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Difficulty: MediumInfectious Diseases

A 42-year-old woman with acute myeloid leukemia presents to the emergency department with a fever. She received her last cycle of induction chemotherapy 12 days ago. She reports no cough, dyspnea, abdominal pain, or dysuria. Her temperature is 38.8°C (101.8°F), blood pressure is 118/76 mm Hg, pulse is 98/min, and respirations are 16/min. Physical examination reveals a right internal jugular totally implantable venous access port with no overlying erythema, induration, or tenderness. The lungs are clear to auscultation. There are no oral ulcers or skin rashes. Laboratory studies show:

Hemoglobin: 9.2 g/dL
Leukocyte count: 400/mm³
Absolute neutrophil count: 120/mm³
Platelet count: 45,000/mm³

Blood and urine cultures have been obtained. Which of the following is the most appropriate next step in pharmacotherapy?

  1. A
    Administer intravenous cefepime and vancomycin
  2. B
    Administer oral ciprofloxacin and amoxicillin-clavulanate
  3. Administer intravenous cefepimeAnswer
  4. D
    Administer intravenous ceftriaxone
  5. E
    Administer intravenous piperacillin-tazobactam and fluconazole

Answer

Administer intravenous cefepime
The correct response is to administer intravenous cefepime. This patient has febrile neutropenia, an oncologic emergency requiring prompt administration of empiric antibiotics after obtaining blood cultures. Because she recently underwent induction chemotherapy for acute myeloid leukemia, her neutropenia is expected to be prolonged (>7 days) and profound, placing her in the high-risk category. High-risk patients must receive intravenous antipseudomonal monotherapy. Acceptable agents include cefepime, meropenem, or piperacillin-tazobactam. The patient lacks indications for the upfront addition of vancomycin.

Step-by-Step Solution

1
Calculate the absolute neutrophil count (ANC) and define the clinical syndrome.
The patient has a fever (38.8°C) and an ANC of 120/mm³.
Febrile neutropenia is defined as a single oral temperature of ≥ 38.3°C (101°F) or a sustained temperature of ≥ 38.0°C (100.4°F) for over 1 hour in a patient with an ANC < 500/mm³ (or anticipated to decrease to < 500/mm³).
2
Stratify the patient's risk to determine the route and setting of antibiotic administration.
The patient is high-risk due to profound (ANC < 100/mm³ or expected to be) and prolonged (> 7 days) neutropenia associated with acute myeloid leukemia induction therapy.
High-risk patients require admission (if not already hospitalized) and immediate intravenous broad-spectrum antibiotics.
3
Select the appropriate initial empiric antibiotic regimen.
Intravenous cefepime (an antipseudomonal beta-lactam) is selected.
Initial therapy must cover Gram-negative organisms, particularly Pseudomonas aeruginosa. Routine addition of Gram-positive coverage (vancomycin) is not indicated unless specific risk factors (e.g., hypotension, port-site infection, severe mucositis) are present.

Key Concept

High-risk febrile neutropenia requires immediate empiric intravenous therapy with an antipseudomonal beta-lactam, avoiding routine initial use of vancomycin or antifungals unless specific indications exist.
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Infectious Diseases

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