. Please refer Red Book 2021 & Malaysian Paediatric Protocol 4th edition.
*14 days if CSF abnormal
*Pyrimethamine 1mg/kg/day PO for 2 months, followed by 0.5 mg/kg/day PO for 10 months
< 60kg: up to 50mg/day
≥ 60kg: up to 75mg/day
PLUS
*Sulfadiazine 100mg/kg/day PO in 2 divided doses for 12 months*
PLUS
Folinic Acid 50 mg PO every 7 days for 12 months
Remarks & Clinical Comments:
Drug regimen is not definitively established. Clinical trials are ongoing.
Prednisolone 0.5 mg/kg (max. 20 mg/dose) q12h can be added if CSF protein ≥ 1g/dL or active severe chorioretinitis. Steroids given till CSF protein < 1g/dL or resolution of severe chorioretinitis.
Fansidar is currently an “orphan” drug that needs special procurement measures to buy. Refer to paediatric ID consultant for treatment and availability of drug.
*Requires DG’s Approval
*Total duration may be extended up to 2 years depending on severity and response to treatment.
Localised skin, eye & mouth (SEM) Central nervous system (CNS) with or without SEM Disseminated disease involving multiple organs
Preferred Regimen
Acyclovir 20mg/kg/dose IV
< 30 weeks: q12h
≥ 30 weeks: q8h
Duration:
Skin, eyes, mouth: 14 days
CNS/disseminated: minimum of 21 days
All infants surviving neonatal HSV infection of any classification should receive oral acyclovir suppression at 300mg/m2/dose administered 3 times daily for 6 months after completion of parenteral therapy (adjust dose monthly to account for growth).
Remarks & Clinical Comments:
Screen for other STDs.
For CNS disease:
Repeat lumbar puncture at end of therapy for HSV PCR. If PCR remains positive, continue IV acyclovir for another one week.
Recurrence of HSV can occur and may be a lifelong problem.
Benzylpenicillin (Penicillin G) 100,000 units/kg/dose IV
GA < 34 weeks:
PNA ≤ 7 days: q12h
PNA > 7 days: q8h
GA > 34 weeks:
PNA ≤ 7 days: q8h
PNA > 7 days: q6h
Remarks & Clinical Comments:
IM Human Tetanus Immunoglobulin 250-500 IU for neutralizing of unbound toxin.
Antibiotics may fail to eradicate C. tetani unless adequate wound debridement is performed.
May need to continue for 48-72h until systemic infection has been ruled out.
Disseminated disease:
Cefotaxime 50mg/kg/dose IV
≤ 1 week of age: q12h
> 1 week of age: q8h
Duration: 7 days. 10–14 days if meningitis is documented.
Remarks & Clinical Comments:
Evaluate for signs of disseminated infection (E.g.: sepsis, arthritis & meningitis).
Screen mother & baby for chlamydial infection.
Screen for other STDs.
Investigate and treat parents.
Azithromycin 20 mg/kg/day PO, once daily for 3 days. (Limited data on efficacy)
Remarks & Clinical Comments:
Initial treatment for chlamydial conjunctivitis should be based upon a positive diagnostic test.
Re-swab after treatment; 20-30% will need a second course to clear infection.
* Second course of treatment might be required
Benzylpenicillin (Penicillin G) 100,000 units/kg/dose IV
GA ≤ 34 weeks:
PNA ≤ 7 days: q12h
PNA > 7 days: q8h
GA >34 weeks:
PNA ≤ 7 days: q8h
PNA >7 days: q6h
OR
Ampicillin
≤ 1 week of age: 200-300 mg/kg/day IV in 3 divided doses
> 1 week of age: 300 mg/kg/day IV in 4 divided doses
PLUS
*Gentamicin 5 mg/kg/dose IV
< 30 weeks of CGA: q48h
> 30-34 weeks of CGA: q36h
≥ 35 weeks of CGA: q24h
Remarks & Clinical Comments:
Duration of treatment for GBS:
Uncomplicated (bacteremia without a defined focus): 10-14 days
*Gentamicin can be discontinued once the infection is under control.
≤ 1 week of age: 200-300 mg/kg/day IV in 3 divided doses
> 1 week of age: 300 mg/kg/day IV in 4 divided doses
PLUS
Gentamicin 5 mg/kg/dose IV
< 30 weeks of CGA: q48h
> 30-34 weeks of CGA: q36h
≥ 35 weeks CGA: q24h
Remarks & Clinical Comments:
Duration for treatment: 14-21 days
Uncomplicated meningitis: 14 days
Complicated: minimum 21 days
For uncomplicated meningitis, may consider repeat lumbar puncture 48-72 hours. If CSF culture negative, gentamicin can be stopped and continue penicillin/ampicillin for 2 weeks
Doses of penicillin for meningitis is higher as recommended by experts (as high as 500,000 unit/kg/day (> 7 days of age).
IV treatment is typically continued until the patient is clinically improved (no fundal tenderness) and afebrile for 24 - 48 hours.
If an oral antibiotic regimen is administered, duration: 14 days.
*TDM for gentamicin is required
Duration in bacteremia: 14 days.
Duration for meningitis: 21 days.
All cases of bacteremia need lumbar puncture to exclude meningitis.
Treatment duration of 14 days can be decided on a case-by-case basis if meningitis is excluded and good clinical response.
Duration: 10-14 days
Intravenous antibiotics are administered until the patient has improved and afebrile for 48 hours, then are typically followed by oral antibiotics.
*TDM for gentamicin is required
Antibiotic regimen is continued postpartum until the patient is afebrile and asymptomatic for at least 48 hours.
There is no evidence that continuation with oral antibiotic are beneficial after discontinuation of parenteral therapy.
5. INTRAPARTUM ANTIBIOTIC PROPHYLAXIS (IAP) FOR GROUP B STREPTOCOCCUS (GBS) POSITIVE MOTHERS
Indications of IAP: Previous infant with invasive GBS disease, preterm labour, GBS carriage in previous pregnancy, PPROM with known GBS carrier, GBS carriage in current pregnancy, GBS bacteriuria
Preferred Regimen
Benzylpenicillin 5MU IV initial dose, then 2.5–3MU IV q4h until delivery
Alternative Regimen (Allergy / Resistance)
Ampicillin 2g IV initial dose, then 1g IV q4h until delivery
Mild antibiotic allergy:
Cefazolin 2g IV initial dose, then 1g q8h until delivery
OR
Cefuroxime 1.5g IV STAT and 750mg IV q8h until delivery
Severe antibiotic allergy:
Vancomycin 15-20mg/kg IV q8-12h until delivery
OR
Clindamycin 900mg IV q8h until delivery
Remarks & Clinical Comments:
Prophylaxis begins at hospital admission for labour or rupture of membrane and continued every four hours until the infant is delivered.
Treatment is not indicated if Caesarean section is performed before onset of labour with intact membrane (please use standard surgical prophylaxis).
Antenatal treatment is not recommended for GBS cultured from a vaginal or rectal swab.
Risk of gram negative or anaerobic infection (e.g. diabetes):
Amoxicillin/clavulanate 1.2g IV q8h
OR
Ampicillin/sulbactam 3g IV q6h
Remarks & Clinical Comments:
Duration: 10-14 days but shorter duration (5-7 days) can be considered if adequate source control and local wound management result in clinical improvement.
Duration: 5-7 days
If the patient has risk factors for sexually transmitted infections (STIs), appropriate investigations should be performed, and empirical treatment initiated as outlined in the STI chapter.
Surgical management is recommended if the abscess does not drain spontaneously.
Common organisms: Streptococcus pneumoniae Staphylococcus aureus Streptococcus pyogenes Haemophilus influenzae
Preferred Regimen
Mild
Amoxicillin/clavulanate
Suspension (Formulation 14:1)
Amoxicillin / Clavulanate 80-90mg/kg/day PO in 2 divided doses (Amoxicillin component, max. 2g/day)
Suspension (Formulation 7:1)
Amoxicillin / Clavulanate 40-50mg/kg/day PO in 2 divided doses (Amoxicillin component, max. 2g/day)
Systemically Unwell
Cloxacillin 200mg/kg/day IV in 4 divided doses (max. 12g/day)
PLUS
Cefotaxime 150-200mg/kg/day IV in 3 divided doses (max. 6g/day)
OR
Ceftriaxone 50mg/kg/dose IV q12h (max. 4g/day)
Alternative Regimen (Allergy / Resistance)
Cephalexin 25-50mg/kg/day PO in 2 divided doses (max. 2g/day) for 10 days
Remarks & Clinical Comments:
Failure to respond within 24-48 hours may indicate orbital cellulitis or underlying sinus disease.
When improving and no organism identified, change to amoxicillin/clavulanate and complete for 7 days.
Ceftriaxone 50mg/kg/dose IV q12h (max. 4g/day) for 7-14 days
PLUS
Cloxacillin 200mg/kg/day IV in 4 divided doses (max. 12g/day) for 7-14 days
**If associated with chronic sinusitis / complicated with intracranial abscess, to add on IV Metronidazole 30mg/kg/day q8hr (max. 1500mg/day)
Inpatient:
48-72 hours IV antibiotic, then oral to complete 14 days following good response (no positive culture)
Amoxicillin/clavulanate
Suspension (Formulation 14:1)
Amoxicillin / Clavulanate 80-90mg/kg/day PO in 2 divided doses (Amoxicillin component, max. 2g/day)
Suspension (Formulation 7:1)
Amoxicillin / Clavulanate 40-50mg/kg/day PO in 2 divided doses (Amoxicillin component, max. 2g/day)
Alternative Regimen (Allergy / Resistance)
Antibiotic allergy:
Clindamycin 30-40mg/kg/day PO in 3 or 4 divided doses (max. 450mg/dose)
CA-MRSA:
Adjust accordingly with sensitivity
E.g.: Vancomycin 60mg/kg/day IV in 3-4 divided doses
Remarks & Clinical Comments:
This condition is considered a surgical emergency and requires immediate consultation with ENT surgeon and ophthalmologist.
Urgent CT scan needed to exclude associated abscess and intracranial extension.
Urgent surgical drainage of the ethmoid sinuses or of an orbital, subperiosteal or intracranial abscess may be needed.
Refer to Appendix 3 for antibiotic allergy.
Frequent eye toileting of the infected eye with topical saline eye drops until discharge reduces.
Topical antibiotics may be considered as ancillary therapy.
Monotherapy is indicated for mild bacterial keratitis.
Combination therapy is indicated for severe bacterial keratitis.
*Prepared extemporaneously using injectable forms.
Monotherapy is indicated for mild bacterial keratitis.
Combination therapy is indicated for severe bacterial keratitis.
*Prepare extemporaneously using injectable forms.
Common organisms: Aspergillus sp. Fusarium sp. Candida sp.
Preferred Regimen
Polyenes:
**Natamycin 5% eye drop q1-2h
OR
*Amphotericin B 0.05-0.15% eye drop q1-2h
Azoles:
*/**Voriconazole 1% eye drop q1-2h
OR
*Fluconozole 0.2% eye drop q1-2h
Oral Therapy:
May be considered in the absence of contraindications.
Fluconazole 200mg PO q24h
OR
Itraconazole 200mg PO q24h
Remarks & Clinical Comments:
Dual combination therapy of polyene and azole antifungal may be used.
Natamycin is the choice of therapy for Fusarium sp.
Amphotericin B is the choice of therapy for yeasts.
*Prepare extemporaneously using injectable forms.
**Requires DG’s approval.
Minimum: 3 weeks duration
*Valganciclovir 900mg PO q12h for 2-3 weeks (induction) followed by 900mg PO q24h (maintenance)
OR
*Foscarnet IV 60mg/kg q8H or 90mg/kg q12h for patients with treatment limiting toxicities to ganciclovir or with ganciclovir resistance
Intravitreal therapy:
*Intravitreal foscarnet 2.4mg/0.1ml (1-2weekly)
Remarks & Clinical Comments:
Systemic therapy is indicated in all cases.
Maintenance therapy may need to be continued until CD4 count is > 100 cells/mm3 for 3 consecutive months.
Intravitreal therapy is indicated in zone 1 and 2 lesions.
Intravitreal therapy to be tapered according to clinical response.
Ganciclovir implant 4.5g is an option for prolonged usage of intravitreal ganciclovir.
*Requires DG’s approval
Vancomycin 15 – 20mg/kg IV q8-12h; not to exceed 2g/dose
PLUS
Ceftazidime 1-2g IV q8h
Deescalate to,
Ciprofloxacin 500mg - 750mg PO q12h with evidence of clinical improvement after 2 weeks of intravenous antibiotic.
For culture negative,
ADD
Clarithromycin 500mg PO q12h for 2 weeks
If suspicious of fungal endopthalmitis, refer section fungal endopthalmitis.
Topical therapy:
Moxifloxacin 5% eye drop
Alternative Regimen (Allergy / Resistance)
Intravitreal antibiotic injections:
*Vancomycin 1-2mg/0.1ml
PLUS
*Amikacin 0.4mg/0.1ml
Systemic therapy:
Ciprofloxacin 750mg PO q12h for 10 days
OR
Moxifloxacin 400mg PO q24h for 10 days
Topical therapy:
Ceftazidime 5% eye drop
Remarks & Clinical Comments:
Systemic antibiotics are indicated in severe, virulent endophthalmitis.
Repeat intravitreal antibiotics after 48 to 72 hours if indicated.
*Prepare extemporaneously using injectable forms
Systemic treatment only indicated in cases of delay of transfer to ophthalmology centre.
Systemic antibiotics are typically continued for a minimum of 2–4 weeks, and up to 6 weeks, depending on observed ophthalmologic improvement.
Fluconazole IV 800mg (12mg/kg) loading dose then 400-800mg (6-12mg/kg daily)
For severe condition:
Amphotericin B 0.5-1mg/kg IV q24h; MAY ADD
**Flucytosine 25mg/kg q6h
Step down therapy:
Fluconazole 200mg PO q24h for total 4-6 weeks (minimum)
Alternative Regimen (Allergy / Resistance)
Intravitreal therapy:
*Voriconazole 50ug-100ug/0.1ml
PLUS
Systemic therapy:
*Voriconazole 400mg (6mg/kg) IV/PO q12h for 2 doses, followed by 200mg (4mg/kg) PO q12h
Remarks & Clinical Comments:
Intravitreal and systemic therapy are indicated in all cases.
Refer to microbiological sensitivity.
Systemic therapy is typically continued for at least 4-6 weeks depending on observed ophthalmologic improvement.
*Requires DG’s approval
**Flucytosine is recommended for less susceptible azole isolates.
Common organism: Streptococcus pneumonia or other streptococcus Neisseria Meningitidis Staphylococcus aureus Klebsiella pneumoneia or other gram negative organism Candida sp
Preferred Regimen
*Systemic therapy:
Ceftriaxone 2g IV q24h
OR
Cefotaxime 2g IV q4h
For culture negative cases,
ADD
Clarithromycin 500mg PO q12h for 7-14 days
AND
Intravitreal antibiotic injections:
Vancomycin 1-2mg/0.1ml
PLUS
Ceftazidime 2mg/0.1ml
If suspicious of fungal endopthalmitis, refer section fungal endopthalmitis.
Topical treatment:
Moxifloxacin 5% eye drop
Alternative Regimen (Allergy / Resistance)
Systemic therapy:
Ciprofloxacin 750mg PO q12h for 10 days
OR
Moxifloxacin 400mg PO q24h for 10 days
Intravitreal antibiotic injections:
Vancomycin 1-2mg/0.1ml
PLUS
Amikacin 0.4mg/0.1ml
Topical treatment:
Ceftazidime 5% eye drop
Remarks & Clinical Comments:
Treatment is based on primary infection (bacterial/fungal) and culture and sensitivity results.
All cases require systemic therapy. Intravitreal injection is indicated in cases with vitreous involvement and sight threatening choroidal lesions.
Topical therapy may supplement therapy. Not to use systemic steroids in these cases.
Review antibiotic regimen after microbiology results. Repeat intravitreal antibiotics after 48 to 72 hours if indicated.
*Systemic antibiotics are typically continued for a minimum of 2–4 weeks, and up to 6 weeks, depending on observed ophthalmologic improvement.
Trimethoprim/sulfamethoxazole 160/800mg PO q12h for at least 6 weeks
Prophylaxis for recurrent lesions:
Trimethoprim/sulfamethoxazole 80/400mg q12h PO for 3 times a week
Alternative Regimen (Allergy / Resistance)
*Pyrimethamine 100mg PO on Day 1
Followed by:
*Pyrimethamine 25-50mg PO q24h
PLUS
Folinic acid 10-25mg PO q24h
PLUS
*Sulfadiazine 1g PO q6h for at least 6 weeks
OR
Azithromycin 500mg PO q24h for 3 weeks
OR
Clindamycin 300mg PO q6h for 3 weeks
Remarks & Clinical Comments:
Pregnancy: May consider intravitreal clindamycin 1.0mg/0.1ml.
