{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:00:04Z","timestamp":1785416404577,"version":"3.56.0"},"reference-count":44,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2026,6,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Carbapenems, often regarded as the last line of defense in treatment of urinary tract infections and urosepsis caused by\n                      <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                      , are under pressure from emerging resistance. Thus, it is necessary to investigate carbapenem-sparing agents to mitigate the dissemination of carbapenem resistance. In this study, we aimed to evaluate the efficacy of ceftazidime\/avibactam plus amikacin combination therapy against two ceftazidime\/avibactam-resistant\n                      <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                      clinical isolates harboring IMP-4 carbapenemase (CTAP #226 and CTAP #233). To achieve this, we used a hollow fiber infection model (HFIM) with clinically relevant regimens of amikacin (15 mg\/kg q24h) and ceftazidime\/avibactam (2 g ceftazidime\/0.5 g avibactam q8h), which were administered to the HFIM either alone or in combination over a 7-day treatment course. Initial inoculum was ~1 \u00d7 10\n                      <jats:sup>7<\/jats:sup>\n                      CFU\/mL. Both amikacin and ceftazidime\/avibactam monotherapies resulted in bacterial killing (~4 log\n                      <jats:sub>10<\/jats:sub>\n                      and ~3 log\n                      <jats:sub>10<\/jats:sub>\n                      , respectively) within the first 8 h; however, regrowth surpassing the baseline was observed over the following 7 days. Conversely, combination therapy resulted in bacterial killing to &lt;the limit of quantification (10\n                      <jats:sup>2<\/jats:sup>\n                      CFU\/mL) within the first 48 h, which was sustained for the entirety of the experiment. This study showed that the combination of amikacin and ceftazidime\/avibactam was superior to both monotherapies and therefore presents a promising carbapenem-sparing option for the treatment of ceftazidime\/avibactam-resistant\n                      <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                      . Further clinical studies are required to assess the suitability for use\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01377-25","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T14:11:12Z","timestamp":1778076672000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Evaluating the efficacy of ceftazidime\/avibactam plus amikacin combination therapy as a carbapenem-sparing agent against ceftazidime\/avibactam-resistant\n                    <i>Escherichia coli<\/i>\n                    using a hollow fiber infection model: a proof-of-concept study"],"prefix":"10.1128","volume":"70","author":[{"given":"Mikaela 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