A 68-year-old man is hospitalized due to a 4-week history of fatigue, intermittent fevers,… — USMLE Step 2 CK

A $68$ -year-old man is hospitalized due to a $4$ -week history of fatigue, intermittent fevers, and unintentional weight loss. Two months ago, he underwent a cystoscopy for evaluation of hematuria. His temperature is $38.2^\circ\text{C}$ ( $100.8^\circ\text{F}$ ), pulse is $92/\text{min}$ , and blood pressure is $118/74\text{ mm Hg}$ . Physical examination reveals small, linear, dark red streaks in the nail beds of both hands and a new grade $3/6$ holosystolic murmur heard best at the cardiac apex.

Echocardiography demonstrates a $1.2\text{-cm}$ mobile vegetation on the mitral valve with moderate mitral regurgitation.

Laboratory studies show:
Leukocyte count: $14,500/\text{mm}^3$
Serum creatinine: $2.2\text{ mg/dL}$ (baseline: $1.0\text{ mg/dL}$ )

Three sets of blood cultures are drawn, and the patient is started empirically on intravenous vancomycin and piperacillin-tazobactam. Forty-eight hours later, all blood culture bottles grow *Enterococcus faecalis*. Susceptibility testing reveals:

Ampicillin: Susceptible
Vancomycin: Susceptible
Piperacillin-tazobactam: Susceptible
Gentamicin: High-level resistance

Which of the following is the most appropriate targeted pharmacotherapy for this patient?

Intravenous ampicillin and intravenous ceftriaxoneCevap
B
Intravenous ampicillin and intravenous gentamicin
C
Intravenous piperacillin-tazobactam monotherapy
D
Intravenous vancomycin and intravenous piperacillin-tazobactam
E
Intravenous linezolid monotherapy

Cevap

Intravenous ampicillin and intravenous ceftriaxone

The correct targeted therapy is the combination of intravenous ampicillin and intravenous ceftriaxone. This patient has *Enterococcus faecalis* native valve infective endocarditis following a genitourinary procedure. Enterococci are intrinsically tolerant to many antibiotics; therefore, endocarditis treatment requires a synergistic, bactericidal regimen. While ampicillin plus an aminoglycoside (like gentamicin) is a traditional regimen, this patient's isolate demonstrates high-level gentamicin resistance (HLGR), which abolishes the synergistic effect. Additionally, the patient has acute kidney injury, making nephrotoxic agents contraindicated. The combination of ampicillin and ceftriaxone provides excellent bactericidal synergy through complementary binding of different penicillin-binding proteins (PBPs), effectively bypassing the need for aminoglycosides, and is the standard of care for HLGR *E. faecalis* endocarditis.

Adım Adım Çözüm

Diagnose the primary condition based on clinical and echocardiographic findings.

The patient has native valve infective endocarditis (IE), evidenced by fever, splinter hemorrhages, a new mitral murmur, and a valvular vegetation on echocardiography.

Identifying the deep-seated nature of the infection is crucial, as IE requires prolonged, bactericidal therapy rather than bacteriostatic drugs.

Identify the pathogen and interpret the susceptibility profile.

The causative organism is Enterococcus faecalis. The susceptibility panel shows it is sensitive to ampicillin but has high-level gentamicin resistance (HLGR).

E. faecalis typically requires synergistic therapy for endocarditis. HLGR indicates that adding an aminoglycoside will not produce the required bactericidal synergy.

Select the optimal targeted antibiotic regimen considering patient comorbidities.

Intravenous ampicillin plus intravenous ceftriaxone is selected.

This combination provides dual beta-lactam synergy, which is bactericidal and highly effective against HLGR strains. It also avoids the nephrotoxicity of aminoglycosides, which is essential given the patient's acute kidney injury (creatinine 2.2 mg/dL).

Anahtar Kavram

Treatment of Enterococcus faecalis infective endocarditis requires bactericidal synergy. For isolates with high-level aminoglycoside resistance or in patients with renal impairment, the combination of ampicillin and ceftriaxone is the first-line targeted therapy.

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