What is the treatment for febrile neutropenia (fever with low neutrophil count)?

From the Guidelines

Febrile neutropenia should be treated as a medical emergency with prompt initiation of empiric broad-spectrum antibiotics after blood cultures are obtained. The recommended first-line treatment is an anti-pseudomonal beta-lactam antibiotic such as cefepime (2g IV every 8 hours), piperacillin-tazobactam (4.5g IV every 6 hours), or meropenem (1g IV every 8 hours) 1. These should be started within one hour of presentation. For patients with penicillin allergy, aztreonam (2g IV every 8 hours) plus vancomycin (15-20 mg/kg IV every 12 hours) can be used. Vancomycin (15-20 mg/kg IV every 12 hours) should be added to the regimen if there is concern for catheter-related infection, skin or soft tissue infection, pneumonia, or hemodynamic instability.

Key Considerations

• Antifungal therapy should be considered if fever persists after 4-7 days of antibiotics 1.
• Treatment should continue until the absolute neutrophil count is greater than 500 cells/mm³ and the patient has been afebrile for at least 48 hours 1.
• Granulocyte colony-stimulating factors like filgrastim (5 μg/kg subcutaneously daily) may be used to accelerate neutrophil recovery 1.
• Patients should be monitored closely for clinical deterioration with frequent vital signs and laboratory assessments.

Special Populations

• Low-risk patients who are anticipated to have a short duration of neutropenia (<7 days) do not require antibiotic prophylaxis 1.
• Carefully selected febrile adult neutropenic patients at low risk for complications during neutropenia may be treated initially with oral broad-spectrum antibiotics 1. The urgency of treatment stems from the fact that neutropenic patients lack the ability to mount an adequate inflammatory response to infection, making rapid progression to sepsis and death possible without prompt intervention.

From the FDA Drug Label

ZARXIO is a leukocyte growth factor indicated to • Decrease the incidence of infection‚ as manifested by febrile neutropenia‚ in patients with nonmyeloid malignancies receiving myelosuppressive anti‑cancer drugs associated with a significant incidence of severe neutropenia with fever Treatment with filgrastim resulted in a clinically and statistically significant reduction in the incidence of infection‚ as manifested by febrile neutropenia, 40% for filgrastim-treated patients and 76% for placebo-treated patients The main efficacy endpoint was the incidence of febrile neutropenia. Febrile neutropenia was defined as an ANC < 1,000/mm3 and temperature > 38.2°C.

Treatment of febrile neutropenia involves the use of filgrastim to decrease the incidence of infection.

• Filgrastim has been shown to reduce the incidence of febrile neutropenia in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs.
• The treatment with filgrastim resulted in a significant reduction in the incidence of infection, as manifested by febrile neutropenia.
• Filgrastim is administered subcutaneously daily beginning on day 4, for a maximum of 14 days, at a dose of 230 mcg/m2 (4 to 8 mcg/kg/day) or 5 mcg/kg/day 2, 2, 2.

From the Research

Treatment of Febrile Neutropenia

• The treatment of febrile neutropenia can involve the use of broad-spectrum antibiotics, with the goal of covering both gram-positive and gram-negative bacteria 3.
• Monotherapy with newer antibiotics, such as cefepime or carbapenems, has been shown to be effective and may offer advantages in terms of cost and tolerability compared to combination therapy 4.
• The use of vancomycin in the initial antibiotic regimen should be decided based on epidemiological considerations, such as the prevalence of meticillin-resistant Staphylococcus aureus or Staphylococcus mitis in certain centers 3.
• Antifungal therapy is indicated in neutropenic patients who remain febrile after one week of broad-spectrum antibiotics or have recurrent fever, with amphotericin B being a commonly used agent 3.

Antibiotic Prophylaxis

• Prophylactic antibiotics are associated with risks and have limited mortality benefit, and their use should be carefully considered 5.
• Fluoroquinolones have become less attractive agents for prophylaxis due to the selection potential of resistant Gram-negative bacteria (GNB) 6.
• Emerging data may help to revitalize long-abandoned aminoglycoside containing combination therapies, particularly in high-risk patients with presumed sepsis 6.

Timing of Antibiotic Administration

• Prompt treatment with empiric broad-spectrum antibiotics is crucial to ensuring best outcomes for patients with febrile neutropenia, with practice guidelines recommending antibiotic administration within one hour of fever onset 7.
• Quality improvement initiatives can help to improve time to antibiotic administration among patients with febrile neutropenia presenting to emergency departments 7.

Patient Risk Assessment

• The identification of subsets of patients with additional risk factors, such as absolute neutrophil count < 100/microL at the onset of fever or delayed neutrophil recovery, can help to establish the role of colony-stimulating factor (CSF) therapy 3.
• Carefully designed, randomized, controlled trials are needed to provide large-scale data that can be analyzed with emerging artificial intelligence (AI) technologies to guide management of febrile neutropenia 6.