{"entity": "publication", "iuid": "22579707ed15411491e1427f9cb0cef6", "timestamp": "2026-05-17T09:15:03.064Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/22579707ed15411491e1427f9cb0cef6.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/22579707ed15411491e1427f9cb0cef6"}}, "title": "Ceftazidime-avibactam tolerance and persistence among difficult-to-treat KPC-producing Klebsiella pneumoniae clinical isolates from bloodstream infections.", "authors": [{"family": "Abichabki", "given": "N", "initials": "N"}, {"family": "Gaspar", "given": "G G", "initials": "GG"}, {"family": "Bortolato", "given": "L R", "initials": "LR"}, {"family": "Lima", "given": "D A F S", "initials": "DAFS"}, {"family": "Silva", "given": "L N", "initials": "LN"}, {"family": "Pocente", "given": "R H C", "initials": "RHC"}, {"family": "Ferreira", "given": "J C", "initials": "JC"}, {"family": "Ogasawara", "given": "T C", "initials": "TC"}, {"family": "Pereira", "given": "D", "initials": "D"}, {"family": "Guerra", "given": "R R", "initials": "RR"}, {"family": "Wilhelm", "given": "C", "initials": "C"}, {"family": "Barth", "given": "P", "initials": "P"}, {"family": "Martins", "given": "A F", "initials": "AF"}, {"family": "Barth", "given": "A", "initials": "A"}, {"family": "Braga", "given": "G U L", "initials": "GUL"}, {"family": "De Martinis", "given": "E C P", "initials": "ECP"}, {"family": "Bengtsson-Palme", "given": "J", "initials": "J", "orcid": "0000-0002-6528-3158", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4c666068e9d34939b0252a627007cec7.json"}}, {"family": "Bellissimo-Rodrigues", "given": "F", "initials": "F"}, {"family": "Bollela", "given": "V R", "initials": "VR"}, {"family": "Darini", "given": "A L C", "initials": "ALC"}, {"family": "Andrade", "given": "L N", "initials": "LN"}], "type": "journal article", "published": "2025-02-00", "journal": {"title": "Eur. J. Clin. Microbiol. Infect. Dis.", "issn": "1435-4373", "volume": "44", "issue": "2", "pages": "343-353", "issn-l": "0934-9723"}, "abstract": "Tolerance and persistence occur \"silently\" in bacteria categorized as susceptible by antimicrobial susceptibility testing in clinical microbiology laboratories. They are different from resistance phenomena, not well-studied, and often remain unnoticeable. We aimed to investigate and characterize ceftazidime-avibactam (CZA) tolerance/persistence in 80 Klebsiella pneumoniae isolates from bloodstream infections.\n\nWe used the Tolerance Disk Test (TDtest) to detect CZA tolerance/persistence and investigate the avibactam (AVI) influence on them, and time-kill assays with minimal duration for killing (MDK) determination to characterize/differentiate CZA tolerance from persistence, for selected isolates. Whole genome sequencing was performed for 49/80 selected isolates to investigate genes related to beta-lactam tolerance/persistence and resistance as well as phylogeny studies.\n\nTolerance/persistence to CZA was detected in 48/80 (60%) isolates, all extensively drug-resistant (XDR) or multidrug-resistant, carbapenem-resistant K. pneumoniae (CRKp), KPC producers, and previously categorized as susceptible (not resistant) to CZA. No heteroresistance was detected. CZA tolerance/persistence occurred due to ceftazidime tolerance/persistence and was not related to AVI in the CZA combination. 5/11 isolates were characterized as CZA-tolerant and 5/11 as CZA-persistent. The single (1/11) XDR and CRKp non-KPC producer was truly susceptible. All the CZA-tolerant/persistent isolates (ST11, ST258, ST340, ST437, ST16, ST17, and ST307) harbored the carbapenemase-encoding gene blaKPC-2. Mutation in only two genes (rpoS and degQ) related to beta-lactam tolerance/persistence was found in only 7/49 CZA-tolerant/persistent isolates, suggesting the presence of yet unknown beta-lactam tolerance/persistence genes.\n\nAmong the K. pneumoniae bloodstream isolates studied, 60%, previously categorized as susceptible to CZA, were, actually, tolerant/persistent to this antibiotic, all these KPC producers.", "doi": "10.1007/s10096-024-05005-4", "pmid": "39614972", "labels": {"Johan Bengtsson-Palme": null, "DDLS Fellow": null}, "xrefs": [{"db": "pii", "key": "10.1007/s10096-024-05005-4"}], "notes": [], "created": "2025-06-04T08:15:04.773Z", "modified": "2025-11-04T14:25:28.060Z"}