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Difficulty: MediumInfectious Diseases

During morning rounds on the inpatient hematology-oncology unit, a 42-year-old woman is evaluated for a new-onset fever. She was admitted seven days ago for induction chemotherapy to treat acute myeloid leukemia. Her temperature is 38.9°C (102.0°F), blood pressure is 118/74 mm Hg, pulse is 92/min, and respiratory rate is 16/min. The patient reports feeling fatigued but denies cough, dysuria, abdominal pain, or skin changes. Physical examination reveals a clean peripherally inserted central catheter site with no surrounding erythema, warmth, or induration. The lungs are clear to auscultation. Laboratory studies show a hemoglobin of 8.2 g/dL, platelet count of 45,000/mm³, and an absolute neutrophil count of 300/mm³. Renal and hepatic function panels are within normal limits. Blood and urine cultures have been obtained. Which of the following is the most appropriate initial pharmacotherapy for this patient?

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

Answer

Intravenous cefepime
The most appropriate initial therapy for high-risk febrile neutropenia is monotherapy with an intravenous antipseudomonal beta-lactam, such as cefepime, meropenem, or piperacillin-tazobactam. This patient is at high risk due to induction chemotherapy for acute myeloid leukemia. Her clinical presentation lacks indications for empiric MRSA coverage (e.g., hemodynamic instability, pneumonia, or signs of a catheter site infection), making monotherapy the standard of care.

Step-by-Step Solution

1
Identify the primary clinical syndrome.
The patient has neutropenic fever, defined by a single oral temperature of ≥ 38.3°C (101.0°F) and an absolute neutrophil count (ANC) < 500/mm³.
Recognizing febrile neutropenia is critical as it is a medical emergency requiring prompt empiric antibiotics.
2
Risk-stratify the patient to determine the required route and setting of therapy.
The patient is classified as high-risk because she is an inpatient undergoing induction chemotherapy for acute myeloid leukemia, which typically results in prolonged and profound neutropenia.
High-risk patients require hospital admission (or continued hospitalization) and intravenous broad-spectrum antibiotics.
3
Select the appropriate empiric antimicrobial regimen based on risk and clinical signs.
Intravenous antipseudomonal beta-lactam monotherapy (e.g., cefepime) is selected.
There are no indications to add Gram-positive/MRSA coverage (such as hemodynamic instability, catheter-site infection, or pneumonia). Adding vancomycin unnecessarily violates antibiotic stewardship principles.

Key Concept

High-risk febrile neutropenia must be treated empirically with an intravenous antipseudomonal beta-lactam; routine addition of vancomycin is not indicated unless specific criteria for MRSA coverage are present.
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Infectious Diseases

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