Infections caused by bacteria and requiring hospitalization are a leading cause of preventable death. The beta lactam antibiotics (e.g. penicillins, cephalosporins) and the aminoglycosides (e.g. gentamicin) kill bacteria by different means. Combining a beta lactam with an aminoglycoside could, therefore, result in more effective treatment of patients with severe infection but with the side effects of both antibiotics. We reviewed clinical trials that compared intravenous treatment with a beta lactam versus treatment with a beta lactam plus an aminoglycoside.
We searched the literature until November 2013. We included in the review 69 trials that randomly assigned 7863 participants . Participants were hospitalized with urinary tract, intra-abdominal, skin and soft tissue infections, pneumonia and infections of unknown source. One set of studies compared a broad-spectrum beta lactam versus a different, generally narrower-spectrum beta lactam combined with an aminoglycoside (47 studies). No clear difference in all-cause deaths was observed, but treatment failures were fewer with single beta lactam antibiotic treatment. A significant survival advantage was seen with single therapy in studies that involved infections of unknown source. The other studies compared one beta lactam versus the same beta lactam combined with an aminoglycoside antibiotic (22 studies). In these trials, no differences between single and combination antibiotic treatments were seen. Overall, adverse event rates did not differ between the study groups, but renal damage was more frequent with the combination therapy. Combination therapy did not prevent the development of secondary infection.
The review authors concluded that beta lactam-aminoglycoside combination therapy does not provide an advantage over beta lactams alone. Furthermore, combination therapy was associated with an increased risk of renal damage. The limited number of trials comparing the same beta lactam in both study arms and the fact that more than a third of the studies did not report on all-cause deaths may limit these conclusions. The subgroup of Pseudomonas aeruginosa infections was underpowered to examine effects.