A 72-year-old man with a history of a bioprosthetic aortic valve replacement three years a… — USMLE Step 2 CK

A 72-year-old man with a history of a bioprosthetic aortic valve replacement three years ago is hospitalized due to a 4-week history of low-grade fever, progressive fatigue, and night sweats. On physical examination, his temperature is $38.2^\circ\text{C}$ ( $100.8^\circ\text{F}$ ), blood pressure is $118/76\text{ mmHg}$ , and heart rate is $92/\text{min}$ . A new grade 2/6 diastolic decrescendo murmur is heard at the right upper sternal border. Laboratory evaluation shows a leukocyte count of $14,500/\text{mm}^3$ and a serum creatinine of $1.1\text{ mg/dL}$ . Transesophageal echocardiography reveals a $1.4\text{ cm}$ vegetation on the prosthetic valve. Three sets of blood cultures obtained prior to antibiotic administration are all positive for *Enterococcus faecalis*. The patient is empirically started on intravenous vancomycin and gentamicin.

Antimicrobial susceptibility testing for the isolate demonstrates the following:
* Ampicillin: Susceptible
* Penicillin: Susceptible
* Vancomycin: Susceptible
* Gentamicin: High-level resistance

Which of the following is the most appropriate antimicrobial regimen for this patient?

Intravenous ampicillin and intravenous ceftriaxoneAnswer
B
Continue intravenous vancomycin and intravenous gentamicin
C
Intravenous ampicillin and intravenous gentamicin
D
Intravenous vancomycin and intravenous ceftriaxone
E
Intravenous linezolid

Answer

The most appropriate regimen is intravenous ampicillin and intravenous ceftriaxone.

The correct answer is the combination of intravenous ampicillin and intravenous ceftriaxone. Enterococcal endocarditis requires bactericidal therapy, which is conventionally achieved through the synergistic combination of a cell-wall active agent (like ampicillin) and an aminoglycoside (like gentamicin). However, this isolate demonstrates high-level gentamicin resistance (HLAR). HLAR indicates that the synergistic bactericidal effect is lost, rendering the addition of an aminoglycoside not only ineffective but also unnecessarily nephrotoxic. The combination of ampicillin and ceftriaxone is a well-established, highly effective alternative. Ceftriaxone alone has minimal activity against Enterococcus, but it saturates specific complementary penicillin-binding proteins (PBPs), specifically PBP2 and PBP3, which allows ampicillin to exert a potent synergistic bactericidal effect. This combination is effective regardless of HLAR and avoids aminoglycoside-induced nephrotoxicity, making it the standard of care.

Step-by-Step Solution

Identify the primary diagnosis and pathogen.

The patient has prosthetic valve infective endocarditis caused by Enterococcus faecalis.

Vegetation on a prosthetic valve with positive blood cultures establishes the diagnosis of infective endocarditis, requiring prolonged bactericidal therapy.

Evaluate the antimicrobial susceptibility results.

The isolate is susceptible to ampicillin but exhibits high-level resistance to gentamicin.

Targeted therapy must be selected based on susceptibility to maximize efficacy and minimize toxicity (antibiotic stewardship).

Determine the optimal bactericidal regimen.

Select ampicillin combined with ceftriaxone.

Enterococcal endocarditis requires synergistic bactericidal therapy. Because high-level gentamicin resistance abolishes synergy with aminoglycosides, the ampicillin plus ceftriaxone combination is required. Ceftriaxone saturates complementary penicillin-binding proteins (PBPs), restoring bactericidal synergy with ampicillin.

Key Concept

Treatment of Enterococcus faecalis endocarditis

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