Resistance to ceftazidime-avibactam and other new β-lactams in Pseudomonas aeruginosa clinical isolates: a multi-center surveillance study.

Autor:	Valzano F; Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy., La Bella G; Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.; Istituto Zooprofilattico Sperimentale della Puglia e della Basilicata, Foggia, Italy., Lopizzo T; Clinical Pathology and Microbiology Unit, AOR San Carlo, Potenza, Italy., Curci A; Clinical Pathology and Microbiology Unit, AOR San Carlo, Potenza, Italy., Lupo L; Clinical Pathology and Microbiology Unit, Vito Fazzi Hospital, Lecce, Italy., Morelli E; Clinical Pathology Unit, SS Annunziata Hospital, Taranto, Italy., Mosca A; Department of Interdisciplinary Medicine, Microbiology Section, University of Bari Aldo Moro, Bari, Italy., Marangi M; Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy., Melfitano R; Microbiology and Virology Unit, AOU Policlinico Riuniti, Foggia, Italy., Rollo T; Microbiology and Virology Unit, AOU Policlinico Riuniti, Foggia, Italy., De Nittis R; Microbiology and Virology Unit, AOU Policlinico Riuniti, Foggia, Italy., Arena F; Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.; Microbiology and Virology Unit, AOU Policlinico Riuniti, Foggia, Italy.; IRCCS Fondazione Don Carlo Gnocchi ONLUS, Florence, Italy.
Jazyk:	angličtina
Zdroj:	Microbiology spectrum [Microbiol Spectr] 2024 Aug 06; Vol. 12 (8), pp. e0426623. Date of Electronic Publication: 2024 Jun 27.
DOI:	10.1128/spectrum.04266-23
Abstrakt:	New β-lactam-β-lactamase inhibitor combinations represent last-resort antibiotics to treat infections caused by multidrug-resistant Pseudomonas aeruginosa . Carbapenemase gene acquisition can limit their spectrum of activity, and reports of resistance toward these new molecules are increasing. In this multi-center study, we evaluated the prevalence of resistance to ceftazidime-avibactam (CZA) and comparators among P. aeruginosa clinical isolates from bloodstream infections, hospital-acquired or ventilator-associated pneumonia, and urinary tract infections, circulating in Southern Italy. We also investigated the clonality and content of relevant β-lactam resistance mechanisms of CZA-resistant (CZA R ) isolates. A total of 120 P . aeruginosa isolates were collected. CZA was among the most active β-lactams, retaining susceptibility in the 81.7% of cases, preceded by cefiderocol (95.8%) and followed by ceftolozane-tazobactam (79.2%), meropenem-vaborbactam (76.1%), imipenem-relebactam (75%), and aztreonam (69.6%). Among non-β-lactams, colistin and amikacin were active against 100% and 85.8% of isolates respectively. In CZA R strains subjected to whole-genome sequencing ( n = 18), resistance was mainly due to the expression of metallo-β-lactamases (66.6% VIM-type and 5.5% FIM-1), followed by PER-1 (16.6%) and GES-1 (5.5%) extended-spectrum β-lactamases, mostly carried by international high-risk clones (ST111 and ST235). Of note, two strains producing the PER-1 enzyme were resistant to all β-lactams, including cefiderocol. In conclusion, the CZA resistance rate among P. aeruginosa clinical isolates in Southern Italy remained low. CZA R isolates were mostly metallo-β-lactamases producers and belonging to ST111 and ST253 epidemic clones. It is important to implement robust surveillance systems to monitor emergence of new resistance mechanisms and to limit the spread of P. aeruginosa high-risk clones. Importance: Multidrug-resistant Pseudomonas aeruginosa infections are a growing threat due to the limited therapeutic options available. Ceftazidime-avibactam (CZA) is among the last-resort antibiotics for the treatment of difficult-to-treat P. aeruginosa infections, although resistance due to the acquisition of transferable β-lactamase genes is increasing. With this work, we report that CZA represents a highly active antipseudomonal β-lactam compound (after cefiderocol), and that metallo-β-lactamases (VIM-type) and extended-spectrum β-lactamases (GES and PER-type) production is the major factor underlying CZA resistance in isolates from Southern Italian hospitals. In addition, we reported that such resistance mechanisms were mainly carried by the international high-risk clones ST111 and ST235. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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