{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T22:40:29Z","timestamp":1772491229002,"version":"3.50.1"},"reference-count":24,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2000,9,1]],"date-time":"2000-09-01T00:00:00Z","timestamp":967766400000},"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":[[2000,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The in vivo efficacy of the echinocandin antifungal caspofungin acetate (caspofungin; MK-0991) was evaluated in models of disseminated aspergillosis and candidiasis in mice with cyclophosphamide (CY)-induced immunosuppression. Caspofungin is a 1,3-\u03b2-\n            <jats:sc>d<\/jats:sc>\n            -glucan synthesis inhibitor efficacious against a number of clinically relevant fungi including\n            <jats:italic>Aspergillus<\/jats:italic>\n            and\n            <jats:italic>Candida<\/jats:italic>\n            species. Models of CY-induced transient or chronic leukopenia were used with once daily administration of therapy initiated 24 h after microbial challenge. Caspofungin was effective in treating disseminated aspergillosis in mice that were transiently leukopenic (significant prolongation of survival at doses of \u22650.125 mg\/kg of body weight and a 50% protective dose [PD\n            <jats:sub>50<\/jats:sub>\n            ] of 0.245 mg\/kg\/day at 28 days after challenge) or chronically leukopenic (50 to 100% survival at doses of \u22650.5 mg\/kg and PD\n            <jats:sub>50<\/jats:sub>\n            s ranging from 0.173 to 0.400 mg\/kg\/day). Caspofungin was effective in the treatment and sterilization of\n            <jats:italic>Candida<\/jats:italic>\n            infections in mice with transient leukopenia with a 99% effective dose based on reduction in log\n            <jats:sub>10<\/jats:sub>\n            CFU of\n            <jats:italic>Candida albicans<\/jats:italic>\n            \/gram of kidneys of 0.119 mg\/kg and 80 to 100% of the caspofungin-treated mice having sterile kidneys at caspofungin doses from 0.25 to 2.0 mg\/kg. In\n            <jats:italic>Candida<\/jats:italic>\n            -infected mice with chronic leukopenia, caspofungin was effective at all dose levels tested (0.25 to 1.0 mg\/kg), with the log\n            <jats:sub>10<\/jats:sub>\n            CFU of\n            <jats:italic>C. albicans<\/jats:italic>\n            \/gram of kidneys of caspofungin-treated mice being significantly lower (&gt;99% reduction) than that of sham-treated mice from day 4 to day 28 after challenge. Also, 70 to 100% of the caspofungin-treated, chronic leukopenic mice had sterile kidneys at caspofungin doses of 0.5 to 1.0 mg\/kg from day 8 to 28 after challenge. Sterilization of\n            <jats:italic>Candida<\/jats:italic>\n            infections by caspofungin in the absence of host leukocytes provides compelling in vivo evidence for fungicidal activity against\n            <jats:italic>C. albicans<\/jats:italic>\n            . Further human clinical trials with caspofungin against serious fungal infections are in progress.\n          <\/jats:p>","DOI":"10.1128\/aac.44.9.2310-2318.2000","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T10:06:42Z","timestamp":1027764402000},"page":"2310-2318","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":142,"title":["Efficacy of the Echinocandin Caspofungin against Disseminated Aspergillosis and Candidiasis in Cyclophosphamide-Induced Immunosuppressed Mice"],"prefix":"10.1128","volume":"44","author":[{"given":"George K.","family":"Abruzzo","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Infectious Diseases,1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles J.","family":"Gill","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Infectious Diseases,1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy M.","family":"Flattery","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Infectious Diseases,1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Kong","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Infectious Diseases,1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claire","family":"Leighton","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Infectious Diseases,1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey G.","family":"Smith","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Virus and Cell Biology,2"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V. Bill","family":"Pikounis","sequence":"additional","affiliation":[{"name":"<!--label omitted: 3-->Biometrics Research,3 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ken","family":"Bartizal","sequence":"additional","affiliation":[{"name":"<!--label omitted: 4-->Animal Health,4 Merck Research Laboratories, Rahway, New Jersey 07065-0900"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hugh","family":"Rosen","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Infectious Diseases,1"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"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":"S43","DOI":"10.1093\/clinids\/14.Supplement_1.S43","article-title":"Opportunistic mycoses in the immunocompromised host: experience at a cancer center and review.","volume":"14","author":"Anaissie E.","year":"1992","unstructured":"Anaissie E. Opportunistic mycoses in the immunocompromised host: experience at a cancer center and review. Clin. Infect. Dis. 14 1992 S43 S53","journal-title":"Clin. Infect. Dis."