A 65-year-old man with COPD presents with acute exacerbation characterized by purulent sputum, fever (38.5°C), and chest pain. Sputum culture grows Streptococcus pneumoniae sensitive to penicillin (MIC 0.06 μg/mL). What is the drug of choice for this community-acquired pneumonia?

Explanation

## First-Line Treatment of Penicillin-Susceptible S. pneumoniae Pneumonia **Key Point:** Benzylpenicillin G (or aqueous penicillin) is the gold-standard first-line agent for penicillin-susceptible S. pneumoniae infections, including community-acquired pneumonia (CAP). ### Mechanism of Action Benzylpenicillin G is a β-lactam antibiotic that inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs) and cross-linking peptidoglycan strands. S. pneumoniae is highly susceptible to this mechanism. ### Dosing & Administration - **IV dose:** 2–4 million units every 4–6 hours (or 12–24 million units/day in divided doses) - **Achieves excellent lung penetration** and bactericidal activity in pneumonia - **MIC interpretation:** MIC ≤0.06 μg/mL = susceptible; this patient's isolate is fully susceptible ### Why Benzylpenicillin G Over Alternatives | Feature | Benzylpenicillin G | Ceftriaxone | Amoxicillin-clavulanate | Fluoroquinolone | |---------|-------------------|-------------|------------------------|----------------| | **Efficacy vs susceptible S. pneumoniae** | Excellent (first-line) | Good (alternative) | Adequate (oral) | Good (alternative) | | **Penetration to lungs** | Excellent | Good | Moderate (oral) | Good | | **Cost** | Low | Moderate | Low | Moderate–High | | **Resistance concerns** | Rare if susceptible | Rare | Possible (β-lactamase) | Increasing resistance | | **Route** | IV/IM preferred | IV | Oral | Oral/IV | | **Use in severe CAP** | Yes, standard | Yes, if β-lactam allergy or resistance | No | No (not first-line) | **High-Yield:** For penicillin-susceptible S. pneumoniae, benzylpenicillin G (IV) remains the preferred agent in hospital settings because of superior bactericidal activity, cost-effectiveness, and established clinical outcomes. ### Clinical Pearl Ceftriaxone is reserved as an alternative when: - Penicillin allergy (non-anaphylactic) is present - Meningitis is suspected (better CNS penetration) - Resistance to penicillin is documented **Warning:** Do not use oral amoxicillin-clavulanate as monotherapy for hospitalized CAP; IV therapy is required for severe pneumonia. Fluoroquinolones are second-line agents and should not be used as first-line for susceptible organisms due to resistance development and inferior outcomes in pneumococcal CAP. [cite:Harrison 21e Ch 297]