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Beta lactam monotherapy versus beta lactam-aminoglycoside combination therapy for fever with neutropenia: systematic review and meta-analysis.

ABSTRACT: OBJECTIVE:To compare the effectiveness of beta lactam monotherapy versus beta lactam-aminoglycoside combination therapy in the treatment of patients with fever and neutropenia. DATA SOURCES:Medline, Embase, Lilacs, the Cochrane Library, and conference proceedings to 2002. References of included studies and contact with authors. No restrictions on language, year of publication, or publication status. STUDY SELECTION:All randomised trials of beta lactam monotherapy compared with beta lactam-minoglycoside combination therapy as empirical treatment for patients with fever and neutropenia. DATA SELECTION:Two reviewers independently applied selection criteria, performed quality assessment, and extracted data. An intention to treat approach was used. Relative risks were pooled with the random effect model. MAIN OUTCOME MEASURE:All cause fatality. RESULTS:Forty seven trials with 7807 patients met inclusion criteria. Nine trials compared the same beta lactam. There was no significant difference in all cause fatality (relative risk 0.85, 95% confidence interval 0.72 to 1.02). For success of treatment there was a significant advantage with monotherapy (0.92, 0.85 to 0.99), though there was considerable heterogeneity among trials. There was no significant difference between monotherapy and combination treatment in trials that compared the same beta lactam, whereas there was major advantage with monotherapy in trials that compared different beta lactams (0.87, 0.80 to 0.93). Rates of superinfection were similar. Adverse events, including those associated with severe morbidity, were significantly more common in the combination treatment group. Detected flaws in methods did not affect results. CONCLUSIONS:For patients with fever and neutropenia there is no clinical advantage in treatment with beta lactam-aminoglycoside combination therapy. Broad spectrum beta lactams as monotherapy should be regarded as the standard of care for such patients.

SUBMITTER: Paul M

PROVIDER: S-EPMC156012 | biostudies-literature | 2003 May

REPOSITORIES: biostudies-literature

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Beta lactam monotherapy versus beta lactam-aminoglycoside combination therapy for fever with neutropenia: systematic review and meta-analysis.

Paul Mical M Soares-Weiser Karla K Leibovici Leonard L

BMJ (Clinical research ed.) 20030501 7399

<h4>Objective</h4>To compare the effectiveness of beta lactam monotherapy versus beta lactam-aminoglycoside combination therapy in the treatment of patients with fever and neutropenia.<h4>Data sources</h4>Medline, Embase, Lilacs, the Cochrane Library, and conference proceedings to 2002. References of included studies and contact with authors. No restrictions on language, year of publication, or publication status.<h4>Study selection</h4>All randomised trials of beta lactam monotherapy compared w ...[more]

PMID: 12763980

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Project description:BackgroundPneumonia and bloodstream infections (BSI) due to extensively drug-resistant (XDR) Acinetobacter baumannii, XDR Pseudomonas aeruginosa, and carbapenem-resistant Enterobacterales (CRE) are associated with high mortality rates, and therapeutic options remain limited. This trial assessed whether combination therapy with colistin and meropenem was superior to colistin monotherapy for the treatment of these infections.MethodsThe OVERCOME (Colistin Monotherapy versus Combination Therapy) trial was an international, randomized, double-blind, placebo-controlled trial. We randomly assigned participants to receive colistin (5 mg/kg once followed by 1.67 mg/kg every 8 hours) in combination with either meropenem (1000 mg every 8 hours) or matching placebo for the treatment of pneumonia and/or BSI caused by XDR A. baumannii, XDR P. aeruginosa, or CRE. The primary outcome was 28-day mortality, and secondary outcomes included clinical failure and microbiologic cure.ResultsBetween 2012 and 2020, a total of 464 participants were randomly assigned to treatment, and 423 eligible patients comprised the modified intention-to-treat population. A. baumannii was the predominant trial pathogen (78%) and pneumonia the most common index infection (70%). Most patients were in the intensive care unit at the time of enrollment (69%). There was no difference in mortality (43 vs. 37%; P=0.17), clinical failure (65 vs. 58%; difference, 6.8 percentage points; 95% confidence interval [CI], -3.1 to 16.6), microbiologic cure (65 vs. 60%; difference, 4.8 percentage points; 95% CI, -5.6 to 15.2), or adverse events (acute kidney injury, 52 vs. 49% [P=0.55]; hypersensitivity reaction, 1 vs. 3% [P=0.22]; and neurotoxicity, 5 vs. 2% [P=0.29]) between patients receiving monotherapy and combination therapy, respectively.ConclusionsCombination therapy with colistin and meropenem was not superior to colistin monotherapy for the treatment of pneumonia or BSI caused by these pathogens. (Funded by the National Institute of Allergy and Infectious Diseases, Division of Microbiology and Infectious Diseases protocol 10-0065; ClinicalTrials.gov number, NCT01597973.).

Dataset Information

Beta lactam monotherapy versus beta lactam-aminoglycoside combination therapy for fever with neutropenia: systematic review and meta-analysis.

Publications

Beta lactam monotherapy versus beta lactam-aminoglycoside combination therapy for fever with neutropenia: systematic review and meta-analysis.

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