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James A Karlowsky

Publications and source records attributed to James A Karlowsky.

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Characterization of ertapenem-resistant Enterobacterales in Canadian hospitals: 17 years of the CANWARD study (2007-23).

OBJECTIVES: To review phenotypic and genotypic characteristics of ertapenem-resistant Enterobacterales isolates identified by the CANWARD study from 2007 to 2023. METHODS: Bacterial isolates were collected as part of the CANWARD surveillance study from 2007 to 2023. CLSI M7 broth microdilution antimicrobial susceptibility testing (12th edition, 2024) was performed. MICs were interpreted by CLSI M100 breakpoints (34th edition, 2024). WGS was performed to identify antimicrobial resistance markers. RESULTS: Only 134 (0.7%) of the 19 642 Enterobacterales were ertapenem-resistant. Carbapenemase producing Enterobacterales (CPE) accounted for 17.9% (n = 24) of ertapenem-resistant isolates and were predominantly Klebsiella pneumoniae (54.2%) and Escherichia coli (20.8%). KPC was the most common carbapenemase identified (62.5%). K. pneumoniae ST834, ST16 and ST258, and E. coli ST131 were the most frequent STs detected. CPE percent resistant values ranged from 20.8% to 25.0% for ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam. Most non-CPE ertapenem-resistant isolates were Enterobacter spp. (51.8%), E. coli (15.5%) and K. pneumoniae (10.9%). Non-CPE STs were most commonly E. cloacae ST108, ST50 and ST133, and E. coli ST131. Non-CPE percent resistant values ranged from 2.7% to 4.5% for ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam. At least one of an AmpC, an ESBL or porin alternations were observed in most non-CPE isolates. CONCLUSIONS: In Canada, ertapenem-resistant Enterobacterales remain uncommon (0.7%). CPE isolates demonstrated higher percent resistant values for multiple antimicrobial classes and harboured more antimicrobial resistance genes than non-CPE isolates. Continued monitoring for ertapenem-resistant Enterobacterales, particularly CPE, is important given their associated multidrug resistance to both established and newer agents.

Ertapenem

Characterization of carbapenem-resistant Pseudomonas aeruginosa in Canadian hospitals: 6 years of the CANWARD study (2018-23).

OBJECTIVES: Antimicrobial resistance in Pseudomonas aeruginosa is of increasing concern in Canada, leading to limited treatment options and poor clinical outcomes. Herein we characterized carbapenem-resistant P. aeruginosa identified through the Canadian national surveillance program CANWARD. METHODS: Antimicrobial susceptibility for 1725 P. aeruginosa isolates was assessed using broth microdilution and 2024 CLSI breakpoints. WGS of carbapenem-resistant isolates was used to identify STs, resistance and virulence markers. Genetic relatedness was further assessed using cgMLST for select STs. RESULTS: From 2018 to 2023, CANWARD collected 1725 P. aeruginosa isolates, of which 371 (21.5%) were carbapenem-resistant. The majority of carbapenem-resistant P. aeruginosa were isolated from respiratory specimens of male patients aged 18-65 years living in central Canada. Only 0.8% (n = 3) of the carbapenem-resistant isolates harboured a carbapenemase gene. WGS identified mutations associated with OprD dysfunction, MexAB-OprM efflux and AmpC overexpression in 73.6%, 1.1% and 4.9% of isolates, respectively. Most isolates (98.1%) harboured at least one of the following class D β-lactamase genes: OXA-2, OXA-5, OXA-10 or OXA-50-like subfamily. Wide genetic diversity was observed with 151 different STs identified. The most common STs were ST17 (4.6%), ST27 (4.6%) and high-risk clones ST235 (4.3%), ST244 (3.5%), ST253 (6.4%) and ST357 (2.7%). cgMLST clusters were identified amongst 34.9% of the high-risk clones, suggesting clonal dissemination. CONCLUSIONS: Currently, >20% of clinical isolates of P. aeruginosa in Canada are carbapenem-resistant. Genetic evidence indicates that clonal dissemination of high-risk clones is occurring in Canada. High-risk clones are virulent and often MDR. Continued surveillance of P. aeruginosa is important.

Pseudomonas aeruginosa