What antibiotics are recommended for treating neutropenic fever in adults?

From the Guidelines

For neutropenic fever in adults, empiric broad-spectrum antibiotics should be initiated immediately with piperacillin-tazobactam (4.5g IV every 6 hours) as the first-line treatment, as recommended by the most recent and highest quality study 1.

Key Considerations

• The choice of antibiotic should cover both gram-negative bacteria (especially Pseudomonas aeruginosa) and gram-positive organisms, as these patients are at high risk for rapid progression to sepsis due to their compromised immune system.
• For patients with severe illness, hemodynamic instability, or suspected resistant organisms, an aminoglycoside (like amikacin 15-20 mg/kg IV daily) or fluoroquinolone (such as ciprofloxacin 400mg IV every 8-12 hours) may be added to the initial regimen.
• Vancomycin (15-20 mg/kg IV every 8-12 hours) should be added for suspected catheter-related infection, skin or soft tissue infection, pneumonia, or if MRSA colonization is known.
• Treatment should continue until the patient has been afebrile for at least 48 hours and the absolute neutrophil count is ≥500 cells/mm³.

Rationale

• The most recent study 1 recommends piperacillin-tazobactam as the first-choice option for treating febrile neutropenia in adults, due to its broad-spectrum coverage and effectiveness against Pseudomonas aeruginosa.
• The study also suggests that meropenem, aminoglycosides, and vancomycin may be used in addition to or instead of the first-line regimen based on local epidemiology and presentation of the patient.
• Prompt administration of antibiotics within one hour of fever onset is crucial, as delays can significantly increase mortality, as emphasized in previous studies 1.

Additional Considerations

• The patient's clinical condition, including the presence of comorbidities, allergies, and previous infections, should be taken into account when selecting the initial antibiotic regimen.
• Regular monitoring of the patient's response to treatment, including blood cultures and clinical assessment, is essential to guide adjustments to the antibiotic regimen as needed.

From the FDA Drug Label

The safety and efficacy of empiric cefepime monotherapy of febrile neutropenic patients have been assessed in two multicenter, randomized trials, comparing cefepime monotherapy (at a dose of 2 g intravenously every 8 hours) to ceftazidime monotherapy (at a dose of 2 g intravenously every 8 hours). Insufficient data exist to support the efficacy of cefepime monotherapy in patients at high risk for severe infection (including patients with a history of recent bone marrow transplantation, with hypotension at presentation, with an underlying hematologic malignancy, or with severe or prolonged neutropenia).

Recommended antibiotics for neutropenic fever in adults include:

• Cefepime monotherapy (at a dose of 2 g intravenously every 8 hours)
• Ceftazidime monotherapy (at a dose of 2 g intravenously every 8 hours) However, caution is advised as insufficient data exist to support the efficacy of cefepime monotherapy in high-risk patients 2.

From the Research

Antibiotic Options for Neutropenic Fever in Adults

• Cefepime and ceftazidime are commonly used antibiotics for treating neutropenic fever in adults, with studies showing they have similar efficacy 3, 4.
• A study comparing cefepime 2 g every 8 hours and ceftazidime 2 g every 8 hours found that both treatments were successful in approximately 57-60% of patients 3.
• Another study suggested that cefepime 1 g every 6 hours may be non-inferior to cefepime 2 g every 8 hours in terms of time to defervescence 5.
• Meropenem is also an option, with a study in pediatric patients showing it to be as effective and safe as cefepime for empiric treatment of febrile episodes in neutropenic cancer patients 6.
• The selection of antibiotics should be based on the patient's symptoms, previous culture data, and institutional antibiograms, with ongoing therapy guided by culture and clinical data 7.

Considerations for Antibiotic Selection

• Antimicrobial resistance is a concern in neutropenic fever, and careful attention to antibiotic selection and duration is needed 7.
• Ceftazidime may no longer be an optimal choice for initial treatment of high-risk patients, according to updates to guidelines published by the Infectious Diseases Society of America and the National Comprehensive Cancer Network 4.
• Cefepime appears to be as effective as ceftazidime in the initial treatment of febrile episodes in adult cancer patients with chemotherapy-associated neutropenia of modest duration 3.