Safety of short versus extended antibiotic therapy for neutropenic fever after hematopoietic cell transplantation

Abstract Objective: To determine safety and effectiveness of short (≤7 d) versus extended (>7 d) antibiotic courses for neutropenic fever in HCT recipients. Design: Retrospective cohort study. Setting: Private tertiary referral center. Participants: Consecutive sample; all patients >18 years old admitted between January 2019 and May 2024 with neutropenic fever during their index hospitalization for HCT. Methods: Data were collected via chart review. Primary outcomes were clinical failure (30-day mortality or ICU admission) and adverse events ( Clostridioides difficile infection or acute kidney injury [AKI]). Secondary outcomes included recurrent fever and length of stay (LOS). Multivariable logistic regression adjusted for age, sex, transplant type, infection type, and malignancy. Results: Among 103 patients (55 short, 48 extended), mean antibiotic duration was 3.6 days (short) and 11.9 days (extended). There were more leukemia and allogeneic HCT recipients in the extended group. In multivariable analyses, antibiotic duration was not predictive of clinical failure (odds ratio [OR] 3.40; 95% confidence interval [CI], 0.50–27.55; P = .222) or composite adverse events (OR, 3.72; 95% CI, 0.94–16.22; P = .067), although the odds of AKI were greater in the extended group (OR, 4.72; 95% CI, 1.08–23.68; P = .046). Recurrent fever was uncommon. LOS was greater in the extended group (43.4 d vs 21.4 d; P = .032). Conclusions: We found that shorter antibiotic courses were not associated with worse clinical outcomes or adverse events in HCT patients with neutropenic fever in the early posttransplant period. These findings support emerging evidence favoring shorter therapy.