Piperacillin-tazobactam versus cefepime monotherapy in pediatric patients with febrile neutropenia: a systematic review and meta-analysis

Clinical Snapshot

Key Findings

• P Value: P = 0.76 for treatment success; P = 0.23 for mortality

• Effect Size: RR = 1.02 for treatment success; RR = 2.09 for mortality

• Primary Outcome: Treatment success showed no significant difference between groups

• Nnt Or Sensitivity: Treatment duration 0.9 days shorter with cefepime (MD = 0.9 day; 95% CI [0.2; 1.6])

• Confidence Interval: Treatment success: 95% CI [0.89; 1.18]; Mortality: 95% CI [0.62; 7.03]

Clinical Application

Both antibiotics are readily available and commonly used in Australian pediatric hospitals Both piperacillin-tazobactam and cefepime are PBS-listed for hospital use; findings support current RACGP and pediatric oncology guidelines allowing either as first-line therapy Pediatric patients with febrile neutropenia in oncology and hematology units

Abstract

UNLABELLED: The purpose of this study is to evaluate whether piperacillin-tazobactam therapy, compared with cefepime monotherapy, results in significant difference in treatment success, mortality, and duration outcomes in pediatric patients with febrile neutropenia (FN). A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted following PRISMA guidelines. PubMed, Embase, Scopus, Web of Science, and Cochrane CENTRAL were searched up to February 3. No starting limits for dates were used. We only included studies of pediatric patients with FN comparing piperacillin-tazobactam to cefepime monotherapy. Risk of bias was assessed using Cochrane RoB 2 tool. Meta-analysis was performed using random-effects model to calculate risk ratios (RR) and mean differences (MD). Five RCTs involving 470 episodes were included. The pooled analysis for treatment success showed no statistically significant difference between groups (RR = 1.02; 95% CI [0.89; 1.18]; P = 0.76) with low heterogeneity (I2 = 0.0%). No significant differences for mortality (RR = 2.09; 95% CI [0.62; 7.03]; P = 0.23; I2 = 0.0%). Duration of treatment was 0.9 day shorter for cefepime group (MD = 0.9 day; 95% CI [0.2; 1.6]; P < 0.1; I2 = 0%). CONCLUSION: No statistically significant difference was found in treatment success or mortality between the groups. Patients receiving cefepime had a treatment duration 0.9 days shorter than those receiving piperacillin-tazobactam, although this finding should be interpreted with caution. The available evidence remains limited. Further RCTs are needed to elucidate potential differences in treatment success, mortality, and duration between the drugs. REGISTRATION: PROSPERO (CRD420261296621). WHAT IS KNOWN: • Cefepime and piperacillin-tazobactam are widely utilized as empirical monotherapy for febrile neutropenia, but evidence regarding their comparative clinical efficacy and safety in children remains inconclusive. WHAT IS NEW: • This meta-analysis quantifies differences in treatment success, mortality and duration of treatment outcomes in pediatric patients with febrile neutropenia.

References

1. 1.Fernandes, B. L. G., Joseph, A., & Andriazzi, V. H. (2026). Piperacillin-tazobactam versus cefepime monotherapy in pediatric patients with febrile neutropenia: a systematic review and meta-analysis. European Journal of Pediatrics. https://doi.org/10.1056/NEJM199305063281808