Systemic steroids are usually indicated in immunocompromised patients.
*Requires DG’s approval.
Requires systemic therapy. Refer to Ministry of Health’s CPG on Management of Tuberculosis (Extra pulmonary TB).
Ethambutol may cause optic neuropathy and should be avoided depending on the case.
Ocular TB presents as a unilateral/ bilateral infective uveitis characterized by multifocal choroiditis/ granuloma and there may be supportive FFA findings of occlusive vasculitis. The diagnosis may be clinical as vitreous sampling for AFB or TB PCR may not be very sensitive due to small sample size and sensitivity of the tests. Clinical response to anti-TB is often diagnostic.
Uveitis secondary to TB Hypersensitivity is an immune response to acid fast bacilli in the eye and manifests predominantly as an inflammatory uveitis. Treatment includes anti-TB in combination with an immunosuppressive dose of systemic steroids for at least 6-9 months.
Systemic steroids may be indicated but is only for
● Non-active systemic TB
● Immunocompetent patients
● Severe ocular inflammation developing after starting anti-TB treatment
● Vision threatening condition
Cloxacillin 200mg/kg/day IV in 4-6 divided doses (max. 2g/dose)
PLUS
Cefotaxime 200mg/kg/day IV in 4 divided doses (max. 2g/dose)
>3 months to 5 years old
Cloxacillin 200mg/kg/day IV in 4-6 divided doses (max. 2g/dose)
MAY ADD
Cefuroxime 100-200mg/kg/day IV in 3 divided doses (max. 1.5g/dose) (monotherapy)
OR
Cefotaxime 200mg/kg/day IV in 4 divided doses (max. 2g/dose)
Older than 5 years old
Cloxacillin 200 mg/kg/day IV in 4-6 divided doses (max. 2g/dose)
Alternative Regimen (Allergy / Resistance)
0 - 3 months old
Cefazolin is alternative anti-staphylococcal agent for infants age 1-3 months if no CNS involvement
>3 months
Cefazolin 100-150mg/kg/day IV in 3 divided doses (max. 1g/dose)
(Can be used in children with suspected S. aureus or S. pyogenes. Less hypersensitivity reaction compared to cloxacillin & more convenient dosing)
Kingella kingae: uncommon organism causing infection in <5 years old; indolent onset; preceding oral ulcers; may affect nontubular bones; sensitive to β-lactam antibiotics e.g., cefuroxime or amoxicillin/clavulanate
Remarks & Clinical Comments:
SEPTIC ARTHRITIS (SA) & OSTEOMYELITIS (OM)
Common organisms according to age groups:
≤ 3 months
S. aureus
Streptococcus agalactiae
Gram-negative enteric organism
>3 months to 5 years old
Staphylococcus aureus
Streptococcus pyogenes
Streptococcus pneumoniae
Non-typeable Haemophilus spp.
Kingella kingae
Older than 5 years
Staphylococcus aureus
Streptococcus pyogenes
Polymicrobial infection: More likely with penetrating trauma or contagious spread
Empiric antibiotics should be started based on clinical diagnosis of SA or OM.
CBC, blood cultures and CRP +/- ESR should be taken prior to antibiotic therapy.
Optimise antimicrobial treatment based on C&S.
Surgical debridement often not required in OM.
Urgent wash out & drainage is needed in SA in hip and other joints to reduce pressure on growth plate.
Synovial fluid and bone culture/analysis is part of diagnostic work up if child is subjected to drainage or debridement.
Duration of antibiotics:
SA: total of 3-4 weeks (*4-6 weeks if hip is involved)
OM: 4-6 weeks
For both SA and OM, transition to oral antibiotic is based on clinical and laboratory improvement if compliance and follow up is assured.
Shorter duration of 3-4 weeks antibiotics for uncomplicated MSSA or culture negative OM responded to initial therapy for children > 3 months old.
Neonatal OM: Similar duration for other age group but at least 4 weeks of IV antibiotics.
Choice of oral regimen is based on culture and susceptibility results. If cultures are negative, oral therapy is directed toward the most likely pathogen with similar spectrum of activity as parenteral therapy. Higher doses are generally given to ensure adequate bone penetration.
Uncomplicated OM is defined as single bone involvement, rapid resolution of bacteremia, rapid clinical response to medical and surgical treatment, rapid fall of CRP with no identified acute or late sequalae of infection.
Complex OM (multifocal, significant bone destruction, immunocompromised host & resistant/unusual pathogens), prolonged IV antibiotics are needed & duration might exceed 6 weeks.
1.1 Infections of the Teeth and Supporting Structures
Preferred Regimen
Superficial:
Systemic antibiotic use not recommended (immunocompetent).
Deep Infection / Immunocompromised patient:
Amoxicillin 500mg PO q8h
MAY ADD
Metronidazole 400mg PO q8h
Alternative Regimen (Allergy / Resistance)
Deep Infection / Immunocompromised patient:
Amoxicillin/clavulanate 625mg PO q8h
Antibiotic allergy:
Clindamycin 300mg PO q6h for 7 days
Remarks & Clinical Comments:
The definitive treatment involves aggressive surgical intervention for source control, which includes drainage of the abscess with or without tooth extraction. If the procedure is successful, a minimum duration of 3 days of antibiotic therapy should be administered.
Duration: 3 – 7 days
Refer to Appendix 3 for antibiotic allergy.
1.1 Infections of the Teeth and Supporting Structures
Antibiotic use can be considered in cases of: 1. Unresponsive to conventional mechanical therapy. 2. Acute infection associated with systemic manifestation. 3. Immunocompromised. 4. Generalized periodontitis stage III in young adults.
Preferred Regimen
Systemic antibiotic use is generally not recommended.
Amoxicillin 500mg PO q8h
PLUS
Metronidazole 400mg PO q8h
OR
Amoxicillin/clavulanate 625mg PO q8h
Alternative Regimen (Allergy / Resistance)
Antibiotic allergy:
Clindamycin 300mg PO q6h
Remarks & Clinical Comments:
First line treatment:
Mechanical plaque control
Duration: 3-7 days
Refer to Appendix 3 for antibiotic allergy.
Culture and sensitivity are necessary to guide the antibiotic.
For chronic cases, start with surgical treatment first. Start antibiotics only when causative organisms are identified.
Duration of antibiotic therapy:
4-6 weeks depending on patient response / microbiological clearance of the pathogen.
Refer to Appendix 3 for antibiotic allergy.
1.3 Spreading Infections and Infections of Fascial Spaces (with/without Systemic Signs)
Preferred Regimen
Benzylpenicillin 2-4MU IV q4-6h
PLUS
Metronidazole 500mg IV q8h
OR
Amoxicillin/Clavulanate 1.2g IV q8h
OR
Cefuroxime 1.5g IV q8h
PLUS
Metronidazole 500mg IV q8h
Alternative Regimen (Allergy / Resistance)
Antibiotic allergy:
Clindamycin 300-450mg PO q6h or 600-900mg IV q8h
Remarks & Clinical Comments:
Incision and drainage are advised and change antibiotics in accordance with the result of culture and sensitivity.
Continue IV therapy for 1 to 2 days following successful abscess drainage, then switch to oral therapy.
Refer to Appendix 6 for IV to PO switch.
Refer to Appendix 3 for antibiotic allergy.
Phenoxymethylpenicillin (penicillin V) 25-50mg/kg/day (max. 2g/day) PO in 4 divided doses
OR
Amoxicillin 50mg/kg/day PO in 1 or 2 divided doses (max. 1g/day)
OR
*Benzylpenicillin 100,000-200,000units/kg IV in 4 divided doses (max. 24 million unit/day)
Switch to oral therapy (penicillin V / amoxicillin) when improving and being able to tolerate orally.
Total duration: 10 days
Alternative Regimen (Allergy / Resistance)
Antibiotic allergy (non-life-threatening)
Cephalexin 25-50mg/kg/day (max. 2g/day) PO in 2 divided doses
OR
Erythromycin ethylsuccinate 40-50mg/kg/day (max. 800mg/dose) PO in 2 divided doses
Duration: 10 days
Remarks & Clinical Comments:
Once-daily dose amoxicillin (50 mg/kg; max:1g/day) for 10 days, is as effective as penicillin V or multiple dose amoxicillin for 10 days endorsed by the American Heart Association and the Infectious Disease Society of America in its guidelines for the treatment of GAS pharyngitis and the prevention of ARF.
Adherence is important for once-daily dosing regimens.
*IV antibiotics are not routinely recommended for uncomplicated tonsillopharyngitis but may be considered in severe cases or if the child is unable to tolerate oral therapy.
Common organisms: Staphylococcus aureus (80%) Group A Streptococcus pyogenes Rarely gram negative bacilli
Preferred Regimen
Empirical coverage:
Cloxacillin 2g IV q6h
To tailor antibiotics according to definitive cultures.
Alternative Regimen (Allergy / Resistance)
Antibiotic allergy:
Cefazolin 2g IV q6-8h
Remarks & Clinical Comments:
Duration:
Initial IV therapy for 2-4 weeks followed by oral therapy. Minimum duration: 6 weeks. Modify according to clinical response.
Antibiotic therapy tailored to tissue/bone C&S result.
4 weeks of IV antibiotics is required for Staphylococcus aureus osteomyelitis associated with bacteraemia.
Conversion from IV to PO therapy with good bioavailability can be done after minimum 2 weeks of IV antibiotics provided:
Patient has no significant comorbidity
Uncomplicated infection with source control
Clinical response seen
Patient able to tolerate orally
Suitable oral antibiotics with good oral bioavailability & proven sensitivity to causative organism
A shorter duration of antibiotics can be considered if the osteomyelitis is fully resected (E.g.: amputation with a clear margin):
No surrounding soft tissue infection: 5 days.
Evidence of soft tissue infection: 10-14 days.
Refer to Appendix 3 for antibiotic allergy.
This includes pyogenic spine infections, both acute and chronic. Common organisms: Staphylococcus aureus (main), Brucella, Salmonella, Gram negative Bacilli
Preferred Regimen
Empirical therapy should be withheld unless the patient is septic or in patients with neurologic compromise.
CT-guided needle biopsy & aspiration should be done & specimen sent for C&S.
Cloxacillin 2g IV q4h
Alternative Regimen (Allergy / Resistance)
Cefazolin 2g IV q6-8h
Remarks & Clinical Comments:
Empiric gram negative (3rd or 4th generation cephalosporin) should be covered if patient had:
Recent spinal hardware inserted or surgery
Intra-abdominal infections
Co-existing or synchronous genitourinary infection
Immunocompromised
Antibiotic therapy tailored to tissue/bone C&S result.
Conversion from IV to oral therapy with good bioavailability can be done after minimum 2 weeks of IV antibiotics.
Duration:
Minimum 6 weeks.
Minimum 8 weeks if undrained paravertebral abscess(es) and/or infection due to drug-resistant organisms.
Up to 12 weeks if extensive bone destruction or infection due to Brucella sp.
Refer to brucellosis under Tropical Infections section for infection due to Brucella sp.
Early onset (within 30 days of implant insertion): Staphylococcus aureus, Beta-hemolytic streptococci, Gram-negative bacilli Late onset (>30 days of implant insertion): Staphylococcus aureus, CoNS, Corynebacterium spp., P. acnes
Preferred Regimen
Empirical treatment before taking adequate cultures is not recommended. Antibiotic selection is based on bone C&S.
Duration: Minimum 12 week, final treatment duration depends on hardware retention/removal.
Clindamycin 600mg IV q6h, followed by oral therapy (same dose)
OR
*Vancomycin 15-20mg/kg (actual body weight) IV q8-12h; not to exceed 2g/dose
Remarks & Clinical Comments:
Drainage, debridement and washout of infected joints is important to limit further damage.
Duration:
Parenteral therapy 2-4 weeks, then oral therapy to complete total 4-6 weeks.
A shorter duration of therapy is possible in immunocompetent patients who have had adequate surgical drainage.
Refer to Appendix 3 for antibiotic allergy.
*Vancomycin: If suspected/confirmed MRSA. Consider loading dose 25-30mg/kg for critically ill or septic patients to achieve faster steady state.
Empirical therapy wherever possible should be directed by the result of the gram stain of the joint aspirate.
To consider gonococcal arthritis In a sexually active patient. Refer to the Sexually Transmitted Infections section.
1.3 Prosthetic Joint Infection & Implant Related Infection after Fracture Fixation
Preferred Regimen
Initial treatment:
Cloxacillin 2g IV q4-6h
OR
Cefazolin 2g IV q6-8h
PLUS
Rifampicin 300mg PO q12h OR 600mg PO q24h
Remarks & Clinical Comments:
Duration:
2-6 weeks for IV therapy (according to treatment strategy).
Followed by an oral combination therapy according to susceptibility. Rifampicin should be included if the implant is in situ.
1.3 Prosthetic Joint Infection & Implant Related Infection after Fracture Fixation
Preferred Regimen
Initial treatment:
*Vancomycin 15-20mg/kg (actual body weight) IV q8-12h; not to exceed 2g/dose
PLUS
Rifampicin 300mg PO q12h OR 600mg PO q24h
Remarks & Clinical Comments:
Duration:
2-6 weeks for IV therapy (according to treatment strategy)
Followed by an oral combination therapy according to susceptibility. Rifampicin should be included if the implant is in situ.
*Refer to Appendix 1 for vancomycin loading dose.
1.3 Prosthetic Joint Infection & Implant Related Infection after Fracture Fixation
Fracture fixation devices include plates, screws, intramedullary nails, rods, and pins from external fixation devices. Early onset (less than 2 weeks): Highly virulent organisms (Staphylococcus aureus or gram-negative bacilli) Delayed onset (2–10 weeks): Less virulent organisms (Staphylococcus epidermidis or Cutibacterium acnes) Late onset (more than 10 weeks): Low virulence organisms (Staphylococcus epidermidis)
Preferred Regimen
Intraoperative tissue culture should be taken to guide antibiotic regimen.
Empirical therapy is not recommended unless patient is septic.
Ampicillin/sulbactam 3g IV q6h
Remarks & Clinical Comments:
Treatment concepts:
Treatment is based on culture and sensitivity.
In staphylococcal infection, rifampicin should be added in combination with at least one other anti-staphylococcal agent, several days after surgical debridement when implant is retained/exchanged following surgery.
Treatment strategy and duration of treatment depends on surgical strategy.
(Most common cause is due to viral infection) Streptococcus pneumoniae Haemophilus influenzae Moraxella catarrhalis Group A Streptococcus
Preferred Regimen
Amoxicillin 80-90mg/kg/day (max.2g/day) PO for 5 days in 2 divided doses
Alternative Regimen (Allergy / Resistance)
Non-life-threatening allergy
Cefuroxime 30mg /kg/day (max. 1g/day) PO for 5 days in 2 divided doses
Severe antibiotic allergy
Erythromycin ethylsuccinate 40-50mg/kg/day (max. 800mg/dose) PO for 5 days in 2 divided doses
Remarks & Clinical Comments:
The most common causes are viral infections. Acute bacterial sinusitis is suspected when child with URI presents with:
1. Persistent illness (nasal discharge or daytime cough or both for ≥ 10 days without improvement)
2. Worsening course
3. Severe onset (concurrent fever & purulent discharge for 3 days)
For rhinosinusitis, most experts recommend using high dose amoxicillin (90mg/kg/day).
At least 2 of these items are present: Local swelling / induration Erythema > 0.5 but < 2cm around the wound Local tenderness / pain Local increased warmth Purulent discharge And no other cause of an inflammatory response of the skin (E.g.: trauma, gout, thrombosis).
Preferred Regimen
Cloxacillin 500mg PO q6h
OR
Cephalexin 1g PO q12h
Alternative Regimen (Allergy / Resistance)
Amoxicillin/clavulanate 625mg PO q8h
OR
Ampicillin/sulbactam 375-750mg PO q12h
Remarks & Clinical Comments:
Duration: 1-2 weeks*
*10 days following surgical debridement
***Vancomycin 15-20mg/kg q8-12h; not to exceed 2g/dose
Alternative Regimen (Allergy / Resistance)
Cefuroxime 1.5g IV q8h
PLUS
*Metronidazole 500mg IV q8h
Remarks & Clinical Comments:
Moderate infections
Infection with no systemic manifestations and involving:
Erythema extending ≥ 2cm from the wound margin, and/or
Tissue deeper than skin and subcutaneous tissues (e.g.: tendon, muscle, joint, and bone)
Severe infections
Any foot infection with associated systemic manifestations (≥ 2 SIRS)
Duration for skin & soft tissues involvement:
Total duration 2-4 weeks
Duration for bone/joint involvement:
Resected: total duration 2-5 days
Debrided for infected soft tissue: total duration 1-2 weeks
Positive culture or histology of bone margins after bone resection: total duration 3 weeks
No surgery or dead bone: total duration 6 weeks
IV to PO switch can be considered if adequate source control is performed.
*Metronidazole: In ischemia limb / necrosis / gas forming.
