Verification of Ceftazidime-Avibactam and Ceftolozane-Tazobactam Susceptibility Testing Methods against Carbapenem-Resistant Enterobacteriaceae and Pseudomonas aeruginosa

Ceftazidime-avibactam and ceftolozane-tazobactam are newly approved agents for the treatment of infections caused by multidrug-resistant Gram-negative bacteria. Resistance to both agents has been described clinically. Susceptibility testing on automated systems is unavailable for either agent. Our objective was to compare the disk diffusion and Etest methods to standard broth microdilution (BMD) methods for testing ceftazidime-avibactam and ceftolozane-tazobactam against a diverse collection of carbapenem-resistant Enterobacteriaceae (CRE) and carbapenem-resistant Pseudomonas aeruginosa (CRP) isolates, respectively. Among 74 ceftazidime-avibactam-susceptible and -resistant CRE isolates, BMD categorical agreement was higher with Etest (96%) than with disk diffusion (72%; P = 0.0003). Twenty-eight percent of ceftazidime-avibactam-susceptible CRE isolates were classified as resistant by disk diffusion. Results were comparable to those obtained with resistance defined genotypically. Among 72 ceftolozane-tazobactam- susceptible and -resistant CRP isolates, the levels of BMD categorical agreement with disk diffusion and Etest were 94% and 96%, respectively; the only errors identified were minor. Our findings demonstrate that Etest measurements of ceftazidime-avibactam and ceftolozane-tazobactam susceptibility correlate closely with standard BMD methods, suggesting a useful role clinically. On the other hand, disk diffusion measurements overcalled CRE resistance to ceftazidime-avibactam. A better understanding of ceftazidime-avibactam interpretive breakpoints is needed before disk diffusion is used routinely in the clinic. Until clinicians and microbiologists understand Etest and disk diffusion performance at their centers, test results should be interpreted cautiously.