An updated meta-analysis including unpublished trials found tigecycline to be no better than comparator drugs in serious infections.

Tigecycline is one of the few new antibiotic agents launched in the past decade. It has a broad spectrum of activity, and although closely related to the tetracyclines, it has a dual mechanism of action that reduces the development of resistance. A meta-analysis of clinical trials was published earlier this year, but used only published reports: the authors of this paper also included data from unpublished studies. They carried out a comprehensive literature search for randomised controlled trials that compared the clinical and microbiological efficacy of tigecycline with other antimicrobial drugs, including use of clinical trial databases to identify studies that had not been published. Relevant data were extracted from eligible reports, which were assessed for trial quality. Primary outcome for the analysis was treatment success in the clinically assessable population, defined as patients who received at least one dose of the study drug, had clinical evidence of disease, and had complete follow-up.

There were 372 unique records identified by the literature search, of which 346 were excluded on the basis of title and abstract leaving 36 that were assessed in full: 14 of these were eligible studies, 10 published and 4 unpublished, with a total study population of about 7,400. In the clinically assessable population (n=5,642), treatment with tigecycline was non-significantly less successful than control, with an odds ratio (OR) of 0.87 (95% CI 0.74 to 1.02, p=0.29).

Adverse events were more frequent in the tigecycline group (OR 1.45; 95% CI 1.11 to 1.88; p<0.0001), particularly nausea and vomiting. There was a higher overall mortality in the tigecycline group, however this was not statistically significant (OR 1.28; 95% CI 0.97 to 1.69; p=0.97) and numbers were small.

The authors conclude that tigecycline was not shown to be superior to standard drugs in controlled trials, including unpublished studies, and it was associated with a high incidence of nausea and vomiting. They note that comparisons in trials were generally to multi-drug regimens in order to gain the spectrum of antibacterial cover, and that the ability to use it as monotherapy in an advantage for tigecycline. They note that the FDA has also commented on the increased overall mortality, noting that risk factors appear to be resistant pathogens, hospital-acquired pneumonia, and increased age.

An accompanying Comment discusses the study and its significance for use of tigecycline. The authors, who published the earlier meta-analysis, suggest that subgroup analysis might also be useful, and call for more controlled trials to assess the efficacy and safety of the drug further.