Beta lactam monotherapy versus beta lactam-aminoglycoside combination therapy for sepsis in immunocompetent patients: systematic review and meta-analysis of randomised trials.
OBJECTIVE
To compare beta lactam monotherapy with beta lactam-aminoglycoside combination therapy for severe infections.


METHODS
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.


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


METHODS
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 beta lactam (1.02, 0.76 to 1.38), and 31 studies compared different beta 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 beta 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 beta lactams should be discouraged. Fatality remains unchanged, while the risk for adverse events is increased.
Department of Medicine E and Infectious Diseases Unit, Rabin Medical Centre, Beilinson Campus, Petah-Tikva 49100, Israel. mica@zahav.net.il
Mical
M
Paul
Ishay
I
Benuri-Silbiger
Karla
K
Soares-Weiser
Leonard
L
Leibovici
D000617:Aminoglycosides / Q000627:therapeutic use*; D004359:Drug Therapy, Combination / Q000627:therapeutic use*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D018805:Sepsis / Q000188:drug therapy*; D016896:Treatment Outcome; D047090:beta-Lactams / Q000627:therapeutic use*
D000617:Aminoglycosides; D047090:beta-Lactams