Efficacy and safety of tigecycline compared with vancomycin or linezolid for treatment of serious infections with methicillin-resistant Staphylococcus aureus or vancomycin-resistant enterococci: a Phase 3, multicentre, double-blind, randomized study

J Antimicrob Chemother. 2008 Sep;62 Suppl 1:i17-28. doi: 10.1093/jac/dkn250.

Abstract

Introduction: Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) are causing serious nosocomial infections. Tigecycline was evaluated in hospitalized patients with MRSA or VRE infection.

Patients and methods: A randomized (3:1), double-blind, multicentre, Phase 3 study compared the safety and efficacy of tigecycline with vancomycin or linezolid in hospitalized patients with MRSA or VRE infection, respectively. Patients were treated for 7-28 days and the test-of-cure (TOC) assessment was made 12-37 days after the last dose. The primary efficacy endpoint was the clinical response (cure, failure and indeterminate) in the co-primary, microbiologically evaluable (ME) and microbiologically modified intent-to-treat (m-mITT) populations at the TOC assessment.

Results: For MRSA infection, clinical cure rates in the ME population (n = 117) were 81.4% (70 of 86 patients) with tigecycline and 83.9% (26 of 31 patients) with vancomycin. In the m-mITT population (n = 133), clinical cure occurred in 75 of 100 tigecycline-treated patients (75.0%) and in 27 of 33 vancomycin-treated patients (81.8%). In patients with complicated skin and skin structure infections caused by MRSA, cure rates were similar with tigecycline or vancomycin (86.4% versus 86.9% in ME population; and 78.6% versus 87.0% in m-mITT population). In patients with MRSA infection, nausea or vomiting occurred more frequently with tigecycline than with vancomycin (41.0% versus 17.9%); most cases were mild, with only three patients discontinuing treatment. In patients with VRE (total enrollment, 15), 3 of 3 and 3 of 8 patients in the ME and m-mITT populations, respectively, were cured by tigecycline, compared with 2 of 3 patients in the ME and m-mITT populations treated with linezolid.

Conclusions: Tigecycline is safe and effective in hospitalized patients with serious infection caused by MRSA. There were too few cases of VRE to draw any conclusions.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides / adverse effects
  • Acetamides / pharmacology
  • Aged
  • Anti-Bacterial Agents / adverse effects*
  • Anti-Bacterial Agents / pharmacology*
  • Cross Infection / microbiology
  • Double-Blind Method
  • Enterococcus / drug effects*
  • Female
  • Gram-Positive Bacterial Infections / microbiology*
  • Hospitalization
  • Humans
  • Linezolid
  • Male
  • Methicillin Resistance*
  • Middle Aged
  • Minocycline / adverse effects
  • Minocycline / analogs & derivatives*
  • Minocycline / pharmacology
  • Oxazolidinones / adverse effects
  • Oxazolidinones / pharmacology
  • Staphylococcus aureus / drug effects*
  • Tigecycline
  • Treatment Outcome
  • Vancomycin / adverse effects
  • Vancomycin / pharmacology
  • Vancomycin Resistance*

Substances

  • Acetamides
  • Anti-Bacterial Agents
  • Oxazolidinones
  • Vancomycin
  • Tigecycline
  • Minocycline
  • Linezolid