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However, CZA-resistant\n                      <jats:italic toggle=\"yes\">K. pneumoniae<\/jats:italic>\n                      strains have been identified, often linked to substitutions and\/or insertions\/deletions in three different loops of KPC: (i) the \u03a9-loop region (amino acids 164\u2013179), (ii) the 237\u2013243 loop; and (iii) the 266\u2013275 loop. This study investigates the impact of the double deletion \u0394G242-T243 present in KPC-14. Our results demonstrate that the lower effectiveness of CZA against KPC-14 can be explained by both increased hydrolysis of ceftazidime and a lower affinity and acylation rate by avibactam. In contrast, the IMR combination was efficient in restoring susceptibility to the KPC-14 producing-clone. Although we also observed a lower affinity and acylation rate for relebactam in KPC-14, this reduction in affinity was accompanied by a loss in the carbapenemase activity, finally resulting in an IMR susceptibility phenotype for KPC-14. Expansion of the substrate profile of KPC-14 toward ceftazidime is associated with a trade-off for carbapenems, other penicillins, and cephalosporins, as well as a higher inhibition by clavulanic acid compared to KPC-2. This study provides a better understanding of how deletions in the 237\u2013243 loop affect the effectiveness of novel DBO-combinations and supports the hypothesis that these mutations result in CZA resistance by other different biochemical mechanisms than mutations in the \u03a9-loop.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01915-24","type":"journal-article","created":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T11:05:03Z","timestamp":1746443103000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":6,"title":["Impact of the double deletion \u0394G242-T243 in KPC-2 in the effectiveness of ceftazidime-avibactam and imipenem-relebactam"],"prefix":"10.1128","volume":"69","author":[{"given":"Florencia","family":"Brunetti","sequence":"first","affiliation":[{"name":"Universidad de Buenos Aires, Instituto de Investigaciones en Bacteriolog\u00eda y Virolog\u00eda Molecular 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