## First-Line Therapy for Streptococcus viridans Endocarditis **Key Point:** Penicillin G IV combined with gentamicin is the gold-standard regimen for native valve endocarditis caused by penicillin-susceptible streptococci (including S. viridans). ### Rationale for Penicillin G + Gentamicin 1. **Bactericidal synergy**: Penicillin G inhibits cell wall synthesis; gentamicin enhances aminoglycoside uptake and provides synergistic bactericidal activity. 2. **Streptococcal susceptibility**: S. viridans is exquisitely sensitive to penicillin (MIC ≤0.1 µg/mL). 3. **Vegetation penetration**: The combination achieves excellent intracardiac and vegetation concentrations. 4. **Duration**: Typically 4 weeks of penicillin G (18–30 million units/day IV) + gentamicin (3 mg/kg/day IV, first 2 weeks). ### Dosing Regimen | Component | Dose | Route | Duration | |-----------|------|-------|----------| | Penicillin G | 18–30 million units/day | IV | 4 weeks | | Gentamicin | 3 mg/kg/day | IV | 2 weeks (first half) | **High-Yield:** In penicillin-allergic patients with non-severe allergy, cephalosporins (ceftriaxone) are acceptable alternatives; in severe allergy, vancomycin ± gentamicin is used. **Clinical Pearl:** Gentamicin is discontinued after 2 weeks in uncomplicated native valve disease; penicillin continues for the full 4 weeks. This reduces nephrotoxicity while maintaining efficacy. ### Why Not Monotherapy? - **Ceftriaxone monotherapy**: Acceptable in penicillin-susceptible streptococci but NOT first-line; lacks the synergistic advantage of gentamicin in early bactericidal activity. - **Vancomycin monotherapy**: Reserved for penicillin-allergic patients or resistant organisms; inferior to penicillin + gentamicin in susceptible strains. - **Cloxacillin + rifampicin**: Cloxacillin is for β-lactamase–producing staphylococci (not streptococci); rifampicin is not standard for streptococcal IE. [cite:Harrison 21e Ch 124]
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