A 38-year-old man with a history of intravenous drug use presents with fever (38.5°C), malaise, and progressive dyspnea for 3 weeks. On examination, a new holosystolic murmur is heard at the left lower sternal border. Blood cultures grow Staphylococcus aureus (methicillin-sensitive). Echocardiography reveals a 12 mm vegetation on the tricuspid valve with moderate tricuspid regurgitation. Which of the following is the most appropriate initial antibiotic regimen?

Question

Accepted Answer

C. Nafcillin 2 g IV 4-hourly plus gentamicin 3 mg/kg IV once daily. ## Diagnosis: Tricuspid Valve Infective Endocarditis (IE)

**Key Point:** Staphylococcus aureus is the most common cause of IE in intravenous drug users, and tricuspid valve involvement is characteristic of right-sided IE in this population.

### Antibiotic Selection for MSSA Tricuspid IE

**High-Yield:** The standard regimen for methicillin-sensitive S. aureus (MSSA) endocarditis is a **beta-lactam (nafcillin or oxacillin) plus gentamicin** for synergy, particularly in right-sided disease.

| Regimen | Indication | Duration |
| --- | --- | --- |
| Nafcillin/Oxacillin + gentamicin | MSSA, native valve, right-sided IE | 4–6 weeks nafcillin; gentamicin 3–5 days |
| Vancomycin + gentamicin | MRSA or beta-lactam allergy | 4–6 weeks |
| Penicillin G + gentamicin | Streptococcus viridans (not applicable here) | 2–4 weeks |
| Cefazolin monotherapy | Prosthetic valve MSSA (not applicable here) | 6 weeks |

**Clinical Pearl:** Right-sided IE (tricuspid valve) in IVDU with MSSA can often be cured with shorter courses (4 weeks) of beta-lactam + gentamicin, compared to left-sided disease. The gentamicin provides early bactericidal synergy and reduces vegetation size.

**Mnemonic: MSSA-IE-RTD** — **M**ethicillin-**S**ensitive **S**taph **A**ureus **I**nfective **E**ndocarditis **R**ight-sided **T**ricuspid **D**isease → nafcillin + gentamicin.

### Why Nafcillin is Preferred Over Penicillin

- Nafcillin is a beta-lactamase-resistant penicillin with superior activity against S. aureus.
- Penicillin G has poor activity against S. aureus and is reserved for penicillin-susceptible streptococci.

**Warning:** Do not use cephalosporins as monotherapy for S. aureus endocarditis — they lack the bactericidal synergy achieved with aminoglycosides and are inferior to beta-lactams in IE.

Answer

A. Penicillin G 4 million units IV 4-hourly plus gentamicin 3 mg/kg IV once daily

Answer

B. Cefazolin 2 g IV 8-hourly monotherapy

Answer

D. Vancomycin 15–20 mg/kg IV 8–12 hourly plus ceftriaxone 2 g IV 12-hourly

Explanation

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