{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T13:53:34Z","timestamp":1761486814190},"reference-count":31,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2001,2,1]],"date-time":"2001-02-01T00:00:00Z","timestamp":980985600000},"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":[[2001,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            In vitro time-kill studies and a rabbit model of endocarditis and pyelonephritis were used to define the impact that the order of exposure of\n            <jats:italic>Candida albicans<\/jats:italic>\n            to fluconazole (FLC) and amphotericin B (AMB), as sequential and combination therapies, had on the susceptibility of\n            <jats:italic>C. albicans<\/jats:italic>\n            to AMB and on the outcome. The contribution of FLC-induced resistance to AMB for\n            <jats:italic>C. albicans<\/jats:italic>\n            also was assessed. In vitro, AMB monotherapy rapidly killed each of four\n            <jats:italic>C. albicans<\/jats:italic>\n            strains; FLC alone was fungistatic. Preincubation of these fungi with FLC for 18 h prior to exposure to AMB decreased their susceptibilities to AMB for 8 to &gt;40 h. Induced resistance to AMB was transient, but the duration of resistance increased with the length of FLC preincubation. Yeast sequentially incubated with FLC followed by AMB plus FLC (FLC\u2192AMB+FLC) showed fungistatic growth kinetics similar to that of fungi that were exposed to FLC alone. This antagonistic effect persisted for at least 24 h. Simultaneous exposure of\n            <jats:italic>C. albicans<\/jats:italic>\n            to AMB and FLC [AMB+FLC(simult)] demonstrated activity similar to that with AMB alone for AMB concentrations of \u22651 \u03bcg\/ml; antagonism was seen using an AMB concentration of 0.5 \u03bcg\/ml. The in vitro findings accurately predicted outcomes in our rabbit infection model. In vivo, AMB monotherapy and treatment with AMB for 24 h followed by AMB plus FLC (AMB\u2192AMB+FLC) rapidly sterilized kidneys and cardiac vegetations. AMB+FLC(simult) and FLC\u2192AMB treatments were slower in clearing fungi from infected tissues. FLC monotherapy and FLC\u2192AMB+FLC were both fungistatic and were the least active regimens. No adverse interaction was observed between AMB and FLC for the AMB\u2192FLC regimen. However, FLC\u2192AMB treatment was slower than AMB alone in clearing fungi from tissues. Thus, our in vitro and in vivo studies both demonstrate that preexposure of\n            <jats:italic>C. albicans<\/jats:italic>\n            to FLC reduces fungal susceptibility to AMB. The length of FLC preexposure and whether AMB is subsequently used alone or in combination with FLC determine the duration of induced resistance to AMB.\n          <\/jats:p>","DOI":"10.1128\/aac.45.2.485-494.2001","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T10:06:42Z","timestamp":1027764402000},"page":"485-494","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":48,"title":["Impact of the Order of Initiation of Fluconazole and Amphotericin B in Sequential or Combination Therapy on Killing of\n            <i>Candida albicans<\/i>\n            In Vitro and in a Rabbit Model of Endocarditis and Pyelonephritis"],"prefix":"10.1128","volume":"45","author":[{"given":"Arnold","family":"Louie","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Division of Infectious Diseases, Department of Medicine,1 and"},{"name":"<!--label omitted: 2-->the Center for Immunology and Microbial Disease,2 Albany Medical College, and"},{"name":"<!--label omitted: 3-->the Clinical Research Institute,3 Albany Medical College and Wadsworth Center for Laboratories and Research, New York State Department of Health, Albany, New York 12208"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pamela","family":"Kaw","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Division of Infectious Diseases, Department of Medicine,1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Partha","family":"Banerjee","sequence":"additional","affiliation":[{"name":"<!--label omitted: 3-->the Clinical Research Institute,3 Albany Medical College and Wadsworth Center for Laboratories and Research, New York State Department of Health, Albany, New York 12208"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiguo","family":"Liu","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Division of Infectious Diseases, Department of Medicine,1 and"},{"name":"<!--label omitted: 2-->the Center for Immunology and Microbial Disease,2 Albany Medical College, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Chen","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Division of Infectious Diseases, Department of Medicine,1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael H.","family":"Miller","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Division of Infectious Diseases, Department of Medicine,1 and"},{"name":"<!--label omitted: 2-->the Center for Immunology and Microbial Disease,2 Albany Medical College, and"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1109\/TAC.1974.1100705"},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1093\/clinids\/23.5.964","article-title":"Management of invasive candidal infections: results of a prospective, randomized, multicenter study of fluconazole versus amphotericin B and review of the literature.","volume":"23","author":"Anaissie E. 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