A 52-year-old man is evaluated in the hospital for fever. He was admitted 12 days ago for … — USMLE Step 2 CK

A 52-year-old man is evaluated in the hospital for fever. He was admitted 12 days ago for induction chemotherapy to treat acute myeloid leukemia. Two days ago, he developed a fever of $38.8^{\circ}\text{C}$ ( $101.8^{\circ}\text{F}$ ). At that time, his blood pressure was $108/68\text{ mm Hg}$ and pulse was $112/\text{min}$ . Laboratory studies showed an absolute neutrophil count (ANC) of $80/\mu\text{L}$ . Empiric intravenous cefepime and vancomycin were initiated after blood and urine cultures were obtained. Today, the patient reports feeling much better. He has been afebrile for the past 24 hours. His blood pressure is $122/78\text{ mm Hg}$ and pulse is $84/\text{min}$ . The central venous catheter site appears clean with no erythema or induration. Today's laboratory results show an ANC of $110/\mu\text{L}$ . Blood cultures drawn two days ago are positive for *Escherichia coli*. Susceptibility testing indicates the organism is susceptible to ceftriaxone, cefepime, piperacillin-tazobactam, and ciprofloxacin, and resistant to ampicillin. Which of the following is the most appropriate next step in the management of this patient's antibiotic therapy?

Discontinue vancomycin and continue cefepimeAnswer
B
Discontinue vancomycin and cefepime, and begin ceftriaxone
C
Continue vancomycin and cefepime
D
Discontinue vancomycin and cefepime, and begin oral ciprofloxacin
E
Discontinue cefepime and continue vancomycin

Answer

Discontinue vancomycin and continue cefepime

The correct action is to discontinue vancomycin and continue cefepime. The patient originally required empiric therapy for febrile neutropenia, which correctly included an anti-pseudomonal beta-lactam (cefepime). Vancomycin was likely added for possible catheter-related infection or initial instability. At 48 hours, blood cultures show only *E. coli*. According to standard guidelines for high-risk febrile neutropenia, empiric vancomycin should be discontinued if no Gram-positive pathogen is identified. However, despite the *E. coli* being susceptible to narrower agents like ceftriaxone, patients who remain profoundly neutropenic (ANC <

500/\mu\text{L}

) must be maintained on an anti-pseudomonal agent (like cefepime, meropenem, or piperacillin-tazobactam) to protect against secondary *Pseudomonas aeruginosa* infections until marrow recovery.

Step-by-Step Solution

Identify the primary clinical scenario and patient risk stratification.

The patient has high-risk febrile neutropenia (ANC <

500/\mu\text{L}

, hematologic malignancy undergoing induction) complicated by Gram-negative bacteremia.

Risk stratification determines the necessary breadth and duration of antimicrobial coverage.

Evaluate the need for continued Gram-positive (MRSA) coverage.

Vancomycin should be discontinued.

Empiric vancomycin is indicated initially for line-associated infections or hemodynamic instability, but must be stopped at 48 hours if no Gram-positive organisms are isolated to prevent resistance and toxicity.

Analyze the appropriate Gram-negative coverage given the culture results.

Although the isolated *E. coli* is susceptible to narrower agents like ceftriaxone, an anti-pseudomonal beta-lactam (cefepime) must be continued.

In high-risk febrile neutropenia, patients remain highly susceptible to fatal secondary infections, including *Pseudomonas aeruginosa*, until their ANC recovers to >

500/\mu\text{L}

. Standard targeted therapy is insufficient; empiric anti-pseudomonal coverage must be maintained simultaneously.

Key Concept

In high-risk febrile neutropenia with a documented non-pseudomonal Gram-negative infection, empiric anti-pseudomonal coverage must be maintained alongside targeted therapy until neutrophil recovery (ANC > 500/μL).

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