Systematic Review of the Short-Term versus Long-Term Duration of Antibiotic Management for Neutropenic Fever in Patients with Cancer

SIMPLE SUMMARY: Empirical administration of broad-spectrum antibiotics during neutropenia has been shown to reduce mortality from bacterial infections. However, prolonged antibiotic exposure, in particular, promotes the development of antimicrobial resistance and the selection of resistant microorganisms, which are often more difficult to treat, and carry a higher risk of complications. Early antibiotic discontinuation has been proposed in patients with hematologic malignancy who have febrile neutropenia. Several studies have found that shorter duration of antimicrobial therapy have better clinical outcomes and lower the exposure to the broad-spectrum antibiotics, but this raises concerns about their implementation in clinical practice. Furthermore, their safety and efficacy have been questioned. In our study, a systematic review was conducted to compare the short-term and long-term durations of antibiotics for febrile neutropenia for the outcomes of clinical failure, mortality, and bacteremia. ABSTRACT: Early antibiotic discontinuation has been proposed in patients with hematologic malignancy with fever of unknown origin during febrile neutropenia (FN). We intended to investigate the safety of early antibiotic discontinuation in FN. Two reviewers independently searched for articles from Embase, CENTRAL, and MEDLINE on 30 September 2022. The selection criteria were randomized control trials (RCTs) comparing short- and long-term durations for FN in cancer patients, and evaluating mortality, clinical failure, and bacteremia. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated. We identified eleven RCTs (comprising 1128 distinct patients with FN) from 1977 to 2022. A low certainty of evidence was observed, and no significant differences in mortality (RR 1.43, 95% CI, 0.81, 2.53, I(2) = 0), clinical failure (RR 1.14, 95% CI, 0.86, 1.49, I(2) = 25), or bacteremia (RR 1.32, 95% CI, 0.87, 2.01, I(2) = 34) were identified, indicating that the efficacy of short-term treatment may not differ statistically from that of long-term treatment. Regarding patients with FN, our findings provide weak conclusions regarding the safety and efficacy of antimicrobial discontinuation prior to neutropenia resolution.