From the Guidelines
Neutropenic fever management involves prompt initiation of empirical antibiotic therapy, as infection can progress rapidly in these patients 1.
Key Principles
- Empirical antibiotic therapy should be administered urgently, within 2 hours of presentation, to all neutropenic patients at the onset of fever 1.
- Initial antibiotic regimen should be guided by clinical and microbiologic data, and should cover both gram-positive and gram-negative organisms 1.
- Modifications to the initial antibiotic regimen should be based on clinical, radiographic, or microbiological evidence of infection, and not on the persistence of fever alone in a patient whose condition is otherwise stable 1.
- Antifungal therapy should be considered after 4-7 days of fever that does not respond to empirical antibiotic therapy 1.
Treatment Approach
- Low-risk patients who are anticipated to have a short duration of neutropenia (<7 days) do not require antibiotic prophylaxis, but may be candidates for outpatient management with close monitoring 1.
- High-risk patients should be managed in the hospital with broad-spectrum empirical antibiotics, and should be closely monitored for response, adverse effects, and emergence of secondary infections 1.
- IV-to-oral switch in antibiotic regimen may be made if patients are clinically stable and gastrointestinal absorption is felt to be adequate 1.
Specific Recommendations
- Carbapenems, such as imipenem or meropenem, may be used as part of the initial antibiotic regimen, but should be used judiciously due to the risk of resistance 1.
- Vancomycin may be used to cover gram-positive organisms, but should be stopped after 2 days if there is no evidence of a gram-positive infection 1.
From the Research
Management of Neutropenic Fever
The management of neutropenic fever involves a combination of antimicrobial prophylaxis, empirical antibiotic therapy, and careful assessment of the patient's risk factors.
- Antibacterial and antifungal prophylaxis are recommended for patients expected to have < 100 neutrophils/μL for > 7 days, unless other factors increase risks for complications or mortality to similar levels 2.
- Patients with febrile neutropenia should receive initial doses of empirical antibacterial therapy within an hour of triage and should either be monitored for at least 4 hours to determine suitability for outpatient management or be admitted to the hospital 2.
- An oral fluoroquinolone plus amoxicillin/clavulanate (or plus clindamycin if penicillin allergic) is recommended as empiric therapy, unless fluoroquinolone prophylaxis was used before fever developed 2.
Risk Assessment and Outpatient Management
The risk of febrile neutropenia should be assessed systematically, and patients with low-risk neutropenic fever can be managed safely as outpatients.
- The Multinational Association for Supportive Care in Cancer (MASCC) score can be used to identify patients with low-risk neutropenic fever who can be managed safely as outpatients 2, 3.
- Patients with MASCC scores ≥ 21 or in Talcott group 4, and without other risk factors, can be managed safely as outpatients 2.
- Outpatient management of low-risk neutropenic fever can reduce length of stay and improve patient outcomes, without increasing morbidity or mortality 3.
Antimicrobial De-escalation and Discontinuation
The optimal duration of antimicrobial treatment in patients with febrile neutropenia is still unclear, but antimicrobial de-escalation and discontinuation can be considered in certain cases.
- Patients with febrile high-risk neutropenia should be treated empirically with an anti-pseudomonal agent such as piperacillin/tazobactam 4.
- The primary antibiotic regimen may be safely discontinued prior to neutrophil reconstitution if the patient is afebrile for several days and all infection-related symptoms have been resolved 4.
- Preemptive antifungal treatment guided by lung imaging and other parameters may reduce the consumption of antifungals compared to the classical empirical approach 4.