200. Antimicrobial Activity of Ceftazidime-Avibactam and Comparators against AmpC Hyperproducing Enterobacterales and P. aeruginosa Collected from United States (US) Medical Centers (2016-2020)

Abstract

Background. E. cloacae species complex (ECL), S. marcescens (SM), C. freundii species complex (CF), and P. aeruginosa (PSA) are common pathogens in a variety of clinical infections. These organisms can overexpress the chromosomal AmpC that encodes resistance to several β-lactams. We evaluated the activity of ceftazidime-avibactam (CAZ-AVI) and comparators against these organisms. Methods. 17,650 isolates, including 4,400 ECL, 2,074 SM, 1,644 CF, and 9,532 PSA, were consecutively collected from 88 US medical centers in 2016-2020. Among these isolates, 3,127 were ceftazidime-nonsusceptible (CAZ-NS; MIC ≥8 mg/L for Enterobacterales [ENT] and ≥16 mg/L for PSA) and considered probable AmpC hyperproducers. Isolates were susceptibility tested by broth microdilution method. Results. Susceptibility to CAZ ranged from 73.6% (ECL) to 97.5% (SM; Table). Overall, 99.8% of ENT (99.7-99.9%) and 97.1% of PSA were CAZ-AVI-S; whereas 84.3% (79.0-97.7%) of ENT and 97.4% of PSA were ceftolozane-tazobactam (C-T)-S, 83.0% (78.5-94.8%) of ENT and 80.0% of PSA were piperacillin-tazobactam (PIPTAZ)-S, and 98.4% (98.3-98.7%) of ENT and 79.5% of PSA were meropenem (MEM)-S. CAZ-AVI retained potent activity and broad spectrum against CAZ-NS ENT (n=1,629; MIC50/90, 0.5/1 mg/L; 99.0%S overall) and CAZ-AVI was more active than MEM (MIC50/90, 0.06/0.5 mg/L; 93.1%S) against these organisms. C-T (MIC50/90, 8/ >16 mg/L; 23.8%S) and PIP-TAZ (MIC50/90, 64/ >64 mg/L; 21.8%S) exhibited limited activity against CAZ-NS ENT. Among comparator agents, only amikacin (99.0%S), tigecycline (95.6%S), and imipenem (92.1%S) showed good activity against CAZ-NS ENT. Also, CAZ-AVI retained activity against 86.7% of ENT isolates that were NS to CAZ and MEM (n=113). CAZ-AVI (MIC50/90, 2/4 mg/L; 97.1%S) and C-T (MIC50/90, 0.5/2 mg/L; 97.4%S) were the most active compounds tested against PSA and both retained activity against CAZ-NS PSA. CAZ-AVI (MIC50/90, 4/16 mg/L; 81.8%S) and C-T (MIC50/90, 2/8 mg/L; 83.9%S) activity against CAZ-NS PSA was comparable to tobramycin (MIC50/90, 1/ >8 mg/L; 82.2%S). Conclusion. CAZ-AVI demonstrated potent activity and broad spectrum against AmpC hyperproducer organisms, such as ECL, SM, CF, and PSA, from US hospitals and remained highly active against CAZ-NS isolates.