What is the recommended treatment for prosthetic valve endocarditis, including antimicrobial regimen and surgical considerations?

Treatment of Prosthetic Valve Endocarditis

Prosthetic valve endocarditis (PVE) requires aggressive combination antimicrobial therapy for a minimum of 6 weeks plus early surgical intervention in most cases, with treatment decisions made by a multispecialty Heart Valve Team including cardiology, cardiothoracic surgery, and infectious disease specialists. 1

Antimicrobial Therapy by Pathogen

Staphylococcal PVE (Most Common)

For oxacillin-resistant staphylococci (most common in early PVE):

• Vancomycin (30 mg/kg/24h IV in 2 divided doses, target trough 10-20 μg/mL) + rifampin (900 mg/24h IV/PO in 3 divided doses) for ≥6 weeks 1
• Add gentamicin (3 mg/kg/24h IV/IM in 2-3 divided doses) for the first 2 weeks only 1
• If gentamicin-resistant but fluoroquinolone-susceptible, substitute a fluoroquinolone for gentamicin 1

For oxacillin-susceptible staphylococci (rare):

• Nafcillin or oxacillin (12 g/24h IV in 6 divided doses) + rifampin (900 mg/24h in 3 divided doses) for ≥6 weeks 1
• Add gentamicin for the first 2 weeks 1
• Substitute cefazolin or vancomycin for penicillin-allergic patients 1

The 2-week aminoglycoside regimen is specifically recommended for staphylococcal PVE due to the high morbidity and mortality, though this is based on limited clinical data 1

Enterococcal PVE

• Enterococci must be tested for susceptibility to penicillin, vancomycin, and high-level resistance to gentamicin and streptomycin 1
• Killing requires synergistic combination of a cell wall-active agent (penicillin, ampicillin, or vancomycin) plus an aminoglycoside (gentamicin or streptomycin) 1
• Treatment duration typically 6 weeks for PVE 1

Coagulase-Negative Staphylococci (CoNS)

• Assume oxacillin resistance unless definitively proven susceptible, especially if PVE develops within 1 year of surgery 1
• Same regimen as oxacillin-resistant S. aureus: vancomycin + rifampin for ≥6 weeks, gentamicin for first 2 weeks 1
• Organisms from surgical specimens or relapsed blood cultures must be retested for antibiotic susceptibility, as CoNS may develop rifampin resistance during therapy 1

Surgical Indications (Class I Recommendations)

Early surgery (during initial hospitalization before completing antibiotics) is indicated for: 1

1. Valve dysfunction causing heart failure symptoms 1
2. Left-sided IE caused by S. aureus, fungal, or highly resistant organisms 1
3. Heart block, annular/aortic abscess, or destructive penetrating lesions 1
4. Persistent infection: bacteremia or fever >5-7 days despite appropriate antibiotics 1
5. Relapsing infection after completing appropriate antibiotics with negative blood cultures and no other infection source 1

Surgery is frequently required and may be lifesaving, particularly when PVE onset is within 12 months of valve implantation or involves an aortic prosthesis, as these are frequently complicated by perivalvular/myocardial abscesses and valvular dysfunction 1

Critical Management Principles

Timing of antibiotic duration:

• Count treatment days from the first day blood cultures are negative, not from treatment initiation 1
• Obtain blood cultures every 24-48 hours until bloodstream infection clears 1

Post-surgical antibiotic regimen:

• If valve replacement occurs during treatment, switch to the prosthetic valve treatment regimen (not native valve regimen) 1
• If resected tissue is culture-positive, give a full course of antimicrobial therapy post-operatively 1
• If resected tissue is culture-negative, give the recommended PVE treatment duration minus the days already treated pre-operatively 1

Combination therapy administration:

• Administer combination agents simultaneously or temporally close together to maximize synergistic killing 1

Common Pitfalls and Caveats

• Early PVE (within 12 months) has different microbiology than late PVE: Early PVE is dominated by oxacillin-resistant CoNS and nosocomial pathogens, while late PVE (>12 months) more closely resembles native valve endocarditis with streptococci and enterococci 1, 2

• Never give antibiotics before obtaining blood cultures in patients with unexplained fever and known valvular heart disease (Class III: Harm) 1

• Prosthetic valve infections involving aortic prostheses or occurring within 12 months are particularly prone to perivalvular extension and abscess formation 1

• S. aureus PVE has extremely high mortality and almost always requires surgical intervention for optimal outcomes 1

• Fungal PVE requires surgical valve replacement as a stand-alone indication, with amphotericin B as the traditional drug of choice, though mortality remains unacceptably high (80% for mold-related endocarditis) 1

• Complete removal of pacemaker/defibrillator systems (all leads and generator) is indicated if device/lead infection is documented, and reasonable for S. aureus or fungal IE even without device infection evidence 1