A 52-year-old man is evaluated for persistent fever. He was admitted 20 days ago for acute… — USMLE Step 2 CK

A $52$ -year-old man is evaluated for persistent fever. He was admitted $20$ days ago for acute myeloid leukemia induction chemotherapy, which resulted in profound bone marrow suppression. Ten days ago, his absolute neutrophil count dropped to $50/\text{mm}^3$ and he developed a fever of $39.1^\circ\text{C}$ ( $102.4^\circ\text{F}$ ). Blood cultures were drawn, and empiric intravenous cefepime was initiated. He remained febrile, and $5$ days ago, intravenous vancomycin was added.

Today, his temperature is $38.6^\circ\text{C}$ ( $101.5^\circ\text{F}$ ). He reports new-onset right-sided pleuritic chest pain. His absolute neutrophil count remains at $50/\text{mm}^3$ . Repeated blood cultures drawn prior to the initiation of antibiotics and $5$ days ago have shown no growth. A non-contrast computed tomography scan of the chest reveals a $3\text{ cm}$ dense macronodule surrounded by a halo of ground-glass attenuation in the right upper lobe. Serum galactomannan testing is strongly positive, and intravenous voriconazole is initiated.

Which of the following is the most appropriate next step regarding this patient's antibacterial regimen?

Continue cefepime and discontinue vancomycinAnswer
B
Discontinue both cefepime and vancomycin
C
Continue both cefepime and vancomycin
D
Switch cefepime to meropenem and continue vancomycin
E
Continue vancomycin and discontinue cefepime

Answer

Continue cefepime and discontinue vancomycin

The correct approach is to continue cefepime and discontinue vancomycin. This patient has febrile neutropenia complicated by a new diagnosis of invasive pulmonary aspergillosis. According to IDSA guidelines, in high-risk patients with profound neutropenia (ANC < 500/mm³), the initial empiric antipseudomonal beta-lactam (in this case, cefepime) must be continued until the ANC recovers to ≥ 500/mm³ and is trending upward. This is crucial because the patient remains at extreme risk for rapidly fatal Gram-negative bacterial sepsis, regardless of whether a secondary fungal pathogen has been identified as the source of the prolonged fever. Conversely, vancomycin is not recommended for routine empiric therapy in febrile neutropenia unless specific indications exist. When added empirically for persistent fever, it should be promptly discontinued if blood cultures remain negative after 48-72 hours. Since this patient's cultures have been negative for 5 days, continuing vancomycin represents poor antibiotic stewardship.

Step-by-Step Solution

Identify the cause of the patient's persistent fever and new symptoms.

The patient has developed invasive pulmonary aspergillosis, evidenced by the chest CT 'halo sign' and strongly positive serum galactomannan assay.

Establishing the etiology of the fever is necessary to determine the appropriate targeted antimicrobial therapy (voriconazole).

Determine the required duration of empiric Gram-negative antibacterial therapy in this host.

Cefepime must be continued until the absolute neutrophil count recovers to at least 500/mm³.

Patients with profound neutropenia remain at extreme risk for life-threatening Gram-negative sepsis (e.g., Pseudomonas aeruginosa) from endogenous flora. Guidelines mandate continuing the empiric antipseudomonal beta-lactam until marrow recovery, even when a secondary fungal infection is diagnosed.

Apply antibiotic stewardship principles to the empiric Gram-positive coverage.

Vancomycin should be discontinued immediately.

Vancomycin was added empirically for persistent fever. Because blood cultures have remained sterile after 5 days, there is no evidence of a Gram-positive infection. Continuing it increases toxicity and the risk of resistance.

Key Concept

In febrile neutropenia, empiric antipseudomonal beta-lactam therapy must be continued until marrow recovery (ANC ≥ 500/mm³), even if a specific fungal pathogen is identified. Empiric vancomycin should be discontinued if blood cultures remain negative after 48-72 hours.

Question

Answer

Step-by-Step Solution

Key Concept

Common Mistakes

Topics

More questions from this topic