Sandbox endocarditis

Streptococci

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Native Valve Endocarditis Caused by Viridans Group Streptococci and Streptococcus bovis   ▸  Viridans Group Streptococci and Streptococcus bovis Highly Penicillin-Susceptible   ▸  Viridans Group Streptococci and Streptococcus bovis Relatively Penicillin Resistant (MIC >0.12 μg/mL- ≤ 0.5 μg/mL) Prosthetic Valves Endocarditis Caused by Viridans Group Streptococci and Streptococcus Bovis   ▸  Viridans Group Streptococci and Streptococcus Bovis Penicillin-Susceptible Strain (MIC ≤ 0.12 μg/mL)   ▸  Viridans Group Streptococci and Streptococcus Bovis Penicillin Relatively or Fully Resistant Strain (MIC >0.12 μg/mL)   ▸  Viridans Group Streptococci and Streptococcus bovis Relatively Penicillin-Resistant Streptococci (MIC 0.2–0.5 µg/ml)   ▸  Relatively Penicillin-Resistant Streptococci (MIC > 0.5 µg/ml)   ▸  Unable to tolerate Penicillin or Ceftriaxone

Native Valve Endocarditis Caused by Highly Penicillin-Susceptible Viridans Group Streptococci and Streptococcus bovis Preferred Regimen ( 4 wks ) Adult dose ▸ Penicillin G sodium † 12–18 million U/24 h IV either continuously or in 4-6 equally divided doses x 4 Wks OR ▸ Ceftriaxone sodium 2 g/24 h IV/IM in 1 dose x 4 Wks Pediatric dose ₳ ▸ Penicillin G sodium 200 000 U/kg q24h IV either continuously or in 4-6 equally divided doses x 4 Wks OR ▸Ceftriaxone 100 mg/kg q24 h IV/IM in 1 dose x 4 Wks Alternative Regimen ( 2 wks ) Adult dose ▸ Penicillin G sodium‡ 12–18 million U/24 h IV either continuously or in 6 equally divided doses x 2 Wks OR ▸ Ceftriaxone sodium 2 g/24 h IV/IM in 1 dose x 2 Wks PLUS ▸ Gentamicin sulfate ฿ 3 mg/Kg per 24h 1 dose x 2 Wks Pediatric dose ▸ Penicillin G sodium 200 000 U/kg q24h IV in 4-6 equally divided doses x 2 Wks OR ▸Ceftriaxone 100 mg/kg q24 h IV/IM in 1 dose x 2 Wks PLUS ▸ Gentamicin sulfate 3 mg/Kg per 24h 1 dose or 3 equally divided doses x 2 Wks Alternative Regimen Adult dose ▸ Vancomycin hydrochloride ¶ 15 mg/kg q12h IV x 4 Wks Doses should not to exceed 2 g/24 h unless concentrations in serum are inappropriately low Pediatric dose ▸Vancomycin hydrochloride 40 mg/kg per 24 h IV in 2–3 equally divided doses Minimum inhibitory concentration ≤ 0.12 μg/mL. † Preferred in most patients >65 y or patients with impairment of 8th cranial nerve function or renal function. ₳ Pediatric dose should not exceed that of a normal adult. ‡ 2-wk regimen not intended for patients with known cardiac or extracardiac abscess or for those with creatinine clearance of <20 mL/min, impaired 8th cranial nerve function, or Abiotrophia, Granulicatella, or Gemella spp infection; gentamicin dosage should be adjusted to achieve peak serum concentration of 3-4 μg/mL and trough serum concentration of >1 μg/mL when 3 divided doses are used; nomogram used for single daily dosing. ¶ Vancomycin therapy recommended only for patients unable to tolerate penicillin or ceftriaxone; vancomycin dosage should be adjusted to obtain peak (1 h after infusion completed) serum concentration of 30–45 μg/mL and a trough concentration range of 10–15 μg/mL ฿ Other potentially nephrotoxic drugs (eg, nonsteroidal antiinflammatory drugs) should be used with caution in patients receiving gentamicin therapy. Although it is preferred that gentamicin (3 mg/kg) be given as a single daily dose to adult patients with endocarditis due to viridans group streptococci, as a second option, gentamicin can be administered daily in 3 equally divided doses.

