{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T17:28:04Z","timestamp":1763746084973},"reference-count":32,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2002,10,1]],"date-time":"2002-10-01T00:00:00Z","timestamp":1033430400000},"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":[[2002,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Antagonism has been described in vitro and in vivo for azole-polyene combinations against<jats:italic>Aspergillus<\/jats:italic>species. Using an established murine model of invasive pulmonary aspergillosis, we evaluated the efficacy of several amphotericin B (AMB) dosages given alone or following preexposure to itraconazole (ITC). Mice were immunosuppressed with cortisone acetate and cyclophosphamide. During immunosuppression, animals were administered either ITC solution (50 mg\/kg of body weight) or saline by oral gavage twice daily for 3 days prior to infection. Infection was induced by intranasally inoculating mice with a standardized conidial suspension (1 \u00d7 10<jats:sup>8<\/jats:sup>CFU\/ml) of<jats:italic>Aspergillus fumigatus<\/jats:italic>strain AF 293. AMB was then administered by daily intraperitoneal injections (0.25, 0.5, 1.0, and 3.0 mg\/kg) starting 24 h after inoculation and continuing for a total of 72 h. Drug pharmacokinetics of AMB and ITC in plasma were determined by high-performance liquid chromatography. Four different endpoints were used to examine the efficacy of antifungal therapy: (i) viable counts from harvested lung tissue (in CFU per milliliter), (ii) the whole-lung chitin assay, (iii) mortality at 96 h, and (iv) histopathology of representative lung sections. At AMB doses of &gt;0.5 mg\/kg\/day, fewer ITC-preexposed mice versus non-ITC-preexposed mice were alive at 96 h (0 to 20 versus 60%, respectively). At all time points, the fungal lung burden was consistently and significantly higher in animals preexposed to ITC, as measured by the CFU counts (<jats:italic>P<\/jats:italic>= 0.001) and the chitin assay (<jats:italic>P<\/jats:italic>= 0.03). Higher doses of AMB did not overcome this antagonism. ITC preexposure was associated with poorer mycological efficacy and survival in mice treated subsequently with AMB for invasive pulmonary aspergillosis.<\/jats:p>","DOI":"10.1128\/aac.46.10.3208-3214.2002","type":"journal-article","created":{"date-parts":[[2002,9,16]],"date-time":"2002-09-16T15:23:02Z","timestamp":1032189782000},"page":"3208-3214","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":76,"title":["Itraconazole Preexposure Attenuates the Efficacy of Subsequent Amphotericin B Therapy in a Murine Model of Acute Invasive Pulmonary Aspergillosis"],"prefix":"10.1128","volume":"46","author":[{"given":"Russell E.","family":"Lewis","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas M. D. 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