What is the management of neutropenic fever (fever in the setting of neutropenia, a condition characterized by a low neutrophil count)?

From the Guidelines

Neutropenic fever management should prioritize prompt empiric antibiotic therapy to prevent progression to sepsis, with broad-spectrum antibiotics administered within one hour of presentation, as recommended by the Infectious Diseases Society of America 1. The recommended first-line therapy is an antipseudomonal beta-lactam such as cefepime (2g IV every 8 hours), piperacillin-tazobactam (4.5g IV every 6 hours), or meropenem (1g IV every 8 hours) 1.

Key Considerations

• Blood cultures should be obtained before starting antibiotics, along with cultures from any suspected sites of infection 1.
• Initial assessment should include a thorough physical examination focusing on potential infection sites (oral cavity, lungs, skin, perianal area, and vascular access sites) 1.
• Complete blood count, renal and liver function tests should be performed 1.
• Patients should be risk-stratified using the MASCC score to determine if outpatient management is appropriate for low-risk patients 1.
• Antibiotics should be continued until the neutrophil count recovers to >500 cells/mm³ and the patient has been afebrile for at least 48 hours 1.

Special Considerations

• If fever persists after 3-5 days of appropriate antibiotics, antifungal coverage with an echinocandin (caspofungin 70mg IV loading dose, then 50mg IV daily) or liposomal amphotericin B (3-5mg/kg IV daily) should be considered 1.
• Vancomycin (15-20mg/kg IV every 8-12 hours) should be added only if there is suspicion of catheter-related infection, skin/soft tissue infection, pneumonia, or hemodynamic instability 1.
• In low-risk patients who have defervesced after 3 days of empirical antibiotic therapy, evidence of imminent marrow recovery may direct cessation of broad-spectrum antibiotics prior to the ANC reaching 500 cells/mm³ 1.

Outpatient Management

• Selected hospitalized patients who meet criteria for being at low risk may be transitioned to the outpatient setting to receive either IV or oral antibiotics, as long as adequate daily follow-up is ensured 1.
• If outpatient management is prescribed, then vigilant observation and prompt access to appropriate medical care must also be ensured 24 h a day, 7 days a week 1.

From the FDA Drug Label

The recommended adult and pediatric dosages and routes of administration are outlined in the following table... Empiric therapy for febrile neutropenic patients (See INDICATIONS AND USAGE and CLINICAL STUDIES.) 2 g IV Every 8 hours 7 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).

Neutropenic Fever Management:

• The recommended dose for empiric therapy in febrile neutropenic patients is 2 g IV every 8 hours for 7 days, or until resolution of neutropenia.
• 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 2.
• Cefepime monotherapy has been shown to be therapeutically equivalent to ceftazidime monotherapy in the treatment of febrile neutropenic patients 2.

From the Research

Neutropenic Fever Management

• Neutropenic fever is a serious condition that requires timely and efficient empirical antibiotic therapy to reduce mortality rates 3.
• The choice of initial antibiotics should be based on the risk of complications, with monotherapy or combination therapy recommended 4.
• Monotherapy with a broad-spectrum antibiotic such as piperacillin-tazobactam, cefepime, meropenem, or imipenem-cilastin is recommended for initial empirical therapy 3.
• The addition of an aminoglycoside to initial empirical therapy is not recommended, as it may increase the risk of adverse events such as nephrotoxicity 3.
• Cefepime monotherapy has been shown to be effective in the treatment of febrile neutropenia, with response rates ranging from 55% to 61% 5, 6.
• The duration of neutropenia is a significant factor in the response to therapy, with patients having prolonged neutropenia being at higher risk of failure 5.
• Smaller, more frequent dosing of cefepime (1g every 6h) may be non-inferior to traditional dosing (2g every 8h) in achieving time to defervescence 7.

Antibiotic Therapy

• Initial antibiotics should be chosen based on the risk of complications, with consideration of local resistance rates and the potential for resistance induction 3.
• Combination therapy with two antibiotics may be recommended for initial empirical therapy, but monotherapy is also a valid option 4.
• The empirical addition of a glycopeptide after 3-4 days of persistent fever may be considered, but its use can be delayed in clinically stable patients without resistant or skin/soft tissue infections 3.
• Antifungal prophylaxis may be considered in patients with long-term neutropenia or mucosal damage 4.

Patient Assessment and Monitoring

• Patients with febrile neutropenia should undergo an adequate physical examination and blood and sputum cultures to identify the causative microorganism 4.
• The condition of the patient should be assessed again at 3-5 days after beginning initial antibiotic therapy to determine whether the fever has subsided or symptoms have worsened 4.
• If the patient's condition has improved, intravenous antibiotics can be replaced with oral antibiotics; if the condition has deteriorated, a change of antibiotics or addition of antifungal agents should be considered 4.