{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T00:26:20Z","timestamp":1793406380920,"version":"4.5.0"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universit\u00e0 del Salento"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Infection"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>\n                      Novel \u03b2-lactam\/\u03b2-lactamase inhibitor combinations (BL\/BLICs) such as ceftazidime\/avibactam (CAZ\/AVI), meropenem\/vaborbactam (MEM\/VAB), imipenem\/relebactam (IMP\/REL) and aztreonam\/avibactam (ATM\/AVI) have expanded therapeutic choices against KPC-producing\n                      <jats:italic>K. pneumoniae<\/jats:italic>\n                      . However, emerging resistance threatens their long-term efficacy. We investigated the prevalence, genomic mechanisms, and clinical correlates of resistance to these agents among KPC-producing\n                      <jats:italic>K. pneumoniae<\/jats:italic>\n                      bloodstream isolates.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Consecutive KPC-producing\n                      <jats:italic>K. pneumoniae<\/jats:italic>\n                      bloodstream isolates collected between 2021 and 2024 at a tertiary university hospital were tested for susceptibility to novel BL\/BLICs and comparators. Whole-genome sequencing (WGS) was performed on isolates resistant to any BL\/BLIC to characterise genetic backgrounds. Clinical data from corresponding patients were analysed to explore risk factors and outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 178\u00a0K\n                      <jats:italic>. pneumoniae<\/jats:italic>\n                      isolates, ATM\/AVI, IMP\/REL and MEM\/VAB retained excellent in vitro activity (\u2265\u200996% susceptible), while 11% were resistant to CAZ\/AVI. One hundred fifty-four (86.5%) were susceptible to all BL\/BLICs, whereas 24 (13.5%) displayed resistance to at least one agent, most commonly CAZ\/AVI. WGS revealed a genetically diverse population mainly comprising high-risk clones ST512 and ST101. Resistance was driven by KPC variants (KPC-31, KPC-167, KPC-93, KPC-49, KPC-14, KPC-121, KPC-33) and porin disruptions (OmpK36 insertions, OmpK35 loss). Most patients (91%) had prior colonisation and recent \u03b2-lactam exposure; median time to resistance emergence was 47\u00a0days. The 28-day mortality among patients with BL\/BLIC-resistant infections was 21.7%.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Resistance to novel BL\/BLICs among KPC-producing\n                      <jats:italic>K. pneumoniae<\/jats:italic>\n                      is emerging in Italian hospitals, largely mediated by\n                      <jats:italic>bla<\/jats:italic>\n                      <jats:sub>KPC<\/jats:sub>\n                      variants and porin defects under selective antibiotic pressure. While ATM\/AVI, MEM\/VAB and IMP\/REL remain highly active, resistance to CAZ\/AVI is increasingly frequent. Continuous genomic surveillance and optimised antimicrobial stewardship are essential to preserve the efficacy of these last-line agents.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s15010-025-02716-4","type":"journal-article","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T18:42:41Z","timestamp":1766515361000},"page":"841-852","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Emergence of resistance to novel \u03b2-lactam\/\u03b2-lactamase inhibitor combinations in KPC-producing Klebsiella pneumoniae: clinical and genomic insights from consecutive bloodstream infections"],"prefix":"10.1007","volume":"54","author":[{"given":"Matteo","family":"Boattini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Comini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Ricciardelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Pastrone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Casale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Guarrasi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossana","family":"Cavallo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Costa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Gaibani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Bianco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,23]]},"reference":[{"key":"2716_CR1","volume-title":"Global antimicrobial resistance and use surveillance system (GLASS) report 2024","author":"World Health Organization","year":"2024","unstructured":"World Health Organization. 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