{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:36:23Z","timestamp":1790876183646,"version":"4.1.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2024,12,19]],"date-time":"2024-12-19T00:00:00Z","timestamp":1734566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To evaluate the in vitro activity of ceftazidime\/avibactam, meropenem\/vaborbactam, imipenem\/relebactam and comparators against KPC-producing Klebsiella pneumoniae (KPC-Kp) clinical isolates collected from a multicentre study in Italy (2022\u201323) and genomic characterization of the molecular mechanisms causing resistance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Consecutive KPC-Kp isolates from blood cultures (n\u200a=\u200a264) were collected from 14 hospital centres in the period 2022\u201323. Antimicrobial susceptibility testing was performed using broth microdilution. WGS was used to investigate KPC-Kp strains resistant to the new approved \u03b2-lactam\/\u03b2-lactam inhibitor combinations (BLICs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Overall, meropenem\/vaborbactam (95.1% susceptible by EUCAST and 93.9% susceptible by CLSI; MIC50\u200a=\u200a0.5\u2005mg\/L; MIC90\u200a=\u200a4\u2005mg\/L) and imipenem\/relebactam (97% susceptible by EUCAST and 92.8% susceptible by CLSI; MIC50\u200a=\u200a0.25\u2005mg\/L; MIC90\u200a=\u200a0.5\u2005mg\/L) showed similar activity, followed by ceftazidime\/avibactam (93.9% susceptible by both EUCAST and CLSI; MIC50\u200a=\u200a2\u2005mg\/L; MIC90\u200a=\u200a8\u2005mg\/L). Ten out of 13 (76.9%) KPC-Kp resistant to ceftazidime\/avibactam carried a blaKPC variant including blaKPC-31, blaKPC-205, blaKPC-203 and blaKPC-93. Among KPC-Kp resistant to meropenem\/vaborbactam and imipenem\/relebactam, 90.9% (10\/11) and 80% (4\/5) harboured a WT carbapenemase (i.e. blaKPC-2 or blaKPC-3), respectively. All strains resistant to meropenem\/vaborbactam and\/or imipenem\/relebactam carried truncated OmpK35 and\/or mutated (ins135GD) OmpK36.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>New BLICs were shown to be the most widely active therapeutic option against KPC-Kp clinical isolates collected in Italy. Ceftazidime\/avibactam resistance is mainly driven by the expression of KPC variants, whereas the loss of function of the OmpK35 and OmpK36 porins appears to play a key but not exclusive role in the development of meropenem\/vaborbactam and\/or imipenem\/relebactam resistance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkae450","type":"journal-article","created":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T15:31:36Z","timestamp":1733758296000},"page":"583-592","source":"Crossref","is-referenced-by-count":26,"title":["<i>In vitro<\/i>\n                    activity and genomic characterization of KPC-producing\n                    <i>Klebsiella pneumoniae<\/i>\n                    clinical blood culture isolates resistant to ceftazidime\/avibactam, meropenem\/vaborbactam, imipenem\/relebactam: an Italian nationwide multicentre observational study (2022\u201323)"],"prefix":"10.1093","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8180-5075","authenticated-orcid":false,"given":"Gabriele","family":"Bianco","sequence":"first","affiliation":[{"name":"Department of Experimental Medicine, University of Salento , Lecce ,","place":["Italy"]},{"name":"Microbiology and Virology Unit, University Hospital Citt\u00e0 della Salute e della Scienza di Torino , Turin ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6726-2716","authenticated-orcid":false,"given":"Matteo","family":"Boattini","sequence":"additional","affiliation":[{"name":"Microbiology and Virology Unit, University Hospital Citt\u00e0 della Salute e della Scienza di Torino , Turin ,","place":["Italy"]},{"name":"Department of Public Health and Paediatrics, University of Torino , Turin ,","place":["Italy"]},{"name":"Lisbon Academic Medical Centre , Lisbon ,","place":["Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Lupo","sequence":"additional","affiliation":[{"name":"Clinical Pathology and Microbiology Unit, Vito Fazzi Hospital , Lecce ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Ambretti","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna , Via Massarenti, 9, Bologna 40138 ,","place":["Italy"]},{"name":"Microbiology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna , Bologna 40138 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Greco","sequence":"additional","affiliation":[{"name":"U.O.C. Microbiology and Virology, A.O.R.N. Sant\u2019Anna e San Sebastiano , Caserta 81100 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Degl\u2019Innocenti","sequence":"additional","affiliation":[{"name":"U.O.S. Microbiology e Virology, Clinical Pathology Division A.O.R.N. A. Cardarelli , Naples 80131 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Chiatamone Ranieri","sequence":"additional","affiliation":[{"name":"Pathology Unit, Department of Services, AUSL 04 Teramo , Teramo 64100 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Fasciana","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo , Palermo 90127 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2729-1007","authenticated-orcid":false,"given":"Annarita","family":"Mazzariol","sequence":"additional","affiliation":[{"name":"Microbiology and Virology Unit, Department of Pathology, Azienda Ospedaliera Universitaria Integrata Di Verona , Verona ,","place":["Italy"]},{"name":"Department of Diagnostic and Public Health, Microbiology Section, University of Verona , Verona ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Gibellini","sequence":"additional","affiliation":[{"name":"Microbiology and Virology Unit, Department of Pathology, Azienda Ospedaliera Universitaria Integrata Di Verona , Verona ,","place":["Italy"]},{"name":"Department of Diagnostic and Public Health, Microbiology Section, University of Verona , Verona ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Antonelli","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Sapienza University of Rome , Rome 00161 ,","place":["Italy"]},{"name":"University Hospital Policlinico Umberto I, Sapienza University , Viale del Policlinico 155, Rome 00161 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Sacco","sequence":"additional","affiliation":[{"name":"University Hospital Policlinico Umberto I, Sapienza University , Viale del Policlinico 155, Rome 00161 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Quirino","sequence":"additional","affiliation":[{"name":"Health Sciences Department, University \u201cMagna Graecia\u201d of Catanzaro , Catanzaro 88100 ,","place":["Italy"]},{"name":"Unit of Clinical Microbiology, Department of Health Sciences, University of Catanzaro \u201cMagna Gr\u00e6cia\u201d , Catanzaro 88100 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Farina","sequence":"additional","affiliation":[{"name":"Microbiology and Virology Laboratory, ASST \u201cPapa Giovanni XXIII\u201d , Bergamo 24127 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca","family":"Paglietti","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Sassari , Sassari 07100 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Comini","sequence":"additional","affiliation":[{"name":"Department of Public Health and Paediatrics, University of Torino , Turin ,","place":["Italy"]},{"name":"Operative Unit of Clinical Pathology, Carlo Urbani Hospital , Ancona ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maura","family":"Fiamma","sequence":"additional","affiliation":[{"name":"Operative Unit of Clinical Pathology, Ospedale \u201cSan Francesco\u201d, ASSL Nuoro , Sardinia 08100 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Broccolo","sequence":"additional","affiliation":[{"name":"Department 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