{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T02:49:16Z","timestamp":1761101356796},"reference-count":30,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[1998,11,1]],"date-time":"1998-11-01T00:00:00Z","timestamp":909878400000},"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":[[1998,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            LY303366 is a novel semisynthetic derivative of echinocandin B and a potent inhibitor of fungal (1,3)-\u03b2-\n            <jats:sc>d<\/jats:sc>\n            -glucan synthase. The antifungal efficacy and safety of LY303366 were investigated in treatment and prophylaxis of primary pulmonary aspergillosis due to\n            <jats:italic>Aspergillus fumigatus<\/jats:italic>\n            in persistently neutropenic rabbits. Treatment study groups were either not treated (controls) or treated with amphotericin B (AmB) at 1 mg\/kg of body weight per day or with LY303366 at 1, 5, 10, and 20 mg\/kg\/day. In rabbits treated with LY303366, there was a significant improvement in survival and a reduction in organism-mediated pulmonary injury measured by the number of infarcts, total lung weight, and ultrafast computerized tomography scan pulmonary lesion score. Rabbits receiving prophylactic LY303366 also demonstrated significant improvement in survival and reduction in organism-mediated pulmonary injury. AmB and LY303366 had comparable therapeutic efficacies by all parameters with the exception of reduction in tissue burden of\n            <jats:italic>A. fumigatus<\/jats:italic>\n            , where AmB was superior to LY303366. LY303366 demonstrated a dose-dependent effect on hyphal injury with progressive truncation, swelling, and vacuolization. LY303366 administered in single doses of 1, 5, 10, and 20 mg\/kg demonstrated dose-proportional increases in the maximum concentration of drug in plasma and the area under the concentration-time curve from 0 to 72 h with no changes in plasma drug clearance. The 1-mg\/kg dosage maintained plasma drug levels above the MIC for 18 h, and dosages of \u22655 mg\/kg maintained plasma drug levels above the MIC for the entire 24-h dosing interval. There was no significant elevation of the concentrations of hepatic transaminases or creatinine in serum in LY303366-treated rabbits. In summary, LY303366 improved survival and decreased pulmonary injury with no apparent toxicity in the treatment and prevention of invasive pulmonary aspergillosis in persistently neutropenic rabbits.\n          <\/jats:p>","DOI":"10.1128\/aac.42.11.2898","type":"journal-article","created":{"date-parts":[[2018,10,9]],"date-time":"2018-10-09T00:29:45Z","timestamp":1539044985000},"page":"2898-2905","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":97,"title":["Antifungal Efficacy, Safety, and Single-Dose Pharmacokinetics of LY303366, a Novel Echinocandin B, in Experimental Pulmonary Aspergillosis in Persistently Neutropenic Rabbits"],"prefix":"10.1128","volume":"42","author":[{"given":"Vidmantas","family":"Petraitis","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute,1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruta","family":"Petraitiene","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute,1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas H.","family":"Groll","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute,1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aaron","family":"Bell","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute,1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana P.","family":"Callender","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute,1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tin","family":"Sein","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute,1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert L.","family":"Schaufele","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute,1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carl L.","family":"McMillian","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana2"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Bacher","sequence":"additional","affiliation":[{"name":"<!--label omitted: 3-->Surgery Branch, Veterinary Resources Services, National Center for Research Resources,3 National Institutes of Health, Bethesda, Maryland, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas J.","family":"Walsh","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute,1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.38.3.518"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.152.3.7663787"},{"key":"e_1_3_2_4_2","unstructured":"Committee on the Care and Use of Laboratory Animals of the Institute of Laboratory Animal Resources Commission on Life Sciences National Research Council\n          Guide for the care and use of laboratory animals.\n          1996\n          National Academy Press\n          Washington D.C"},{"key":"e_1_3_2_5_2","unstructured":"Debono\n              M.\n              Turner\n              W. W.\n              LaGrandeur\n              L. M.\n              Molloy\n              R. M.\n              Burkhardt\n              F. J.\n              Rodriguez\n              M.\n              Zweifel\n              M. J.\n              Nissen\n              J. S.\n              Clingerman\n              K.\n              Gordee\n              R. S.\n              Zeckner\n              D. J.\n              Parr\n              T. R.\n              Tang\n              J.\n          LY303366\u2014a new semi-synthetic lipopeptide antifungal agent related to echinocandin B. 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A.\n              Schaufele\n              R. L.\n              Walsh\n              T. J.\n          Efficacy of LY303366 a novel echinocandin against disseminated candidiasis in persistently neutropenic rabbits abstr. J-73\n          Program and abstracts of the 38th Meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy in press.\n          1998\n          472\n          American Society for Microbiology\n          Washington D.C"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0732-8893(97)00246-0"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.4.763"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.5.1156"},{"key":"e_1_3_2_24_2","unstructured":"Verweij\n              P. E.\n              Oakley\n              K. L.\n              Morrissey\n              J.\n              Morrissey\n              G.\n              Denning\n              D. W.\n          Efficacy of LY303 366 against amphotericin B \u201csusceptible\u201d and \u201cresistant\u201d A. fumigatus infection in an immunocompromised murine model abstr. F-73\n          Abstracts of the 37th Interscience Conference on Antimicrobial Agents and Chemotherapy.\n          1997\n          158\n          American Society for Microbiology\n          Washington D.C"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5520(05)70303-2"},{"key":"e_1_3_2_26_2","first-page":"467","article-title":"Chronic silastic central venous catheterization for induction, maintenance, and support of persistent granulocytopenia in rabbits.","volume":"38","author":"Walsh T. J.","year":"1988","unstructured":"Walsh T. J. Bacher P. Pizzo P. A. Chronic silastic central venous catheterization for induction, maintenance, and support of persistent granulocytopenia in rabbits. Lab. Anim. Med. 38 1988 467 470","journal-title":"Lab. Anim. Med."},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.25.5.931-932.1987"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.39.5.1065"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.35.7.1321"},{"key":"e_1_3_2_30_2","unstructured":"Zeckner\n              D.\n              Butler\n              T.\n              Boylan\n              C.\n              Boyll\n              B.\n              Lin\n              Y.\n              Raab\n              P.\n              Schmidtke\n              J.\n              Current\n              W.\n          LY303366 activity against systemic aspergillosis and histoplasmosis in murine models abstr. 364\n          Program and abstracts of the 33rd Interscience Conference on Antimicrobial Agents and Chemotherapy.\n          1993\n          186\n          American Society for Microbiology\n          Washington D.C"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.4.863"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.42.11.2898","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.42.11.2898","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T15:41:44Z","timestamp":1645458104000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.42.11.2898"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,11]]},"references-count":30,"journal-issue":{"issue":"11","published-print":{"date-parts":[[1998,11]]}},"alternative-id":["10.1128\/AAC.42.11.2898"],"URL":"https:\/\/doi.org\/10.1128\/aac.42.11.2898","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[1998,11]]},"assertion":[{"value":"1998-02-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1998-08-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1998-11-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}