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.

Fig 1

Trials identified for study and exclusions

Fig 2

All cause fatality

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Treatment failure

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Bacterial superinfections

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Any adverse event

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Nephrotoxicity

Fig 7

Sensitivity analysis. Number in parenthesis refers to number of studies included in analysis. Studies in which number of dropouts for failure analysis was not specified are not included. †Analysis performed counting all dropouts as treatment failures