Comparative in vitro Activities of Ceftazidime–Avibactam and Ceftolozane-tazobactam Against Characterized β-Lactamase-producing Pseudomonas aeruginosa

BACKGROUND: Ceftazidime-avibactam (CAZ-AVI) and ceftolozane-tazobactam (TOL-TAZ) are cephalosporin/β-lactamase inhibitor combinations recently approved for the treatment of complicated intra-abdominal infections (cIAI) and complicated urinary tract infections (cUTI). Both agents are reported to have antibacterial activity against P. aeruginosa including multi-drug-resistant strains, but few studies have directly compared the activities of both agents against the same strains in a single study. This study evaluated the activities of both agents against characterized β-lactamase-producing P. aeruginosa using broth microdilution (BMD) and disk diffusion (DD) methods. METHODS: A total of 98 clinical isolates of P. aeruginosa, including characterized β-lactamase-producing strains were tested for susceptibility to CAZ-AVI and TOL-TAZ using BMD and DD and results were interpreted using FDA/CLSI breakpoints. The isolates tested included CTX-M (ESBL), AmpC, KPC, OXA and metallo-β-lactamase (MBL) producing organisms. The results from both BMD and DD were analyzed to assess the correlation between the testing methods and ability to differentiate isolates susceptible and resistant to both agents. RESULTS: CAZ-AVI and TOL-TAZ exhibited similar MIC values against all isolates with MIC(50/90) values of 2 and 16 µg/mL, respectively. When results were interpreted using FDA/CLSI breakpoints, the susceptibility rates for CAZ-AVI and TOL-TAZ were 82.7% and 62.2%, respectively. Isolates resistant to CAZ-AVI were predominantly MBL-producers whereas isolates resistant to TOL-TAZ included both MBL and KPC-producing P. aeruginosa. Both agents were active against AmpC-producing P. aeruginosa and both agents showed good correlation between BMD and DD methods. CONCLUSION: CAZ-AVI and TOL-TAZ were active against β-lactamase-producing subsets of P. aeruginosa isolates in this challenge set. Both AmpC and KPC-producing P. aeruginosa were susceptible to CAZ-AVI whereas TOL-TAZ activity was limited to AmpC-producing organisms. Neither agent was active against MBL-producing organisms. DISCLOSURES: L. Y. Lin, Allergan plc: Employee, Salary; M. Vail, Allergan plc: Employee and Intern during study conduct and analysis, Educational support; D. Debabov, Allergan plc: Employee, Salary; I. Critchley, Allergan plc: Employee, Salary