**Piperacillin/tazobactam: if given as q8h, to be given as extended infusion (over 3-4 hours)
***Refer to Appendix 1 for vancomycin loading dose.
Refer to Appendix 3 for antibiotic allergy.
Surgical debridement is URGENT for severe infections. Antibiotics should be streamlined based on intraoperative culture and sensitivity.
Necrotizing fasciitis is a rapidly progressing, life-threatening soft tissue infection with extensive fascial necrosis & relative sparing of underlying muscle caused by a toxin-producing bacterium. Presentation is acute (over hours); rarely, subacute (over days), and is followed by rapid progression to extensive destruction, which can lead to systemic toxicity, limb loss, and/or death.
The rapidness of erythema progression (~1-2 hours) helps differentiate necrotizing fasciitis from cellulitis and indicates the need for urgent surgical intervention.
Immediate aggressive surgical debridement is the primary treatment modality. Repeated surgical debridement for source control is normally necessary.
Etiology may be polymicrobial (mixed aerobic-anaerobic microbes) or monomicrobial (most commonly Group A streptococcus).
Empirical therapy should be broad and antibiotics should be streamlined based on intraoperative culture & sensitivity.
Necrotizing fasciitis commonly involves the extremities. Refer to the respective organ/system sections for other presentations i.e. necrotizing fasciitis of the perineum (Fournier gangrene), head and neck region, and neonatal infection.
Risk factor: older age group, immunocompromised or chronic diseases. E.g.: diabetes. Organisms: Anaerobes (E.g.: Bacteroides, Clostridium or Peptostreptococcus) Facultative anaerobic Enterobacteriaceae (E.g.: Escherichia coli, Enterobacter, Klebsiella, Proteus) Facultative anaerobic streptococci (other than Group A streptococcus [GAS]) Obligate aerobes (E.g.: Pseudomonas aeruginosa)
Preferred Regimen
*Piperacillin/tazobactam 4.5g IV q6-8h
MAY ADD
**Clindamycin 600-900mg IV q8h
Alternative Regimen (Allergy / Resistance)
Meropenem 1g IV q8h
OR
Imipenem 1g IV q6-8h
MAY ADD
**Clindamycin 600-900mg IV q8h
Remarks & Clinical Comments:
Duration:
There is a lack of any convincing evidence regarding the ideal duration of antibiotic therapy, which varies between 7 and 14 days. In general, antibiotics should be continued until no further debridement is needed and the patient’s hemodynamic status has normalized.
*Piperacillin/tazobactam: if given as q8h, to be given as extended infusion (over 3-4 hours)
**Clindamycin should be started empirically if there is risk of Group A Streptococcus or presence of gas crepitus.
Duration: 3-5 days. To stop clindamycin if there is no evidence of Group A Streptococcus.
Duration:
There is a lack of any convincing evidence regarding the ideal duration of antibiotic therapy, which varies between 7 and 14 days. In general, antibiotics should be continued until no further debridement is needed and the patient’s hemodynamic status has normalized.
*If confirmed Group A Streptococcus: Clindamycin & penicillin combination therapy is given until patients are clinically and hemodynamically stable for at least 48 to 72 hours; followed by penicillin monotherapy thereafter.
Aggressive surgical debridement is necessary to remove all necrotic tissue.
Duration: total 10-28 days
Refer to Urinary Tract Infection and Gastrointestinal Infection sections for other gas forming infections (E.g.: emphysematous pyelonephritis and emphysematous cholecystitis)
*Piperacillin/tazobactam: if given as q8h, to be given as extended infusion (over 3-4 hours).
Common organisms: Streptococcus pneumonia Haemophilus influenzae Moraxella catarrhalis
Preferred Regimen
Amoxicillin 80-90mg/kg/day (max. 1g/dose) PO in 2-3 divided doses
For clinical failure, history of using amoxicillin in the last 30 days and has concurrent purulent conjunctivitis:
Suspension (Formulation 14:1)
Amoxicillin / Clavulanate 80-90mg/kg/day PO in 2 divided doses (Amoxicillin component, max. 3g/day)
Suspension (Formulation 7:1)
Amoxicillin / Clavulanate 40-50mg/kg/day PO in 2 divided doses (Amoxicillin component, max. 3g/day)
Alternative Regimen (Allergy / Resistance)
Antibiotic allergy (non-life-threatening)
Cefuroxime 30mg/kg/day (max. 1g/day) PO in 2 divided doses
Severe antibiotic allergy
Erythromycin ethylsuccinate 40-50mg/kg/day PO (max. 800mg/dose) in 2 divided doses
OR
Azithromycin 10mg/kg/dose PO on Day 1 (max. 500mg/day), followed by 5mg/kg/dose PO q24h on Day 2-Day 5 (max. 250mg/day)
Remarks & Clinical Comments:
Most uncomplicated otitis media do not require antibiotics with certain exception:
children <2 years
immunosuppression
severe disease
Duration:
< 2yrs: 7- 10 days
> 2yrs: 5 - 7 days
90 mg/kg/day of amoxicillin, with 6.4 mg/kg/day of clavulanate, a ratio of amoxicillin to clavulanate of 14:1, given in 2 divided doses, which is less likely to cause diarrhea than other amoxicillin clavulanate preparations.
Amoxicillin/Clavulanate (40-50mg/kg/day) may not be adequate to treat AOM due to penicillin nonsusceptible S. pneumoniae.
Common organisms: Pseudomonas aeruginosa Staphylococcus aureus
Preferred Regimen
Mild to moderate:
Topical antibiotic with/without topical steroids.
E.g.:
Gentamicin 0.3% ear drops: 3-4 drops 3 times/day for 7 days
Polymyxin B sulphate 10,000U, neomycin sulphate 5mg & hydrocortisone 10g ear drops: 4 drops 3 or 4 times/day for 7 days
Ofloxacin 0.3% otic solution: Instill 5 drops into affected ear(s) once daily for 7 days (Indication: for 1-12 years old)
Remarks & Clinical Comments:
Consult ORL surgeon
Ototoxic agents like gentamicin or neomycin should not be used in the presence of tympanostomy tubes or perforated tympanic membrane.
Clinical response should be seen within 48 to 72 hours, but full response may take up 6 days.
Non-response should prompt an evaluation for obstruction, presence of foreign body, non-adherence or an alternative diagnosis.
Azithromycin 10mg/kg/day IV/PO q24h (max. 500mg/dose) for 14 days
OR
Benzylpenicillin 100,000 – 150,000 units/kg/day in 4 divided doses (max. 1 MU/dose), followed by Phenoxymethylpenicillin (Penicillin V) 50mg/kg/day in 4 divided doses PO (max. 500mg/dose) for total of 14 days of therapy (intravenous + oral)
Alternative Regimen (Allergy / Resistance)
Diphtheria Antitoxin (refer to the table above)
PLUS
Erythromycin 40-50mg/kg/day IV/PO in 4 divided doses (max. IV 500mg/dose; PO 800mg/dose) for 14 days
Remarks & Clinical Comments:
Antibiotics are not a substitute for treatment with diphtheria antitoxin. The role of adjunctive antibiotic treatment is to eradicate C.diphtheriae, which prevents further toxin production.
IV to PO switch:
Parenteral treatment is preferred for patients unable to swallow. Once the patient improves and can swallow comfortably, switch to oral therapy. Refer to Appendix 6 for IV to PO switch.
Close contact prophylaxis:
IM Benzathine Penicillin
BW < 30kg 600,000 U
BW > 30kg 1.2 MU single dose
OR
Erythromycin ethylsuccinate 40-50mg/kg/day PO q6h for 7-10 days
OR
Azithromycin 10mg/kg/day PO OD for 7-10 days
Pneumonia (outpatient) Infant (≥3 months) & children Viral infection is more common (Influenza, RSV, human metapneumovirus (hMPV), Parainfluenza, Adenovirus) Bacteria (S. pneumoniae, Group A Streptococcus, S. aureus, H. influenza)
Preferred Regimen
*High dose amoxicillin (80-90mg/kg/day) PO in 2-3 divided doses (max. 1g/dose, 3g/day) for 5 days
Oral weight bands*:
3-5kg: 250mg q12h
6-9kg: 375mg q12h
10-14kg: 500mg q12h
15-19kg: 750mg q12h
> 20kg: 500mg q8h or 1g q12h
*Prescribers can use either weight-band or mg/kg dosing. The World Health Organization endorses weight-band dosing to streamline prescribing and minimize errors. Higher doses resulting from weight-band ranges are considered safe and appropriate, given amoxicillin’s wide therapeutic index.
For influenza: If suspected, treatment to be initiated as early as possible.
Oseltamivir
<9 months old: 3mg/kg PO q12h for 5 days
9-11 months old: 3.5mg/kg PO q12h for 5 days
1-12 years old:
≤15 kg: 30mg PO q12h
>15-23kg: 45mg PO q12h
>23-40kg: 60mg PO q12h
>40 kg: 75mg PO q12h
Treatment for 5 days
Alternative Regimen (Allergy / Resistance)
Erythromycin ethylsuccinate 40-50mg/kg/day PO in 2 divided doses (max. 800mg/dose)
Remarks & Clinical Comments:
Antibiotics are not routinely recommended since viral infection is more common. For infant & children admitted to hospital, treat as presumed bacterial unless viral origin is known.
Macrolide antibiotics should be used if either mycoplasma or chlamydia pneumonia is suspected. It may be started in school-going children where disease predominates.
Duration: minimum 5 days and until afebrile for 2-3 days in empiric therapy with absence of an identified specific etiology and specific therapy with known pneumonia due to pneumococcus, HI & Moraxella catarrhalis.
*At least 40mg/kg/dose, children who do not respond to oral amoxicillin should be referred to the center with appropriate second line treatment.
Experts recommend using high dose amoxicillin to overcome resistance conferred by cell wall changes of the bacteria (pneumococcus).
Standard dose: Amoxicillin 45-50mg/kg/day PO in 3 divided doses (max. 500mg/dose) for 5 days, to be considered only for children who cannot tolerate high doses.
Common organism: Respiratory virus (>80% of cases) Group A Streptococcus
Preferred Regimen
Phenoxymethylpenicillin (Pen V) 500mg PO q6h or 1g PO q12h
OR
Benzathine Penicillin 1.2MU IM, one single dose
Alternative Regimen (Allergy / Resistance)
Amoxicillin 500mg PO q8h
Antibiotic allergy:
Erythromycin ethylsuccinate 800mg q12h
Remarks & Clinical Comments:
Treatment for Modified Centor Score <3:
Modified Centor Score < 3 does not require antibiotic treatment, as sore throats are commonly viral in origin. Give symptomatic treatment only (E.g.: analgesics, antipyretics).
Treatment for Modified Centor Score 3-5:
Modified Centor Score ≥ 3 requires antibiotic therapy due to a higher risk of Group A Streptococcus (GAS) infection.
Duration: 5-10 days
Consider 10 days in settings with a high prevalence of rheumatic fever or in patients with a history of rheumatic fever or rheumatic heart disease and who are aged between 3 and 21 years.
Refer to Appendix 3 for antibiotic allergy.
Common organisms: Group A Streptococcus Fusobacterium necrophorum Streptococcus anginosus group
Preferred Regimen
Benzylpenicillin 2MU IV q6h
PLUS
Metronidazole 500mg IV q6-8h
OR
Ampicillin/sulbactam 3g IV q6h
OR
Amoxicillin/clavulanate 1.2g IV q8h
Alternative Regimen (Allergy / Resistance)
Antibiotic allergy:
Clindamycin 600 - 900mg IV q8h
Remarks & Clinical Comments:
Drainage or aspiration of the abscess is the mainstay of treatment for peritonsillar abscess.
Duration: 10-14 days of therapy (Intravenous + Oral)
Refer to Appendix 6 for IV to PO switch.
Refer to Appendix 3 for antibiotic allergy.
followed by **Erythromycin ethylsuccinate 800 mg PO q6h
OR
*Benzylpenicillin 25,000 units/kg q6h to a maximum of 1 MU IV/IM q6h, followed by Phenoxymethylpenicillin (Pen V) 500mg PO q6h
PLUS
Diphtheria Antitoxin
Alternative Regimen (Allergy / Resistance)
***Azithromycin 500mg OD IV/PO
***(There is no CLSI / EUCAST breakpoint for azithromycin. Thus, azithromycin is adviced to be given only for patients who cannot tolerate penicillin or erythromycin)
PLUS
Diphtheria Antitoxin
Remarks & Clinical Comments:
Duration: 14 days (intravenous + oral therapy)
Antibiotics are not a substitute for treatment with diphtheria antitoxin. The role of adjunctive antibiotic treatment is to eradicate C.diphtheriae, which prevents further toxin production.
*IV to PO switch:
Parenteral treatment is preferred for patients who are unable to swallow. Once the patient improves and can swallow comfortably, switch to oral therapy. Refer to Appendix 6 for IV to PO switch.
Close contact management:
IM Benzathine Penicillin 1.2 MU single dose
OR
Erythromycin ethylsuccinate 800mg q6h for 7-10 days
OR
***Azithromycin 500mg OD for 7-10 days
**Erythromycin base 250mg = Erythromycin Ethylsuccinate 400mg
Common organisms: Streptococcus pneumoniae Group A Streptococcus Haemophilus influenzae Type B Virus
Preferred Regimen
Ceftriaxone 2g IV q24h
OR
Ampicillin/sulbactam 3g IV q6h
OR
Amoxycillin/clavulanate 1.2g IV q8h
Alternative Regimen (Allergy / Resistance)
Antibiotic allergy:
Clindamycin 600-900mg IV q8h
PLUS
Ciprofloxacin 400mg IV q12h
Remarks & Clinical Comments:
Duration: 7 to 10 days (intravenous + oral). Longer in cases of bacteremia, concomitant meningitis or immunocompromised.
Requires urgent hospitalisation. May present with life-threatening upper airway obstruction, especially in paediatrics.
Consider adding vancomycin for patients with moderate to severe sepsis, concomitant meningitis or previously colonized with MRSA.
Refer to Appendix 3 for antibiotic allergy.
Refer to Appendix 6 for IV to PO switch.
Duration: 10-14 days (intravenous + oral)
For significant abscess, surgical drainage and debridement are required.
If there is evidence of necrotising fasciitis (clinical / radiological evidence), may add IV clindamycin.
Once the patient improves, switch to oral therapy after a minimum of 3 to 5 days of intravenous therapy. Refer to Appendix 6 for IV to PO switch.
Cefotaxime 150-200mg/kg/day in 3 to 4 divided doses (max. 8g/day)
OR
Ceftriaxone 75-100mg/kg/day in 2 divided doses (max. 4g/day)
MAY ADD
*Azithromycin 10mg/kg/dose (max. 500mg) IV q24h on Day 1; then 5mg/kg/dose (max. 250mg) on Day 2-5 if considering atypical organisms
Alternative Regimen (Allergy / Resistance)
Cefuroxime 75-150mg/kg/day IV in 3 divided doses (max. 6g/day)
MAY ADD
*Azithromycin 10mg/kg/dose (max. 500mg/day) IV q24h on Day 1; then 5mg/kg/dose (max. 250mg/day) on Day 2-5 if considering atypical organisms
Remarks & Clinical Comments:
Duration: 5-7 days. Consider longer treatment and assess for complications e.g empyema, if patient not fully recovered.
For the management of empyema, refer to Empyema thoracis section.
*The role of antimicrobials in treating both M. pneumoniae and C. pneumoniae is unknown because most children resolve infection without macrolides, treatment may be appropriate to hasten recovery in children who are more seriously ill or have a persistent cough.
Macrolide resistance is now very common in M. pneumoniae in Asia and routine use should be avoided.
Common organisms: Virus (most common) Bacterial (0.5 - 2%)
Antibiotics are not needed in the great majority of cases. Most cases of sinusitis occur as a complication of a viral upper respiratory tract infection and are self-limited.
Use the algorithm below to determine the infection origin (bacterial or viral) and whether antibiotics are necessary.
Cefuroxime 100-200mg/kg/day IV in 3 divided doses (max. 6g/day)
OR
Cefotaxime 200-300mg/kg/day IV in 4 divided doses (max.8g/day)
PLUS
Cloxacillin 200-300mg/kg/day IV in 4-6 divided doses (max.12g/day)
Duration: 4-6 weeks
Alternative Regimen (Allergy / Resistance)
Staphylococcus aureus (methicillin-sensitive)
Cloxacillin 200-300mg/kg/day IV in 4-6 divided doses (max.12g/day) for 4-6 weeks
Streptococcus pneumoniae (penicillin-sensitive)
Benzylpenicillin 200,000-300,000 units/kg/day IV in 4-6 divided doses (max. 24 million unit/day)
Streptococcus pneumoniae (penicillin- resistant, use result of C&S)
Cefotaxime 200-300mg/kg/day IV in 4 divided doses (max. 8g/day)
OR
Ceftriaxone 100mg/kg/day IV in 1-2 divided doses (max. 4g/day)
Remarks & Clinical Comments:
Empyema thoracis (lung empyema)
Staphylococcus aureus
Streptococcus pneumoniae
Empirical treatment needs to cover organisms mentioned above.
