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. 2022 May 17;66(5):e0018922.
doi: 10.1128/aac.00189-22. Epub 2022 May 2.

In Vitro Activity of Ceftolozane-Tazobactam, Imipenem-Relebactam, Ceftazidime-Avibactam, and Comparators against Pseudomonas aeruginosa Isolates Collected in United States Hospitals According to Results from the SMART Surveillance Program, 2018 to 2020

James A Karlowsky  1   2 , Sibylle H Lob  1 , C Andrew DeRyke  3 , David W Hilbert  3 , Michael T Wong  3 , Katherine Young  3 , Fakhar Siddiqui  3 , Mary R Motyl  3 , Daniel F Sahm  1
Affiliations

In Vitro Activity of Ceftolozane-Tazobactam, Imipenem-Relebactam, Ceftazidime-Avibactam, and Comparators against Pseudomonas aeruginosa Isolates Collected in United States Hospitals According to Results from the SMART Surveillance Program, 2018 to 2020

James A Karlowsky et al. Antimicrob Agents Chemother. .

Abstract

Ceftolozane-tazobactam (C/T), imipenem-relebactam (IMR), and ceftazidime-avibactam (CZA) were tested against 2,531 P. aeruginosa strains isolated from patients in the United States from 2018 to 2020 as part of the SMART (Study for Monitoring Antimicrobial Resistance Trends) surveillance program. MICs were determined by CLSI broth microdilution and interpreted using CLSI M100 (2021) breakpoints. Imipenem-, IMR-, or C/T-nonsusceptible isolates were screened for β-lactamase genes: 96.4% of all isolates and ≥70% of multidrug-resistant (MDR), pan-β-lactam-nonsusceptible, and difficult-to-treat resistance (DTR) isolates were C/T-susceptible; 52.2% of C/T-nonsusceptible isolates remained susceptible to IMR compared to 38.9% for CZA; and 1.7% of isolates tested were nonsusceptible to both C/T and IMR versus 2.2% of isolates with a C/T-nonsusceptible and CZA-resistant phenotype (a difference of 12 isolates). C/T and IMR modal MICs for pan-β-lactam-nonsusceptible isolates remained at or below their respective susceptible MIC breakpoints from 2018 to 2020, while the modal MIC for CZA increased 2-fold from 2018 to 2019 and exceeded the CZA-susceptible MIC breakpoint in both 2019 and 2020. Only six of 802 molecularly characterized isolates carried a metallo-β-lactamase, and two isolates carried a GES carbapenemase. Most P. aeruginosa isolates were C/T-susceptible, including many with MDR, pan-β-lactam-nonsusceptible, DTR, CZA-resistant, and IMR-nonsusceptible phenotypes. While C/T was the most active antipseudomonal agent, IMR demonstrated greater activity than CZA against isolates nonsusceptible to C/T.

Keywords: Pseudomonas aeruginosa; SMART; United States; ceftazidime-avibactam; ceftolozane-tazobactam; imipenem-relebactam; surveillance.

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Conflict of interest statement

The authors declare a conflict of interest. S.H.L. and D.F.S. work for IHMA, which receives funding from Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, New Jersey, USA for the SMART surveillance program. J.A.K. is a consultant to IHMA, and an employee of Shared Health Manitoba and the University of Manitoba. C.A.D., D.W.H., M.T.W., K.Y., F.S., and M.R.M. are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, New Jersey, USA, and own stock in Merck & Co., Inc., Kenilworth, New Jersey, USA. The IHMA authors do not have personal financial interests in the sponsor of this manuscript (Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, New Jersey, USA).

Figures

FIG 1
FIG 1
Distribution of ceftolozane-tazobactam, ceftazidime-avibactam, and imipenem-relebactam MIC values against all P. aeruginosa isolates and resistant subsets. C/T, ceftolozane-tazobactam; IMR, imipenem-relebactam; CZA, ceftazidime-avibactam; MDR, multidrug resistant (resistant to ≥3 sentinel agents [amikacin, aztreonam, cefepime, colistin, imipenem, levofloxacin, and piperacillin-tazobactam]); pan-β-lactam-nonsusceptible, nonsusceptible to all tested β-lactams (excluding C/T, IMR, and CZA); DTR, difficult-to-treat resistance (nonsusceptible to all tested β-lactams [excluding C/T, IMR, and CZA] and fluoroquinolones). Dashed lines indicate the respective susceptible breakpoints. Arrows indicate the mode of the respective MIC distributions.
FIG 2
FIG 2
MIC distributions for ceftolozane-tazobactam, imipenem-relebactam, and ceftazidime-avibactam against pan-β-lactam-nonsusceptible P. aeruginosa isolates, by year. C/T, ceftolozane-tazobactam; IMR, imipenem-relebactam; CZA, ceftazidime-avibactam. CLSI susceptibility breakpoints are indicated by dashed lines.
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