CARDIOVASCULAR SYSTEM INFECTIONS

Acute Rheumatic Fever Group A Streptococcus

All patients with ARF should receive antibiotic to treat precipitating Group A Streptococcus infection. Primary Prevention of ARF means timely and complete treatment of Group A Streptococcus sore throat with antibiotics. If commenced within 8 days of sore throat onset, a course of penicillin will prevent almost all the cases of ARF that would otherwise have developed.

Infection/Condition and Likely Organism	Suggested Treatment		Comment
	Preferred	Alternative
Primary prophylaxis	Benzathine penicillin G 1.2MU IM OR Phenoxymethylpenicillin 500mg orally q12h for 10 days OR Penicillin hypersensitivity (non-severe) Cephalexin 1 gm PO q12h for 10 days OR Penicillin immediate hypersensitivity Azithromycin 500mg PO q24h for 5 days		Streptococcal infection may not be evident by the time ARF manifests (e.g. cultures often negative) but eradication therapy for possible persisting streptococci is recommended nonetheless. Intramuscular penicillin is preferred due to better adherence and its ongoing use in secondary prophylaxis.
Secondary prophylaxis	Parenteral Prophylaxis: Benzathine penicillin G 1.2MU IM every 3 to 4 weeks Oral Prophylaxis: Phenoxymethylpenicillin (Penicillin V) 250mg PO q12h daily	Penicillin allergy: Erythromycin ethylsuccinate 800mg PO q12h
	Type of infection	Duration of Prophylaxis
	Rheumatic fever with carditis and residual heart disease (persistent valvular disease)	10 years or until 40 years of age, whichever is longer; sometimes lifelong prophylaxis
	Rheumatic fever with carditis but no residual heart disease (no valvular disease)	10 years or until 21 years of age, whichever is longer
	Rheumatic fever without carditis	5 years or until 21 years of age whichever is longer