Other bacteria implicated:
Streptococcus pyogenes,
Haemophilus influenzae & other Gram-negative organisms in immunocompromised individuals
If patient is not responding to treatment, need to rule out TB
Based on C&S of pleural fluid/tissue or blood culture.
All children with empyema need to receive high dose antibiotic therapy via intravenous route to ensure pleural penetration.
Pneumatocele on chest x-ray indicate S. aureus BUT they can also be seen in pneumococcal disease.
There is NO CONSENSUS on how long antibiotic needs to be given. Most recommend 3-6 weeks of total antibiotics depending on severity.
For moderate to severe or Stage 1-2 parapneumonic effusion, to consider pleural drainage and intrapleural fibrinolytic agent on top of antimicrobial therapy.
Stage 2 failed medical therapy and stage 3 empyema thoracis need surgical intervention. (Refer Empyema Thoracic in Children: Consensus Guideline from Malaysia Pediatric Empyema Thoracic Working Group 2020 Edition)
Common organism: Pseudomonas aeruginosa (95%) Staphylococcus aureus
Preferred Regimen
Ceftazidime 2g IV q8h
OR
*Piperacillin/tazobactam 4.5g IV q6–8h
Alternative Regimen (Allergy / Resistance)
Ciprofloxacin 400mg IV q8h (option for beta-lactam allergic patients)
Remarks & Clinical Comments:
Duration: 6 weeks (intravenous + oral)
Once showing a clinical response, consider switching to oral therapy:
Ciprofloxacin 750mg PO q12h to complete 6 weeks.
*Piperacillin/tazobactam: if given as q8h, to be given as extended infusion (over 3 – 4 hours).
*Cloxacillin 50-100mg/kg/day PO in 4 divided doses (max. 2g/day) for 5-7 days
Severe
Cloxacillin 200mg/kg/day IV in 4 divided doses (max. 12g/day) for 5-7 days
CA-MRSA
Clindamycin 30-40mg/kg/day PO in 3-4 divided doses (max. 2.7g/day) for 5-7 days
OR
Trimethoprim/sulfamethoxazole 8-12mg/kg/day (TMP dose) PO in 2 divided doses (max. 320mg/day) for 5-7 days
Alternative Regimen (Allergy / Resistance)
Mild
Cephalexin 25-50mg/kg/day PO in 2 divided doses (max. 2g/day) for 5-7 days
Remarks & Clinical Comments:
Incision & drainage (I&D) is the MAINSTAY of therapy. If needle aspiration is inadequate, can send pus obtained during I&D for C&S.
Use parenteral route for severe infections. Consider CA-MRSA if poorly resolving, based on local epidemiology (still generally uncommon).
*Doses recommended are for children weighing less than 25kg. For children weighing more than 25kg, use adult dosage (500mg PO q6h).
Alternatively, CRB-65 can also be used. It does not require laboratory values for its calculation, and the score value interpretation is the same as for CURB-65.
Remarks & Clinical Comments:
The diagnosis of CAP generally requires the demonstration of an infiltrate on chest radiograph in a patient with a clinically compatible syndrome (E.g.: fever, dyspnoea, cough and sputum production).
Previous relevant encounters at any health care facilities and antibiotic exposure must be obtained.
Pulmonary tuberculosis (PTB) must be considered and further investigated in an appropriate clinical situation such as prolonged symptoms, presence of risk factors for PTB and radiological changes compatible with PTB.
Choice of antibiotic treatment must also be based on likely etiology and local antibiogram whenever possible.
Assessment of severity and decision for admission can be guided by using CURB-65 or SMART-COP scoring. Physician should use the scoring tools to support, not to replace clinical judgment.
CURB-65 and SMART-COP scoring
Comorbidities: Chronic heart, lung, liver, or renal disease, diabetes mellitus, alcoholism, malignancy, or asplenia.
*If atypical pathogen is suspected (E.g.: extrapulmonary manifestations and diffuse infiltrations radiologically).
**Levofloxacin should be strictly reserved for antibiotic allergy due to higher risk of adverse events.
Refer to Appendix 3 for antibiotic allergy.
CURB-65 Score 2 or SMART-COP Score 3-4
*If atypical pathogen is suspected (E.g.: extrapulmonary manifestations and diffuse infiltrations radiologically). May need a longer duration of therapy among immunocompromised patients or those with confirmed Legionella pneumonia.
**Levofloxacin should be strictly reserved for antibiotic allergy due to higher risk of adverse events.
To switch to oral therapy when clinical condition improves and patient is able to tolerate orally.
If suspected melioidosis infection, refer to Tropical Infection section.
**Piperacillin/tazobactam 4.5g IV q6-8h for 7 days
OR
Cefepime 2g IV q8h for 7 days
MAY ADD
*Azithromycin 500mg IV/PO q24h for 3 days
Remarks & Clinical Comments:
CURB-65 score ≥ 3 or SMART-COP score ≥ 5
Strong risk factors for pseudomonal infection:
Prior respiratory infection or isolation of Pseudomonas aeruginosa
Hospitalization with receipt of IV antibiotics in past 3 months
Detection of gram-negative rods on a good-quality sputum gram stain
Other risk factors for pseudomonal infection:
Recent hospitalization or stay in a long-term care facility
Recent antibiotic use
Frequent COPD exacerbations requiring glucocorticoid/antibiotic
Structural lung diseases (E.g.: bronchiectasis)
Immunosuppressed
*If atypical pathogen is suspected (E.g.: extrapulmonary manifestations and diffuse infiltrations radiologically). May need a longer duration of therapy among immunocompromised patients or those with confirmed Legionella pneumonia.
**Piperacillin/tazobactam: if given as q8h, to be given as extended infusion (over 3-4 hours)
IV Ceftazidime is not recommended for empirical therapy due to poor activity against Streptococcus pneumoniae. If suspected melioidosis infection, refer to Tropical Infections section.
Common organisms: Staphylococcus aureus Streptococcus pyogenes
Preferred Regimen
Mild
*Cloxacillin 50-100mg/kg/day PO in 4 divided doses (max. 2g/day) for 5-7 days
Severe
Cloxacillin 200mg/kg/day IV in 4 divided doses (max. 12g/day) for 5-7 days
Alternative Regimen (Allergy / Resistance)
Cephalexin 25-50mg/kg/day PO in 2 divided doses (max. 2g/day) for 5-7 days
Remarks & Clinical Comments:
Administer using parenteral route for extensive lesions.
Total treatment until 3 days after acute inflammation disappears.
*Doses recommended are for children weighing less than 25kg. For children weighing more than 25kg, use adult dosage (500mg PO q6h).
Clinical benefit is greatest if initiated within 48 hours.
In hospitalized / immunocompromised patients, treatment is started regardless of symptom duration, and may need longer duration of treatment.
*Not listed in MOH Drug Formulary.
Post-procedure (E.g. pleural interventions, thoracic or oesophageal surgery) or presence of HAP/VAP:
*Piperacillin-tazobactam 4.5g IV q6-8h
OR
Cefepime 2g IV q8h
PLUS
Metronidazole 500mg IV q8h
MAY ADD **Vancomycin 15-20mg/kg (actual body weight) IV q8-12h; not to exceed 2g/dose
Alternative Regimen (Allergy / Resistance)
No recent thoracic surgery/ procedure or HAP/VAP:
Ceftriaxone 2g IV q24h
PLUS
Metronidazole 500mg IV q8h
Antibiotic allergy:
Clindamycin 600mg IV/PO q8h
Post-procedure (E.g. pleural interventions, thoracic or oesophageal surgery) or presence of HAP/VAP:
Meropenem 1g IV q8h
MAY ADD
**Vancomycin 15-20mg/kg IV q8-12h
Remarks & Clinical Comments:
Duration of treatment:
Adequate source control: 2-4 weeks of antibiotics from the time of drainage/surgery and defervescence.
Inadequate source control: 4-6 weeks of antibiotics.
Lung empyema: Attempts should be made to drain the collection to improve clinical outcome.
Change to oral regime once clinical improvement is seen. Refer to Appendix 6 for IV to PO switch.
Avoid aminoglycosides in the management of empyema.
*Piperacillin/tazobactam: if given as q8h, to be given as extended infusion (over 3-4 hours).
**MRSA coverage is to be based on local hospital MRSA prevalence. Refer to Appendix 1 for vancomycin dose.
If melioidosis is suspected, refer to Tropical Infection section.
Refer to Appendix 3 for antibiotic allergy.
Duration: 4-6 weeks, depending on clinical response. In rare cases (slow response to antibiotics) may need prolonged therapy.
Change to oral therapy (E.g. Amoxicillin/clavulanate 625mg PO q8h or cephalexin 1g PO q6h) to complete the duration once patient stabilized and improved.
4. INFECTIVE EXACERBATION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)
4.3 Inpatient with Risk Factor of Pseudomonal Infection
Preferred Regimen
*Piperacillin-tazobactam 4.5g IV q6-8h for 7 days
MAY ADD
Azithromycin 500mg IV/PO for 3 days
Alternative Regimen (Allergy / Resistance)
Cefepime 2g IV q8h for 7 days
MAY ADD
Azithromycin 500mg IV/PO for 3 days
Remarks & Clinical Comments:
Risk factors for pseudomonal infection:
Chronic colonization of previous isolation of Pseudomonas aeruginosa from sputum
Very severe COPD (FEV1<30% predicted)
Bronchiectasis
Broad spectrum antibiotic use within the past 3 months
Chronic systemic glucocorticoid use
*Piperacillin/tazobactam: if given as q8h, to be given as extended infusion (over 3-4 hours)
2 - 4 days of admission/intubation
Need to adjust to local antibiogram/ prevalent organisms.
Consider broader spectrum antibiotic if deteriorated while on adequate antibiotic therapy.
Benzylpenicillin 200,000-300,000units/kg/day IV in 4-6 divided doses (max. 24 million units/day)
PLUS
Clindamycin 30-40mg/kg/day IV in 3-4 divided doses (max. 2.7g/day)
Remarks & Clinical Comments:
50% of patients have associated streptococcal toxic shock syndrome (STSS).
Prompt and aggressive surgical debridement of the deep-seated infection is the mainstay of therapy.
Tissues should be sent for Gram stain and culture to determine etiology.
Combination therapy is needed with clindamycin to block toxin production whether or not patient manifests toxic shock syndrome.
IVIG can be used as an adjunct in Group A streptococcal infection, typically at 1g/kg on Day 1, followed by 0.5g/kg on 1-2 subsequent days.
Duration: at least 2 weeks if no foci is found (no deep-seated involvement plus no involvement of heart, bone, joint etc.)
5.2 Late Onset HAP/VAP OR Severe Pneumonia OR At Risk of Pseudomonal Infection
Preferred Regimen
*Piperacillin-tazobactam 4.5g IV q6-8h for 7 days
OR
Cefepime 2g IV q8h for 7 days
Alternative Regimen (Allergy / Resistance)
High risk of MDR organisms:
Meropenem 1g IV q8h for 7 days
OR
Imipenem/cilastatin 500mg IV q6h for 7 days
Remarks & Clinical Comments:
Late onset HAP/VAP: 5 days or more of admission/intubation
Refer to CAP section for Risk of Pseudomonal Infection.
Severe pneumonia:
Septic shock
Respiratory failure, need for ventilation support
Rapid progression of infiltrates on chest X-ray
Ideal empirical antibiotic coverage depends on local prevalence of organisms. To de-escalate antibiotics according to culture and sensitivity results.
Longer duration may be indicated depending upon clinical, radiological and laboratory parameters.
*Piperacillin/tazobactam: if given as q8h, to be given as extended infusion (over 3-4 hours).
Cloxacillin 200mg/kg/day IV in 4-6 divided doses (max. 2g/dose, 12g/day)
PLUS
Clindamycin 30-40mg/kg/day IV in 3-4 divided doses (max: 2.7g/day)
Alternative Regimen (Allergy / Resistance)
If CA-MRSA is suspected:
Vancomycin 60mg/kg/day IV in 3-4 divided doses (max. 2g/day)
Remarks & Clinical Comments:
Prompt and aggressive surgical debridement of the deep-seated infection is the mainstay of therapy.
Tissues should be sent for Gram stain and culture to determine etiology.
Combination therapy is needed with clindamycin to block toxin production whether or not patient manifests toxic shock syndrome.
Vancomycin is NOT RECOMMENDED for the treatment of serious MSSA infections because outcomes are INFERIOR compared with cases in which anti-staphylococcus β-lactam (cloxacillin) is used AND to minimise the emergence of vancomycin resistance.
Duration: at least 2 weeks if no foci is found (no deep-seated involvement plus no involvement of heart, bone, joint etc.)
It is important to distinguish aspiration pneumonia from aspiration events/ aspiration pneumonitis.
Aspiration pneumonia: a bacterial infection caused by aspiration of organisms from oropharynx.
Aspiration (chemical) pneumonitis: acute chemical injury to the lung parenchyma after aspiration of acidic stomach contents. Antibiotic is not indicated.
Indications of antibiotic therapy:
Delayed symptoms (suggestive of aspiration pneumonia, as compared to rapid onset within hours in pneumonitis)
Patients taking gastric acid suppression therapy or with bowel obstruction
Duration: 7 days
*Anaerobic coverage is not routinely required for suspected aspiration pneumonia unless lung abscess or empyema is suspected.
To switch to oral therapy when clinical condition improves and patient is able to tolerate orally.
Cloxacillin 200mg/kg/day IV in 4-6 divided doses (max. 12g/day)
Step down
Cloxacillin 50-100mg/kg/day PO in 4 divided doses (max. 2g/day)
Total treatment duration: 7-10 days
Alternative Regimen (Allergy / Resistance)
Cefazolin 100mg/kg/day IV in 3-4 divided doses (max. 6g/day)
Step down
Cephalexin 50mg/kg/day PO in 2 divided doses (max. 2g/day)
Remarks & Clinical Comments:
Switch to oral therapy when the patient shows clinical improvement and negative blood culture results.
Doses recommended are for children weighing less than 25kg. For children weighing more than 25kg, use adult dosage.
Griseofulvin 10-20mg/kg/day PO daily (max. 750mg/day) for at least 6 weeks until clinically clear
Alternative Regimen (Allergy / Resistance)
Terbinafine 4-6mg/kg/day PO daily (max. 250mg/day) for 4 weeks or longer depend on pathogen
10-20kg: 62.5mg daily
20-40kg: 125mg daily
> 40kg: 250mg daily
OR
Itraconazole 3-5mg/kg/day PO daily (max. 200mg/day) for 2-6 weeks
OR
Fluconazole 5-6mg/kg/day PO (max. 300mg/day) for 3-6 weeks
Remarks & Clinical Comments:
Griseofulvin:
First line treatment for Microsporum sp
Take with fatty food. Monitor liver function if treatment duration > 8 weeks
Adjunctive selenium or ketoconazole shampoo can reduce transmissibility.
Metronidazole 30mg/kg/day IV in 3-4 divided doses (max. 750 mg/dose) for 7-10 days
Neutralisation of toxin:
Human tetanus globulin (TIG) 500IU IM as a single dose.
Alternative Regimen (Allergy / Resistance)
Benzylpenicillin 200,000units/kg/day IV in 4 divided doses (max. 24 million units/day) for 7-10 days
Neutralisation of toxin:
If TIG not available: IVIG 200-400mg/kg as a single dose
Remarks & Clinical Comments:
Primary tetanus infection:
Clinical diagnosis to be made as negative culture is often negative.
Steps in care:
1. Early airway protection & treatment of reflex spasm with benzodiazepine (midazolam).
2. Neutralisation of toxin: TIG single dose, administered IM 250-500IU.
3. Surgical debridement of infected tissues.
4. Refer Table for tetanus wound prophylaxis
Trimethoprim/sulfamethoxazole 4-6 mg/kg/dose (of TMP component) PO q12h up to 240mg then to follow adult dose
PLUS (if high risk relapse)*
Doxycycline 4mg/kg/day PO in 2 divided doses (children above 8 years old) (max. 200mg/day)
Alternative Regimen (Allergy / Resistance)
Children below 8 years old:
Amoxicillin/clavulanate 20mg/kg/dose (of amoxicillin component) PO q8h
(higher relapse rate)
Ratio dose depends on product available (7:1 or 14:1)
Remarks & Clinical Comments:
Duration:12- 20 weeks
Folic acid 5mg PO q24h to be given for patients on Trimethoprim/sulfamethoxazole.
*Consider combination therapy of two drugs in maintenance phase if high risk of relapse.
Artemether/lumefantrine (Riamet®) (20mg artemether/ 120mg lumefantrine per tablet)
The patient should receive an initial STAT dose, followed by second dose 8 hours later, then 1 dose q12h for the following two days
5-14kg: 1 tablet per dose
15-24kg: 2 tablet per dose
25-35kg: 3 tablet per dose
≥35 kg: 4 tablet per dose
PLUS
Primaquine 0.25mg base/kg to be given on Day 1 as a single dose in addition to artemisinin-based combination therapy (ACT) (G6PD testing is not required prior to administration of this dose).
