{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T14:45:28Z","timestamp":1778856328442,"version":"3.51.4"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T00:00:00Z","timestamp":1678406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"crossref","award":["#52321751"],"award-info":[{"award-number":["#52321751"]}],"id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,5,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>While the treatment of ESBL-producing Enterobacterales osteomyelitis relies on carbapenems, the optimal regimen for OXA48 types remains unclear. We evaluated the efficacy of ceftazidime\/avibactam in different combinations in an experimental model of OXA-48-\/ESBL-producing Escherichia coli osteomyelitis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>E. coli pACYC184 is a clinical strain harbouring blaOXA-48 and blaCTX-M-15 inserts, with \u2018increased exposure susceptibility\u2019 to imipenem (MIC, 2 mg\/L), gentamicin (MIC, 0.5 mg\/L), colistin (MIC, 0.25 mg\/L), ceftazidime\/avibactam (MIC, 0.094 mg\/L) and fosfomycin (MIC, 1 mg\/L), and resistance to ceftazidime (MIC, 16 mg\/L). Osteomyelitis was induced in rabbits by tibial injection of 2\u200a\u00d7\u200a108 cfu of OXA-48\/ESBL E. coli. Treatment started 14 days later for 7 days in six groups: (1) control, (2) colistin 150.000 IU\/kg subcutaneously (SC) q8h, (3) ceftazidime\/avibactam 100\/25 mg\/kg SC q8h, (4) ceftazidime\/avibactam\u200a+\u200acolistin, (5) ceftazidime\/avibactam\u200a+\u200afosfomycin 150 mg\/kg SC q12h, (6) ceftazidime\/avibactam\u200a+\u200agentamicin 15 mg\/kg intramuscularly (IM) q24h. Treatment was evaluated at Day 24 according to bone cultures.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In vitro, time\u2013kill curves of ceftazidime\/avibactam in combination showed a synergistic effect. In vivo, compared with controls, rabbits treated with colistin alone had similar bone bacterial density (P\u200a=\u200a0.50), whereas ceftazidime\/avibactam alone or in combinations significantly decreased bone bacterial densities (P\u200a=\u200a0.004 and P\u200a&amp;lt;\u200a0.0002, respectively). Bone sterilization was achieved using ceftazidime\/avibactam in combination with colistin (91%) or fosfomycin (100%) or gentamicin (100%) (P\u200a&amp;lt;\u200a0.0001), whereas single therapies were not different from controls. No ceftazidime\/avibactam-resistant strains emerged in rabbits treated, regardless of the combination.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>In our model of E. coli OXA-48\/ESBL osteomyelitis, ceftazidime\/avibactam in combination was more effective than any single therapy, whatever the companion drug used (gentamicin or colistin or fosfomycin).<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkad070","type":"journal-article","created":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T15:56:01Z","timestamp":1678463761000},"page":"1211-1218","source":"Crossref","is-referenced-by-count":12,"title":["Efficacy of ceftazidime\/avibactam in various combinations for the treatment of experimental osteomyelitis in rabbits caused by OXA-48-\/ESBL-producing <i>Escherichia coli<\/i>"],"prefix":"10.1093","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2859-8417","authenticated-orcid":false,"given":"Benjamin","family":"Davido","sequence":"first","affiliation":[{"name":"Infectious Disease Department, UMR 1173, Versailles Saint-Quentin University , Versailles , France"},{"name":"Infectious Disease Department, Raymond Poincar\u00e9 Paris Saclay University Hospital , Garches , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne-Claude","family":"Cr\u00e9mieux","sequence":"additional","affiliation":[{"name":"Infectious Disease Department, UMR 1173, Versailles Saint-Quentin University , Versailles , France"},{"name":"FHU PROTHEE, St Louis-Lariboisi\u00e8re Hospital, Paris-Cit\u00e9 University , Paris , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabelle","family":"Vaugier","sequence":"additional","affiliation":[{"name":"CIC, Raymond Poincar\u00e9 Paris Saclay University Hospital , Garches , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre","family":"De Truchis","sequence":"additional","affiliation":[{"name":"Infectious Disease Department, UMR 1173, Versailles Saint-Quentin University , Versailles , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamel","family":"Hamami","sequence":"additional","affiliation":[{"name":"Pharmacy Unit, Raymond Poincar\u00e9 Paris Saclay University Hospital , Garches , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Laurent","sequence":"additional","affiliation":[{"name":"Institut for Infectious Agents, Department of Bacteriology\u2014CNR des staphylocoques, Croix-Rousse Hospital, North Biology Centre, Hospices Civils de Lyon , Lyon , France"},{"name":"Team \u2018Staphylococcal pathogenesis\u2019, International Centre for Infectiology Research, INSERM U1111\u2014CNRS UMR5308\u2014ENS Lyon\u2014Lyon 1 University , Lyon , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Azzam","family":"Saleh-Mghir","sequence":"additional","affiliation":[{"name":"Infectious Disease Department, UMR 1173, Versailles Saint-Quentin University , Versailles , France"},{"name":"Infectious Disease Department, Raymond Poincar\u00e9 Paris Saclay University Hospital , Garches , France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,3,10]]},"reference":[{"key":"2023050300200744900_dkad070-B1","doi-asserted-by":"crossref","first-page":"76","DOI":"10.4103\/jms.jms_25_17","article-title":"World Health Organization releases global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics","volume":"32","author":"Shrivastava","year":"2018","journal-title":"J Med 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