Infections with multidrug-resistant pathogens such as extended-spectrum β-lactamase-producing Enterobacteriaceae, carbapenem resistant Enterobacteriaceae, multidrug-resistant Pseudomonas aeruginosa; methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus spp. are associated with increased mortality, morbidity, and length of hospital stay. Antimicrobial resistance in gram-negative organisms in particular has been progressive and traditional agents used to treat these pathogens have become obsolete and might have become targets for bacterial mechanisms of resistance.1,2 Tigecycline is the first drug of the glycylcycline class that inhibits protein synthesis via binding to the 30S subunit of ribosome and has favorable pharmacokinetic and pharmacodynamic characteristics. The US Food and Drug Administration (FDA) has approved its use in 2005 for complicated intra-abdominal infections and complicated skin and soft tissue infection, and in 2009 for community-acquired pneumonia.3,4 Despite the fact that multiple systematic reviews assessing the clinical efficacy and safety of tigecycline have been published, no result synthesis was performed.5-12 The only effort to assess the efficacy and safety of tigecycline by synthesis of the results of existing trials was done by Cai and colleagues11 with only eight published randomized controlled trials included. The authors suggested that tigecycline monotherapy might be as effective as comparator treatments.
A current meta-analysis was recently published in Lancet13, the authors assessed the efficacy and safety of tigecycline compared with other antimicrobial agents by updating Cai and colleagues’ meta-analysis with inclusion of subsequent trials and unpublished studies. PubMed, Cochrane Central Register, Embase and clinical trial registries were searched up to March 30, 2011 to identify published and unpublished studies, respectively. Eligible studies were randomized trials that assessed the clinical efficacy and safety 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 drug, had clinical evidence of disease, and had complete follow-up. Meta-analysis was done with random-effects models because of heterogeneity across the trials. Fourteen (n=14) randomized clinical trials, about 7400 patients, were included. Treatment success was lower with tigecycline than with control, but the difference was not statistically significant (OR 0·87, 95% CI 0·74–1·02). Adverse events occurred more frequently in the tigecycline group than in the control groups (OR 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 statistically significant (OR 1·28, 0·97–1·69). The authors concluded that tigecycline is not superior to other standard antimicrobial agents for the management of serious infections. Subgroup analysis and more controlled trials to further assess the efficacy and safety of tigecycline is crucial.
1. Kanj SS, Kanafani ZA. Current concepts in antimicrobial therapy against resistant Gram-negative organisms: extended-spectrum β-lactamase-producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae and multidrug-resistant Pseudomonas aeruginosa
. Mayo Clin Proc
2. Eckmann C, Dryden M. Treatment of complicated skin and soft-tissue infections caused by resistant bacteria: value of linezolid, tigecycline, daptomycin and vancomycin. Eur J Med Res 2010;15:554–63. ...