title: Efficacy and safety of tigecycline: a systematic review and meta-analysis.
abstract: BACKGROUND
  Tigecycline is a novel glycylcycline that exhibits broad-spectrum antibacterial activity. Recently, the US FDA issued a warning concerning increased mortality with tigecycline in randomized controlled trials (RCTs).
  
  
  METHODS
  We conducted a systematic review and meta-analysis of RCTs that compared tigecycline with any other antibiotic regimen for the treatment of any infection. A comprehensive search, without publication status or other restrictions, was conducted. The primary outcome was overall 30 day mortality. The secondary outcome included clinical and microbiological failure, superinfections and adverse events (AEs). The trials' risks of bias and their effects on results were assessed. Two reviewers independently extracted the data. Individual trials' relative risks (RRs) were pooled using a fixed effect meta-analysis.
  
  
  RESULTS
  Fifteen trials (7654 patients) were included. Overall mortality was higher with tigecycline compared with other regimens [RR 1.29, 95% confidence interval (CI) 1.02-1.64, without heterogeneity]. The type of infection assessed and the trials' reported risks of bias did not affect this result. Clinical failure was significantly higher with tigecycline (RR 1.16, 95% CI 1.06-1.27) and non-statistically significant higher rates of microbiological failure were demonstrated (RR 1.13, 95% CI 0.99-1.30). Development of septic shock was significantly more frequent with tigecycline (RR 7.01, 95% CI 1.27-38.66). Superinfections were significantly more common with tigecycline and so were AEs, including all AEs and AEs requiring discontinuation.
  
  
  CONCLUSIONS
  In the light of the increased mortality, probably explained by decreased clinical and microbiological efficacy, clinicians should avoid tigecycline monotherapy in the treatment of severe infections and reserve it as a last-resort drug.
authors.affiliation: Department of Medicine E, Rabin Medical Center, Beilinson Hospital, Petah-Tiqva, Israel. dafna.yahav@gmail.com
authors.forename: Dafna
authors.initials: D
authors.lastname: Yahav
authors.forename: Adi
authors.initials: A
authors.lastname: Lador
authors.forename: Mical
authors.initials: M
authors.lastname: Paul
authors.forename: Leonard
authors.initials: L
authors.lastname: Leibovici
mesh_terms: D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D016001:Confidence Intervals; D006801:Humans; D008911:Minocycline / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012772:Shock, Septic / Q000209:etiology; D000078304:Tigecycline; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D000078304:Tigecycline; D008911:Minocycline