{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:06:04Z","timestamp":1792785964079,"version":"4.5.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2019,7,2]],"date-time":"2019-07-02T00:00:00Z","timestamp":1562025600000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"French National Agency"},{"name":"Agence Nationale de S\u00e9curit\u00e9 du M\u00e9dicament","award":["AAP-2013\u2013055"],"award-info":[{"award-number":["AAP-2013\u2013055"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>In a new experimental model of carbapenemase-producing Klebsiella pneumoniae osteomyelitis we evaluated the efficacy of colistin alone and in various combinations and examined the emergence of colistin-resistant strains and cross-resistance to host defence peptides (HDPs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>KPC-99YC is a clinical strain with intermediate susceptibility to meropenem (MIC\u205f=\u205f4\u2009mg\/L) and full susceptibility to gentamicin, colistin and tigecycline (MICs\u205f=\u205f1\u2009mg\/L) and fosfomycin (MIC\u205f=\u205f32\u2009mg\/L). Time\u2013kill curves were performed at 4\u00d7 MIC. Osteomyelitis was induced in rabbits by tibial injection of 2\u205f\u00d7\u205f108\u2009cfu. Treatment started 14\u2009days later for 7\u2009days in seven groups: (i) control; (ii) colistin; (iii) colistin\u2009+\u2009gentamicin; (iv) colistin\u2009+\u2009tigecycline; (v) colistin\u2009+\u2009meropenem; (vi) colistin\u2009+\u2009meropenem\u2009+\u2009gentamicin; and (vii) colistin\u2009+\u2009fosfomycin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In vitro, colistin was rapidly bactericidal, but regrowth occurred after 9\u2009h. Combinations of colistin with meropenem or fosfomycin were synergistic, whereas combination with tigecycline was antagonistic. In vivo, colistin alone was not effective. Combinations of colistin with meropenem or fosfomycin were bactericidal (P\u205f&lt;\u205f0.001) and the addition of gentamicin enhanced the efficacy of colistin\u2009+\u2009meropenem (P\u205f=\u205f0.025). Tigecycline reduced the efficacy of colistin (P\u205f=\u205f0.007). Colistin-resistant strains emerged in all groups except colistin\u2009+\u2009fosfomycin and two strains showed cross-resistance to HDP LL-37.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this model, combinations of colistin plus meropenem, with or without gentamicin, or colistin plus fosfomycin were the only effective therapies. The combination of colistin and tigecycline should be administered with caution, as it may be antagonistic in vitro and in vivo.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkz257","type":"journal-article","created":{"date-parts":[[2019,5,30]],"date-time":"2019-05-30T07:07:25Z","timestamp":1559200045000},"page":"2666-2675","source":"Crossref","is-referenced-by-count":28,"title":["Efficacy of colistin alone and in various combinations for the treatment of experimental osteomyelitis due to carbapenemase-producing Klebsiella pneumoniae"],"prefix":"10.1093","volume":"74","author":[{"given":"Anne-Claude","family":"Cr\u00e9mieux","sequence":"first","affiliation":[{"name":"St Louis Hospital, Paris 7 University, Paris, France"},{"name":"UMR 1173, Versailles Saint-Quentin University, Versailles, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lien","family":"Dinh","sequence":"additional","affiliation":[{"name":"UMR 1173, Versailles Saint-Quentin University, Versailles, France"},{"name":"Raymond Poincar\u00e9 University Hospital, Garches, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrice","family":"Nordmann","sequence":"additional","affiliation":[{"name":"Medical and Molecular Microbiology Unit, Department of Medicine, Faculty of Science and Medicine, INSERM European Unit (IAME, France), Swiss National Reference Center for Emerging Antibiotic Resistance (NARA), University of Fribourg, Fribourg, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Mouton","sequence":"additional","affiliation":[{"name":"Team \u2018Staphylococcal pathogenesis\u2019, International Centre for Infectiology Research, INSERM U1111 - 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