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

2. ACUTE PERICARDITIS

2.1 Viral

(commonest cause)

Treatment mainly supportive.

2.2 Bacterial

Staphylococcus aureus

Haemophilus influenza

Salmonella spp.

M. tuberculosis

Non-infectious causes (especially post cardiac surgery) are becoming more common.

Preferred

*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

Antibiotic allergy:

Cefazolin 100mg/kg/day IV in 3 divided doses (max. 6g/day)

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

3. INFECTIVE ENDOCARDITIS

3.1 Empirical Therapy for Infective Endocarditis

3.1.1 Community-acquired Organisms

Streptococcus

Enterococcus

HACEK Gram-negative organisms

Preferred

Ampicillin 200-300mg/kg/day IV/PO in 4-6 divided doses (max. 12g/day)

PLUS

Gentamicin 1mg/kg/dose IV q8h

MAY ADD

*Cloxacillin 200 mg/kg/day IV in 4-6 divided doses (max. 12g/day)

Alternative

Comments

*For acute presentation, need to cover for MSSA since Streptococcus, Enterococcus & HACEK presentations are usually sub-acute.

3.1.2 Healthcare-associated Organisms

MRSA

Non-HACEK Gram-negative organisms

Enterococcus sp.

Preferred

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)

Alternative

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.

3.2 Specific Organisms

3.2.1 Streptococcus viridans

Preferred

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

Strains fully susceptible to penicillin (MIC < 0.125 mg/l):

Ampicillin 300mg/kg/day IV in 4-6 divided doses (max. 12g/day)

Ceftriaxone 100mg/kg/day IV in 1-2 divided doses (max. 4g/day)

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

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.

3.2.2 Enterococcus sp.

Preferred

Penicillin-sensitive (MIC ≤ 8 mg/l):

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

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)

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.

3.2.3 Staphylococcus aureus

Preferred

Methicillin-sensitive (left-sided):

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

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

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

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.

3.2.4 HACEK organisms

Slow growth or no growth in blood culture

Preferred

Ceftriaxone 100mg/kg/day in 2 divided doses (max. 4g/day) for 4 weeks

Alternative

Comments

4. CULTURE-NEGATIVE ENDOCARDITIS

Preferred

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

Alternative

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.

References:

American Academy of Paediatrics. Committee on Infectious Diseases. Red Book: Report of the Committee on Infectious Diseases (2021)
Malaysian Clinical Practice Guideline for the Prevention, Diagnosis and Management of Infective Endocarditis 2017

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