What is the treatment for febrile neutropenia?

From the Guidelines

Febrile neutropenia is a medical emergency that requires prompt treatment with broad-spectrum antibiotics, typically started within one hour of presentation. The standard approach is empiric therapy with an antipseudomonal beta-lactam antibiotic such as piperacillin-tazobactam (4.5g IV every 6 hours) or meropenem (1g IV every 8 hours) 1. For patients with penicillin allergy, aztreonam plus vancomycin is an alternative. Vancomycin (15-20 mg/kg IV every 8-12 hours) should be added for patients with suspected catheter-related infection, skin or soft tissue infection, pneumonia, or hemodynamic instability.

Key Considerations

• Treatment typically continues until the neutrophil count recovers to above 500 cells/mm³ and the patient has been afebrile for at least 48 hours.
• Granulocyte colony-stimulating factors like filgrastim may be administered to stimulate neutrophil production, especially in high-risk patients 1.
• Patients should be monitored closely for clinical deterioration, with blood cultures taken before starting antibiotics.
• Empirical antifungal therapy should be started after 4–7 days of fever that does not respond to empirical antibiotic therapy, especially in high-risk patients 1.
• Hospitalization is typically required, though low-risk patients may sometimes be managed as outpatients with oral antibiotics after initial assessment.

Antibiotic Regimens

• Piperacillin-tazobactam (4.5g IV every 6 hours) or meropenem (1g IV every 8 hours) are recommended as first-line therapy for high-risk patients 1.
• Cefepime is no longer recommended as a first-line agent due to concerns about increased mortality 1.
• Vancomycin should be added for patients with suspected catheter-related infection, skin or soft tissue infection, pneumonia, or hemodynamic instability.

Patient Monitoring

• Patients should be monitored closely for clinical deterioration, with blood cultures taken before starting antibiotics.
• Treatment should be adjusted based on clinical, radiographic, or microbiological evidence of infection, rather than persistence of fever alone 1.

From the FDA Drug Label

Cefepime Injection as monotherapy is indicated for empiric treatment of febrile neutropenic patients

• Febrile neutropenia is a condition characterized by:
  • Fever
  • Neutropenia (low neutrophil count)
• The treatment for febrile neutropenia is empiric antibiotic therapy, such as cefepime monotherapy 2
• Cefepime is indicated for empiric treatment of febrile neutropenic patients, but insufficient data exist to support the efficacy of cefepime monotherapy in patients at high risk for severe infection 2
• The recommended dosage for cefepime in febrile neutropenic patients is 2 g IV every 8 hours 2

From the Research

Definition of Febrile Neutropenia

• Febrile neutropenia is an oncological emergency and serious complication often resulting from chemotherapy, characterized by a fever and a low neutrophil count 3.
• It is a condition where the patient has a fever and a significantly reduced number of neutrophils, which are a type of white blood cell that helps fight infections.

Treatment of Febrile Neutropenia

• The empirical administration of a broad-spectrum beta-lactam antibiotic, either as monotherapy or in combination with an aminoglycoside, is an essential component of the initial management of patients with fever and severe neutropenia 4.
• Cefepime monotherapy has been shown to be effective as an initial, empirical treatment of febrile neutropenia, with a high success rate and low treatment failure rate 5, 4.
• However, the use of cefepime for febrile neutropenia has been associated with increased mortality in some studies, and its use should be carefully considered pending further analysis 6.
• Other beta-lactams, such as carbapenems, ceftazidime, and piperacillin/tazobactam, have also been shown to be effective for monotherapy, with varying rates of treatment modifications and adverse events 6.
• Prompt treatment with empiric broad-spectrum antibiotics is crucial to ensuring best outcomes for patients, and practice guidelines recommend antibiotic administration within one hour of fever onset 7.

Key Considerations

• Risk evaluation scores can be used to stratify individual patient degree of risk, and all patients warrant immediate antibiotic coverage 3.
• Prophylactic antimicrobials may be used in specific high-risk situations, and antibiotic treatment of febrile neutropenia is broadened or narrowed based on individualized clinical scenarios 3.