Alternative Regimen (Allergy / Resistance)
Artesunate/mefloquine FDC (ASMQ)
(ASMQ is available as FDC tablet 25/55mg & 100/220mg)
5-8kg: 25/55mg PO q24h
9-17kg: 50/110mg PO q24h
18-29kg: 100/220mg PO q24h
>30kg: 200/440mg PO q24h
Duration: 3 days
PLUS
Primaquine 0.25mg base/kg to be given on Day 1 as a single dose in addition to artemisinin-based combination therapy (ACT) (G6PD testing is not required prior to administration of this dose).
Remarks & Clinical Comments:
Artesunate/mefloquine may cause seizure in children with epilepsy.
Riamet® should be served with high-fat diet e.g. milk to enhance absorption.
An alternative artemisinin-based combination therapy (ACT) regimen to be used.
(If Riamet® is used as the first line regimen, use ASMQ & vice versa)
PLUS
Primaquine 0.25mg base/kg to be given on Day 1 as a single dose in addition to artemisinin-based combination therapy (ACT) (G6PD testing is not required prior to administration of this dose).
Alternative Regimen (Allergy / Resistance)
Artesunate 4mg/kg/dose PO q24h
PLUS
Clindamycin 10mg/kg/dose PO q12h for 7 days
OR
Quinine 10mg salt/kg/dose PO q8h
PLUS
Clindamycin 10mg/kg/dose PO q12h for 7 days
Remarks & Clinical Comments:
Artesunate/mefloquine may cause seizure in children with epilepsy.
Riamet® should be served with high-fat diet e.g. milk to enhance absorption.
Almost always due to P. falciparum. Suspect mixed infections if P. vivax/P. knowlesi malaria appears more severe than usual.
Preferred Regimen
Children > 20 kg
Day 1:
IV artesunate 2.4mg/kg on admission, then repeat again at 12 & 24 hours
Day 2-7:
IV artesunate 2.4 mg/kg OD or switch to oral ACT
Children < 20 kg
Day 1:
IV artesunate 3.0mg/kg on admission, then repeat again at 12 & 24 hours
Day 2-7:
IV artesunate 3.0mg/kg OD or switch to oral ACT
Duration: 7 days
(Parenteral artesunate should be given for a minimum of 24 hours (3 doses) or until patient is able to tolerate orally and thereafter to complete treatment with a complete course of oral ACT (3 days of ASMQ or Riamet®).
Alternative Regimen (Allergy / Resistance)
Day 1: *Quinine loading dose 20mg/kg IV (dilute in 250 ml D5%) run over 4 hours; followed by maintenance dose 8 hours later;
Quinine 10mg/kg IV q8h till Day 7 (max. 600mg base)
PLUS
Doxycycline 2.2mg/kg/dose (max. 100mg/dose) PO q12h
OR
Clindamycin 10mg/kg/dose PO q12h
Duration: 7 days
Remarks & Clinical Comments:
Avoid using ASMQ (artesunate/ mefloquine) if patient presents initially with impaired consciousness as increased incidence of neuropsychiatric complications associated with mefloquine following cerebral malaria have been reported.
Do not use IV artesunate as monotherapy. If IV artesunate needs to be continued indefinitely, clindamycin must be added to the regimen to complete 7 days of treatment.
IM artesunate (same dose as IV) can be used in patients with difficult intravenous access.
Children with severe malaria should be started on broad-spectrum antibiotic treatment immediately at the same time as antimalarial treatment.
*Change to quinine PO if able to tolerate orally (max. quinine per dose = 600 mg). Reduce quinine IV dose by one third of total dose if unable to change to quinine PO after 48 hours (10 mg/kg q8h to 10 mg/kg q12h) or in renal failure or liver impairment.
Primaquine 0.5mg/kg PO q24h for 14 days (max. 30mg base/dose)
(Primaquine is ONLY needed for P. vivax)
Alternative Regimen (Allergy / Resistance)
Quinine 10mg salt/kg PO q8h for 7 days
PLUS
Primaquine 0.5mg/kg PO q24h for 14 days (max. 30mg base/dose)
(Primaquine is ONLY needed for P. vivax)
Mefloquine 15 mg/kg single dose combined with primaquine have been found to be effective (except for P. knowlesi)
Remarks & Clinical Comments:
Primaquine (0.5mg/kg) may cause haemolysis in individuals with G6PD deficiency, hence G6PD testing is required before administration of primaquine above 0.25mg/kg.
For those found to have mild to moderate G6PD deficiency, an intermittent primaquine regimen of 0.75 mg base/kg weekly for 8 weeks can be given under medical supervision.
In severe G6PD deficiency, primaquine is contraindicated and should not be used.
P. knowlesi (zoonotic malaria) can cause severe malaria and should be treated as severe malaria secondary to P. falciparum.
Common organisms: Escherichia coli Proteus spp. Klebsiella spp. Enterobacter spp
Preferred Regimen
0-2 months old
First line:
Ampicillin 50mg/kg/dose IV
≤ 1 week of age: q12h
> 1 week of age: q8h
PLUS
Gentamicin 5mg/kg/dose IV
≤ 30 week of CGA: q48h
> 30-34 week of CGA: q36h
> 35 weeks of CGA: q24h
Second line:
Cefotaxime 150-200mg/kg/day IV in 3 divided doses (max. 6g/day), MAY ADD
Amikacin 15mg/kg/dose IV daily
≥ 3 months old
First line:
Cephalexin 25-50mg/kg/day PO in 2 divided doses (max. 2g/day)
OR
Amoxicillin/clavulanate
Suspension (Formulation 14:1)
Amoxicillin/clavulanate 80-90mg/kg/day PO in 2 divided doses (Amoxicillin component, max. 2g/day)
Suspension (Formulation 7:1)
Amoxicillin/clavulanate 40-50mg/kg/day PO in 2 divided doses (Amoxicillin component, max. 2g/day)
Second line:
Cefotaxime 150-200 mg/kg/day IV in 3 divided doses (max. 6g/day)
OR
Ceftriaxone 100mg/kg/day IV in 1-2 divided doses (max. 2g/day)
MAY ADD
Amikacin 15mg/kg/dose IV daily
Remarks & Clinical Comments:
Duration: 7 – 10 days
Adjust therapy based on culture result.
Switch to oral therapy when improving and able to tolerate oral therapy.
For Aminoglycoside (Gentamicin):
In obese patients, use ideal weight for height to calculate parenteral dose and monitor serum concentration closely.
1.1.1 Primary syphilis, Secondary syphilis, Early latent syphilis (history of syphilis infection within the last 2 years)
1.1 Syphilis
Preferred Regimen
Benzathine Penicillin 2.4MU IM STAT
OR
Procaine Penicillin 600,000units IM q24h for 10 days
Alternative Regimen (Allergy / Resistance)
For penicillin allergy:
Doxycycline 100mg PO q12h for 14 days
Remarks & Clinical Comments:
Sexual partner(s) should be examined, investigated and treated epidemiologically.
Abstain from sex for 1 week after the patient and partner(s) have completed treatment.
If drug administration is interrupted for ≥ 1 day at any point during the treatment course, the entire course may need to be restarted.
Patients should be warned of possible reactions to treatment:
Jarisch-Herxheimer reaction
Anaphylaxis/allergy
1.1.2 Late latent syphilis, Gumma (benign tertiary) syphilis, Cardiovascular syphilis
1.1 Syphilis
Preferred Regimen
Benzathine Penicillin 2.4MU IM weekly for 3 weeks (Day 1, 8, and 15)
OR
Procaine penicillin 600,000units IM q24h for 14 days
Alternative Regimen (Allergy / Resistance)
For penicillin allergy:
Doxycycline 100mg PO q12h for 28 days
Remarks & Clinical Comments:
Sexual partner(s) should be examined, investigated and treated epidemiologically.
Abstain from sex for 1 week after the patient and partner(s) have completed treatment.
Cardiovascular syphilis: Consider prednisolone 40-60mg PO q24h for 3 days starting 24 hours before the antibiotics.
If benzathine penicillin is interrupted by ≥ 2 weeks in between the weekly doses, the entire course needs to be restarted.
1.2.1 Primary syphilis, Secondary syphilis, Early latent syphilis (history of syphilis infection within the last 2 years)
1.2 Syphilis in Pregnancy
Preferred Regimen
Benzathine Penicillin 2.4MU IM STAT
OR
Procaine Penicillin 600,000units IM q24h for 10 days
Alternative Regimen (Allergy / Resistance)
For penicillin allergy:
*Desensitize and treat with penicillin as there are no proven alternatives.
If failed desensitization:
Ceftriaxone 500mg IM q24h for 10 days
OR
Azithromycin 2g PO STAT
OR
Erythromycin ethylsuccinate 800mg PO q6h for 14 days
Remarks & Clinical Comments:
Sexual partner(s) should be examined, investigated and treated epidemiologically.
If macrolide is used, for neonate assessment and treatment at birth.
*The benefit of treatment outweighs the risk of allergic reaction in skin test and desensitization. Refer to Appendix 3 for the penicillin desensitization protocol.
1.2.2 Late latent syphilis, Gumma (benign tertiary) syphilis, Cardiovascular syphilis
1.2 Syphilis in Pregnancy
Preferred Regimen
Benzathine Penicillin 2.4MU IM weekly for 3 weeks (Day 1, 8, and 15)
OR
Procaine penicillin 600,000units IM q24h for 14 days
Alternative Regimen (Allergy / Resistance)
For penicillin allergy:
Erythromycin ethylsuccinate 800mg PO q6h for 28 days
Remarks & Clinical Comments:
Sexual partner(s) should be examined, investigated and treated epidemiologically.
If macrolide is used, for neonate assessment and treatment at birth.
Cardiovascular syphilis: Consider prednisolone 40-60mg PO q24h for 3 days starting 24 hours before the antibiotics.
Physical supportive measures (saline bathing, analgesia, local anaesthetics) are recommended.
Oral antiviral drugs indicated within 5 days of the start of the episode and while new lesions are still forming.
Topical antivirals are less effective than oral agents and not recommended, due to the association with acyclovir resistant strain.
Addition of topical antivirals to oral treatment is of no benefit.
*Not listed in MOH Drug Formulary.
Erythromycin ethylsuccinate 800mg PO q8h for 7 days
Remarks & Clinical Comments:
Sexual partner(s) within 10 days before onset of the patient’s symptoms should be examined and treated even in the absence of symptoms.
Patients should be re-examined 3-7 days after initiation of therapy.
Successful treatment: Ulcers improve symptomatically within 3 days and substantial re-epithelization occurs within 7 days after onset of therapy.
In pregnancy/breastfeeding, to use azithromycin, ceftriaxone or erythromycin.
Erythromycin ethylsuccinate 800mg PO q6h for 21 days
Remarks & Clinical Comments:
Sexual partner(s) within 60 days should be evaluated and treated if symptomatic. If asymptomatic, they should be empirically treated for exposure with doxycycline 100mg PO q12h for 7 days.
Proctitis and anorectal discharge are common especially in the MSM population.
Fluctuant buboes: Should be aspirated through healthy adjacent skin. Surgical incision contraindicated.
If an alternative treatment regimen is given or pregnant, consider test-of-cure 4 weeks after completion of treatment.
*Doxycycline is contraindicated in pregnancy.
Sexual partner(s) within 60 days before onset of the patient’s symptoms must be screened and treated.
Duration of treatment: at least 3 weeks or until all lesions have completely healed.
*Doxycycline is contraindicated in pregnancy.
Ceftriaxone 500mg IM STAT (if BW>150kg, 1g IM STAT)
PLUS
*Doxycycline 100mg PO q12h for 7 days
(if Chlamydia has not been excluded)
Pharynx:
Ceftriaxone 500mg IM STAT (if BW>150kg, 1g IM STAT)
PLUS
*Doxycycline 100mg PO q12h for 7 days
(if Chlamydia has not been excluded)
Alternative Regimen (Allergy / Resistance)
Cervix, urethra, rectum:
Cephalosporin allergy:
Gentamicin 240mg IM STAT
PLUS
Azithromycin 2g PO STAT
Pharynx:
Anaphylaxis or severe reaction to cephalosporin:
Consult for expert opinion
Remarks & Clinical Comments:
Sexual partner(s) within 60 days should be examined, investigated and treated epidemiologically irrespective of the test results.
Abstain from sex for 1 week after the patient and partner(s) have completed treatment and symptoms are resolved.
*Doxycycline is contraindicated in pregnancy.
Sexual partner(s) within 60 days should be examined, investigated and treated epidemiologically irrespective of the test results.
Abstain from sex for 1 week after the patient and partner(s) have completed treatment and symptoms are resolved.
Sexual partner(s) within 60 days should be examined, investigated and treated epidemiologically irrespective of the test results.
Abstain from sex for 1 week after the patient and partner(s) have completed treatment and symptoms are resolved.
Sexual partner(s) within 60 days should be examined, investigated and treated epidemiologically, irrespective of the test results.
Abstain from sex for 1 week after the patient and partner(s) have completed treatment and symptoms are resolved.
* Indication not listed in MOH Drug Formulary.
Sexual partner(s) within 60 days should be examined, investigated and treated epidemiologically, irrespective of the test results.
Abstain from sex for 1 week after the patient and partner(s) have completed treatment and symptoms are resolved.
Azithromycin 500mg PO STAT, then 250mg q24h for 4 days
Remarks & Clinical Comments:
Sexual partner(s) within 60 days should be examined, investigated and treated epidemiologically, irrespective of the test results.
Abstain from sex for 1 week after the patient and partner(s) have completed treatment and symptoms are resolved
Consider empiric treatment for chlamydia for sexual partner(s).
Azithromycin 500mg PO STAT, then 250mg PO q24h for the next 4 days
PLUS
Metronidazole 400mg PO q12h for 5 days
If treated with azithromycin as first line:
*Moxifloxacin 400mg PO q24h for 10-14 days
PLUS
Metronidazole 400mg PO q24h for 5 days
Remarks & Clinical Comments:
Sexual partner(s) within 60 days should be examined, investigated and treated epidemiologically, irrespective of the test results.
Abstain from sex for 1 week after the patient and partner(s) have completed treatment and symptoms are resolved
Consider empiric treatment for chlamydia for sexual partner(s).
*Indication not listed in MOH Drug Formulary
Abstain from sex until the patient and partner(s) have completed treatment and symptoms are resolved.
To review the diagnosis if no clinical improvement after 3 days.
Review at 2 weeks to assess treatment compliance, partner(s) notification and resolution of symptoms.
Look out for complications i.e., hydrocoele, abscess, infarction, infertility.
Abstain from sex until the patient and partner(s) have completed treatment and symptoms are resolved.
To review the diagnosis If no clinical improvement after 3 days.
Review at 2 weeks to assess treatment compliance, partner(s) notification and resolution of symptoms.
Look out for complications i.e., hydrocoele, abscess, infarction, infertility.
Prophylaxis for infants & children with recurrent UTI
Preferred Regimen
Trimethoprim 1-2mg/kg PO at night (max. 100mg ON)
OR
Trimethoprim/sulfamethoxazole 2mg/kg (TMP dose) PO at night
OR
Nitrofurantoin 1-2mg/kg PO at night (max. 100mg ON)
Alternative Regimen (Allergy / Resistance)
Cephalexin 12.5mg/kg PO at night (max. 250mg/dose)
Remarks & Clinical Comments:
Antibiotic prophylaxis should not be routinely recommended in children with first-time UTI.
Prophylactic antibiotics should be given for 3 days with MCUG (micturatingcystourethogram) taking place on the second day.
Children with Grade I-IV vesicoureteral reflux (VUR) may experience a decrease in recurrent UTI by 50% following first or second febrile or symptomatic UTI with increased detection of resistant organisms following antibiotic prophylaxis.
Sexual partner(s) should be treated simultaneously.
Abstain from sex for 1 week after the patient and partner(s) have completed treatment and symptoms are resolved.
*Single high dose metronidazole is associated with gastrointestinal side effects and higher failure rate, especially if partner(s) are not treated concurrently.
Cloxacillin 200mg/kg/day IV in 4-6 divided doses (max. 2g/dose)
Methicillin-resistant (MRCoNS):
Vancomycin 45-60mg/kg/day IV in 3-4 divided doses (max. 3600mg/day)
Target AUC24 of 400-600 mg*hour/L
Alternative Regimen (Allergy / Resistance)
Methicillin-sensitive (MSCoNS):
Cefazolin 100mg/kg/day IV in 3 divided doses (max. 6 g/day if no endocarditis)
Remarks & Clinical Comments:
Diagnosis needs:
1. Paired blood cultures drawn from both catheters and peripheral vein.
2. If blood cultures cannot be drawn from peripheral vein, it is recommended that two or more blood cultures should be drawn through different catheter lumen.
