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

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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.