What is the recommended empiric and definitive antibiotic regimen, dosing, and treatment duration for native‑valve and prosthetic‑valve Corynebacterium endocarditis, including considerations for β‑lactam resistance, vancomycin use, and adjunctive gentamicin?

Corynebacterium Endocarditis: Antibiotic Management

Empiric Therapy

For suspected Corynebacterium endocarditis, initiate vancomycin 30 mg/kg/24h IV in 2 divided doses (targeting trough 15-20 mg/L) plus gentamicin 3 mg/kg/24h IV/IM pending susceptibility results. 1

• This empiric regimen provides coverage while awaiting species identification and susceptibility testing, which is critical because Corynebacterium species demonstrate variable resistance patterns 2, 1
• Vancomycin demonstrates universal activity against all Corynebacterium species tested in contemporary series, whereas penicillin resistance is common 2
• The addition of gentamicin provides potential synergy and covers the possibility of polymicrobial infection 1

Definitive Therapy for Penicillin-Susceptible Isolates

Native Valve Endocarditis

For penicillin-susceptible Corynebacterium diphtheriae native valve endocarditis, use penicillin G 12-18 million units/24h IV in 4-6 divided doses for 4-6 weeks. 3

• A β-lactam alone (without aminoglycoside) demonstrates equivalent outcomes to combination therapy in penicillin-susceptible C. diphtheriae endocarditis, with no difference in mortality or need for surgical intervention 3
• Adding gentamicin 3 mg/kg/24h IV/IM for the first 2 weeks is reasonable if the patient has normal renal function, prosthetic material, or complicated infection, though not mandatory for uncomplicated native valve disease 3, 1
• Alternative β-lactams include ampicillin 12 g/24h IV in 6 divided doses or ceftriaxone 2 g/24h IV once daily for 4-6 weeks 3

Prosthetic Valve Endocarditis

For prosthetic valve Corynebacterium endocarditis with penicillin-susceptible isolates, administer penicillin G 18-24 million units/24h IV in 4-6 divided doses plus gentamicin 3 mg/kg/24h IV/IM for at least 6 weeks. 3, 4

• Prosthetic valve involvement is disproportionately common with Corynebacterium species (70% of cases), significantly higher than S. aureus (14%) or streptococcal endocarditis (26%) 2
• The prolonged duration (≥6 weeks) and combination therapy reflect the difficulty eradicating infection from prosthetic material 3, 4
• Corynebacterium striatum is the most frequently identified species causing prosthetic valve endocarditis within this genus 2

Definitive Therapy for β-Lactam Resistant Isolates

For penicillin-resistant or β-lactam intolerant patients, use vancomycin 30 mg/kg/24h IV in 2 divided doses (targeting trough 15-20 mg/L) for 4-6 weeks (native valve) or ≥6 weeks (prosthetic valve). 2, 1

• Vancomycin resistance has not been detected in vitro among contemporary Corynebacterium isolates causing endocarditis 2
• Adding gentamicin 3 mg/kg/24h IV/IM for the entire treatment course is recommended for prosthetic valve infections treated with vancomycin 1
• For native valve disease treated with vancomycin, gentamicin can be limited to the first 2-4 weeks if renal function permits 1

Species-Specific Considerations

Corynebacterium striatum

• Most common species causing endocarditis (37% of cases) 2
• Frequently demonstrates penicillin resistance, making vancomycin the preferred agent 2
• Strongly associated with prosthetic valve involvement 2, 1

Corynebacterium jeikeium

• Second most common species (17% of cases) 2
• Typically multidrug-resistant; vancomycin is usually the only reliably active agent 2
• Associated with immunocompromised hosts and indwelling devices 2

Corynebacterium diphtheriae (non-toxigenic)

• Demonstrates favorable penicillin susceptibility 3
• β-lactam monotherapy is acceptable for uncomplicated native valve disease 3

Critical Monitoring and Adjustments

Obtain weekly gentamicin peak (target 3-4 µg/mL) and trough (target <1 µg/mL) levels, along with weekly serum creatinine and BUN. 5, 6

• Discontinue gentamicin if creatinine clearance falls below 30 mL/min; continue β-lactam or vancomycin monotherapy 5
• For vancomycin, target trough 15-20 mg/L for staphylococcal-equivalent coverage in endocarditis 5
• Monitor for ototoxicity throughout aminoglycoside therapy with clinical assessment 7

Surgical Indications

Surgery is required in approximately 50% of Corynebacterium endocarditis cases, particularly for prosthetic valve infections with perivalvular extension or persistent bacteremia despite appropriate antibiotics. 8, 2

• Indications include heart failure from valvular dysfunction, perivalvular abscess formation, persistent bacteremia beyond 5-7 days of appropriate therapy, or large vegetations (>10 mm) with embolic risk 8
• Early surgical consultation is essential given the high prosthetic valve involvement rate 2
• One case series demonstrated 13% in-hospital mortality despite aggressive medical and surgical management 2

Common Pitfalls

• Do not dismiss Corynebacterium as a contaminant when isolated from multiple blood cultures or in the setting of prosthetic valves—it represents true infection in these contexts 2, 1
• Do not assume penicillin susceptibility—resistance is common, particularly with C. striatum and C. jeikeium; always obtain formal susceptibility testing 2, 1
• Do not use monotherapy for prosthetic valve infections—combination therapy with an aminoglycoside is critical for adequate bactericidal activity 3, 4
• Blood cultures may require prolonged incubation (7-15 days) for growth, so alert the microbiology laboratory to hold cultures in suspected cases 4