Long term catheters should be removed in patients with CRBSI with:
Severe sepsis, suppurative thrombophlebitis, endocarditis, blood stream infections that continue despite 72 hours of antimicrobial therapy or longer to which the infecting organism is susceptible or infections due to Staphylococcus aureus, Pseudomonas aeruginosa, fungi & mycobacterium.
Attempts at catheter salvage are only recommended in uncomplicated CRBSI or CLABSI caused by bacteria that are neither too virulent nor too difficult to eradicate.
Exact optimal duration of therapy has not been established in children with or without catheter removal. 10-14 days after first negative blood culture is usually recommended.
*For CoNS, need to decide whether isolates from blood culture is coloniser or true pathogen.
General measures include warm compress, antiseptic washes, good skin hygiene and clean sharp razors when shaving.
Obtain a pus or swab for culture and sensitivity if accessible.
Topical antibiotic therapy is preferred for folliculitis that persists with general measures and involves a limited area of the skin.
Systemic antimicrobial therapy with S. aureus coverage is suggested for patients with deep or extensive folliculitis that fails to resolve or recurs after topical therapy.
Consider the etiology of the folliculitis and the severity and the distribution of the lesions.
Referral to a dermatologist if other etiologies are considered, especially when initial systemic treatment fails:
1.Gram-negative folliculitis (e.g. Enterobacter, Klebsiella, Escherichia, Serratia, Morganella, and Proteus species): primarily in patients on long-term antibiotic therapy, most often during treatment for acne.
2. Pseudomonal folliculitis: appears 8-48 hours after exposure to contaminated water (e.g. hot tub/spa) or wet suits.
3. Folliculitis caused by Malassezia furfur, Demodex mites or herpes simplex virus: seen in immunocompromised patients.
Cloxacillin 200mg/kg/day IV in 4-6 divided doses (max. 2g/dose)
Methicillin-resistant (MRSA):
Vancomycin 45-60mg/kg/day in 3-4 divided doses (max. 3600mg/day)
Target AUC24 of 400-600 mg*hour/L
Alternative Regimen (Allergy / Resistance)
Methicillin-sensitive (MSSA):
Cefazolin 100mg/kg/day IV in 3 divided doses (max. 6 g/day if no endocarditis)
Remarks & Clinical Comments:
Diagnosis needs:
1. Paired blood cultures drawn from both catheters and peripheral vein.
2. If blood cultures cannot be drawn from peripheral vein, it is recommended that two or more blood cultures should be drawn through different catheter lumen.
Long term catheters should be removed in patients with CRBSI with:
Severe sepsis, suppurative thrombophlebitis, endocarditis, blood stream infections that continue despite 72 hours of antimicrobial therapy or longer to which the infecting organism is susceptible or infections due to Staphylococcus aureus, Pseudomonas aeruginosa, fungi & mycobacterium.
Attempts at catheter salvage are only recommended in uncomplicated CRBSI or CLABSI caused by bacteria that are neither too virulent nor too difficult to eradicate.
Exact optimal duration of therapy has not been established in children with or without catheter removal. 10-14 days after first negative blood culture is usually recommended.
*For CONS, need to decide whether isolates from blood culture is coloniser or true pathogen.
Moderate to severe (Extensive/generalised; with or without systemic symptoms, or immunocompromised patients):
Amoxicillin/clavulanate 1.2g IV q8h
OR
Ampicillin/sulbactam 3g IV q6-8h
Alternative Regimen (Allergy / Resistance)
Mild (Localised):
Amoxicillin/clavulanate 625mg PO q8h
Remarks & Clinical Comments:
Duration: 5 days
Consider warm compresses and drainage first; if these measures fail, then initiate antibiotic therapy.
For moderate to severe boils, or those presenting with systemic manifestations, manage according to the treatment protocol for carbuncles.
Consider switching from IV to PO therapy if condition improves.
Duration: 7-10 days
Surgical drainage is the mainstay of treatment.
Consider IV to PO switch if adequate surgical treatment and rapid clinical response.
Consider targeted therapy once culture results are available.
300-400mg of piperacillin/kg/day in 3-4 divided doses (max. 16g/day)
Remarks & Clinical Comments:
*Empiric treatment with piperacillin/ tazobactam covers most of the Gram-negative organisms (Enterobacteriaceae), Gram-positive organisms and pseudomonas; follow through with C&S.
Ceftazidime 150-200 mg/kg/day in 3 divided doses (max. 6g/day)
OR
Piperacillin/tazobactam:
300-400mg of piperacillin/kg/day in 3-4 divided doses (max. 16 g/day)
Alternative Regimen (Allergy / Resistance)
Cefepime 50mg/kg/dose IV q8h (max. 2g/dose)
Remarks & Clinical Comments:
Not all pseudomonas is drug resistant. If ceftazidime remains susceptible, please use ceftazidime with/without an anti-pseudomonas aminoglycoside to treat. De-escalation is important to preserve antibiotic for future use.
*Caspofungin loading dose 70 mg/m2/dose IV q24hr on Day 1, followed by 50 mg/m2/dose IV q24hr thereafter (max. 70 mg/dose)
OR
Amphotericin B lipid complex 3-5 mg/kg/dose IV q24hr (max. 5mg/kg/dose)
Remarks & Clinical Comments:
Fungaemia: treatment without catheter removal is associated with low success rate and higher mortality.
*Example of alternative echinocandins that may also be used:
Micafungin 2-4mg/kg q24h (max. 150mg)
Anidulafungin 1.5-3mg/kg loading dose (max. 200mg/dose), then 0.75-1.5mg/kg q24h (age >28 days) (max. 100mg/dose)
Cloxacillin 200mg/kg/day IV in 4-6 divided doses (max. 2g/dose)
MRSA:
Vancomycin 45-60mg/kg/day in 3-4 divided doses (max. 3600mg/day)
Target AUC24 of 400-600 mg*hour/L
Alternative Regimen (Allergy / Resistance)
MSSA:
Cefazolin 100mg/kg/day IV in 3 divided doses (max. 6g/day)
Remarks & Clinical Comments:
Diagnosis requires positive blood culture plus radiographic demonstration of thrombus.
Remove catheter and a minimum antibiotic treatment of 3-4 weeks. Surgical resection of involved vein if failed conservative therapy.
Most common causative organism is Pseudomonas sp., however antibiotics need to be tailored according to susceptibility result.
Preferred Regimen
Ciprofloxacin 400mg IV q12h
OR
*Piperacillin/tazobactam 4.5g IV q6 – 8h
Alternative Regimen (Allergy / Resistance)
Ceftazidime 2g IV q8h
OR
Cefepime 2g IV q8h
Remarks & Clinical Comments:
Duration: 7 days (based on clinical response)
Consider IV to PO switch once patient's condition improves. Refer to Appendix 6 .
*Piperacillin/tazobactam: if given as q8h, to be given as extended infusion (over 3 – 4 hours).
(Deescalate once cultures are available/ Necrotizing fasciitis ruled out)
**Antibiotic Prophylaxis:
Phenoxymethylpenicillin (Penicillin V) 250mg PO q12h (500mg PO q12h if BMI ≥ 33)
Alternative Regimen (Allergy / Resistance)
Mild:
Amoxicillin/clavulanate 625mg PO q8h
OR
Ampicillin/sulbactam 375mg PO q12h
OR
Cefuroxime 500mg PO q12h
Moderate:
Ampicillin/sulbactam 3g IV q6h
OR
Amoxicillin/clavulanate 1.2g IV q8h
OR
Cefuroxime 750mg-1.5g IV q8h
Severe:
Ampicillin/sulbactam 3g IV q6h
OR
Amoxicillin/clavulanate 1.2g IV q8h
Antibiotic allergy:
Clindamycin 600mg IV q6h
(Deescalate once cultures are available/ Necrotizing fasciitis ruled out)
Antibiotic Prophylaxis:
Antibiotic allergy:
Clarithromycin 250mg PO q24h
OR
Erythromycin ethylsuccinate 400mg PO q12h
Remarks & Clinical Comments:
Mild cellulitis: without systemic signs of infection. Common organisms: Streptococcus pyogenes & Staphylococcus aureus
Moderate cellulitis: with *SIRS but no hypotension. Common organisms: Streptococcus pyogenes & Staphylococcus aureus
Severe cellulitis: with *SIRS and hypotension. Common organisms:Streptococcus pyogenes & Staphylococcus aureus
*Systemic inflammatory response syndrome (SIRS):
1. fever,
2. tachypnea,
3. tachycardia
4. abnormal white cell count
Duration: 5-10 days (longer duration may be required in case of no clinical improvement or if an underlying medication condition is present).
Consider IV to PO switch once patient's condition improves. Refer to Appendix 6 .
Refer to Appendix 3 for antibiotic allergy.
*Piperacillin/tazobactam: if given as q8h, to be given as extended infusion (over 3 – 4 hours).
**Antibiotic prophylaxis may be considered in patients with 3 to 4 episodes of recurrent cellulitis per year despite attempts to treat or control predisposing factors such as lymphoedema, obesity, inflammatory dermatoses, tinea pedis and venous insufficiency.
Duration of antibiotic prophylaxis: 6-12 months depending on recurrence of event. Reassess the need for further prophylaxis if indicated thereafter.
Consider antibiotic prophylaxis in these cases:
Human bite
Cat bite
Delayed presentation > 8 hours
Deep puncture wound extending or close to bone and joint
Crush associated injury
Immunocompromised patients
For all bite-related wounds, thorough wound irrigation and/or debridement must be of utmost priority. All injuries with broken skin require exploration and washout.
Consultation with a Plastic Surgeon should be considered for involvement of high-risk or special areas such as the face, hands, feet, and genitalia.
Role of ATT: The risk of tetanus needs to be evaluated to provide adequate post-exposure prophylaxis by vaccination. For further information on tetanus vaccine, please refer to Guidelines for Adult Immunisation .
For management of rabies, please refer to MOH Guideline on Rabies Management in Human and Animals .
Amoxicillin/clavulanate 625mg PO q8h or 1.2g IV q8h
Monkey bite:
Amoxicillin/clavulanate 625mg PO q8h or 1.2g IV q8h
PLUS
*Acyclovir 800 mg PO 5 times daily for 14 days
Alternative Regimen (Allergy / Resistance)
Antibiotic allergy:
Cefuroxime 750mg-1.5g IV q8h
OR
Ceftriaxone 2g IV q24h
PLUS
Metronidazole 500mg IV q8h
Oral Option:
Doxycycline 200mg PO q24h on Day 1 followed by 100mg-200mg PO q24h
OR
Cefuroxime 500mg PO q12h
PLUS
Metronidazole 400mg PO q8h
Remarks & Clinical Comments:
Duration:
Prophylaxis: 3 days
Treatment: 5 days
*Add acyclovir only when exposed to a macaque via bites and scratches, exposure to tissue culture material, exposure to tissue obtained during autopsies of monkeys, needlestick injuries, cage scratches, mucosal splash.
Common organisms:
Aeromonas sp.
Plesiomonas
Staphylococcus aureus
Streptococcus pyogenes
Oral therapy is encouraged if wounds are not associated with systemic features or involving deeper tissues.
Add metronidazole if wounds immersed in soil- or sewage-contaminated water.
To load with vancomycin 25-30mg/kg IV, followed by 15-20mg/kg (actual body weight) IV q8-12h; not exceeding 2g/dose
Alternative Regimen (Allergy / Resistance)
Linezolid 600mg IV/PO q12h
Depending on culture and susceptibility testing, can consider the following options:
Clindamycin 300-600mg IV/PO q6-8h
OR
Trimethoprim/sulfamethoxazole 160/800mg PO q12h
OR
Doxycyline 100mg PO q12h
Remarks & Clinical Comments:
Consider IV to PO switch if condition improves. Refer to Appendix 6 for IV to PO switch.
Refer to Appendix 1 for vancomycin loading dose.
MRSA Decolonisation strategy:
Use mupirocin 2% for nasal application bilateral nostrils.
Use chlorhexidine 4% bath or 2% wipe for body application (especially for high carriage sites such as axilla, groin and perineal region).
Consider CA-MRSA if:
Outbreaks of known CA-MRSA
Non-resolving cellulitis
Common organisms: Staphylococcus aureus Coagulase negative Staphylococcus Gram-negative organisms
Preferred Regimen
Grade 3-5:
Empirical treatment:
Cloxacillin 1g IV q6h
If blood culture negative and clinical improvement, to switch to oral:
Cloxacillin 500mg PO q6h
OR
Cephalexin 1000mg PO q12h
Alternative Regimen (Allergy / Resistance)
Grade 3-5:
Cefazolin 2g IV q8h
Remarks & Clinical Comments:
Grade 1:
Observe cannula
Grade 2:
Resite/Remove the intravenous cannula
Grade 3-4:
Remove the intravenous cannula and take blood culture;
Consider treatment
Grade 5:
Take blood culture
Resite/remove cannula
Initiate treatment
Duration: 5 days (depending on clinical response)
Peripheral intravenous catheters with associated pain, induration, erythema, or exudate should be removed.
VISUAL INFUSION PHLEBITIS SCORE
Score 0:
Insertion site healthy, no signs of phlebitis
Score 1:
Presence of one of the following signs: Slight pain or slight redness at IV insertion site.
Score 2:
Presence of 2 of the following signs:
Pain at IV site, redness or swelling.
Score 3:
Presence of all of the following signs:
Pain along the path of the cannula, redness around the insertion site and swelling.
Score 4:
Presence of all of the following signs:
Pain along the path of the cannula, redness around the insertion site, swelling, palpable venous cord.
Score 5:
Presence of all of the following signs:
Pain along the path of the cannula, redness around the insertion site, swelling, palpable venous cord, febrile.
To consider antibiotic if presence of systemic infection:
Ampicillin/sulbactam 3g IV q6h
OR
Amoxicillin/clavulanate 1.2g IV q8h
Remarks & Clinical Comments:
To consider other sources of infection and escalate antibiotics accordingly.
May consider oral antibiotics in localised infection.
Consider IV to PO switch if condition improves. Refer to Appendix 6 for IV to PO switch.
Clofazimine 300mg PO once a month and 50mg PO q24h
Duration:
Paucibacillary: 6 months
Multibacillary: 1 year
Alternative Regimen (Allergy / Resistance)
*Bacterial resistance or hypersensitivity to first line:
Can be substituted with one of the following:
Ofloxacin 400mg PO q24h
OR
Minocycline 100mg PO q24h
OR
Clarithromycin 500mg PO q24h
Remarks & Clinical Comments:
*Second line or drug-resistant regimen can only be initiated by a dermatologist.
Prophylaxis of leprosy with single dose rifampicin for contacts of leprosy patients after excluding leprosy and TB disease, and in the absence of other contraindication:
10-14 years old: 450 mg
≥15 years old: 600 mg
5.2 Non-tuberculous Mycobacterial (NTM) Skin and Soft Tissue Infections
Treatment depends on the patient’s individual susceptibility and the site of infection. It often involves combination therapy with two to three antimicrobial agents for a prolonged period of time (often 6 months to a year).
NTM are intrinsically resistant to many antibiotics. Antibiotic susceptibility testing can be performed at appropriate reference laboratories. Selection of antibiotics are often empirically chosen based on guideline.
5.2 Non-tuberculous Mycobacterial (NTM) Skin and Soft Tissue Infections
Preferred Regimen
Rifampicin 10mg/kg PO q24h
PLUS
Clarithromycin 7.5mg/kg PO q12h
Alternative Regimen (Allergy / Resistance)
Rifampicin 10mg/kg PO q24h
PLUS
Streptomycin 15mg/kg IM q24h for 4 weeks
Followed by:
Rifampicin 10mg/kg PO q24h
PLUS
Clarithromycin 7.5mg/kg PO q12h
Remarks & Clinical Comments:
Wide surgical excision and debridement are important.
Duration
WHO category 1:
Pre-ulcerative lesions and skin lesions smaller than 5 cm, duration of antibiotic 4 weeks with simple excision or 8 weeks of antibiotic therapy only
WHO category 2:
Antibiotic at least 8 weeks with supportive care (E.g.: surgery)
WHO category 3:
Lesions > 15cm, antibiotic plus surgical debridement and reconstruction. Duration of treatment depends on clinical response as complications are common (joint and bone involvement)
Griseofulvin 500mg PO q12h for 6 to 12 weeks or longer until fungal cultures are negative
OR
Terbinafine 250mg PO q24h
PLUS
2.5% selenium sulphide shampoo
OR
2% ketoconazole shampoo,
2 – 3 times per week for 2 weeks
Alternative Regimen (Allergy / Resistance)
*Itraconazole 5mg/kg PO q24h
OR
Fluconazole 6mg/kg PO q24h
Duration is based on mycological result/ type of treatment agent and clinical response. E.g.:
Trichophyton sp : 2-4 weeks
Microsporum sp : 8-12 weeks
Remarks & Clinical Comments:
Other recommendations:
For kerion, griseofulvin should be considered as first line unless Tricophyton has been cultured as the pathogen. Duration of treatment may be longer.
