{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T10:29:46Z","timestamp":1778236186631,"version":"3.51.4"},"reference-count":0,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[1997,11,1]],"date-time":"1997-11-01T00:00:00Z","timestamp":878342400000},"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":[[1997,11]]},"abstract":"<jats:p>The in vivo activity of the Merck antifungal echinocandin drug candidate MK-0991 (L-743,872) was evaluated in mouse models of disseminated candidiasis, aspergillosis, and cryptococcosis. The echinocandins are potent inhibitors of 1,3-beta-D-glucan synthase. Two models of disseminated candidiasis were used. In a Candida albicans mouse survival model with both DBA\/2N and CD-1 mice, estimates of the 50% effective doses (ED50s) of MK-0991 were 0.04 and 0.10 mg\/kg of body weight\/dose at 21 days after challenge, respectively. In a C. albicans target organ assay (TOA) with DBA\/2N mice, MK-0991 at levels of &gt; or =0.09 mg\/kg\/dose significantly reduced the numbers of C. albicans CFU\/g of kidneys compared to the numbers in the kidneys of control mice from 1 to 28 days after challenge. Even when given as a single intraperitoneal dose either 30 min or 24 h after challenge, MK-0991 was effective and significantly reduced the numbers of C. albicans CFU\/g of kidney compared to those in the controls. MK-0991 was &gt;300-fold less active when it was administered orally than when it was administered parenterally. MK-0991 was efficacious in mouse TOAs against other C. albicans strains and Candida species including Candida tropicalis, Candida (Torulopsis) glabrata, Candida lusitaniae, Candida parapsilosis, and Candida krusei. MK-0991 was ineffective against disseminated Cryptococcus neoformans infections. In the model of disseminated aspergillosis in mice, MK-0991 at doses of &gt; or =0.02 mg\/kg\/dose significantly prolonged the survival of DBA\/2N mice, with estimates of the ED50 and ED90 of MK-0991 being 0.03 and 0.12 mg\/kg\/dose, respectively, at 28 days after challenge. MK-0991 is a potent, parenterally administered therapeutic agent against disseminated candidiasis and aspergillosis that warrants further investigation in human clinical trials.<\/jats:p>","DOI":"10.1128\/aac.41.11.2333","type":"journal-article","created":{"date-parts":[[2018,10,9]],"date-time":"2018-10-09T00:27:12Z","timestamp":1539044832000},"page":"2333-2338","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":212,"title":["Evaluation of the echinocandin antifungal MK-0991 (L-743,872): efficacies in mouse models of disseminated aspergillosis, candidiasis, and cryptococcosis"],"prefix":"10.1128","volume":"41","author":[{"given":"G K","family":"Abruzzo","sequence":"first","affiliation":[{"name":"Antibiotic Discovery and Development, Merck Research Laboratories, Rahway, New Jersey 07065-0900, USA. george_abruzzo@merck.com"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A 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george_abruzzo@merck.com"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V B","family":"Pikounis","sequence":"additional","affiliation":[{"name":"Antibiotic Discovery and Development, Merck Research Laboratories, Rahway, New Jersey 07065-0900, USA. george_abruzzo@merck.com"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J M","family":"Balkovec","sequence":"additional","affiliation":[{"name":"Antibiotic Discovery and Development, Merck Research Laboratories, Rahway, New Jersey 07065-0900, USA. george_abruzzo@merck.com"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A F","family":"Bouffard","sequence":"additional","affiliation":[{"name":"Antibiotic Discovery and Development, Merck Research Laboratories, Rahway, New Jersey 07065-0900, USA. george_abruzzo@merck.com"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J F","family":"Dropinski","sequence":"additional","affiliation":[{"name":"Antibiotic Discovery and Development, 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