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

From the Guidelines

Neutropenic fever requires immediate empiric broad-spectrum antibiotic therapy, and the initial management should include an anti-pseudomonal beta-lactam such as cefepime, piperacillin-tazobactam, or meropenem, as recommended by the Infectious Diseases Society of America 1. For patients with neutropenic fever (defined as a single oral temperature ≥38.3°C or ≥38.0°C sustained over one hour, with an absolute neutrophil count <500 cells/mm³),

• start with an anti-pseudomonal 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)
• this should be initiated within one hour of presentation, after blood cultures are drawn but without waiting for results
• for patients with severe penicillin allergy, use aztreonam (2g IV every 8 hours) plus vancomycin (15-20 mg/kg IV every 12 hours)
• add vancomycin (15-20 mg/kg IV every 12 hours) to the regimen if there is suspicion of catheter-related infection, skin/soft tissue infection, pneumonia, or hemodynamic instability
• antibiotics should be continued until the neutrophil count recovers to >500 cells/mm³ and the patient has been afebrile for at least 48 hours Neutropenic fever is a medical emergency because neutropenic patients can rapidly develop life-threatening sepsis due to their compromised immune system's inability to contain infections. The empiric antibiotic choices target the most common pathogens in neutropenic patients, particularly gram-negative bacteria like Pseudomonas aeruginosa, which can cause fulminant sepsis. In addition to antibiotics,
• empirical antifungal therapy and investigation for invasive fungal infections should be considered for patients with persistent or recurrent fever after 4–7 days of antibiotics and whose overall duration of neutropenia is expected to be >7 days 1.
• modifications to the initial antibiotic regimen should be guided by clinical and microbiologic data 1.
• low-risk patients who have initiated IV or oral antibiotics in the hospital may have their treatment approach simplified if they are clinically stable 1.
• an IV-to-oral switch in antibiotic regimen may be made if patients are clinically stable and gastrointestinal absorption is felt to be adequate 1.
• 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. It is essential to note that the management of neutropenic fever should be individualized based on the patient's specific clinical situation, and the recommendations provided are general guidelines that may need to be adapted to the particular circumstances of each patient.

From the Research

Management Options for Neutropenic Fever

The management of neutropenic fever involves several strategies, including:

• Antibiotic prophylaxis for patients at high risk of infection due to anticancer chemotherapy 2
• Antifungal prophylaxis for patients with long-term neutropenia or mucosal damage 2
• Initial empirical antibiotic therapy with broad-spectrum intravenous bactericidal, anti-pseudomonal antibiotics 3, 4, 5
• Modification of the initial regimen based on the patient's clinical course and microbiological results 2, 5
• Discontinuation of antibiotics after 72 h or later in patients with fever of unknown origin who are hemodynamically stable and afebrile for at least 48 h 5, 6

Antibiotic Regimens

Different antibiotic regimens have been compared in various studies, including:

• Piperacillin-tazobactam (PIP-TAZO) versus cefoperazone-sulbactam (CS) 3
• Piperacillin/tazobactam (PIP/TAZ) versus cefepime (CEFP) 4
• These studies found that PIP-TAZO and CS, as well as PIP/TAZ and CEFP, are equally effective and safe for the empirical treatment of febrile neutropenic patients 3, 4

De-escalation and Discontinuation of Antibiotics

The de-escalation and discontinuation of antibiotics are important strategies to minimize the risk of antibiotic resistance and reduce the duration of antibiotic treatment:

• A 'de-escalation' approach, with initial broad-spectrum antibiotics or combinations, should be used only in patients with known prior colonization or infection with resistant pathogens, complicated presentation, or in centers where resistant pathogens are prevalent 5
• Discontinuation of antibiotics after 72 h or later should be considered in neutropenic patients with fever of unknown origin who are hemodynamically stable and afebrile for at least 48 h 5, 6

Patient-Specific Factors

Patient-specific factors, such as the risk of complications and the presence of microbiologically documented infections, should be taken into account when selecting an antibiotic regimen:

• Patients with febrile high-risk neutropenia should be treated empirically with an anti-pseudomonal agent such as piperacillin/tazobactam 6
• Primary empirical treatment with carbapenems or antibiotic combinations should commonly only be considered in selected patient subgroups, such as patients with severe neutropenic sepsis or colonization with multidrug-resistant bacteria 6