In Vitro Activity of Ceftazidime-Avibactam against Clinical Isolates of Enterobacteriaceae and Pseudomonas aeruginosa Collected in Asia-Pacific Countries: Results from the INFORM Global Surveillance Program, 2012 to 2015

Antimicrob Agents Chemother. 2018 Jun 26;62(7):e02569-17. doi: 10.1128/AAC.02569-17. Print 2018 Jul.

Abstract

The in vitro activities of ceftazidime-avibactam and comparators against 9,149 isolates of Enterobacteriaceae and 2,038 isolates of Pseudomonas aeruginosa collected by 42 medical centers in nine countries in the Asia-Pacific region from 2012 to 2015 were determined as part of the International Network for Optimal Resistance Monitoring (INFORM) global surveillance program. Antimicrobial susceptibility testing was conducted by Clinical and Laboratory Standards Institute (CLSI) broth microdilution, and isolate subset analysis was performed on the basis of the resistant phenotypes and β-lactamase content. Ceftazidime-avibactam demonstrated potent in vitro activity (MIC, ≤8 μg/ml) against all Enterobacteriaceae tested (99.0% susceptible) and was the most active against isolates that were metallo-β-lactamase (MBL) negative (99.8% susceptible). Against P. aeruginosa, 92.6% of all isolates and 96.1% of MBL-negative isolates were susceptible to ceftazidime-avibactam (MIC, ≤8 μg/ml). The rates of susceptibility to ceftazidime-avibactam ranged from 97.0% (Philippines) to 100% (Hong Kong, South Korea) for Enterobacteriaceae and from 83.1% (Thailand) to 100% (Hong Kong) among P. aeruginosa isolates, with lower susceptibilities being observed in countries where MBLs were more frequently encountered (Philippines, Thailand). Ceftazidime-avibactam inhibited 97.2 to 100% of Enterobacteriaceae isolates, per country, that carried serine β-lactamases, including extended-spectrum β-lactamases, AmpC cephalosporinases, and carbapenemases (KPC, GES, OXA-48-like). It also inhibited 91.3% of P. aeruginosa isolates that were carbapenem nonsusceptible in which no acquired β-lactamase was detected. Among MBL-negative Enterobacteriaceae isolates that were ceftazidime nonsusceptible, meropenem nonsusceptible, colistin resistant, and multidrug resistant, ceftazidime-avibactam inhibited 96.1, 87.7, 100, and 98.8% of isolates, respectively, and among MBL-negative P. aeruginosa isolates that were ceftazidime nonsusceptible, meropenem nonsusceptible, colistin resistant, and multidrug resistant, ceftazidime-avibactam inhibited 79.6, 83.6, 83.3, and 68.2% of isolates, respectively. Overall, clinical isolates of Enterobacteriaceae and P. aeruginosa collected in nine Asia-Pacific countries from 2012 to 2015 were highly susceptible to ceftazidime-avibactam.

Keywords: Asia-Pacific; Enterobacteriaceae; Gram negative; INFORM; Pseudomonas aeruginosa; ceftazidime-avibactam; surveillance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Azabicyclo Compounds / pharmacology*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Ceftazidime / pharmacology*
  • Drug Combinations
  • Drug Resistance, Multiple, Bacterial / genetics
  • Enterobacteriaceae / drug effects*
  • Enterobacteriaceae / genetics
  • Enterobacteriaceae / metabolism
  • Microbial Sensitivity Tests
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas aeruginosa / enzymology
  • Pseudomonas aeruginosa / metabolism
  • beta-Lactamases / genetics
  • beta-Lactamases / metabolism

Substances

  • Anti-Bacterial Agents
  • Azabicyclo Compounds
  • Bacterial Proteins
  • Drug Combinations
  • avibactam, ceftazidime drug combination
  • Ceftazidime
  • beta-Lactamases
  • carbapenemase