What are the criteria and treatment for neutropenic fever?

From the Guidelines

Neutropenic fever requires prompt recognition and immediate antibiotic therapy to prevent serious complications, with treatment guided by the most recent and highest quality evidence, such as the 2010 update by the Infectious Diseases Society of America 1. The criteria for neutropenic fever include an absolute neutrophil count (ANC) below 500 cells/mm³ or expected to fall below 500 cells/mm³ within 48 hours, plus a single oral temperature of ≥38.3°C (101°F) or a temperature of ≥38.0°C (100.4°F) sustained over one hour. Key considerations in managing neutropenic fever include:

• Prompt initiation of empiric broad-spectrum antibiotics, typically an antipseudomonal beta-lactam such as cefepime, piperacillin-tazobactam, or meropenem, as recommended by guidelines 1.
• Blood cultures should be drawn before starting antibiotics, but treatment should not be delayed while waiting for results.
• Risk assessment to determine the type of empirical antibiotic therapy (oral vs IV), venue of treatment (inpatient vs outpatient), and duration of antibiotic therapy, with high-risk patients (prolonged neutropenia >7 days, significant comorbidities, or clinically unstable) requiring hospitalization and low-risk patients potentially eligible for oral antibiotics with close follow-up 1.
• Antibiotics should continue until the patient is afebrile and the ANC is >500 cells/mm³, typically for at least 7 days, with antifungal therapy considered if fever persists after 4-7 days of appropriate antibiotics 1.
• The use of antifungal agents, such as liposomal amphotericin B or voriconazole, should be guided by clinical judgment and the presence of risk factors for invasive fungal infections, as outlined in guidelines 1. Rapid intervention is critical because neutropenic patients lack the normal inflammatory response to infection, and seemingly minor infections can quickly become life-threatening, emphasizing the need for prompt and effective treatment based on the best available evidence 1.

From the FDA Drug Label

1.2 Empiric Therapy for Febrile Neutropenic Patients Cefepime Injection as monotherapy is indicated for empiric treatment of febrile neutropenic patients 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), antimicrobial monotherapy may not be appropriate Insufficient data exist to support the efficacy of cefepime monotherapy in such patients [see Clinical Studies (14)].

The criteria for neutropenic fever are not explicitly defined in the provided drug label, but it does mention febrile neutropenic patients as an indication for cefepime injection.

• The treatment for neutropenic fever with cefepime injection is 2 g IV every 8 hours for 7 days, or until resolution of neutropenia 2.
• In patients whose fever resolves but who remain neutropenic for more than 7 days, the need for continued antimicrobial therapy should be re-evaluated frequently.

From the Research

Neutropenic Fever Criteria

• Neutropenic fever is considered an oncologic emergency and occurs at high rates in patients with chemotherapy-induced neutropenia 3
• Fever may be the only sign of infection in patients with cancer who are undergoing chemotherapy, as the immune response is attenuated 3
• A thorough workup is essential to risk stratify patients as being at low or high risk for infectious complications 3

Treatment of Neutropenic Fever

• Prompt care and the initiation of empiric antibiotic therapy are critically important universal aspects of treatment-decision schemata 3
• Broad-spectrum monotherapy for Gram-negative bacteria is often started, with consideration of Gram-positive or antifungal coverage based on the clinical picture 3
• Cefepime monotherapy has been shown to be effective as an initial, empirical treatment of febrile neutropenia 4
• The combination of aztreonam and piperacillin has also been evaluated as an empiric treatment of neutropenic fever in gynecology-oncology patients receiving cisplatin-based chemotherapy 5
• Practice guidelines recommend antibiotic administration within one hour of fever onset to ensure best outcomes for patients 6

Key Considerations

• Every patient may present and respond differently to neutropenic fever, and management algorithms should be tailored to individual patient needs 3
• The early addition of amikacin and/or vancomycin may be necessary to resolve monotherapy failures 4
• A standard therapy regimen with prolonged administration of broad-spectrum antibiotics may not be necessary in febrile neutropenic patients on selective decontamination 7