{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T11:53:46Z","timestamp":1753876426429,"version":"3.41.2"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T00:00:00Z","timestamp":1750204800000},"content-version":"vor","delay-in-days":50,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["2020-02320"],"award-info":[{"award-number":["2020-02320"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Sweden\u2019s Innovation Agency VINNOVA","award":["2021-02699"],"award-info":[{"award-number":["2021-02699"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Ceftazidime\/avibactam is used for severe infections caused by carbapenemase-producing Klebsiella pneumoniae. Combination therapy with older antibiotics is frequently used, but the supporting data are limited. This study aimed to evaluate ceftazidime\/avibactam in combination with colistin against KPC-2-producing K. pneumoniae.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Material and methods<\/jats:title>\n                  <jats:p>Five clinical KPC-2-producing K. pneumoniae strains were characterized by phenotypic antibiotic susceptibility testing and whole-genome sequencing. Single antibiotics and combinations were evaluated in 24-h static time-kill experiments with ceftazidime\/avibactam concentrations of 0.5\u00d7 MICratio and colistin at 0.5\u00d7 and 1\u00d7 MIC. One strain was subjected to 32-h dynamic time-kill experiments with ceftazidime\/avibactam at concentrations mimicking patient pharmacokinetics in plasma and colistin added to 1\u2005mg\/L, i.e. the average free steady-state concentration. Population analysis was performed at 0, 16, and 32\u2005h by plating at 4\u00d7 and 8\u00d7 MICratio (ceftazidime\/avibactam) or MIC (colistin) to assess resistance development.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>All strains were susceptible to ceftazidime\/avibactam and colistin, had mutations in ompK35 and ompK36, and carried multiple \u03b2-lactamase genes. Ceftazidime\/avibactam combined with colistin demonstrated 24-h synergy in static time-kill experiments against 3 of 5 strains. Although ceftazidime\/avibactam and colistin alone showed rapid initial killing in the dynamic experiments, regrowth occurred after 4\u20138\u2005h. The three-drug combination displayed a bactericidal effect and synergy at 14\u201332\u2005h. Resistance development resulting in 64-fold MIC increases was observed in experiments with colistin alone.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This study showed synergy with ceftazidime\/avibactam and colistin against KPC-2-producing K. pneumoniae at clinically relevant concentrations. More studies are warranted to investigate the clinical potential of this combination.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jacamr\/dlaf105","type":"journal-article","created":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T13:18:29Z","timestamp":1751030309000},"source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of ceftazidime\/avibactam in combination with colistin against KPC-2-producing <i>Klebsiella pneumoniae<\/i> in static and dynamic time-kill experiments"],"prefix":"10.1093","volume":"7","author":[{"given":"Lisa","family":"Allander","sequence":"first","affiliation":[{"name":"Department of Medical Sciences, Uppsala University , Uppsala ,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma","family":"Vikdahl","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Uppsala University , Uppsala 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