Native Valve Endocarditis Caused by Strains of Viridans Group Streptococci and Streptococcus bovis Relatively Resistant to Penicillin (MIC >0.12 μg/mL- ≤ 0.5 μg/mL)) Preferred Regimen Adult dose ▸ Penicillin G sodium 24 million U/24 h IV either continuously or in 4–6 equally divided doses x 4 wks OR ▸ Ceftriaxone 2 g/24 h IV/IM in 1 dose x 4 wks PLUS ▸ Gentamicin sulfate 3 mg/kg per 24 h IV/IM in 1 dose x 2 wks Pediatric dose ▸ Penicillin G sodium 300 000 U/kg per 24 h IV in 4–6 equally divided doses OR ▸ Ceftriaxone 100 mg/kg per 24 h IV/IM in 1 dose PLUS ▸ Gentamicin sulfate 3 mg/kg per 24 h IV/IM in 1 dose or equally divided doses Alternative Regimen Adult dose ▸ Vancomycin hydrochloride 30 mg/kg per 24 h IV in 2 equally divided doses x 4 wks Pediatric dose ▸ Vancomycin hydrochloride 40 mg/kg per 24 h IV or in 2 or 3 equally divided doses

Penicillin-susceptible strain (MIC ≤ 0.12 g/mL) Preferred Regimen Adult dose ▸ Penicillin G sodium † 24 million U/24 h IV either continuously or in 4–6 equally divided doses x 6 wks OR ▸ Ceftriaxone 2 g/24 h IV/IM in 1 dose x 6 wks WITH OR WITHOUT ▸ Gentamicin sulfate ‡ 3 mg/kg per 24 h IV/IM in 1 dose x 2 wks Pediatric dose ▸ Penicillin G sodium 300 000 U/kg per 24 h IV in 4–6 equally divided doses OR ▸ Ceftriaxone 100 mg/kg IV/IM once daily WITH OR WITHOUT ▸Gentamicin 3 mg/kg per 24 h IV/IM, in 1 dose or 3 equally divided doses Alternative Regimen Adult dose ▸ Vancomycin hydrochloride 30 mg/kg per 24 h IV in 2 equally divided doses x 6 wks Pediatric dose ▸ 40 mg/kg per 24 h IV or in 2 or 3 equally divided doses *Dosages recommended are for patients with normal renal function. † Penicillin or ceftriaxone together with gentamicin has not demonstrated superior cure rates compared with monotherapy with penicillin or ceftriaxone for patients with highly susceptible strain; gentamicin therapy should not be administered to patients with creatinine clearance of <30 mL/min. ‡ Although it is preferred that gentamicin (3 mg/kg) be given as a single daily dose to adult patients with endocarditis due to viridans group streptococci, as a second option, gentamicin can be administered daily in 3 equally divided doses.

Penicillin relatively or fully resistant strain (MIC >0.12 >μg/mL)) Preferred Regimen Adult dose ▸ Penicillin G sodium 24 million U/24 h IV either continuously or in 4–6 equally divided doses x 6 wks OR ▸ Ceftriaxone 2 g/24 h IV/IM in 1 dose x 6 wks PLUS ▸ Gentamicin sulfate 3 mg/kg per 24 h IV/IM in 1 dose x 6 wks Pediatric dose ▸ Penicillin G sodium 300 000 U/kg per 24 h IV in 4–6 equally divided doses Alternative Regimen Adult dose ▸ Vancomycin hydrochloride 30 mg/kg per 24 h IV in 2 equally divided doses x 6 wks Pediatric dose ▸ Vancomycin hydrochloride 40 mg/kg per 24 h IV or in 2 or 3 equally divided doses

Relatively Penicillin-Resistant Streptococci (MIC 0.2–0.5 µg/ml Preferred Regimen Adult dose ▸ Penicillin G potassium 24 million U/24 h IV either continuously or in 4–6 equally divided doses X 4 Wks OR ▸Ceftriaxone 2 g/24 h IV/IM in 1 dose AND ▸ Gentamicin 3 mg/kg I.M. or I.V. daily in divided doses q. 8 hr X 2 Wks Pediatric dose ▸ Penicillin G potassium 300 000 U/24 h IV in 4–6 equally divided doses X 4 Wks OR ▸ Ceftriaxone 100 mg/kg per 24 h IV/IM in 1 dose AND ▸ Gentamicin 3 mg/kg per 24 h IV/IM in 1 dose or 3 equally divided doses X 2 Wks

Relatively Penicillin-Resistant Streptococci(MIC > 0.5 µg/ml, consider Enterococcal regimen Preferred Regimen Adult dose ▸ Penicillin G potassium 24 million U/24 h IV either continuously or in 4–6 equally divided doses x 4 Wks PLUS ▸ Gentamicin 3 mg/kg I.M. or I.V. daily in divided doses q. 8 hr x 2 Wks Pediatric dose ▸ Penicillin G potassium 24 million U/24 h IV either continuously or in 4–6 equally divided doses x 4 Wks PLUS ▸ Gentamicin 3 mg/kg I.M. or I.V. daily in divided doses q. 8 hr x 2 Wks

