Activity of ceftolozane/tazobactam, imipenem/relebactam and ceftazidime/avibactam against clinical Gram-negative isolates-SMART United States 2019-21

James A Karlowsky; Sibylle H Lob; Karri A Bauer; John Esterly; Fakhar Siddiqui; Katherine Young; Mary R Motyl; Daniel F Sahm

doi:10.1093/jacamr/dlad152

Activity of ceftolozane/tazobactam, imipenem/relebactam and ceftazidime/avibactam against clinical Gram-negative isolates-SMART United States 2019-21

JAC Antimicrob Resist. 2024 Jan 12;6(1):dlad152. doi: 10.1093/jacamr/dlad152. eCollection 2024 Feb.

Authors

James A Karlowsky^{1

2}, Sibylle H Lob¹, Karri A Bauer³, John Esterly³, Fakhar Siddiqui³, Katherine Young³, Mary R Motyl³, Daniel F Sahm¹

Affiliations

¹ IHMA, Schaumburg, IL 60173, USA.
² Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3E 0J9, Canada.
³ Merck & Co., Inc., Rahway, NJ 07065, USA.

Abstract

Background: Ongoing national and international surveillance efforts are critical components of antimicrobial stewardship, resistance monitoring, and drug development programs. In this report, we summarize the results of ceftolozane/tazobactam, imipenem/relebactam, ceftazidime/avibactam and comparator agent testing against 10 509 Enterobacterales and 2524 Pseudomonas aeruginosa collected by USA clinical laboratories in 2019-21 as part of the SMART global surveillance programme.

Methods: MICs were determined by CLSI broth microdilution and interpreted using 2023 CLSI M100 breakpoints.

Results: Most Enterobacterales were ceftazidime/avibactam susceptible (>99%), meropenem susceptible (99%) and ceftolozane/tazobactam susceptible (94%). Non-Morganellaceae Enterobacterales were also highly susceptible to imipenem/relebactam (99%). Ceftolozane/tazobactam inhibited 94% of Escherichia coli and 89% of Klebsiella pneumoniae with ceftriaxone non-susceptible/non-carbapenem-resistant phenotypes. Against P. aeruginosa, ceftolozane/tazobactam (97% susceptible) was more active than ceftazidime/avibactam (95%) and imipenem/relebactam (91%). MDR and difficult-to-treat resistance (DTR) phenotypes were identified in 13% and 7% of P. aeruginosa isolates, respectively. Ceftolozane/tazobactam remained active against 78% of MDR P. aeruginosa (13% and 23% higher than ceftazidime/avibactam and imipenem/relebactam, respectively) and against 74% of DTR P. aeruginosa (24% and 37% higher than ceftazidime/avibactam and imipenem/relebactam, respectively). Length of hospital stay at the time of specimen collection, ward type and infection type resulted in percent susceptible value differences of >5% across isolate demographic strata for some antimicrobial agent/pathogen combinations.

Conclusions: We conclude that in the USA, in 2019-21, carbapenem (meropenem) resistance remained uncommon in Enterobacterales and ceftolozane/tazobactam was more active than both ceftazidime/avibactam and imipenem/relebactam against P. aeruginosa.