Empirical antibiotic monotherapy for febrile neutropenia: systematic review and meta-analysis of randomized controlled trials.
OBJECTIVE
Early, empirical broad-spectrum antibiotic treatment is the established practice for febrile neutropenia. Several beta-lactams are accepted for monotherapy. We asked whether patients' outcomes are influenced by the chosen beta-lactam.


METHODS
Systematic review and meta-analysis of randomized controlled trials comparing anti-pseudomonal beta-lactams administered as empirical monotherapy for febrile neutropenia, with or without vancomycin. The search included The Cochrane Library, PubMed, Embase, Lilacs databases, bibliography, conference proceedings, trial registries and FDA new drug approvals. Two reviewers independently applied selection criteria, performed quality assessment and extracted the data. Trials assessing the same beta-lactam were pooled using the fixed effect model. Relative risks (RRs) with 95% confidence intervals (CIs) were calculated. The primary outcome assessed was all-cause mortality.


RESULTS
Thirty-three trials fulfilled inclusion criteria. Cefepime was associated with higher all-cause mortality at 30 days than other beta-lactams (RR 1.44, 95% CI 1.06-1.94, 3123 participants). Carbapenems were associated with fewer treatment modifications, including addition of glycopeptides, than ceftazidime or other comparators. Adverse events were significantly more frequent with carbapenems, specifically pseudomembranous colitis (RR 1.94, 95% CI 1.24-3.04, 2025 participants). All-cause mortality was unaltered. Piperacillin/tazobactam was compared only with cefepime and carbapenems, in six trials. No significant differences were demonstrated with paucity of data for all-cause mortality.


CONCLUSIONS
The use of cefepime for febrile neutropenia is associated with increased mortality and should be carefully considered pending further analysis. Empirical use of carbapenems entails fewer treatment modifications, but an increased rate of pseudomembranous colitis. Ceftazidime, piperacillin/tazobactam, imipenem/cilastatin and meropenem appear to be suitable agents for monotherapy.
Paul
Mical
M
Department of Medicine E, Rabin Medical Center, Beilinson Campus, 49100 Petah-Tiqva, Israel. pil1pel@zahav.net.il
Yahav
Dafna
D
Fraser
Abigail
A
Leibovici
Leonard
L
D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D015780:Carbapenems / Q000627:therapeutic use; D000077723:Cefepime; D002511:Cephalosporins / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005334:Fever / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D009503:Neutropenia / Q000150:complications / Q000188:drug therapy*; D010397:Penicillanic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D010406:Penicillins / Q000627:therapeutic use; D011785:Quality Assurance, Health Care; D016032:Randomized Controlled Trials as Topic; D000078142:Tazobactam; D016896:Treatment Outcome; D065093:beta-Lactamase Inhibitors
D000900:Anti-Bacterial Agents; D015780:Carbapenems; D002511:Cephalosporins; D004791:Enzyme Inhibitors; D010406:Penicillins; D065093:beta-Lactamase Inhibitors; D000077723:Cefepime; D010397:Penicillanic Acid; D000078142:Tazobactam