Resistance to novel β-lactam/β-lactamase inhibitors among carbapenem-resistant Pseudomonas aeruginosa and clinical implications in the prospective observational Pseudomonas study
Recommended Citation
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 ML, Munita JM, Stryjewski ME, Reyes J, Chen L, Kreiswirth BN, Hill C, Baum K, Villegas MV, Paterson DL, Bonomo RA, Chambers HF, Fowler VG, Jr., 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. Antimicrob Agents Chemother. 2026;70(6):e0038825.
Document Type
Article
Publication Date
6-3-2026
Publication Title
Antimicrobial agents and chemotherapy
Keywords
Humans, Anti-Bacterial Agents, Azabicyclo Compounds, beta-Lactamase Inhibitors, beta-Lactamases, Carbapenems, Ceftazidime, Drug Combinations, Imipenem, Microbial Sensitivity Tests, Prospective Studies, Pseudomonas aeruginosa, Pseudomonas Infections, Tazobactam, Third Generation Cephalosporins, Cephalosporins
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.
Medical Subject Headings
Humans; Anti-Bacterial Agents; Azabicyclo Compounds; beta-Lactamase Inhibitors; beta-Lactamases; Carbapenems; Ceftazidime; Drug Combinations; Imipenem; Microbial Sensitivity Tests; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas Infections; Tazobactam; Third Generation Cephalosporins; Cephalosporins
PubMed ID
42138639
Volume
70
Issue
6
First Page
0038825
Last Page
0038825
