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Objectives: To evaluate the genotypic and ceftazidime/avibactam-susceptibility profiles amongst ceftolozane/tazobactam-non-susceptible (NS), MBL-negative Pseudomonas aeruginosa in a global surveillance programme.

Methods: Isolates were collected as part of the ERACE-PA Global Surveillance programme. Carbapenem-resistant P. aeruginosa deemed clinically relevant by the submitting laboratories were included. Broth microdilution MICs were conducted per CLSI standards to ceftolozane/tazobactam, ceftazidime/avibactam, ceftazidime and cefepime. Genotypic carbapenemases were detected using CarbaR and CarbaR NxG (research use only). Isolates negative for carbapenemases by PCR were assessed via WGS. Isolates were included in the analysis if they were ceftolozane/tazobactam-NS and lacked detection of known MBLs.

Results: Of the 807 isolates collected in the ERACE-PA programme, 126 (16%) were ceftolozane/tazobactam-NS and lacked MBLs. Cross-resistance to ceftazidime and cefepime was common, with only 5% and 16% testing susceptible, respectively. Ceftazidime/avibactam retained in vitro activity, with 65% of isolates testing susceptible. GES was the most common enzymology, detected in 57 (45%) isolates, and 89% remained susceptible to ceftazidime/avibactam. Seven isolates harboured KPC and all tested susceptible to ceftazidime/avibactam. In the remaining 62 isolates, WGS revealed various ESBLs or OXA β-lactamases. While 39% remained susceptible to ceftazidime/avibactam, marked variability was observed among the diverse resistance mechanisms.

Conclusions: Ceftazidime/avibactam remained active in vitro against the majority of ceftolozane/tazobactam-NS, MBL-negative P. aeruginosa. Ceftazidime/avibactam was highly active against isolates harbouring GES and KPC β-lactamases. These data highlight the potential clinical utility of genotypic profiling as well as the need to test multiple novel agents when carbapenem-resistant P. aeruginosa are encountered.

Titel:	Phenotypic and genotypic profile of ceftolozane/tazobactam-non-susceptible, carbapenem-resistant Pseudomonas aeruginosa.
Autor/in / Beteiligte Person:	Gill, CM ; Nicolau, DP
Link:	Zum Volltext
Zeitschrift:	The Journal of antimicrobial chemotherapy, Jg. 78 (2022-12-23), Heft 1, S. 252-256
Veröffentlichung:	1997- : London : Oxford University Press ; <i>Original Publication</i>: London, New York, Academic Press., 2022
Medientyp:	academicJournal
ISSN:	1460-2091 (electronic)
DOI:	10.1093/jac/dkac385
Schlagwort:	Humans Pseudomonas aeruginosa genetics Anti-Bacterial Agents pharmacology Cefepime Cephalosporins pharmacology Tazobactam pharmacology Azabicyclo Compounds pharmacology beta-Lactamases genetics Drug Combinations Carbapenems pharmacology Microbial Sensitivity Tests Ceftazidime pharmacology Pseudomonas Infections
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Corporate Authors: ERACE-PA Global Study Group Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [J Antimicrob Chemother] 2022 Dec 23; Vol. 78 (1), pp. 252-256. MeSH Terms: Ceftazidime* / pharmacology ; Pseudomonas Infections* ; Humans ; Pseudomonas aeruginosa / genetics ; Anti-Bacterial Agents / pharmacology ; Cefepime ; Cephalosporins / pharmacology ; Tazobactam / pharmacology ; Azabicyclo Compounds / pharmacology ; beta-Lactamases / genetics ; Drug Combinations ; Carbapenems / pharmacology ; Microbial Sensitivity Tests References: Antimicrob Agents Chemother. 2014 Jun;58(6):3091-9. (PMID: 24637685) ; Curr Drug Targets. 2016;17(9):1006-28. (PMID: 26960341) ; Antimicrob Agents Chemother. 2022 Mar 15;66(3):e0216121. (PMID: 35007130) ; Clin Microbiol Infect. 2021 Nov;27(11):1631-1637. (PMID: 34015532) ; J Antimicrob Chemother. 2022 Sep 30;77(10):2803-2808. (PMID: 35848936) ; Clin Infect Dis. 2021 Apr 8;72(7):1109-1116. (PMID: 33830222) ; J Clin Microbiol. 2020 May 26;58(6):. (PMID: 32238433) ; mSphere. 2021 Jan 27;6(1):. (PMID: 33504661) ; Eur J Clin Microbiol Infect Dis. 2021 Dec;40(12):2533-2541. (PMID: 34291323) ; J Clin Microbiol. 2017 Dec 26;56(1):. (PMID: 29070655) ; J Antimicrob Chemother. 2019 Jul 1;74(7):1934-1939. (PMID: 31225611) ; Antimicrob Agents Chemother. 2022 May 17;66(5):e0018922. (PMID: 35491836) ; FEMS Microbiol Lett. 2017 Oct 2;364(18):. (PMID: 28922838) ; J Antimicrob Chemother. 2021 Mar 12;76(4):836-864. (PMID: 33382875) ; Emerg Microbes Infect. 2022 Dec;11(1):811-814. (PMID: 35240944) ; J Clin Microbiol. 2020 Nov 18;58(12):. (PMID: 33115845) ; Antimicrob Agents Chemother. 2021 Aug 17;65(9):e0098621. (PMID: 34125593) Contributed Indexing: Investigator: E Aktas; W Alfouzan; L Bourassa; A Brink; CD Burnham; R Canton; Y Carmeli; M Falcone; C Kiffer; A Marchese; O Martinez; S Pournaras; M Satlin; H Seifert; AK Thabit; KS Thomson; MV Villegas; J Wille; TTF Rezende; Z Cekin; G Malkocoglu; D Gijón; LA Tarakmeh; CY Chu; CJ Opperman; HD Tootla; C Moodley; J Coetzee; S Vourli; G Dimopoulos; DM Attallah; G Tiseo; A Leonildi; C Giordano; S Barnini; F Menichetti; V Di Pilato; G Codda; A Vena; DR Giacobbe; L Westblade; A Cardona; L Curtis; F Fang; G Thomson Substance Nomenclature: 37A4IES95Q (ceftolozane) ; 9M416Z9QNR (Ceftazidime) ; 7352665165 (avibactam) ; 0 (Anti-Bacterial Agents) ; 807PW4VQE3 (Cefepime) ; 0 (Cephalosporins) ; 0 (ceftolozane, tazobactam drug combination) ; SE10G96M8W (Tazobactam) ; 0 (Azabicyclo Compounds) ; EC 3.5.2.6 (beta-Lactamases) ; 0 (Drug Combinations) ; 0 (Carbapenems) Entry Date(s): Date Created: 20221121 Date Completed: 20221226 Latest Revision: 20240227 Update Code: 20240227 PubMed Central ID: PMC9780534

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Phenotypic and genotypic profile of ceftolozane/tazobactam-non-susceptible, carbapenem-resistant Pseudomonas aeruginosa.