{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T17:51:27Z","timestamp":1792950687946,"version":"4.5.0"},"reference-count":46,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T00:00:00Z","timestamp":1739404800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T00:00:00Z","timestamp":1739404800000},"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":[[2025,2,13]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              The combination of aztreonam (ATM) and avibactam (AVI) is an attractive option to treat infections caused by extended spectrum \u03b2-lactamase plus NDM-1-producing\n              <jats:italic>Enterobacteriaceae<\/jats:italic>\n              . Since ATM activity was shown to be severely impacted by an increase in the inoculum size\n              <jats:italic>in vitro<\/jats:italic>\n              , we wondered whether ATM-AVI activity could be impaired in high-inoculum infections. We analyzed the impact of the inoculum size on ATM-AVI activity\n              <jats:italic>in vitro<\/jats:italic>\n              and in a murine model of peritonitis due to susceptible\n              <jats:italic>Escherichia coli<\/jats:italic>\n              CFT073-pTOPO and its isogenic derivatives producing NDM-1 (\n              <jats:italic>E. coli<\/jats:italic>\n              CFT073-NDM1) and CTX-M-15 plus NDM-1 (\n              <jats:italic>E. coli<\/jats:italic>\n              CFT073-CTXM15-NDM1). The impact of the inoculum size on bacterial morphology was studied by microscopic examination.\n              <jats:italic>In vitro<\/jats:italic>\n              , at standard (10\n              <jats:sup>5<\/jats:sup>\n              ) inoculum,\n              <jats:italic>E. coli<\/jats:italic>\n              CFT073-CTXM15-NDM1 was resistant to ATM but susceptible to the ATM-AVI combination. At high (10\n              <jats:sup>7<\/jats:sup>\n              ) inoculum, MICs of ATM alone and of the ATM-AVI combination reached &gt;512 and 64 mg\/L, respectively, against all tested strains. ATM led to bacterial filamentation when active against the bacteria, i.e., in monotherapy or in combination with AVI against susceptible\n              <jats:italic>E. coli<\/jats:italic>\n              CFT073-pTOPO and only in combination with AVI against\n              <jats:italic>E. coli<\/jats:italic>\n              CFT073-CTXM15-NDM1.\n              <jats:italic>In vivo<\/jats:italic>\n              , increase in the inoculum led to a drastic decrease in the activity of ATM alone against\n              <jats:italic>E. coli<\/jats:italic>\n              CFT073-pTOPO and ATM-AVI against\n              <jats:italic>E. coli<\/jats:italic>\n              CFT073-CTXM15-NDM1. Our results suggest a high\n              <jats:italic>in vivo<\/jats:italic>\n              impact of the inoculum increase on the activity of ATM alone against ATM-susceptible\n              <jats:italic>E. coli<\/jats:italic>\n              and of ATM-AVI against CTX-M-15 plus NDM-1 producing\n              <jats:italic>E. coli<\/jats:italic>\n              . Clinicians must be aware of the risk of failures when using ATM-AVI in high-inoculum infections.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.01288-22","type":"journal-article","created":{"date-parts":[[2024,12,19]],"date-time":"2024-12-19T14:06:19Z","timestamp":1734617179000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["Impact of the inoculum size on the\n            <i>in vivo<\/i>\n            activity of the aztreonam-avibactam combination in a murine model of peritonitis due to\n            <i>Escherichia coli<\/i>\n            expressing CTX-M-15 and NDM-1"],"prefix":"10.1128","volume":"69","author":[{"given":"Ariane","family":"Amoura","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM, IAME","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Benchetrit","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM, IAME","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Magr\u00e9ault","sequence":"additional","affiliation":[{"name":"Universite Sorbonne Paris Nord, INSERM, IAME","place":["Bobigny, France"]},{"name":"Laboratoire de Pharmacologie, H\u00f4pital Jean Verdier","place":["Bondy, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Chosidow","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM, IAME","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Le Menestrel","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM, IAME","place":["Paris, 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