{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:25:27Z","timestamp":1790915127564,"version":"4.1.0"},"reference-count":14,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[1998,8,1]],"date-time":"1998-08-01T00:00:00Z","timestamp":901929600000},"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":[[1998,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            In addition to its potent efficacy in animal models against\n            <jats:italic>Candida<\/jats:italic>\n            sp.,\n            <jats:italic>Aspergillus fumigatus<\/jats:italic>\n            , and\n            <jats:italic>Histoplasma capsulatum<\/jats:italic>\n            , the clinical candidate pneumocandin MK-991 (formerly L-743,872) was also extremely potent against\n            <jats:italic>Pneumocystis carinii<\/jats:italic>\n            in models of immune-compromised animals. MK-991 was approximately 14 times more potent than the original natural product lead, pneumocandin B\n            <jats:sub>0<\/jats:sub>\n            . The 90% effective dose (ED\n            <jats:sub>90<\/jats:sub>\n            ) of MK-991 for cyst clearance in the rat model for pneumocystis was 0.011 mg\/kg of body weight when delivered parenterally for 4 days twice a day (b.i.d.). In a mouse model, under the same experimental parameters, the ED\n            <jats:sub>90<\/jats:sub>\n            was 0.02 mg\/kg. MK-991 was also effective orally, with an ED\n            <jats:sub>90<\/jats:sub>\n            for cyst clearance of 2.2 mg\/kg against acute infection in rats (b.i.d. for 4 days). Complete prevention of\n            <jats:italic>P. carinii<\/jats:italic>\n            development was achieved in immunocompromised mice at a daily oral dose of 2.25 mg\/kg. As reported previously for other pneumocandins and echinocandins, MK-991 selectively prevented the development of\n            <jats:italic>P. carinii<\/jats:italic>\n            cysts. When used as a prophylactic agent, neither stage of the organism appeared in the lungs of animals. In response to an acute infection, cysts were eliminated rapidly, while trophozoite forms persisted. Despite good efficacy as an oral agent in murine models, the low oral absorption of this class may limit the use of MK-991 to parenteral therapy.\n          <\/jats:p>","DOI":"10.1128\/aac.42.8.1985","type":"journal-article","created":{"date-parts":[[2018,10,9]],"date-time":"2018-10-09T00:33:13Z","timestamp":1539045193000},"page":"1985-1989","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":105,"title":["Efficacy of MK-991 (L-743,872), a Semisynthetic Pneumocandin, in Murine Models of\n            <i>Pneumocystis carinii<\/i>"],"prefix":"10.1128","volume":"42","author":[{"given":"Mary Ann","family":"Powles","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Merck Research Laboratories, Rahway, New Jersey 070651;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Liberator","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Merck Research Laboratories, Rahway, New Jersey 070651;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Anderson","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Merck Research Laboratories, Rahway, New Jersey 070651;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yashwant","family":"Karkhanis","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Merck Research Laboratories, Rahway, New Jersey 070651;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James F.","family":"Dropinski","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Merck Research Laboratories, Rahway, New Jersey 070651;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. Aileen","family":"Bouffard","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Merck Research Laboratories, Rahway, New Jersey 070651;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James M.","family":"Balkovec","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Merck Research Laboratories, Rahway, New Jersey 070651;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisashi","family":"Fujioka","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 441062; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masamichi","family":"Aikawa","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 441062; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"McFadden","sequence":"additional","affiliation":[{"name":"<!--label omitted: 3-->Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, California 94305-54023"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Schmatz","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Merck Research Laboratories, Rahway, New Jersey 070651;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.11.2333"},{"key":"e_1_3_1_3_2","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1016\/S0091-6749(94)70048-6","article-title":"Desensitization to trimethoprim\/sulfamethoxazole in HIV-infected patients.","volume":"93","author":"Absar N.","year":"1994","unstructured":"Absar N. 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