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Contemporary \u03b2-lactamase inhibitors (BLIs) such as avibactam were developed to neutralize the activity of KPCs and other clinically important carbapenemases. Ceftazidime-avibactam (CZA), a BL\/BLI combination in which the cephalosporin ceftazidime is protected from KPC-mediated hydrolysis, demonstrated improved outcomes in early clinical use. However, CZA-resistant isolates soon emerged. Herein, we describe a challenging clinical case in which high-level resistance to CZA evolved during therapy for a complicated infection caused by carbapenem-resistant\n                      <jats:italic toggle=\"yes\">Serratia marcescens<\/jats:italic>\n                      harboring\n                      <jats:italic toggle=\"yes\">bla<\/jats:italic>\n                      <jats:sub>KPC-2<\/jats:sub>\n                      . Whole-genome sequencing, analysis of antibiotic resistance genes, and phenotypic susceptibility assays of serial\n                      <jats:italic toggle=\"yes\">S. marcescens<\/jats:italic>\n                      isolates revealed that resistance arose via a 45-nucleotide in-frame duplication within\n                      <jats:italic toggle=\"yes\">bla<\/jats:italic>\n                      <jats:sub>KPC-2<\/jats:sub>\n                      , yielding KPC variant 44 (\n                      <jats:italic toggle=\"yes\">bla<\/jats:italic>\n                      <jats:sub>KPC-44<\/jats:sub>\n                      ). Notably, the evolution of\n                      <jats:italic toggle=\"yes\">bla<\/jats:italic>\n                      <jats:sub>KPC-44<\/jats:sub>\n                      not only conferred resistance to CZA but also marked cross-resistance to meropenem-vaborbactam and imipenem-relebactam while remaining susceptible to cefiderocol. To our knowledge, this report represents the first description of\n                      <jats:italic toggle=\"yes\">bla<\/jats:italic>\n                      <jats:sub>KPC-44<\/jats:sub>\n                      emerging outside of\n                      <jats:italic toggle=\"yes\">K. pneumoniae<\/jats:italic>\n                      and among the few documenting a CZA-resistance-conferring KPC variant emerging in a non\n                      <jats:italic toggle=\"yes\">-K<\/jats:italic>\n                      .\n                      <jats:italic toggle=\"yes\">pneumoniae Enterobacterales<\/jats:italic>\n                      species. Ultimately, the evolved strain persisted despite therapy throughout a fatal clinical course, underscoring the potential for CZA selective pressure to drive treatment-emergent resistance to multiple contemporary BL\/BLI agents.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01651-25","type":"journal-article","created":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T14:00:22Z","timestamp":1772719222000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["<i>In vivo<\/i>\n                    evolution of resistance to contemporary \u03b2-lactam\/\u03b2-lactamase inhibitor combinations during treatment of a KPC-producing\n                    <i>Serratia marcescens<\/i>\n                    infection"],"prefix":"10.1128","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4126-8700","authenticated-orcid":true,"given":"Daniel 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