Background: Ceftazidime and avibactam (CAZ-AVI) diffusion disks have been widely used in hospitals and clinical laboratories in the US for susceptibility testing of infections caused by Enterobacteriaceae and Pseudomonas aeruginosa. A few cases of high error rates and overcalling of resistance in some carbapenem resistant Enterobacteriaceae (CRE) isolates have been reported. The purpose of this study was to evaluate the performance of CAZ-AVI diffusion disks made by two manufacturers in comparison with that of the standard broth microdilution (BMD) method for susceptibility testing against a large collection of CRE.
Methods: A panel of 110 meropenem non-susceptible Enterobacteriaceae clinical isolates, including 98 Klebsiella pneumoniae, 8 Enterobacter cloacae, and 4 Escherichia coli were tested using CAZ-AVI (30/20 µg) diffusion disks manufactured by Hardy Diagnostics (Hardy) and BD Biosciences (BD). These isolates harbored various carbapenemase genes including KPC-2, KPC-3, VIM, NDM, OXA, ESBL, and altered OmpK35 and OmpK36. The same isolates were tested for susceptibility to CAZ-AVI by BMD using a custom-made Trek panel. Correlation between minimal inhibitory concentration (MIC) and disk diffusion inhibition zones was assessed based on Clinical and Laboratory Standards Institute (CLSI) breakpoints and error rate analysis.
Results: Overall disk diffusion inhibition zones correlated well with MIC for disks manufactured by both Hardy and BD according to CLSI CAZ-AVI breakpoints (susceptible/resistant): MIC ≤8/4/≥16/4 µg/mL, disk diffusion ≥21/≤20 mm. Error rates were low for the Hardy disks grown on Hardy and BD Mueller-Hinton agar (MHA) with 0.9% very major errors (VME)/1.8% major errors (ME) and 1.8% VME/5.5% ME, respectively. The error rates for BD disks grown on Hardy and BD MHA plates were 1.8% VME/0% ME and 1.8% VME/6.4 ME, respectively. ME rates appeared to be lower when Hardy MHA plates were used for both Hardy and BD disks.
Conclusion: CAZ-AVI (30/20 µg) disks manufactured by Hardy and BD performed well in susceptibility testing against a challenging set of CRE isolates. These data showed good categorical agreement between disk diffusion and BMD methods. Error rates were lowest when Hardy MHA plates were used for both Hardy and BD disks.
L. Y. Lin,