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  5. Resistance to novel β-lactam/β-lactamase inhibitors among carbapenem-resistant Pseudomonas aeruginosa and clinical implications in the prospective observational Pseudomonas study

Resistance to novel β-lactam/β-lactamase inhibitors among carbapenem-resistant Pseudomonas aeruginosa and clinical implications in the prospective observational Pseudomonas study

File(s)
42138639.pdf (1.16 MB)
Permanent Link(s)
https://hdl.handle.net/1813/128187
Collections
Department of Medicine
Author
Gottesdiener, Lee S.
Li, Yixuan
Greenwood-Quaintance, Kerryl E.
Komarow, Lauren
Arias, Cesar A.
Cober, Eric
Herc, Erica S.
Kaye, Keith S.
Huskins, W Charles
Figueroa, Jairo
Vilchez, Samuel
Fries, Bettina C.
Leroi, Marcel
McCarty, Todd P.
Rioseco, María L.
Munita, Jose M.
Stryjewski, Martin E.
Reyes, Jinnethe
Chen, Liang
Kreiswirth, Barry N.
Hill, Carol
Baum, Keri
Villegas, Maria Virginia
Paterson, David L.
Bonomo, Robert A.
Chambers, Henry F.
Fowler, Vance G.
Patel, Robin
Doi, Yohei
van Duin, David
Satlin, Michael J.
Abstract

Novel β-lactam/β-lactamase inhibitors (βL/βLIs) are important therapies for carbapenem-resistant Pseudomonas aeruginosa (CRPA). However, the global extent of resistance to these agents and the impact of resistance on patient outcomes are unclear. We therefore evaluated patients with CRPA isolates at 35 hospitals (nine countries) from December 2018 to November 2019. Antimicrobial susceptibility testing was performed at a central laboratory by agar dilution for ceftolozane-tazobactam (C/T) and ceftazidime-avibactam (CZA) and by broth microdilution for imipenem-relebactam (I/R). Characteristics and outcomes, including desirability of outcome rankings (DOOR), were compared between patients infected with isolates not susceptible vs susceptible to each agent. Of 800 CRPA isolates, susceptibility to C/T, CZA, and I/R was 69%, 67%, and 33%, respectively. USA isolates (n = 526) were more frequently susceptible to these agents than isolates from other countries (n = 274; C/T: 83% vs 42%; CZA: 77% vs 47%; I/R: 37% vs 23%; P < 0.001 for each comparison) and isolates with carbapenemases (n = 157) were less frequently susceptible than isolates without carbapenemases (n = 643; C/T: 7% vs 84%; CZA: 24% vs 77%; I/R: 6% vs 39%; P < 0.001 for each comparison). Thirty-day mortality and DOOR were similar overall in patients infected with isolates not susceptible vs susceptible to each βL/βLI. However, the adjusted probability of a better DOOR outcome for a randomly selected patient with bacteremia due to a C/T-not susceptible vs -susceptible isolate was 38.2% (95% confidence interval, 25.6%-52.7%). Resistance to novel βL/βLIs, especially I/R, is common in CRPA, particularly outside the USA and in carbapenemase-producing isolates. Additional treatment options are needed for CRPA infections.

Journal / Series
Antimicrobial agents and chemotherapy
Volume & Issue
70(6)
Date Issued
2026-05-15
Publisher
American Society for Microbiology
Keywords
WCM Library Coordinated Deposit
•
Humans
•
Anti-Bacterial Agents/pharmacology/therapeutic use
•
Azabicyclo Compounds/pharmacology
•
beta-Lactamase Inhibitors/pharmacology/therapeutic use
•
beta-Lactamases/metabolism
•
Carbapenems/pharmacology
•
Ceftazidime/pharmacology/therapeutic use
•
Drug Combinations
•
Imipenem/pharmacology
•
Microbial Sensitivity Tests
•
Prospective Studies
•
Pseudomonas aeruginosa/drug effects/isolation & purification
•
Pseudomonas Infections/drug therapy/microbiology
•
Tazobactam/pharmacology
•
Third Generation Cephalosporins/pharmacology/therapeutic use
•
Cephalosporins
•
Pseudomonas aeruginosa
•
carbapenem resistance
•
ceftazidime-avibactam
•
ceftolozane-tazobactam
•
imipenem-relebactam
Related DOI
https://doi.org/10.1128/aac.00388-25
Previously Published as
Gottesdiener LS, Li Y, Greenwood-Quaintance KE, Komarow L, Arias CA, Cober E, Herc ES, Kaye KS, Huskins WC, Figueroa J, Vilchez S, Fries BC, Leroi M, McCarty TP, Rioseco MíL, Munita JM, Stryjewski ME, Reyes J, Chen L, Kreiswirth BN, Hill C, Baum K, Villegas MV, Paterson DL, Bonomo RA, Chambers HF, Fowler VG, Patel R, Doi Y, van Duin D, Satlin MJ. Resistance to novel β-lactam/β-lactamase inhibitors among carbapenem-resistant Pseudomonas aeruginosa and clinical implications in the prospective observational Pseudomonas study. Antimicrobial agents and chemotherapy. 2026;70(6):e0038825. doi: 10.1128/aac.00388-25. PMID: 42138639.
Rights
Attribution 4.0 International
Rights URI
https://creativecommons.org/licenses/by/4.0/
Type
article

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