In vitro activity of ceftazidime/avibactam against urinary isolates from patients in a Phase 3 clinical trial programme for the treatment of complicated urinary tract infections

J Antimicrob Chemother. 2017 May 1;72(5):1396-1399. doi: 10.1093/jac/dkw561.

Abstract

Objectives: To evaluate the in vitro activity of ceftazidime/avibactam relative to comparator agents against Gram-negative isolates from a Phase 3 clinical trial programme for complicated urinary tract infections (RECAPTURE).

Methods: The in vitro activity of ceftazidime/avibactam was evaluated against 840 Gram-negative pathogens isolated at baseline from 1033 randomized patients in two pivotal Phase 3 clinical trials for the treatment of complicated urinary tract infections. The trials were conducted in 160 institutions from 25 countries worldwide. Susceptibility testing was performed by broth microdilution at a central laboratory according to CLSI methodologies.

Results: Overall, ceftazidime/avibactam showed significant activity against the Enterobacteriaceae and Pseudomonas aeruginosa with MIC 90 values of 0.5 and 8 mg/L, respectively. Against the most common Enterobacteriaceae, MIC 90 values were 0.25 mg/L for Escherichia coli , 1 mg/L for Klebsiella pneumoniae , 0.06 mg/L for Proteus mirabilis and 2 mg/L for Enterobacter cloacae . The ceftazidime/avibactam MIC 90 for 154 ceftazidime-non-susceptible isolates of Enterobacteriaceae was 1 mg/L and the ceftazidime/avibactam MIC 90 for 15 non-susceptible isolates of P. aeruginosa was 64 mg/L. There was a significant reduction in the ceftazidime/avibactam MIC relative to ceftazidime alone for most of the Enterobacteriaceae isolates.

Conclusions: The ceftazidime/avibactam in vitro activity against these clinical urinary tract isolates demonstrates the potential utility of the drug in complicated urinary tract infections.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Anti-Bacterial Agents / pharmacokinetics
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use
  • Azabicyclo Compounds / pharmacokinetics
  • Azabicyclo Compounds / pharmacology*
  • Azabicyclo Compounds / therapeutic use
  • Ceftazidime / pharmacokinetics
  • Ceftazidime / pharmacology*
  • Ceftazidime / therapeutic use
  • Cephalosporin Resistance
  • Drug Combinations
  • Enterobacter cloacae / drug effects
  • Enterobacteriaceae / drug effects*
  • Enterobacteriaceae / isolation & purification
  • Escherichia coli / drug effects
  • Gram-Negative Bacterial Infections / drug therapy
  • Gram-Negative Bacterial Infections / microbiology*
  • Humans
  • Intraabdominal Infections / drug therapy
  • Intraabdominal Infections / microbiology
  • Klebsiella pneumoniae / drug effects
  • Microbial Sensitivity Tests
  • Pseudomonas aeruginosa / drug effects
  • Urinary Tract Infections / complications
  • Urinary Tract Infections / drug therapy
  • Urinary Tract Infections / microbiology*

Substances

  • Anti-Bacterial Agents
  • Azabicyclo Compounds
  • Drug Combinations
  • avibactam, ceftazidime drug combination
  • Ceftazidime