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[e-drug] Avoid aminoglycosides with beta lactams!

E-DRUG: Avoid aminoglycosides with beta lactams!
-----------------------------------------------
[Millions of scripts have combined aminoglycosides with beta lactams, but
now a systematic review in BMJ finds no added benefit, and only more harm!
Read it for yourself in this weeks' BMJ. The full text is at
http://bmj.bmjjournals.com/cgi/content/full/328/7441/668
 Copied as fair use. WB]

http://bmj.bmjjournals.com/cgi/content/abstract/328/7441/668

BMJ  2004;328:668 (20 March)

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

Mical Paul, consultant1, Ishay Benuri-Silbiger, researcher2, Karla
Soares-Weiser, coordinator of clinical research2, Leonard Leibovici,
associate professor2

1 Department of Medicine E and Infectious Diseases Unit, Rabin Medical
Centre, Beilinson Campus, Petah-Tikva 49100, Israel, 2 Department of
Medicine E, Rabin Medical Centre, Beilinson Campus, Petah-Tikva

Correspondence to: M Paul mica@zahav.net.il

Objective To compare  beta lactam monotherapy with  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 beta lactam monotherapy compared
with beta 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 beta lactam (1.02, 0.76 to 1.38), and 31
studies compared different  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.

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