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Difficulty: HardInfectious Diseases

A 45-year-old man with newly diagnosed acute myeloid leukemia is hospitalized for induction chemotherapy. On day 10 of his hospital stay, he develops a new-onset fever. He reports feeling mildly fatigued but denies cough, shortness of breath, dysuria, or abdominal pain. Temperature is 38.8°C (101.8°F), blood pressure is 122/78 mm Hg, heart rate is 98/min, and respiratory rate is 16/min. Physical examination reveals clear lungs, normal bowel sounds, and no skin rashes. His totally implantable venous access port in the right upper chest is clean, with no surrounding erythema, induration, or tenderness. Laboratory studies show a leukocyte count of 400/mm³ with an absolute neutrophil count of 100/mm³. Blood and urine cultures are obtained. Which of the following is the most appropriate next step in the pharmacologic management of this patient?

  1. Intravenous cefepimeAnswer
  2. B
    Intravenous vancomycin and cefepime
  3. C
    Intravenous ceftriaxone
  4. D
    Oral ciprofloxacin and amoxicillin-clavulanate
  5. E
    Intravenous caspofungin

Answer

Intravenous cefepime
This patient presents with high-risk febrile neutropenia (absolute neutrophil count <500/mm³ and a single oral temperature ≥38.3°C). Because neutropenic patients lack the normal inflammatory response, an occult infection can rapidly progress to life-threatening sepsis. The standard of care for high-risk patients (such as those undergoing induction chemotherapy for leukemia) is immediate empiric monotherapy with an intravenous anti-pseudomonal beta-lactam, such as cefepime, meropenem, or piperacillin-tazobactam. This approach provides excellent coverage against Pseudomonas aeruginosa and other serious gram-negative pathogens, which are the most rapidly lethal organisms in this population.

Step-by-Step Solution

1
Calculate the absolute neutrophil count and identify the clinical syndrome.
The patient has an absolute neutrophil count of 100/mm³ and a fever of 38.8°C (101.8°F), meeting the diagnostic criteria for febrile neutropenia.
Febrile neutropenia is a medical emergency because patients can rapidly deteriorate from overwhelming bacterial sepsis.
2
Stratify the patient's risk level to determine the route and setting of care.
The patient is high-risk because he has profound neutropenia (<100/mm³) expected to last greater than 7 days due to AML induction chemotherapy.
High-risk patients require hospital admission and prompt administration of intravenous broad-spectrum antibiotics.
3
Select the appropriate empiric antimicrobial coverage, specifically targeting Pseudomonas aeruginosa.
Intravenous cefepime (or piperacillin-tazobactam, or a carbapenem) is selected as monotherapy.
Empiric therapy must cover gram-negative organisms, particularly Pseudomonas aeruginosa, which can cause rapidly fatal infections in neutropenic hosts.
4
Evaluate the need for empiric Gram-positive coverage (MRSA) with vancomycin.
Vancomycin is deferred because the patient lacks specific indications.
According to IDSA guidelines, empiric vancomycin should only be added for hemodynamic instability, clinically suspected catheter-related infection (erythema/purulence), skin/soft tissue infection, severe mucositis, or known MRSA colonization.

Key Concept

High-risk febrile neutropenia requires immediate empiric intravenous monotherapy with an anti-pseudomonal beta-lactam (e.g., cefepime). Routine upfront addition of vancomycin is not indicated unless specific risk factors (e.g., hypotension, overt catheter-site infection) are present.
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Infectious Diseases

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