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Difficulty: HardHematology and Oncology

A 54-year-old woman is hospitalized for induction chemotherapy for acute myeloid leukemia. Seven days after completing the regimen, she develops a fever of 38.7°C (101.7°F). Her absolute neutrophil count is 150/mm³. Blood and urine cultures are drawn, and she is started on empiric intravenous cefepime. Five days later, she continues to have daily fevers up to 38.9°C (102.0°F). She is hemodynamically stable. She has no new symptoms. Physical examination reveals a clean, non-tender central venous catheter insertion site. There are no skin rashes, oral ulcers, or abnormal breath sounds. Her absolute neutrophil count is now 80/mm³. Blood cultures drawn on the first day of fever and repeat cultures drawn 48 hours ago show no growth. A chest radiograph is unremarkable. Which of the following is the most appropriate next step in management?

  1. A
    Add intravenous vancomycin
  2. Add intravenous caspofunginAnswer
  3. C
    Switch cefepime to meropenem
  4. D
    Remove the central venous catheter
  5. E
    Administer granulocyte colony-stimulating factor

Answer

The most appropriate next step is to add an intravenous antifungal agent, such as caspofungin.
This patient has persistent febrile neutropenia. The standard initial management for high-risk patients with neutropenic fever (absolute neutrophil count less than 500/mm³) is empiric broad-spectrum antipseudomonal antibacterial therapy, such as cefepime. If a patient remains febrile after 4 to 7 days of appropriate broad-spectrum antibacterial therapy and has an expected duration of neutropenia greater than 7 days (which is typical following acute myeloid leukemia induction), there is a high risk of an occult invasive fungal infection, most commonly Candida or Aspergillus species. Therefore, the addition of empiric antifungal therapy, such as an echinocandin (e.g., caspofungin) or liposomal amphotericin B, is the most appropriate next step in management.

Step-by-Step Solution

1
Identify the patient's clinical state and current treatment.
The patient has high-risk febrile neutropenia and has been on empiric cefepime for 5 days without defervescence.
Establishing the duration of broad-spectrum antibiotic therapy is critical for determining the next step in algorithmic management.
2
Evaluate for specific indications for altering antibacterial therapy or removing devices.
The patient is hemodynamically stable, has a clean catheter site, and has negative cultures, ruling out the immediate need for vancomycin or catheter removal.
Guidelines recommend adding Gram-positive coverage (e.g., vancomycin) only if specific complications are present.
3
Apply the guideline for persistent febrile neutropenia.
Determine that empiric antifungal therapy must be added.
Patients who remain febrile after 4-7 days of broad-spectrum antibiotics with an expected prolonged neutropenia are at high risk for occult invasive fungal infections.

Key Concept

Empiric antifungal therapy should be added in high-risk patients with neutropenia who have persistent or recurrent fever after 4 to 7 days of broad-spectrum antibiotics and no identified source.
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Topics

Hematology and Oncology

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