A 35-year-old man presents with acute bacterial endocarditis caused by methicillin-sensitive Staphylococcus aureus (MSSA) with no prosthetic valve involvement. What is the drug of choice for treatment?

Question

Accepted Answer

B. Nafcillin or oxacillin. ## Drug of Choice for MSSA Endocarditis (Native Valve)

**Key Point:** Nafcillin or oxacillin are the first-line agents for methicillin-sensitive S. aureus endocarditis involving a native valve. These are beta-lactamase-resistant penicillins (antistaphylococcal penicillins) that achieve excellent intracardiac penetration and bactericidal activity.

**High-Yield:** For native valve MSSA endocarditis, the standard regimen is:
- **Nafcillin 2 g IV Q4H** or **Oxacillin 2 g IV Q4H** for 4–6 weeks
- Addition of gentamicin (3 mg/kg/day in divided doses) for the first 3–5 days may be considered for synergy, but is optional in uncomplicated cases

**Clinical Pearl:** Nafcillin is preferred over oxacillin in many centres due to lower hepatotoxicity, but both are equivalent in efficacy. These agents are superior to vancomycin for MSSA because they achieve higher serum and tissue concentrations and have superior bactericidal kinetics.

## Comparison Table: S. aureus Endocarditis Treatment

| Agent | Indication | Duration | Notes |
| --- | --- | --- | --- |
| Nafcillin/Oxacillin | MSSA, native valve | 4–6 weeks | First-line; excellent intracardiac penetration |
| Vancomycin | MRSA or beta-lactam allergy | 4–6 weeks | Reserved for resistant strains; lower serum levels |
| Cephalexin | Not recommended | — | Oral agent; inadequate for endocarditis |
| Clindamycin | Not recommended | — | Inferior bactericidal activity; not standard |

**Warning:** Do NOT use cephalosporins as monotherapy in S. aureus endocarditis—there is a risk of treatment failure. Vancomycin should be reserved for MRSA or documented beta-lactam allergy.

[cite:Harrison 21e Ch 124]

Answer

A. Cephalexin

Answer

C. Vancomycin

Answer

D. Clindamycin

A 35-year-old man presents with acute bacterial endocarditis caused by methicillin-sensitive Staphylococcus aureus (MSSA) with no prosthetic valve involvement. What is the drug of choice for treatment?

Explanation

Drug of Choice for MSSA Endocarditis (Native Valve)

Comparison Table: S. aureus Endocarditis Treatment

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Agent	Indication	Duration	Notes
Nafcillin/Oxacillin	MSSA, native valve	4–6 weeks	First-line; excellent intracardiac penetration
Vancomycin	MRSA or beta-lactam allergy	4–6 weeks	Reserved for resistant strains; lower serum levels
Cephalexin	Not recommended	—	Oral agent; inadequate for endocarditis
Clindamycin	Not recommended	—	Inferior bactericidal activity; not standard