{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:13:27Z","timestamp":1785413607476,"version":"3.56.0"},"reference-count":39,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["NIH R01AI146241"],"award-info":[{"award-number":["NIH R01AI146241"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI170889"],"award-info":[{"award-number":["R01AI170889"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007197","name":"U.S. Public Health Service","doi-asserted-by":"publisher","award":["SC3GM125556"],"award-info":[{"award-number":["SC3GM125556"]}],"id":[{"id":"10.13039\/100007197","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2026,3,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Achromobacter xylosoxidans<\/jats:italic>\n                      harbors robust intrinsic and acquired resistance mechanisms and is responsible for severe nosocomial infections in high-risk individuals. Here, we investigated the effectiveness of \u03b2-lactam antibiotic combinations against three sequentially collected\n                      <jats:italic toggle=\"yes\">A. xylosoxidans<\/jats:italic>\n                      isolates from a pediatric patient with chronic myeloid leukemia, which were previously genotyped and sequenced to assess and characterize the evolution of resistance. The time course killing activity from\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      static concentration time-kill (SCTK) assays and genomics of these longitudinally collected isolates guided the development of an\n                      <jats:italic toggle=\"yes\">in silico<\/jats:italic>\n                      mechanistic pharmacokinetic\/pharmacodynamic (PK\/PD) model. As previously described, the sequentially collected\n                      <jats:italic toggle=\"yes\">A. xylosoxidans<\/jats:italic>\n                      isolates developed resistance to meropenem and ceftazidime\/avibactam during treatment, along with reduced susceptibility to cefiderocol, driven by the acquisition of \u03b2-lactamase genes, point mutations, and increased \u03b2-lactamase expression. Building on these findings, SCTK assays showed that the combination of ceftazidime\/avibactam and cefiderocol achieved \u22652-log reductions in bacterial colony-forming units. The PK\/PD model included two bacterial subpopulations, one resistant to ceftazidime but susceptible to cefiderocol and another resistant to both. Avibactam\u2019s mechanistic synergy restored ceftazidime activity. However, the acquisition of resistance genes and mutations led to a 14-fold and 1.5-fold reduction in susceptibility to ceftazidime\/avibactam and cefiderocol, respectively. Simulations with the developed model at clinical exposures revealed that this combination had bactericidal activity, and the infusion duration was a critical driver of efficacy. These findings underscore the therapeutic promise of combining ceftazidime\/avibactam with cefiderocol for managing complex\n                      <jats:italic toggle=\"yes\">A. xylosoxidans<\/jats:italic>\n                      bacteremia and highlight the potential of integrated mechanism-based modeling to guide treatment strategies in resistant infections.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01263-25","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T13:00:36Z","timestamp":1769432436000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["A genomics-informed mechanism-based pharmacokinetic\/pharmacodynamic model of cefiderocol and ceftazidime\/avibactam against carbapenem-resistant\n                    <i>Achromobacter xylosoxidans<\/i>"],"prefix":"10.1128","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7784-0241","authenticated-orcid":false,"given":"Bhavatharini","family":"Arun","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03taz7m60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Clinical Pharmacy, USC Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California","place":["Los Angeles, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajnikant","family":"Sharma","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03taz7m60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Clinical Pharmacy, USC Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California","place":["Los Angeles, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quentin","family":"Vall\u00e9","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03taz7m60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Clinical Pharmacy, USC Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California","place":["Los Angeles, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ngoc Minh","family":"Bui","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03taz7m60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Clinical Pharmacy, USC Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California","place":["Los Angeles, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Furtado","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02avqqw26","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biological Science, Center for Applied Biotechnology Studies, College of Natural Sciences and Mathematics, California State University Fullerton","place":["Fullerton, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9904-7890","authenticated-orcid":true,"given":"Mar\u00eda Soledad","family":"Ramirez","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02avqqw26","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biological Science, Center for Applied Biotechnology Studies, College of Natural Sciences and Mathematics, California State University Fullerton","place":["Fullerton, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8704-7770","authenticated-orcid":true,"given":"Gauri","family":"Rao","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03taz7m60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Clinical Pharmacy, USC Alfred E. 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