Development of EUCAST zone diameter breakpoints and quality control criteria for ceftazidime-avibactam 10-4 μg

Eur J Clin Microbiol Infect Dis. 2018 Jun;37(6):1047-1053. doi: 10.1007/s10096-018-3215-9. Epub 2018 Mar 30.

Abstract

Ceftazidime-avibactam disk studies were performed for disk mass selection and for establishing EUCAST quality control ranges and zone diameter breakpoints. The disk mass study included disk diffusion testing with ceftazidime-avibactam 10-4 and 10-6 μg disks and broth microdilution MIC testing for challenge set of 94 Enterobacteriaceae and 45 Pseudomonas aeruginosa. EUCAST SOP 9.0-based QC and MIC-disk correlations studies were followed for development of ceftazidime-avibactam 10-4 μg ranges for Escherichia coli ATCC 25922, P. aeruginosa ATCC 27583, and Klebsiella pneumoniae ATCC 700603 and for zone diameter breakpoint determination. The ceftazidime-avibactam 10-4 and 10-6 μg disks performed similar in comparison to broth microdilution, with zones ≤ 14 mm for all resistant strains. The 10-4 μg disk was selected and used in QC and breakpoint studies. There was minimal variation of ceftazidime-avibactam 10-4 μg QC study results between disks, media, and sites. The QC ranges were within 7 mm for all strains. The zone diameter breakpoint study demonstrated good correlation of MIC and disk results. The established zone diameter breakpoints resulted in false susceptible rates of 1.6 and 4.0% for Enterobacteriaceae and P. aeruginosa. EUCAST selected the ceftazidime-avibactam 10-4 μg disk and established QC ranges for E. coli 25922 of 24-30 mm, P. aeruginosa ATCC 27853 of 21-27 mm, and K. pneumoniae ATCC 700603 of 18-24 mm. The zone diameter breakpoints that correlated best with the MIC breakpoints of susceptible ≤ 8 mg/L and resistant > 8 mg/L were Enterobacteriaceae (S ≥ 13, R < 13 mm) and P. aeruginosa (S ≥ 17, R < 17 mm).

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Azabicyclo Compounds / pharmacology*
  • Ceftazidime / pharmacology*
  • Disk Diffusion Antimicrobial Tests / instrumentation
  • Disk Diffusion Antimicrobial Tests / methods*
  • Drug Combinations
  • Enterobacteriaceae / drug effects*
  • Escherichia coli / drug effects
  • Humans
  • Klebsiella pneumoniae / drug effects
  • Pseudomonas aeruginosa / drug effects
  • Quality Control
  • beta-Lactamases / drug effects

Substances

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