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Principles of Antibiotic Selection
The mainstay of endocarditis treatment is antimicrobial therapy, which should be initiated as soon as possible after the diagnosis is confirmed.
The choice of antibiotic depends on the suspected or confirmed causative organism, its susceptibility profile, the patient’s allergies and comorbidities, and the potential for drug interactions. In addition, pharmacokinetic and pharmacodynamic properties, such as the ability to achieve adequate drug concentrations at the site of infection, are important considerations in antibiotic selection.
Antibiotics Based on Causative Organisms
Streptococci
- Infections caused by streptococci, such as viridans group streptococci and Streptococcus bovis, are typically treated with a beta-lactam antibiotic like penicillin or ceftriaxone. In some cases, the addition of gentamicin may be considered for a synergistic effect.
| Organism | Antibiotic | Dose and Route | Duration | Notes |
| Streptococci | ||||
| Penicillin-susceptible | ||||
| Penicillin G | 12-18 million units/day IV, divided every 4-6 hours | 4 weeks | Preferred for highly susceptible strains (MIC ≤0.12 µg/mL) | |
| Ceftriaxone | 2 g/day IV/IM | 4 weeks | Alternative for patients with penicillin allergy or intolerance | |
| Penicillin-resistant | ||||
| Penicillin G + Gentamicin | 12-18 million units/day IV (Penicillin G), divided every 4-6 hours<br>3 mg/kg/day IV/IM (Gentamicin), divided every 8 hours | 2 weeks (Penicillin G) <br> 2 weeks (Gentamicin) | Combination therapy for strains with MIC >0.12 µg/mL but ≤0.5 µg/mL | |
| Ceftriaxone + Gentamicin | 2 g/day IV/IM (Ceftriaxone) <br> 3 mg/kg/day IV/IM (Gentamicin), divided every 8 hours | 2 weeks (Ceftriaxone)<br> 2 weeks (Gentamicin) | Alternative combination therapy for patients with penicillin allergy or intolerance |
Staphylococci
- For methicillin-sensitive Staphylococcus aureus (MSSA) endocarditis, treatment with a high-dose penicillinase-resistant penicillin, such as nafcillin or oxacillin, is recommended. In cases of methicillin-resistant S. aureus (MRSA) endocarditis, vancomycin or daptomycin are the preferred options.
Enterococci
- Enterococcal endocarditis typically requires treatment with a combination of a cell-wall active agent (e.g., ampicillin or vancomycin) and an aminoglycoside (e.g., gentamicin) for synergistic bactericidal activity. Daptomycin may be considered as an alternative in cases of vancomycin-resistant Enterococcus (VRE) infection.
Gram-Negative Bacilli
- Endocarditis caused by Gram-negative bacilli, such as HACEK organisms (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, and Kingella), can be treated with a third-generation cephalosporin like ceftriaxone. For Pseudomonas aeruginosa endocarditis, an antipseudomonal beta-lactam (e.g., piperacillin-tazobactam or ceftazidime) plus an aminoglycoside is recommended.
Fungi and Other Uncommon Organisms
- Fungal endocarditis is rare but often requires prolonged treatment with antifungal agents like amphotericin B or an echinocandin, and in some cases, surgical intervention. For other uncommon pathogens (e.g., Brucella, Bartonella), specific treatment regimens based on susceptibility data should be consulted.
Susceptibility Patterns and Resistance
Monitoring local antimicrobial susceptibility patterns and resistance trends is crucial for guiding empiric therapy.
Antimicrobial susceptibility testing of the isolated organism should be performed to confirm the appropriate choice of therapy.
Prolonged Courses of Therapy
Endocarditis generally requires prolonged courses of antimicrobial therapy, typically ranging from 4 to 6 weeks or longer, depending on the causative organism, the presence of complications, and the response to treatment.
Combination Therapy and Special Cases
In some cases, such as prosthetic valve endocarditis, resistant infections, or persistent bacteremia, combination therapy with multiple antibiotics may be necessary to achieve adequate coverage and synergistic bactericidal activity.
Specific recommendations for combination therapy should be tailored to the individual patient and pathogen.
Adjusting Treatment Based on Clinical Response and Follow-Up
Treatment should be regularly reassessed based on clinical response, laboratory data, and follow-up imaging studies.
Adjustments to the antimicrobial regimen may be necessary if the patient’s condition worsens or if new information about the causative organism becomes available.