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β lactam monotherapy versus β lactam-aminoglycoside combination therapy for sepsis in immunocompetent patients: systematic review and meta-analysis of randomised trials

BMJ 2004; 328 doi: https://doi.org/10.1136/bmj.38028.520995.63 (Published 18 March 2004) Cite this as: BMJ 2004;328:668

This article has a correction. Please see:

  1. Mical Paul, consultant (mica{at}zahav.net.il)1,
  2. Ishay Benuri-Silbiger, researcher2,
  3. Karla Soares-Weiser, coordinator of clinical research2,
  4. Leonard Leibovici, associate professor2
  1. 1Department of Medicine E and Infectious Diseases Unit, Rabin Medical Centre, Beilinson Campus, Petah-Tikva 49100, Israel
  2. 2Department of Medicine E, Rabin Medical Centre, Beilinson Campus, Petah-Tikva
  1. Correspondence to: M Paul
  • Accepted 22 December 2003

Abstract

Objective To compare β lactam monotherapy with β lactam-aminoglycoside combination therapy for severe infections.

Data sources Medline, Embase, Lilacs, Cochrane Library, and conference proceedings, to 2003; references of included studies; contact with all authors. No restrictions, such as language, year of publication, or publication status.

Study selection All randomised trials of β lactam monotherapy compared with β lactam-aminoglycoside combination therapy for patients without neutropenia who fulfilled criteria for sepsis.

Data selection Two reviewers independently applied selection criteria, performed quality assessment, and extracted the data. The primary outcome assessed was all cause fatality by intention to treat. Relative risks were pooled with the random effect model (relative risk < 1 favours monotherapy).

Results 64 trials with 7586 patients were included. There was no difference in all cause fatality (relative risk 0.90, 95% confidence interval 0.77 to 1.06). 12 studies compared the same β lactam (1.02, 0.76 to 1.38), and 31 studies compared different β lactams (0.85, 0.69 to 1.05). Clinical failure was more common with combination treatment overall (0.87, 0.78 to 0.97) and among studies comparing different β lactams (0.76, 0.68 to 0.86). There was no advantage to combination therapy among patients with Gram negative infections (1835 patients) or Pseudomonas aeruginosa infections (426 patients). There was no difference in the rate of development of resistance. Nephrotoxicity was significantly more common with combination therapy (0.36, 0.28 to 0.47). Heterogeneity was not significant for these comparisons.

Conclusions In the treatment of sepsis the addition of an aminoglycoside to β lactams should be discouraged. Fatality remains unchanged, while the risk for adverse events is increased.

Footnotes

  • Contributors MP and LL performed the search. All authors selected trials for inclusion, performed data extraction and quality assessment of the trials, and analysed the data. MP and LL contacted authors and requested missing data. All authors participated drafting the manuscript for the Cochrane review and for the journal article. MP is guarantor for the article.

  • Funding This work was supported by an EU 5th framework grant (TREAT project, grant No 1999-11459).

  • Competing interests None declared.

  • Ethical approval Not required.

  • Embedded Image A full list of references to excluded studies can be found on bmj.com>

  • Accepted 22 December 2003
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