Could Less Be More in Febrile Neutropenia, Too?

Jesse D. Sutton, PharmD


June 05, 2018

Editorial Collaboration

Medscape &

Antibiotics and Neutropenia

Antibiotic treatment durations for febrile neutropenia, in the absence of confirmed infection, may be safely shortened compared with currently recommended durations in the United States, according to two recent studies.[1,2] European febrile neutropenia management guidelines[1] recommend discontinuing empirical antibiotics after 72 hours, irrespective of neutrophil count, if no infection is confirmed, the patient has been hemodynamically stable since admission, and the patient has been afebrile for 48 hours. In contrast, US febrile neutropenia guidelines[2,3] recommend continuing empirical antibiotics until neutrophil count recovery.

Patients With Hematologic Cancer

Aguilar-Guisado and colleagues[4] conducted an open-label, multicenter, randomized, controlled trial in adults with febrile neutropenia without a confirmed etiology. Patients with hematologic cancer or hematopoietic stem-cell transplant were included.

All patients were started on empirical broad-spectrum antibiotics consistent with national guidelines. In the intervention arm (n = 78), empirical antibiotics were discontinued after the patient recovered clinically and was afebrile for 72 hours. Universal antibacterial prophylaxis, apart from trimethoprim/sulfamethoxazole, was not routinely used after discontinuation of empirical antibiotics for febrile neutropenia. In the control arm (n = 79), empirical antibiotics were continued until neutrophil count recovery.

Findings for the primary endpoint (the mean number of empirical antibiotic-free days in the 28 days after onset of febrile neutropenia) were 16.1 ± 6.3 days in the intervention arm compared with 13.6 ± 7.2 days in the control arm, which was statistically significant (difference, -2.4 ; 95% confidence interval [CI], -4.6 to -0.3). There were no differences between the two groups in the rates of recurrent fever, infections per 1000 patient-days, crude mortality, or adverse events per 1000 patient-days. The combination of infectious and noninfectious serious adverse events was more frequent in the control group than the intervention group (12.7 ± 27 per 1000 patient-days vs 5.1 ± 11 per 1000 patient-days, respectively; difference, 7.6; 95% CI, 1.9-13.2).

The investigators concluded that in this group of high-risk patients with hematologic cancer and febrile neutropenia, clinicians need not wait for the neutrophil count to normalize. Empirical antibiotics can be discontinued after 72 hours of apyrexia and clinical recovery.

Patients With Hematopoietic Stem Cell Transplantation

Snyder and colleagues[5] performed a single-center, retrospective cohort study in patients with febrile neutropenia of unknown origin and previous allogeneic hematopoietic stem cell transplant. All patients were initiated on empirical broad-spectrum antibiotics consistent with institutional and national guidelines.

One cohort (n = 46) consisted of patients who were deescalated from empirical broad-spectrum antibiotics back to their original prophylactic antibiotics (eg, levofloxacin, ciprofloxacin, or cefdinir) while still neutropenic as long as they received a minimum of 5 days of empirical broad-spectrum antibiotics and remained afebrile for 48 hours. The other cohort (n = 74) consisted of patients whose empirical broad-spectrum antibiotics were continued until neutrophil count recovery.

The primary endpoint (rate of recurrent fever) was 15% in the deescalation group compared with 19% in the group whose antibiotics were continued (90% CI, -0.09 to 0.1629; P = .026). There were no differences between the cohorts in the need for antibiotic reescalation, intensive care admissions, bacteremia, or in-hospital mortality.

The investigators concluded that broad-spectrum antimicrobial therapy does not need to be continued until the neutrophil count recovers, but can be safely discontinued after 5 days in afebrile patients.


Although more studies that are adequately powered for additional clinical endpoints are needed, these two studies add to a growing body of evidence supporting early deescalation of empirical antibiotics for febrile neutropenia without a confirmed infection.


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