Infective Endocarditis

Infection/Condition and Likely Organism	Suggested Treatment			Comment
	Preferred	Alternative
Empirical Treatment for native valve / late prosthetic valve (>1 year post surgery) endocarditis
	Ampicillin 12 gm/day IV in 4-6 doses PLUS Gentamicin 3mg/kg IV q24h PLUS* (Flu)Cloxacillin 12 gm/day IV in 4-6 doses	Penicillin allergy: Vancomycin 30-60mg/kg/ day IV in 2-3 doses PLUS Gentamicin 3mg/kg IV q24h		For suspected Staphylococcus aureus* infection (e.g. IVDU, prosthesis) Duration and regimen decided after confirmation of organism.
Empirical Treatment for early prosthetic valve (<12 months post-surgery) or healthcare associated endocarditis
	Vancomycin 30-60mg/kg/ day IV in 2 doses PLUS Gentamicin 3mg/kg IV q24h PLUS Rifampicin 900-1200mg PO in 2-3 divided doses			Rifampicin is only recommended for prosthetic valve endocarditis and it should be started 3-5 days after Vancomycin and Gentamicin.
Viridans Streptococci and Streptococcus bovis
Native and Prosthetic Valves Penicillin- Susceptible	Penicillin G 12-18 MU/day IV either in 4-6 doses or continuously OR Ampicillin 2gm IV q4h OR Ceftriaxone 2gm/day IV	For Beta-lactam allergic patient Vancomycin 30mg/kg/day IV in 2 doses		Duration – 4 weeks (native valve) or 6 weeks (prosthetic valve).
Native and Prosthetic Valves Penicillin- Resistant	Penicillin G 24 MU/day IV either in 4-6 doses or continuously OR Ampicillin 2gm IV q4h OR Ceftriaxone 2gm/day IV PLUS Gentamicin 3mg/kg IV q24h	For Beta-lactam allergic patient Vancomycin 30mg/kg/day IV in 2 doses PLUS Gentamicin 3mg/kg IV q24h
Enterococcus - Test for high level aminoglycoside resistance (HLAR)
Beta lactam and HLA-susceptible strain	Ampicillin 2gm IV q4h for 4 - 6 weeks (prosthetic valve) PLUS *Gentamicin 1mg/kg IV q8h for4-6 weeks		Ampicillin 2gm IV q4h for 4-6 weeks PLUS **Ceftriaxone 2gm IV q12h for 4-6 weeks (for renal impairment, elderly patients or those with resistance to Gentamicin)	This is active against Enterococcus faecalis strain with and without HLAR, being the combination of choice in patient with HLAR E. faecalis endocarditis. *Ceftriaxone should not be used alone due to intrinsic resistance of Enterococcus*.
			If resistant to Penicillin and susceptible to Vancomycin and aminoglycoside Vancomycin 30mg/kg/day IV in 2 doses for 6 weeks PLUS Gentamicin 1mg/kg IV q8h for 6 weeks	* In order to maximize synergistic effect, administer Gentamicin at the same time or temporally close to Ampicillin.
Staphylococcus spp
Native valve Methicillin - Susceptible Staphylococci (MSSA)	(Flu)Cloxacillin 12gm/day IV in 4-6 doses for 4-6 weeks		For Penicillin allergic patient Non-immediate type hypersensitivity Cefazolin 2gm IVq8h for 4-6 weeks For immediate type hypersensitivity Vancomycin 30mg/kg/day IV in 2 doses for 4-6 weeks
Prosthetic valves Methicillin – Susceptible Staphylococci	(Flu)Cloxacillin 12 gm/day IV in 4-6 doses for>6 weeks PLUS Rifampicin 900-1200mg PO in 2-3 divided doses for >6 weeks PLUS Gentamicin 1mg/kg IV q8h for 2 weeks		For Penicillin allergic patient replace (Flu) Cloxacillin with I. Non-immediate type hypersensitivity Cefazolin 2gm IVq8h for 4-6 weeks II. For immediate type hypersensitivity Vancomycin 30mg/kg/day IV in 2 doses for 4-6 weeks	Rifampicin: start after 3-5 days of effective initial Cloxacillin therapy and / or once the bacteremia has been cleared.
Native valves Methicillin – Resistant Staphylococci	Vancomycin 30-60mg/kg/day IV in 2 doses for 4-6 weeks
Prosthetic valves Methicillin – Resistant Staphylococci	Vancomycin 30-60mg/kg/ day IV in 2 -3 doses for > 6 weeks PLUS Rifampicin 900-1200mg PO in 2-3 divided doses for >6 weeks PLUS Gentamicin 1mg/kg IV q8h for 2 weeks			Rifampicin: start after 3-5 days of effective initial Cloxacillin therapy and / or once the bacteremia has been cleared.
HACEK group of microorganism (Haemophilus parainfluenzae, Haemophilus aphrophilus, Actinobacillus actinimycetemcomitans, Cardiobacterium hominis, Eikenella corrodens and Kingella kingae)
Native and Prosthetic valves	Ceftriaxone 2 gm IV q24h for 4 weeks (native valve) or 6 weeks (prosthetic valve)		Ampicillin-sulbactam 3gm IV q6h for 4-6 weeks OR *Ciprofloxacin 400mg IV q12h for 4-6 weeks	*Ciprofloxacin can be changed to oral 500mg q12h for remaining duration once clinically stable.
Therapy for Culture Negative Endocarditis
Brucella spp.	Gentamicin 5mg/kg IV q24h (for first 2-4 weeks) PLUS Doxycycline 100mg IV/PO q12h PLUS Rifampicin 300-600mg PO q24h			Duration of treatment 3-6 months depending on clinical response
Legionella spp.	Levofloxacin 500mg/12h/ IV or PO ≥ 6weeks OR Clarithromycin 500mg/12h IV for 2 weeks then PO for 4 weeks
Mycoplasma spp.	Levofloxacin 500mg/12h/ IV or PO ≥ 6weeks
Therapy for Candida Endocarditis (Native and Prosthetic valve)
Candida Endocarditis (Native and prosthetic valve)	Initial therapy Amphotericin B deoxycholate 0.5-1mg/kg IV q12h for at least 6 weeks after surgery OR Lipid formulation Amphotericin B 3-5mg/ kg IV q24 h for at least 6 weeks after surgery PLUS* Flucytosine 25mg/kg PO q6h for at least 6 weeks after surgery (if available)			Surgery is mandatory. Continue therapy for 6 weeks after the 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. *Flucytosine: for synergistic effect. Causes dose related marrow toxicity. Avoid using in patients with renal failure.
	Step down therapy: Fluconazole 400-800mg (6-12mg/kg) PO q24h after negative blood cultures

References

ESC Clinical Practice guidelines. Infective Endocarditis (Guidelines on Prevention, Diagnosis and Treatment of) 2015.
Harrisons Principles of Internal Medicine. 20 E (2019).
National Antimicrobial Guideline, Third Edition. Petaling Jaya: Ministry of Health, Malaysia; 2019.
The 2020 Australian guideline for prevention, diagnosis and management of acute rheumatic fever and rheumatic heart disease (3rd edition); 2020 pp105-106 (https://www.rhdaustralia.org.au/arf-rhd-guideline).