Contacts of patient may be treated with 2% ketoconazole shampoo 2 – 3 times per week for 2 weeks.
Surgical excision is to be avoided.
Topical therapy alone is not recommended for the management of tinea capitis.
Consider adding oral prednisolone in selected cases.
*Itraconazole: Absorption depends on gut acidity. Take capsule with food and acidic beverage (E.g.: cola or oranges drinks). Avoid PPIs and H2 blockers.
Common organism: Trichophyton Microsporum Epidermophyton
Preferred Regimen
Mild infections:
Topical imidazoles or allylamines cream/lotion. E.g.:
Clotrimazole 1% LA q12h
OR
Miconazole 2% LA q12h
OR
Ketoconazole 2% shampoo LA q12h
OR
Terbinafine 1% LA q12h
Duration: Until clinical clearance with additional 2 weeks.
Extensive infections:
Terbinafine 250mg PO q24h for 2 weeks
OR
*Itraconazole 200mg PO q24h for 2 weeks
OR
Griseofulvin 500mg PO q12h or q24h for 4-6 weeks
Alternative Regimen (Allergy / Resistance)
Extensive Infections:
Fluconazole 100mg PO daily for 1-2 weeks
OR
Fluconazole 200mg PO once weekly for 3-4 weeks
Remarks & Clinical Comments:
Other recommendations:
In patients with renal or hepatic impairment, caution should be exercised while prescribing systemic antifungals.
Terbinafine clearance is significantly reduced in patient with renal impairment. Other systemic antifungals are preferred in these patients.
Topical nystatin should not be used in dermatophytosis as they are not effective against dermatophytes.
*Itraconazole: Absorption depends on gut acidity. Take capsule with food and acidic beverage (E.g.: cola or orange drinks). Avoid PPIs and H2 blockers.
Antifungal therapy should be adjusted based on culture results and susceptibility findings.
Common organism: Trichophyton Microsporum Epidermophyton
Preferred Regimen
First line:
Topical antifungals as mentioned in tinea corporis for 4-8 weeks
Resistant cases:
Terbinafine 250mg PO q24h for 2-4 weeks
OR
*Itraconazole 200mg PO q24h for 2-4 weeks
OR
Griseofulvin 500mg PO q12h for 6-12 weeks
Alternative Regimen (Allergy / Resistance)
Resistant cases:
Fluconazole 150mg/week PO for 4 weeks
Remarks & Clinical Comments:
Other recommendations:
● Topical keratolytic agents can be used in conjunction with antifungals for hyperkeratotic type of tinea pedis/manuum.
● Potassium permanganate in 1:10,000 dilution wet dressings, applied for 20 min 2–3 times/day, may be helpful if vesiculation or maceration is present.
● Systemic antifungals can be prescribed as first line treatment in severe moccasin-type tinea pedis or severe recurrent tinea with blisters.
*Itraconazole: Absorption depends on gut acidity. Take capsule with food and acidic beverage (E.g.: cola or orange drinks). Avoid PPIs and H2 blockers.
Common organism: Trichophyton Microsporum Epidermophyton
Preferred Regimen
*Amorolfine 5% Nail Lacquer once weekly application
Duration:
Fingernails: 6 months
Toenails: 12 months
OR
**Pulse itraconazole 200mg PO q12h for 1 week per month
Duration:
Fingernails: 2 months
Toenails: 3 months
OR
Terbinafine 250mg PO q24h
Duration:
Fingernails: 6 weeks
Toenails: 12 weeks
Alternative Regimen (Allergy / Resistance)
Griseofulvin 500mg PO q12h
Duration:
Fingernails: 6 months
Toenails: 12 months
OR
Fluconazole 150mg PO once weekly
Duration:
Fingernails: ≥ 3 months
Toenails: 6-12 months
Remarks & Clinical Comments:
*Amorolfine 5% Nail Lacquer is not indicated for children less than 12 years old.
Patients with contraindications to systemic agents may consider topical antifungal agents.
Diagnosis of onychomycosis should be confirmed with a KOH preparation test, culture, or PAS Stain. Empirical treatment is not recommended.
**Itraconazole: Absorption depends on gut acidity. Take capsule with food and acidic beverage (E.g.: cola or orange drinks). Avoid PPIs and H2 blockers.
Common organism: Malassezia furfur Pityrosporum orbiculare
Preferred Regimen
First line: Topical treatment only
Selenium sulphide 2% shampoo;
Apply to affected areas 10 minutes before bathing, or
Dilute to 1:1 with water, apply and leave overnight (treat for 1-2 weeks)
OR
Ketoconazole 2% shampoo, apply to affected areas 10 minutes before bathing
For face:
Topical imidazole for 4-6 weeks. E.g.: Miconazole 2% cream, clotrimazole 1% cream LA q12h
For recurrent or resistant cases:
*Itraconazole 200mg PO q24h for 1 week or 400mg single dose
OR
Fluconazole 300mg PO weekly dose for 2 weeks
Alternative Regimen (Allergy / Resistance)
Alternative for selenium sulphide and ketoconazole shampoo:
Sulfur preparation
OR
Salicylic solution
Remarks & Clinical Comments:
Recommendations:
Ketoconazole shampoo or selenium sulphide shampoo can be used once every two to four weeks for approximately six months in order to try and prevent recurrence.
*Itraconazole: Absorption depends on gut acidity. Take capsule with food and acidic beverage (e.g.: Cola or orange drinks). Avoid PPIs and H2 blockers.
Fluconazole 100mg PO q24h for 1 week (in severe and immunocompromised patients)
Remarks & Clinical Comments:
Treatment of sexual partner is advisable in case of recurrent infection.
*Itraconazole: Absorption depends on gut acidity. Take capsule with food and acidic beverage (E.g.: cola or orange drinks). Avoid PPIs and H2 blockers.
Lymphocutaneous and Cutaneous Sporotrichosis / Chromoblastomycosis
Preferred Regimen
*Itraconazole 200mg PO q12h until all lesions have resolved
(usually for a total of 3–6 months)
Alternative Regimen (Allergy / Resistance)
For patients not able to tolerate itraconazole:
Terbinafine 500mg PO q12h
OR
Fluconazole 400mg q24h
Remarks & Clinical Comments:
In some immunocompromised condition such as AIDS, longer treatment may be necessary. Refer to Infections in Immunocompromised Patients - Opportunistic Infections in HIV Patients section.
*Itraconazole: Absorption depends on gut acidity. Take capsule with food and acidic beverage (E.g.: cola or orange drinks). Avoid PPIs and H2 blockers.
**Avoid azole in pregnancy
(pulmonary, osteoarticular, meningeal, or disseminated sporotrichosis)
Preferred Regimen
Amphotericin B deoxycholate 0.7-1mg/kg IV q24h for 2 weeks
OR
*Amphotericin B (lipid formulation) 3–5mg/kg q24h for 2 weeks
Followed by;
**Itraconazole 200mg PO q12-24h for at least of 12 months duration
***In pregnancy and breastfeeding:
Terbinafine 500mg PO q12h
Alternative Regimen (Allergy / Resistance)
**In pregnancy and breastfeeding:
Amphotericin B deoxycholate 0.7-1mg/kg IV q24h for 2 weeks
OR
*Amphotericin B (lipid formulation) 3–5mg/kg q24h for 2 weeks
Remarks & Clinical Comments:
In some immunocompromised condition such as AIDS, longer treatment may be necessary. Refer to Infections in Immunocompromised Patients - Opportunistic Infections in HIV Patients section.
*Not listed in MOH Drug Formulary.
**Itraconazole: Absorption depends on gut acidity. Take capsule with food and acidic beverage (E.g.: cola or orange drinks). Avoid PPIs and H2 blockers.
***Avoid azole in pregnancy.
6.10 Cutaneous fungal infection in immunocompromised patients
Refer to treatment of disseminated fungal infection in Infections in Immunocompromised Patients - Opportunistic Infections in HIV patients section.
Skin biopsy for histopathological examination (HPE) and culture are advised before commencing treatment.
For Lomentospora prolificans, consider surgical debridement and reduction of immunosuppression.
Consider IV to PO switch once clinically improving and can tolerate orally.
*Not listed in MOH Drug Formulary.
Duration: 7 days
Vesiculation for trunk and limbs:
Potassium permanganate in 1:10,000 dilution wet dressings, applied for 20 min 2–3 times/day, may be helpful.
Vesiculation for head and neck:
Normal saline wet dressings, applied for 20 min 2–3 times/day, may be helpful.
*Not listed in MOH Drug Formulary.
Acyclovir 10mg/kg IV q8h for 7 days (change to oral once there is an improvement)
Remarks & Clinical Comments:
Advisable to start treatment early within 48 hours.
Vesiculation for trunk and limbs:
Potassium permanganate in 1:10,000 dilution wet dressings, applied for 20 min 2–3 times/day, may be helpful.
Vesiculation for head and neck:
Normal saline wet dressings, applied for 20 min 2–3 times/day, may be helpful.
Topical antiviral treatment is not recommended for herpes zoster.
Vesiculation for trunk and limbs:
Potassium permanganate in 1:10,000 dilution wet dressings, applied for 20 min 2–3 times/day, may be helpful.
Vesiculation for head and neck:
Normal saline wet dressings, applied for 20 min 2–3 times/day, may be helpful.
Systemic antiviral treatment is recommended for all immunocompromised patients or for immunocompetent patients with the following criteria:
1. >50 years of age
2. Moderate or severe pain
3. Moderate or severe rash
4. Non-truncal involvement
Advisable to start treatment early within 48-72 hours.
Surgical drainage is the mainstay of management.
Duration: 10 to 14 days but shorter antibiotic duration (5 to 7 days) can be considered if adequate source control and local wound management has shown clinical improvement.
Refer to Appendix 3 for antibiotic allergy.
Antibiotics may be necessary in certain high-risk groups:
Inhalation injury
Immunocompromised patients (E.g.: extreme age groups (elderly and children), diabetes mellitus, obesity, impaired immunity)
Delay in burn wound excision
Mechanical ventilation
Total body surface area (TBSA) burn > 20%
2.1 Spreading infections and infections of fascial spaces (with/without systemic signs)
Traumatic wound infection is usually caused by endogenous organisms rather than exogenous. Common organisms: Viridans Streptococci Staphylococci Prevotella intermedia Peptostreptococcus Eubacterium Fusobacterium nucleatum
Preferred Regimen
Benzylpenicillin 2-4MU IV q4-6h
PLUS
Metronidazole 500mg IV q8h
OR
Amoxicillin/Clavulanate 1.2gm IV q8h
OR
Cefuroxime 1.5g IV q8h
PLUS
Metronidazole 500mg IV q8h
Alternative Regimen (Allergy / Resistance)
If not responding to first-line antibiotics:
Ceftriaxone 1-2g IV q24h
PLUS
Metronidazole 500mg IV q8h
Antibiotic allergy:
Clindamycin 300-450mg PO q6h or 600-900mg IV q8h
Remarks & Clinical Comments:
Empirical antibiotics are started.
Incision and drainage are advised and the antibiotic is changed in accordance with the result of culture and sensitivity.
Continue intravenous therapy for 1 to 2 days following successful abscess drainage, then switch to oral therapy.
Refer to Appendix 6 for IV to PO switch.
3.2.1 Penetrating and puncture-type wounds / Complex soft tissue wounds without open fractures
3.2 Complex Soft Tissue Injuries
Common organisms: Staphylococcus aureus Beta-haemolytic streptococci Polymicrobial infection
Preferred Regimen
Cloxacillin 2g IV q6h
MAY ADD
*Metronidazole 500mg IV q8h
MAY ADD
**Gentamicin 5mg/kg IV q24h
Alternative Regimen (Allergy / Resistance)
Cefazolin 2g IV q6-8h
OR
Cefuroxime 1.5g IV q8h
PLUS
*Metronidazole 500mg IV q8h
OR
Amoxicillin/Clavulanate 1.2g IV q8h
Remarks & Clinical Comments:
*Metronidazole: In soil/rust contamination or heavy machinery.
**Gentamicin: If there’s extensive skin and soft tissue involvement (for gram negative coverage).
Tetanus immunization should be given in addition to appropriate antibiotics.
Antibiotic therapy should be tailored to the susceptibility of deep wound cultures isolates once available.
Duration: depends on the extent of infection.
For combat-related isolated soft tissue injury, antibiotic duration of 1 - 3 days may be adequate.
For severe penetrating injuries, especially those involving joints and/or tendons, antibiotics must be given for at least 5 days.
E.g.: penetrating injury through the plantar foot Common organisms: Pseudomonas aeruginosa Staphylococcus aureus
Preferred Regimen
*Piperacillin/tazobactam 4.5g IV q6-8h
OR
Cefepime 2g IV q8h
Alternative Regimen (Allergy / Resistance)
Ciprofloxacin 750mg PO q12h
Remarks & Clinical Comments:
Tetanus immunization should be given in addition to appropriate antibiotics.
Antibiotic therapy should be tailored to the susceptibility of deep wound cultures isolates once available.
Duration: total 7-14 days following adequate surgical debridement if no evidence of established osteomyelitis upon presentation.
If there is osteomyelitis, refer to the Orthopaedic Infection section – Bone and Joint Infections: Osteomyelitis.
*Piperacillin/tazobactam: if given as q8h, to be given as extended infusion (over 3 -4 hours).
Pre-debridement and post-debridement cultures are not representative of actual infection.
Duration:
Gustilo Type I: stop after 24 hours
Gustilo Type II: discontinue after 24 hours to 48 hours
*Metronidazole: In soil/rust contamination or heavy machinery.
Common organisms: Gram positive organisms Gram negative organisms
Preferred Regimen
As per Gustilo Type I & II fractures
PLUS
Gentamicin 5mg/kg IV q24h
MAY ADD
*Metronidazole 500mg IV q8h
Alternative Regimen (Allergy / Resistance)
Ceftriaxone 2g IV q24h
MAY ADD
*Metronidazole 500mg IV q8h
Presence of water contamination
Fresh water contamination:
**Piperacillin/tazobactam 4.5g IV q6-8h
Sea water contamination:
**Piperacillin/tazobactam 4.5g IV q6-8h
PLUS
Doxycycline 100mg PO q12h
Remarks & Clinical Comments:
Pre-debridement and post-debridement cultures are not representative of actual infection.
Duration:
Gustilo Type III: 24 hours after wound closure or up to a maximum of 72 hours (whichever is earlier)
*Metronidazole: In soil/rust contamination or heavy machinery.
**Piperacillin/tazobactam: if given as q8h, to be given as extended infusion (over 3-4 hours).
4.1.1 Open Fracture / Penetrating Injuries without Dura Breach
4.1 Cranial Trauma
Preferred Regimen
Cefazolin 2g IV q8h
OR
Cefuroxime 1.5g IV q8h
MAY ADD
Metronidazole 500mg IV q8h
Alternative Regimen (Allergy / Resistance)
Amoxicillin clavulanate 1.2g IV q8h
Remarks & Clinical Comments:
Duration:
Until 24 hours after wound closure or 72 hours total (whichever occurs first).
The use on antibiotic here is pre-emptive antibiotics and should not be continued beyond a short course.
(Refer susceptibility testing result before considering alternative treatment regime)
Remarks & Clinical Comments:
Notifiable disease
IV to PO switch is recommended once symptoms improve based on susceptibility testing result. Refer Appendix 6 .
Duration: minimum 7-14 days
Notes: longer duration of fever defervescence may be observed in patients treated with cephalosporin.
Severe sepsis or shock, gastrointestinal bleeding, intestinal perforation, encephalopathy, metastatic infection or other complications.
Preferred Regimen
Ceftriaxone 50-75mg/kg/24h (2-4 g/day) IV q12-24h
OR
Cefotaxime 40-80mg/kg/24h (2-6 g/day) IV q8-12h
Alternative Regimen (Allergy / Resistance)
Ciprofloxacin 400mg IV q8-12h
OR
Azithromycin 20mg/kg IV q24h (maximum 1 g q24h)
(Refer susceptibility testing result before considering alternative treatment regime)
Remarks & Clinical Comments:
Consult ID Physician for complicated/severe typhoid or drug-resistant typhoid.
Duration: 10-14 days. Once symptoms improve, may consider IV to oral antibiotic switch based on susceptibility testing results. Refer Appendix 6 .
In case of persistent fever after 5-7 days of effective antimicrobial therapy, re-evaluate and repeat culture. Longer duration of antimicrobial therapy may be necessary in the presence of metastatic or deep seated infection.
Adjunctive corticosteroid may be considered after consultation with an ID physician in severe typhoid with delirium, obtundation, coma or shock. In such cases, administer IV dexamethasone 3 mg/kg followed by 8 doses of 1 mg/kg every q6h for 48 hours. Monitor patients closely as corticosteroid use is associated with increased risk of gastrointestinal bleeding and perforation.
