BACKGROUND: Multidrug resistance among bacteria increases the need for new antimicrobial drugs with high potency and stability. Tigecycline is one candidate drug, and a previous meta-analysis of only published randomised controlled trials suggested that it might as effective as comparator treatments; we did a meta-analysis to include new and unpublished trials to assess its efficacy for the treatment of adult patients with serious bacterial infection. METHODS: We searched PubMed, Cochrane Central Register, and Embase up to March 30, 2011, to identify published studies, and we searched clinical trial registries to identify completed unpublished studies, the results of which were obtained through the manufacturer. Eligible studies were randomised trials assessing the clinical efficacy, safety, and eradication efficiency of tigecycline versus other antimicrobial agents for any bacterial infection. The primary outcome was treatment success in patients who received at least one dose of the study drug, had clinical evidence of disease, and had complete follow-up (the clinically assessable population). Meta-analysis was done with random-effects models because of heterogeneity across the trials. FINDINGS: 14 randomised trials, comprising about 7400 patients, were included. Treatment success was lower with tigecycline than with control antibiotic agents, but the difference was not significant (odds ratio 0·87, 95% CI 0·74-1·02). Adverse events were more frequent in the tigecycline group than in the control groups (1·45, 1·11-1·88), with significantly more vomiting and nausea. All-cause mortality was higher in the tigecycline group than in the comparator groups, but the difference was not significant (1·28, 0·97-1·69). Eradication efficiency did not differ between tigecycline and control regimens, but the sample size for these comparisons was small. INTERPRETATION: Tigecycline is not better than standard antimicrobial agents for the treatment of serious infections. Our findings show that assessment with unpublished studies is needed to make appropriate decisions about new agents. FUNDING: None.
BACKGROUND: Multidrug resistance among bacteria increases the need for new antimicrobial drugs with high potency and stability. Tigecycline is one candidate drug, and a previous meta-analysis of only published randomised controlled trials suggested that it might as effective as comparator treatments; we did a meta-analysis to include new and unpublished trials to assess its efficacy for the treatment of adult patients with serious bacterial infection. METHODS: We searched PubMed, Cochrane Central Register, and Embase up to March 30, 2011, to identify published studies, and we searched clinical trial registries to identify completed unpublished studies, the results of which were obtained through the manufacturer. Eligible studies were randomised trials assessing the clinical efficacy, safety, and eradication efficiency of tigecycline versus other antimicrobial agents for any bacterial infection. The primary outcome was treatment success in patients who received at least one dose of the study drug, had clinical evidence of disease, and had complete follow-up (the clinically assessable population). Meta-analysis was done with random-effects models because of heterogeneity across the trials. FINDINGS: 14 randomised trials, comprising about 7400 patients, were included. Treatment success was lower with tigecycline than with control antibiotic agents, but the difference was not significant (odds ratio 0·87, 95% CI 0·74-1·02). Adverse events were more frequent in the tigecycline group than in the control groups (1·45, 1·11-1·88), with significantly more vomiting and nausea. All-cause mortality was higher in the tigecycline group than in the comparator groups, but the difference was not significant (1·28, 0·97-1·69). Eradication efficiency did not differ between tigecycline and control regimens, but the sample size for these comparisons was small. INTERPRETATION:Tigecycline is not better than standard antimicrobial agents for the treatment of serious infections. Our findings show that assessment with unpublished studies is needed to make appropriate decisions about new agents. FUNDING: None.
Authors: Francesco Giuseppe De Rosa; Silvia Corcione; Giorgia Montrucchio; Luca Brazzi; Giovanni Di Perri Journal: Turk J Anaesthesiol Reanim Date: 2016-12-01