Unable to Tolerate Aqueous crystalline penicillin G sodium or Ceftriaxone Preferred Regimen Adult dose ▸ Vancomycin 30 mg/kg per 24 h IV in 2 equally divided doses not to exceed 2 g/24 h, unless serum concentrations are inappropriately low Pediatric dose ▸ Vancomycin 40 mg/kg 24 h in 2 or 3 equally divided doses X 4 Wks

Enterococci

Endocarditis Caused by Enterococci   ▸  Enterococci Strains Susceptible to Penicillin, Gentamicin, and Vancomycin   ▸  Enterococci Strains Susceptible to Penicillin, Streptomycin, and Vancomycin and Resistant to Gentamicin   ▸  Enterococci Strains Resistant to Penicillin and Susceptible to Aminoglycoside and Vancomycin   ▸  Enterococci Strains Resistant to Penicillin, Aminoglycoside, and Vancomycin

Enterococci Strains Susceptible to Penicillin, Gentamicin, and Vancomycin Preferred Regimen Adult dose ▸ Ampicillin 12 g/24 h I.V.in 6 equally divided doses x 4–6 Wks OR ▸Penicillin G sodium 18–30 million U. I.V. daily in 6 equally divided doses x 4–6 Wks PLUS ▸Gentamicin sulfate 3 mg/kg per 24 h IV/IM in 3 equally divided doses x 4-6 Wks Pediatric dose ▸ Ampicillin 300 mg/kg per 24 h IV in 4–6 equally divided doses; X 4–6 Wks OR ▸Penicillin G sodium 300 000 U/kg per 24 h IV in 4–6 equally divided doses X 4–6 Wks PLUS ▸Gentamicin sulfate 3 mg/kg per 24 h IV/IM in 3 equally divided doses X 4-6 Wks Alternative Regimen ▸ Vancomycin 30 mg/kg I.V. daily in 2 equally divided doses x 6 Wks PLUS ▸Gentamicin sulfate 3 mg/kg per 24 h IV/IM in 3 equally divided doses x 6 Wks Pediatric dose ▸ Vancomycin 30 mg/kg I.V. daily in divided doses q. 12 hour X 4–6 Wks PLUS ▸Gentamicin sulfate 3 mg/kg per 24 h IV/IM in 3 equally divided doses X 4-6 Wks *Native valve: 4-wk therapy recommended for patients with symptoms of illness < 3 months. 6-wk therapy recommended for patients with symptoms >3 months. Prosthetic valve or other prosthetic cardiac material: minimum of 6 wk of therapy recommended. Vancomycin therapy recommended only for patients unable to tolerate penicillin or ampicillin. 6 wk of vancomycin therapy recommended because of decreased activity against enterococci.

Enterococci Strains Susceptible to Penicillin, Streptomycin, and Vancomycin and Resistant to Gentamicin Preferred Regimen Adult dose ▸ Ampicillin 12 g/24 h I.V.in 6 equally divided doses x 4–6 Wks OR ▸Penicillin G sodium 24 million U. I.V. continuously or in 6 equally divided doses x 4–6 Wks PLUS ▸Streptomycin sulfate 15 mg/kg per 24 h IV/IM in 2 equally divided doses x 4-6 Wks Pediatric dose ▸ Ampicillin 300 mg/kg per 24 h IV in 4–6 equally divided doses; x 4–6 Wks OR ▸Penicillin G sodium 300 000 U/kg per 24 h IV in 4–6 equally divided doses x 4–6 Wks PLUS ▸Streptomycin sulfate 20–30 mg/kg per 24 h IV/IM in 2 equally divided doses Alternative Regimen Adult dose ▸ Vancomycin 30 mg/kg I.V. daily in 2 equally divided doses x 6 Wks PLUS ▸Streptomycin sulfate 15 mg/kg per 24 h IV/IM in 2 equally divided doses x 4-6 Wks Pediatric dose ▸ Vancomycin 40 mg/kg per 24 h IV in 2 or 3 equally divided doses X 4–6 Wks PLUS ▸Streptomycin sulfate 20–30 mg/kg per 24 h IV/IM in 2 equally divided doses Native valve: 4-wk therapy recommended for patients with symptoms of illness < 3 months. 6-wk therapy recommended for patients with symptoms >3 months. Prosthetic valve or other prosthetic cardiac material: minimum of 6 wk of therapy recommended. Vancomycin therapy recommended only for patients unable to tolerate penicillin or ampicillin.

