Systematic review and meta-analysis of antimicrobial treatment effect estimation in complicated urinary tract infection

Antimicrob Agents Chemother. 2013 Nov;57(11):5284-90. doi: 10.1128/AAC.01257-13. Epub 2013 Aug 12.

Abstract

Noninferiority trial design and analyses are commonly used to establish the effectiveness of a new antimicrobial drug for treatment of serious infections such as complicated urinary tract infection (cUTI). A systematic review and meta-analysis were conducted to estimate the treatment effects of three potential active comparator drugs for the design of a noninferiority trial. The systematic review identified no placebo trials of cUTI, four clinical trials of cUTI with uncomplicated urinary tract infection as a proxy for placebo, and nine trials with reports of treatment effect estimates for doripenem, levofloxacin, or imipenem-cilastatin. In the meta-analysis, the primary efficacy endpoint of interest was the microbiological eradication rate at the test-of-cure visit in the microbiological intent-to-treat population. The estimated eradication rates and corresponding 95% confidence intervals (CI) were 31.8% (26.5% to 37.2%) for placebo, 81% (77.7% to 84.2%) for doripenem, 79% (75.9% to 82.2%) for levofloxacin, and 80.5% (71.9% to 89.1%) for imipenem-cilastatin. The treatment effect estimates were 40.5% for doripenem, 38.7% for levofloxacin, 34.7% for imipenem-cilastatin, and 40.8% overall. These treatment effect estimates can be used to inform the design and analysis of future noninferiority trials in cUTI study populations.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Anti-Bacterial Agents / therapeutic use*
  • Carbapenems / therapeutic use*
  • Cilastatin / therapeutic use*
  • Cilastatin, Imipenem Drug Combination
  • Clinical Trials as Topic
  • Databases, Bibliographic
  • Doripenem
  • Drug Combinations
  • Female
  • Humans
  • Imipenem / therapeutic use*
  • Levofloxacin / therapeutic use*
  • Male
  • Research Design
  • Treatment Outcome
  • Urinary Tract Infections / drug therapy*
  • Urinary Tract Infections / microbiology
  • Urinary Tract Infections / pathology

Substances

  • Anti-Bacterial Agents
  • Carbapenems
  • Drug Combinations
  • Cilastatin
  • Levofloxacin
  • Imipenem
  • Cilastatin, Imipenem Drug Combination
  • Doripenem