A 32-year-old man presents with a 3-day history of fever, purulent wound discharge, and erythema following a surgical procedure. Gram stain of the wound exudate shows Gram-positive cocci in clusters. Culture on blood agar grows golden-yellow colonies that are coagulase-positive and DNase-positive. The organism is susceptible to methicillin. What is the drug of choice for this methicillin-sensitive Staphylococcus aureus (MSSA) wound infection?

## Methicillin-Sensitive S. aureus (MSSA) — First-Line Therapy **Key Point:** For confirmed MSSA infections (susceptible to methicillin/oxacillin), **β-lactamase-resistant penicillins** (nafcillin, oxacillin, flucloxacillin) or **first-generation cephalosporins** (cephalexin, cefazolin) are the drugs of choice. ### Mechanism of Action Nafcillin is a semi-synthetic penicillin resistant to β-lactamase produced by S. aureus. It binds penicillin-binding proteins (PBPs) and inhibits cell wall synthesis, achieving bactericidal activity. ### Why Nafcillin is Preferred 1. **Superior tissue penetration** — achieves excellent levels in bone, soft tissue, and wound fluid 2. **Proven clinical efficacy** — gold standard for MSSA bacteremia, endocarditis, and invasive infections 3. **Lower resistance rates** — β-lactams remain the most reliable class for MSSA 4. **Cost-effective** — less expensive than glycopeptides or oxazolidinones ### Dosing Context - **IV nafcillin:** 1–2 g every 4–6 hours (severe infections: up to 2 g every 4 hours) - **Oral alternative (MSSA):** Flucloxacillin 500 mg–1 g every 6 hours **High-Yield:** Oxacillin is equally effective but less commonly used in India; nafcillin and flucloxacillin are preferred in most guidelines [cite:Harrison 21e Ch 297]. ### Clinical Pearl If β-lactam allergy is documented, **cephalosporins** (cefazolin, cephalexin) are safe alternatives in non-anaphylaxis penicillin allergy (cross-reactivity ~1–3%). For true IgE-mediated allergy, use **vancomycin** or **clindamycin** (if susceptible).