TY - JOUR
T1 - Empirical antibiotic monotherapy for febrile neutropenia
T2 - Systematic review and meta-analysis of randomized controlled trials
AU - Paul, Mical
AU - Yahav, Dafna
AU - Fraser, Abigail
AU - Leibovici, Leonard
N1 - Funding Information:
We thank all the authors who provided complementary data for their studies (Table 1). In addition, we thank Alice Baruch (Pfizer) and John F. Tomayko (GlaxoSmithKline) for conducting independent searches for additional studies. This work was supported in part by an EC 5th framework IST grant (TREAT project, grant no. 1999-11459). Preliminary results were presented at the Fifteenth European Congress of Clinical Microbiology and Infectious Diseases, 2004. The protocol for this review is published in The Cochrane Library,12 where the complete review will be published and updated.
PY - 2006/2
Y1 - 2006/2
N2 - Objectives: Early, empirical broad-spectrum antibiotic treatment is the established practice for febrile neutropenia. Several β-lactams are accepted for monotherapy. We asked whether patients' outcomes are influenced by the chosen β-lactam. Methods: Systematic review and meta-analysis of randomized controlled trials comparing anti-pseudomonal β-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 β-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 β-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.
AB - Objectives: Early, empirical broad-spectrum antibiotic treatment is the established practice for febrile neutropenia. Several β-lactams are accepted for monotherapy. We asked whether patients' outcomes are influenced by the chosen β-lactam. Methods: Systematic review and meta-analysis of randomized controlled trials comparing anti-pseudomonal β-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 β-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 β-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.
KW - -lactams
KW - Carbapenems
KW - Cefepime
KW - Ceftazidime
KW - Piperacillin/tazobactam
KW - β
UR - http://www.scopus.com/inward/record.url?scp=31544456662&partnerID=8YFLogxK
U2 - 10.1093/jac/dki448
DO - 10.1093/jac/dki448
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C2 - 16344285
AN - SCOPUS:31544456662
SN - 0305-7453
VL - 57
SP - 176
EP - 189
JO - Journal of Antimicrobial Chemotherapy
JF - Journal of Antimicrobial Chemotherapy
IS - 2
ER -
