A 74-year-old man is admitted to the hospital with a four-week history of low-grade fevers… — USMLE Step 2 CK

A $74$ -year-old man is admitted to the hospital with a four-week history of low-grade fevers, progressive fatigue, and an unintentional weight loss of $4\text{ kg}$ ( $8.8\text{ lbs}$ ). His medical history is significant for ischemic cardiomyopathy, type 2 diabetes mellitus, and a surgical aortic valve replacement with a bioprosthetic valve three years ago. His temperature is $38.2^\circ\text{C}$ ( $100.8^\circ\text{F}$ ), blood pressure is $122/76\text{ mmHg}$ , and pulse is $92/\text{min}$ . Physical examination reveals a grade 3/6 diastolic murmur at the right upper sternal border. Inspection of the hands reveals small, painless, erythematous macules on the palms. A transesophageal echocardiogram shows an oscillating $1.1\text{ cm}$ mass on the bioprosthetic aortic valve. Three sets of blood cultures grow gram-positive cocci in pairs and short chains that are catalase-negative and capable of growing in $6.5\%$ sodium chloride broth. Susceptibility testing indicates that the organism is susceptible to ampicillin, vancomycin, and daptomycin, but it exhibits high-level resistance to gentamicin and streptomycin. His serum creatinine is $1.9\text{ mg/dL}$ . Which of the following is the most appropriate targeted intravenous antibiotic regimen for this patient?

A
Ampicillin and gentamicin
B
Daptomycin monotherapy
Ampicillin and ceftriaxoneAnswer
D
Vancomycin and gentamicin
E
Vancomycin and rifampin

Answer

The most appropriate regimen is intravenous ampicillin and ceftriaxone.

The correct answer is intravenous ampicillin and ceftriaxone. This patient's clinical presentation (prolonged fever, a new diastolic murmur indicating aortic regurgitation, and Janeway lesions on the palms) combined with the echocardiographic finding of a vegetation confirms the diagnosis of prosthetic valve infective endocarditis. The microbiological findings—catalase-negative, gram-positive cocci in pairs and short chains capable of growing in

6.5\%

sodium chloride—are classic for Enterococcus species (predominantly Enterococcus faecalis). Treatment of enterococcal endocarditis requires prolonged, bactericidal combination therapy. Historically, this synergy was achieved using a cell wall-active agent (e.g., ampicillin) combined with an aminoglycoside (e.g., gentamicin). However, this patient's isolate exhibits high-level gentamicin resistance (HLAR), which entirely abolishes the synergistic effect of the aminoglycoside. Adding gentamicin would be completely ineffective and would only introduce the risk of acute kidney injury, which is particularly dangerous given the patient's already elevated serum creatinine of

1.9\text{ mg/dL}

. The treatment of choice for HLAR E. faecalis endocarditis is the combination of ampicillin and ceftriaxone. This double beta-lactam therapy achieves bactericidal synergy because ampicillin and ceftriaxone saturate complementary penicillin-binding proteins (PBPs) on the bacterial cell membrane—ampicillin binds PBP4 and PBP5, while ceftriaxone binds PBP2 and PBP3.

Step-by-Step Solution

Identify the causative pathogen based on the provided microbiological characteristics.

The organism is identified as Enterococcus species (most likely Enterococcus faecalis).

Gram-positive cocci in pairs and short chains that are catalase-negative and grow in 6.5% NaCl broth are pathognomonic microbiological features of Enterococci.

Diagnose the clinical syndrome.

The patient has prosthetic valve infective endocarditis.

The clinical triad of prolonged fever, a new diastolic murmur (aortic regurgitation), and peripheral stigmata (Janeway lesions) alongside an echocardiographically confirmed vegetation confirms the diagnosis.

Analyze the susceptibility profile to determine the feasibility of traditional therapy.

The isolate is susceptible to ampicillin but has high-level aminoglycoside resistance (HLAR).

Enterococcal endocarditis requires bactericidal synergistic therapy. The historical standard of ampicillin plus gentamicin cannot be used because HLAR abolishes the synergistic effect of the aminoglycoside.

Select the appropriate alternative bactericidal synergistic regimen.

Intravenous ampicillin and ceftriaxone is selected.

This dual beta-lactam therapy provides excellent bactericidal synergy against Enterococcus faecalis by saturating different penicillin-binding proteins without requiring an aminoglycoside, which is especially important given the patient's elevated creatinine.

Key Concept

Management of Enterococcal endocarditis exhibiting high-level aminoglycoside resistance (HLAR)

Estimated Time:2m 0s

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