*Erythromycin Ethylsuccinate 800mg PO q12h for 3 days
Remarks & Clinical Comments:
Notifiable disease
Indication for antibiotics:
Oral or intravenous hydration is the mainstay of cholera treatment.
Antibiotics are recommended for patients with moderate to severe illness who are hospitalized.
*Azithromycin / Erythromycin is recommended in pregnancy.
For high-risk laboratory exposures to Brucella isolates
Preferred Regimen
Doxycycline 100mg PO q12h for 3 weeks
PLUS
Rifampicin 600mg for 3 weeks
Alternative Regimen (Allergy / Resistance)
*Doxycycline 100mg PO q12h for 3 weeks
PLUS
Trimethoprim/Sulphamethoxazole 160/800mg PO q12h for 3 weeks
*In case of exposure to Brucella abortus RB51 strain (which is resistant to rifampicin)
Remarks & Clinical Comments:
PEP should be offered as soon as high-risk laboratory exposure to Brucella isolates has been identified and be administered for up to six months following exposure.
PEP may be considered for low risk exposure in pregnant women or immunosuppressed individuals (consult ID physician).
*Amoxicillin 25-50mg/kg/day PO in 3 divided doses or 500mg PO q8h for 7 days
Alternative Regimen (Allergy / Resistance)
*Azithromycin 500mg PO q24h for 3 days
Remarks & Clinical Comments:
Notifiable disease
Early antibiotic therapy is recommended if leptospirosis is clinically suspected following recent high risk exposure (E.g.: flood, recreational activities).
*Amoxicillin or azithromycin is recommended for pregnant women.
*IV to PO switch is recommended once symptoms improve. Refer to Appendix 6 .
Duration: 7 - 10 days
There is insufficient evidence to support routine use of corticosteroid therapy. However, use of steroids as an adjunct to antibiotic therapy may be considered in severe leptospirosis with pulmonary haemorrhage (consult ID physician).
Consider on a case-by-case basis in short periods of high risk exposure (E.g.: soldiers, outbreak response personnel involved in occupational/recreational activities (see comments))
Preferred Regimen
Doxycycline 200 mg PO weekly starting 1-2 days before exposure and continue during exposure
Remarks & Clinical Comments:
The mainstay prevention of leptospirosis is avoidance of direct contact with contaminated water or environment.
Evidence on effectiveness of prophylactic antibiotics in prevention of leptospirosis is limited. Routine use of prophylactic antibiotics is not recommended.
In situations of major outbreaks, the use of mass chemoprophylaxis is not recommended.
Notes: Doxycycline is contraindicated in pregnancy and breastfeeding. Gastrointestinal side effects are common.
Anti-tetanus toxoid vaccine IM (initiate age appropriate active immunization at a different site)
Alternative Regimen (Allergy / Resistance)
Benzylpenicillin 100,000-200,000 unit/kg/24h IV q6h for 7-10 days
PLUS
Human Tetanus Immunoglobulin single dose 500IU IM
PLUS
Anti-tetanus toxoid vaccine IM (initiate age appropriate active immunization at a different site)
Remarks & Clinical Comments:
Notifiable disease
All patients with tetanus should undergo wound debridement to eradicate spores and necrotic tissue.
*IV to oral switch is recommended once symptoms improve.
(usual dose : 500mg IV q6h; 1g q6-8h for severe infection)
Neuromelioidosis and adults with septic shock requiring intensive care support and with augmented renal clearance:
Meropenem 2g IV q8h
For neurological melioidosis, osteomyelitis and septic arthritis, genitourinary infection including prostatic abscesses, and skin and soft tissue infections,
MAY ADD
*Trimethoprim 80mg/ Sulphamethoxazole 400mg
< 40 kg: 160/800mg PO q12h
40-60kg: 240/1200mg PO q12h
> 60kg: 320/1600 mg PO q12h
Refer to comment section for graded dosing.
(Consider de-escalate to ceftazidime once symptoms improve/stable)
Remarks & Clinical Comments:
*Add on Trimethoprim/Sulphamethoxazole in eye, neurologic, testicular, prostatic, pericardium, bone and joint melioidosis.
To minimise side effects, trimethoprim/sulfamethoxazole should be introduced gradually, except in neurological melioidosis or critically ill patients with multifocal abscess where full dosage is administered as soon as feasible.
The graded dose will take 1-2 weeks to reach full dose, depending on circumstances. Cessation of intravenous therapy and commencement of timed eradication phase is set only once the full planned dose of trimethoprim/sulfamethoxazole is reached. Refer below for graded dosing of trimethoprim/sulfamethoxazole:
Body weight > 60kg with normal renal function
Day 1- Day 2: 40/200mg (½ tab of 80/400mg) q12h
Day 3 - Day 4: 80/400mg (1 tab of 80/400mg) q12h
Day 5 - Day 6: 160/800mg (2 tabs of 80/400mg) q12h
Day 7 - Day 8: 240/1200mg (3 tabs of 80/400mg) q12h
Day 9 onwards: 320/1600mg (4 tabs of 80/400mg) q12h
Body weight <60kg or impaired renal function Consult ID physicians to determine graded dosing schedule.
All patients who undergo intensive therapy and eradication therapy for melioidosis require counselling regarding monitoring for adverse effects of medication
Drainage of abscesses should be attempted wherever appropriate such as prostatic, empyema and pericardium.
Duration of intensive therapy:
Skin and soft tissue infection, mild pneumonia: 2 weeks
Bacteraemia with no foci: 2-4 weeks
Complicated pneumonia, prostatic, deep-seated foci, septic arthritis: 4 - 6 weeks
Osteomyelitis: 6 weeks
Neurologic/CNS: 8 weeks
Arterial infection e.g.: mycotic aneurysm: 8 weeks
Use clinical judgement to guide prolongation of intensive phase in patients with slow clinical improvement or persistent bacteraemia.
Carbapenems are potentially neurotoxic especially at higher doses. Use with caution in patients with renal impairment or CNS disorders.
Urine bacterial growth ≥105cfu/mL in 2 serial samples in women or a single sample in men without urinary tract infection (UTI) symptoms.
Preferred Regimen
Treatment is NOT indicated unless:
*In pregnant women
**Prior to transurethral resection of prostate (TURP) or urological procedures breaching the mucosa
Remarks & Clinical Comments:
*Duration of treatment for pregnant women: 5 days.
**Duration of treatment for preemptive treatment of ABU before TURP or urological procedures breaching the mucosa: 3-5 days. Follow up urine culture is not necessary prior to the procedure.
Do not screen or treat asymptomatic bacteriuria in the following conditions:
Women without risk factors
Post-menopausal women
Patients with indwelling or suprapubic catheters and nephrostomy tubes
Elderly institutionalized patients
Patients with dysfunctional and/or reconstructed lower urinary tracts
Patients with renal transplants
Patients prior to arthroplasty surgeries
Patients with history of recurrent urinary tract infections
Infection confined to the bladder in afebrile men and women. Common organisms: Escherichia coli Klebsiella pneumoniae Streptococcus agalactiae
Preferred Regimen
*Nitrofurantoin 50-100mg PO q6h (macrocrystals, immediate-release)
OR
Nitrofurantoin 100mg PO q12h (monohydrate/macrocrystals, sustained-release)
OR
Amoxicillin/clavulanate 625mg PO q8h
OR
Ampicillin/sulbactam 375-750mg PO q12h
Alternative Regimen (Allergy / Resistance)
Cephalexin 500mg PO q12h
OR
Cefuroxime 250-500mg PO q12h
OR
**Fosfomycin 3g PO x 1 dose
(Unlikely to be effective for gram negative other than E. coli. Other gram-negative infection carry FosA hydrolase gene that may deactivate fosfomycin and leads to clinical failure)
Remarks & Clinical Comments:
Duration: 3-5 days. The treatment duration is counted starting from the first day of effective antibiotic therapy.
*Avoid Nitrofurantoin if GFR < 30ml/min and pregnant women at third trimester.
Trimethoprim-sulfamethoxazole is not recommended to be used as empirical therapy for UTI as the local resistance rates of E. coli and Klebsiella pneumoniae has been consistently > 30%.
Amoxicillin or ampicillin should not be used for empirical treatment given the relatively poor efficacy and the very high prevalence of antimicrobial resistance.
**If confirmed ESBL E.coli sensitive to fosfomycin, to give every 48hrs for total 3 doses.
Infection beyond the bladder in men and women
Pyelonephritis
Febrile or bacteremic UTI
Catheter-associated (CAUTI)
Prostatitis (Refer to section prostatitis)
For patients with sepsis due to complicated UTI, please refer to the section on Urosepsis.
Duration: 5-7 days
*Consider using ceftazidime or adding aminoglycoside (E.g.: amikacin) in patients at risk of Pseudomonas aeruginosa infection.
Consider stepping down to oral antibiotics based on culture and sensitivity result once patient is afebrile for > 48 hours, clinically improving and able to take oral medications.
Pyuria alone in the absence of other symptoms is not diagnostic of CA-UTI and treatment is not indicated.
Systemic urinary tract infections that may lead to organ dysfunction. Common organisms: Escherichia coli Klebsiella pneumoniae Enterococcus faecalis Streptococcus agalactiae Pseudomonas aeruginosa
Preferred Regimen
Urosepsis WITHOUT shock:
Ceftriaxone 2g IV q24h
OR
Cefotaxime 2g IV q8h
Urosepsis WITH shock:
*Piperacillin-tazobactam 4.5g IV q6-8h
Alternative Regimen (Allergy / Resistance)
Urosepsis WITHOUT shock:
Ceftazidime 2g IV q8h
OR
Cefepime 2g IV q8h
Urosepsis WITH shock:
**Meropenem 1g IV q8h
OR
**Imipenem 500mg IV q6h
Remarks & Clinical Comments:
Early source control should be the mainstay of treatment for urosepsis.
For patients with urosepsis, broad-spectrum antibiotic therapy should be selected based on the following criteria:
Severity of illness
Patient-specific risk factors for resistant organisms
Local antibiogram, if available
Other patient-specific consideration (allergies, immunocompromised state, elderly, etc)
Duration: 7 days or more
For patients with abscesses in the urinary tract or bacterial prostatitis, please refer to respective sections for the duration and choice of antibiotics.
*Piperacillin/tazobactam: if given as q8h, to be given as extended infusion (over 3 – 4 hours).
**Carbapenem should be reserved for urosepsis with risk factors for MDR or ESBL-producing organism.
Common organisms for Aerobic infection: Staphylococcus sp. Streptococcus sp
Preferred Regimen
Aerobic infection:
Mupirocin ointment 2% LA q12h to q8h for 7-10 days
MAY ADD
Amoxicillin/clavulanate 625 mg PO q8h for 7 days (for severe cases)
Anaerobic infection:
Amoxicillin/clavulanate 625 mg PO q8h for 7 days
Remarks & Clinical Comments:
Antibiotics are only indicated if there is clinical suspicion or evidence of bacterial balanitis. Please refer to the Sexually Transmitted Infection section for antibiotic choice if there is evidence of STI
5.1 Prophylaxis for Recurrent Urinary Tract Infections (rUTIs)
Preferred Regimen
Nitrofurantoin 50-100mg PO ON (macrocrystals)
OR
Nitrofurantoin 100mg PO ON (monohydrate/macrocrystals, dual release)
OR
Cephalexin 250mg PO ON
Alternative Regimen (Allergy / Resistance)
Trimethoprim/sulfamethoxazole 80/400mg PO ON
OR
Trimethoprim 100mg PO ON
Remarks & Clinical Comments:
Antimicrobial prophylaxis is indicated if non-antimicrobial measures (behavioral and personal hygiene) fail.
Continuous prophylaxis for 3-12 months or intermittent post-coital prophylaxis (a single dose of antibiotics taken within the 2-hour period after sexual intercourse).
Long-term use of nitrofurantoin has been associated with an increased risk of rare adverse effects, including pulmonary toxicity, hepatotoxicity and peripheral polyneuropathy.
Common organisms: Escherichia coli Klebsiella pneumoniae Staphylococcus aureus Enterococcus faecalis Streptococcus agalactiae Pseudomonas aeruginosa Less common organism: Mycobacterium tuberculosis
Preferred Regimen
Amoxicillin/clavulanate 1.2g IV q6-8h
OR
Ampicillin/sulbactam 3g IV q6h
MAY ADD
Gentamicin 5mg/kg IV q24h
Alternative Regimen (Allergy / Resistance)
Cefuroxime 750mg-1500mg IV q8h
OR
Ceftriaxone 2g IV q24h
MAY ADD
Gentamicin 5mg/kg IV q24h
Remarks & Clinical Comments:
Source control by surgical or pigtail drainage is the mainstay of treatment.
Duration of antibiotics: 2-3 weeks (of both IV and oral). The duration of antibiotics should be determined by the extent of infection, source control, clinical response, resolution on follow-up imaging, and normalization of inflammatory markers.
Consider stepping down to oral antibiotics based on culture and sensitivity results once the patient is afebrile for >48 hours, clinically improving and able to take oral medications.
Common organisms: Escherichia coli Klebsiella pneumoniae Enterococcus faecalis Pseudomonas aeruginosa
Preferred Regimen
Outpatient treatment:
Ciprofloxacin 500-750mg PO q12h
Inpatient treatment:
*Ciprofloxacin 400mg IV q12h
OR
Amoxicillin/clavulanate 1.2g IV q6h
OR
Ampicillin/sulbactam 3g IV q6h
MAY ADD
**Aminoglycoside
Alternative Regimen (Allergy / Resistance)
Outpatient treatment:
Trimethoprim/Sulfamethoxazole 160/800mg PO q12h
Inpatient treatment:
Cefuroxime 750mg-1500mg IV q8h
OR
Ceftriaxone 2g IV q24h
OR
**Ceftazidime 2g IV q8h
Remarks & Clinical Comments:
Obtain urine culture before starting treatment.
Duration of antibiotics: Minimum 10-14 days or up to 6 weeks depending on the severity and clinical response.
Consider stepping down to oral antibiotics based on culture and sensitivity results once the patient is afebrile for >48 hours, clinically improving and able to take oral medications.
If the patient has risk factors for sexually transmitted disease, please refer to Sexually Transmitted Infection section for choice of antibiotics.
*PO ciprofloxacin may be considered for patients who are not septic and can tolerate orally, as it has similar bioavailability to the IV formulation.
**Consider using ceftazidime or adding aminoglycoside (E.g.: amikacin) in patients at risk of Pseudomonas aeruginosa infection.
Chronic or recurrent urogenital symptoms that persist for at least 3 months.
Preferred Regimen
Ciprofloxacin 500-750mg PO q12h for 4-6 weeks
Alternative Regimen (Allergy / Resistance)
Trimethoprim/ Sulfamethoxazole 160/800mg PO q12h for 4-12 weeks
OR
*Doxycycline 100mg PO q24h for 10 days
OR
**Azithromycin 500mg PO q24h for 3 weeks
Remarks & Clinical Comments:
Referral to urologist is recommended to differentiate from chronic non-bacterial prostatitis before starting antibiotics.
Ciprofloxacin, despite the high resistance rates of uropathogens, is recommended as first line agent in the empirical treatment of chronic bacterial prostatitis due to the favorable pharmacokinetic properties.
*Doxycycline - Only for C. trachomatis or mycoplasma infections
**Azithromycin - Only for Trichomonas vaginalis infections
Common organisms: Escherichia coli Klebsiella pneumoniae Enterococcus faecalis Pseudomonas aeruginosa
Preferred Regimen
Levofloxacin 500mg PO q24h for 10 days
Alternative Regimen (Allergy / Resistance)
Ciprofloxacin 500mg PO q12h for 10-14 days
OR
Trimethoprim/ Sulfamethoxazole 160/800mg PO q12h for 10 days
OR
Ofloxacin 200mg PO q12h for 14 days
Remarks & Clinical Comments:
If patient has risk factors for sexually transmitted disease or sexually active, please refer to Sexually Transmitted Infection section for choice of antibiotics.
Common organisms: Escherichia coli Klebsiella pneumoniae Enterococcus faecalis Pseudomonas aeruginosa
Preferred Regimen
Amoxicillin/clavulanate 1.2g IV q6-8h
OR
Ampicillin/sulbactam 3g IV q6h
Alternative Regimen (Allergy / Resistance)
Cefuroxime 750mg-1500mg IV q8h
OR
Ceftriaxone 2g IV q24h
OR
*Ciprofloxacin 400mg IV q12h
Remarks & Clinical Comments:
Surgical drainage is the mainstay of treatment.
*Ciprofloxacin 500-750mg PO q12h may be considered as outpatient treatment for small testicular abscesses that are not suitable for drainage.
Aggressive surgical debridement is the mainstay of treatment.
Antibiotics are given until source control is achieved.
*Piperacillin/tazobactam: if given as q8h, to be given as extended infusion (over 3 – 4 hours).
**Carbapenem should be reserved for Fournier’s Gangrene with risk factors for MDR or ESBL-producing organisms.