β-Lactamase–producing strain Preferred Regimen Adult dose ▸ Ampicillin-sulbactam 12 g/24 h IV in 4 equally divided doses x 6 Wks PLUS ▸Gentamicin sulfate 3 mg/kg per 24 h IV/IM in 3 equally divided doses x 6 Wks Pediatric dose ▸ Ampicillin-sulbactam 300 mg/kg per 24 h IV in 4 equally divided doses x 6 Wks PLUS ▸Gentamicin sulfate 3 mg/kg per 24 h IV/IM in 3 equally divided doses x 6 Wks Alternative Regimen ▸Vancomycin hydrochloride 30 mg/kg per 24 h IV in 2 equally divided doses x 6 Wks PLUS ▸Gentamicin sulfate 3 mg/kg per 24 h IV/IM in 3 equally divided doses x 6 Wks Pediatric dose ▸ Vancomycin hydrochloride 40 mg/kg per 24 h in 2 or 3 equally divided doses PLUS ▸Gentamicin sulfate 3 mg/kg per 24 h IV/IM in 3 equally divided doses x 6 Wks Intrinsic penicillin resistance Adult dose ▸Vancomycin hydrochloride 30 mg/kg per 24 h IV in 2 equally divided doses x 6 Wks PLUS ▸Gentamicin sulfate 3 mg/kg per 24 h IV/IM in 3 equally divided doses x 6 Wks Pediatric dose ▸ Vancomycin hydrochloride 40 mg/kg per 24 h in 2 or 3 equally divided doses PLUS ▸Gentamicin sulfate 3 mg/kg per 24 h IV/IM in 3 equally divided doses x 6 Wks

E faecium Adult dose ▸ Linezolid 1200 mg/24 h IV/PO in 2 equally divided doses x ≥8 Wks OR ▸Quinupristin-dalfopristin 22.5 mg/kg per 24 h IV in 3 equally divided doses x ≥ 8 Wks Pediatric dose ▸ Linezolid 30 mg/kg per 24 h IV/PO in 3 equally divided doses ≥8 Wks OR ▸Quinupristin-dalfopristin 22.5 mg/kg per 24 h IV in 3 equally divided doses ≥8 Wks E faecalis Adult dose Preferred Regimen ▸ Imipenem/cilastatin 2 g/24 h IV in 4 equally divided doses x ≥8 Wks PLUS ▸Ampicillin sodium 12 g/24 h IV in 6 equally divided doses x ≥ 8 Wks Pediatric dose ▸ Imipenem/cilastatin 60–100 mg/kg per 24 h IV in 4 equally divided doses x ≥8 Wks PLUS ▸Ampicillin sodium 300 mg/kg per 24 h IV in 4–6 equally divided doses x ≥ 8 Wks Alternative Regimen Adult dose ▸ Ceftriaxone sodium 4 g/24 h IV/IM in 2 equally divided doses x ≥8 Wks PLUS ▸Ampicillin sodium 12 g/24 h IV in 6 equally divided doses x ≥ 8 Wks Pediatric dose ▸ Ceftriaxone sodium 100 mg/kg per 24 h IV/IM in 2 equally divided doses x ≥8 Wks PLUS ▸Ampicillin sodium 300 mg/kg per 24 h IV in 4–6 equally divided doses x ≥ 8 Wks Patients with endocarditis caused by these strains should be treated in consultation with an infectious diseases specialist. Cardiac valve replacement may be necessary for bacteriologic cure. Cure with antimicrobial therapy alone may be < 50% Severe, usually reversible thrombocytopenia may occur with use of linezolid, especially after 2 wk of therapy. Quinupristin-dalfopristin only effective against E faecium and can cause severe myalgias, which may require discontinuation of therapy Only small no. of patients have reportedly been treated with imipenem/cilastatin-ampicillin or ceftriaxone + ampicillin.

