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Clinical-microbiological investigation and characterization of longitudinal strains by Whole-Genome Sequencing were performed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Four patients with KPC-Kp bloodstream infections were included. Most frequent clinical features were kidney disease, obesity, cardiac surgery as reason for admission, ICU stay, treatment with ceftazidime\/avibactam, and pneumonia and\/or acute kidney injury needing renal replacement therapy as KPC-Kp sepsis-associated complications. The development of resistance to ceftazidime\/avibactam was observed in four longitudinal strains (three of which were co-resistant to aztreonam\/avibactam and cefiderocol) following treatments with ceftazidime\/avibactam (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20093) or cefiderocol (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091). Resistance to meropenem\/vaborbactam and imipenem\/cilastatin\/relebactam was observed in one case after exposure to ceftazidime\/avibactam and imipenem\/cilastatin\/relebactam. Resistome analysis showed that resistance to novel \u03b2L\/\u03b2LICs was related to specific mutations within\n                      <jats:italic>bla<\/jats:italic>\n                      <jats:sub>KPC<\/jats:sub>\n                      carbapenemase gene (D179Y mutation [KPC-33]; deletion \u0394242-GT-243 [KPC-14]) in three longitudinal strains, while porin loss (truncated OmpK35 and OmpK36 porins) was observed in one case.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Therapy with novel \u03b2L\/\u03b2LICs or cefiderocol may lead to the selection of resistant mutants in the presence of factors influencing the achievement of PK\/PD targets. KPC variants are mainly associated with resistance to ceftazidime\/avibactam, and some of them (e.g. KPC-14) may also be associated with reduced susceptibility to aztreonam\/avibactam and\/or cefiderocol. Loss of function of the OmpK35 and OmpK36 porins appears to play a role in the development of resistance to meropenem\/vaborbactam and\/or imipenem\/relebactam, but other mechanisms may also be involved.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10096-024-04958-w","type":"journal-article","created":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T23:41:06Z","timestamp":1728517266000},"page":"2407-2417","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["In vivo development of resistance to novel \u03b2-lactam\/\u03b2-lactamase inhibitor combinations in KPC-producing Klebsiella pneumoniae infections: a case series"],"prefix":"10.1007","volume":"43","author":[{"given":"Matteo","family":"Boattini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Bianco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Comini","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"}]}],"member":"297","published-online":{"date-parts":[[2024,10,10]]},"reference":[{"issue":"4","key":"4958_CR1","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1128\/CMR.05035-11","volume":"25","author":"LS Tzouvelekis","year":"2012","unstructured":"Tzouvelekis LS, Markogiannakis A, Psichogiou M, Tassios PT, Daikos GL (2012) Carbapenemases in Klebsiella pneumoniae and other Enterobacteriaceae: an evolving crisis of global dimensions. 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