Staphylococci

Native Valve Endocarditis caused by Staphylococci in the Absence of Prosthetic Material   ▸  Staphylococci (Methicillin Susceptible)   ▸  Staphylococci (Methicillin-resistant) with Penicillin G Anaphylactoid Hypersensitivity Prosthetic Valves Endocarditis or Other Prosthetic Material Caused by Staphylococci   ▸  Oxacillin-Susceptible Strains   ▸  Oxacillin-Resistant Strains

Staphylococci (Methicillin Susceptible) Preferred Regimen Adult dose ▸ Nafcillin or Oxacillin † 12 g I.V. daily in equally divided doses x 6 Wks PLUS (optional) ▸ Gentamicin sulfate ‡ 3 mg/kg per 24 h IV/IM in 2-3 equally divided doses x 3-5 days Altenative Regimen( in non anaphylactoid Penicillin hypersensitivity) ▸ Cefazolin 6 g/ 24 h I.V. in 3 divided doses x 6 wks PLUS (optional) ▸ Gentamicin 3 mg/kg per 24 h IV/IM in 2-3 equally divided doses x 3-5 days Pediatrics dose ▸ Nafcillin or oxacillin 200 mg/kg per 24 h IV in 4–6 equally divided doses x 4-6 wks OR ( in non anaphylactoid Penicillin hypersensitivity) ▸Cefazolin 100 mg/kg per 24 h IV in 3 equally divided doses x 4-6 wks AND (optional) ▸ Gentamicin 3 mg/kg per 24 h IV/IM in 3 equally divided doses † Penicillin G 24 million U/24 h IV in 4 to 6 equally divided doses may be used in place of nafcillin or oxacillin if strain is penicillin susceptible (MIC ≤ 0.1 μg/mL) and does not produce β-lactamase. ‡ Gentamicin should be administered in close temporal proximity to vancomycin, nafcillin, or oxacillin dosing.

Staphylococci (Methicillin-resistant) (in anaphylactoid Penicillin hypersensitivity) Preferred Regimen Adult dose ▸ Vancomycin 30 mg/kg per 24 h IV in 2 equally divided doses x 6 wks Adjust vancomycin dosage to achieve 1-h serum concentration of 30–45 > g/mL and trough concentration of 10–15 >g/mL Pediatrics dose ▸ Vancomycin 40 mg/kg per 24 h IV in 2 or 3 equally divided doses x 6 wks

Oxacillin-susceptible strains Adult dose ▸ Nafcillin or oxacillin 2 g q4h IV x ≥6 weeks PLUS ▸ Rifampin 300 mg q8h IV/PO x ≥6 weeks PLUS ▸ Gentamicin 3 mg/kg per 24 h IV/IM in 2 or 3 equally divided doses x 2 weeks Pediatric dose ▸Nafcillin or oxacillin 200 mg/kg per 24 h IV in 4–6 equally divided doses PLUS ▸Rifampin 20 mg/kg per 24 h IV/PO in 3 equally divided doses PLUS ▸Gentamicin 1 mg/kg q8h IV/IM

Oxacillin-resistant strains Adult dose ▸ Vancomycin 15 mg/kg q12h x ≥6 Wks PLUS ▸ Rifampin 300 mg q8h IV/PO x ≥6 Wks PLUS ▸ Gentamicin 3 mg/kg per 24 h IV/IM in 2 or 3 equally divided doses x 2 wks Pediatric dose ▸ Vancomycin 40 mg/kg per 24 h IV in 2-3 equally divided doses x ≥6 wks PLUS ▸Rifampin 20 mg/kg per 24 h IV/PO in 3 equally divided doses x ≥6 wks PLUS ▸ Gentamicin 1 mg/kg q8h IV/IM x 2 Wks

HACEK Organisms

▸  Therapy for Both Native and Prosthetic Valve Endocarditis Caused by HACEK Microorganisms

Therapy for Both Native and Prosthetic Valve Endocarditis Caused by HACEK Microorganisms Adult dose ▸ Ceftriaxone sodium † 2 g/24 h IV/IM in 1 dose x 4 weeks OR ▸ Ampicillin- sulbactam ‡ 12 g/24 h IV in 4 equally divided doses x 4 weeks OR ▸ Ciprofloxacin ‡¶ 500 mg q12h PO or 400 mg q12h IV x 4 weeks Pediatric dose ▸ Ceftriaxone 100 mg/kg per 24 h IV/IM once daily OR ▸Ampicillin- sulbactam 300 mg/kg per 24 h IV divided into 4 or 6 equally divided doses OR ▸Ciprofloxacin 10-15 mg/kg q12h IV/PO HACEK: Haemophilus parainfluenzae, H aphrophilus, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae. † Patients should be informed that IM injection of ceftriaxone is painful. ‡ Dosage recommended for patients with normal renal function. ¶ Fluoroquinolones are highly active in vitro against HACEK microorganisms. Published data on use of fluoroquinolone therapy for endocarditis caused by HACEK are minimal.