},{"key":"e_1_3_1_4_2","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.1016\/S0960-894X(01)81010-6","article-title":"Pneumocandin antifungal lipopeptides. The phenolic hydroxyl is required for 1,3-\u03b2-d-glucan synthesis inhibition.","volume":"3","author":"Balkovec J. M.","year":"1993","unstructured":"Balkovec J. M. Black R. M. Abruzzo G. K. Bartizal K. Dreikorn S. Nollstadt K. Pneumocandin antifungal lipopeptides. The phenolic hydroxyl is required for 1,3-\u03b2-d-glucan synthesis inhibition. Bioorganic Med. Chem. Lett. 3 1993 2039 2042","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.11.2326"},{"key":"e_1_3_1_6_2","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1017\/S095375629800687X","article-title":"Reclassification of a pneumocandin-producing anamorph, Glarea lozoyensis, gen et sp. nov., previously identified as Zalerion arboricola.","volume":"103","author":"Bills G. F.","year":"1998","unstructured":"Bills G. F. Platas G. Pel\u00e1ez F. Mazurekar P. Reclassification of a pneumocandin-producing anamorph, Glarea lozoyensis, gen et sp. nov., previously identified as Zalerion arboricola. Mycol. Res. 103 1998 179 192","journal-title":"Mycol. Res."},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.8.1835"},{"key":"e_1_3_1_8_2","unstructured":"Draper\n              N. R.\n              Smith\n              H.\n          Applied regression analysis.\n          1981\n          John Wiley & Sons Inc.\n          New York N.Y"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.36.10.2950-2956.1998"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.8.1775"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.9.1937"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.1958.10501452"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.38.7.1480"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1080\/02681219780000961"},{"key":"e_1_3_1_15_2","doi-asserted-by":"crossref","unstructured":"Morgan\n              B. J. T.\n          The analysis of quantal response data\n          1992\n          59\n          65\n          Chapman and Hall\n          London United Kingdom","DOI":"10.1007\/978-1-4899-4539-6"},{"key":"e_1_3_1_16_2","unstructured":"National Committee for Clinical Laboratory Standards\n          Reference method for broth dilution antifungal susceptibility testing of conidium-forming filamentous fungi. Proposed standard M38-P.\n          1998\n          National Committee for Clinical Laboratory Standards\n          Wayne Pa"},{"key":"e_1_3_1_17_2","unstructured":"National Committee for Clinical Laboratory Standards\n          Reference method for broth dilution antifungal susceptibility testing of yeasts. Approved standard M27-A.\n          1997\n          National Committee for Clinical Laboratory Standards\n          Wayne Pa"},{"key":"e_1_3_1_18_2","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1080\/02681219780001291","article-title":"In vitro growth-inhibitory activity of pneumocandins, L-733,560 and L-743,872 against putatively amphotericin B- and fluconazole-resistant Candida isolates: influence of assay conditions.","volume":"35","author":"Nelson P. W.","year":"1997","unstructured":"Nelson P. W. Lozano-Chiu M. Rex J. H. In vitro growth-inhibitory activity of pneumocandins, L-733,560 and L-743,872 against putatively amphotericin B- and fluconazole-resistant Candida isolates: influence of assay conditions. J. Med. Vet. Mycol. 35 1997 285 287","journal-title":"J. Med. Vet. Mycol."},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.37.3.870-872.1999"},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.8.1985"},{"key":"e_1_3_1_21_2","doi-asserted-by":"crossref","first-page":"485","DOI":"10.2307\/2530463","article-title":"Resistant fits for some commonly used logistic models with medical applications.","volume":"38","author":"Pregibon D.","year":"1982","unstructured":"Pregibon D. Resistant fits for some commonly used logistic models with medical applications. Biometrics 38 1982 485 498","journal-title":"Biometrics"},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199411173312001"},{"key":"e_1_3_1_23_2","first-page":"1480","article-title":"In vitro activity of a new pneumocandin antifungal, L-743,872, against azole-susceptible and -resistant Candida species.","volume":"38","author":"Vasquez J. A.","year":"1997","unstructured":"Vasquez J. A. Lynch M. Boikov D. Sobel J. D. In vitro activity of a new pneumocandin antifungal, L-743,872, against azole-susceptible and -resistant Candida species. Antimicrob. Agents Chemother. 38 1997 1480 1489","journal-title":"Antimicrob. Agents Chemother."},{"key":"e_1_3_1_24_2","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1093\/clinids\/20.4.900","article-title":"Fungemia in children infected with the human immunodeficiency virus: new epidemiologic patterns, emerging pathogens, and improved outcome with antifungal therapy.","volume":"20","author":"Walsh T. J.","year":"1995","unstructured":"Walsh T. J. Gonzales C. Roilides E. Mueller B. U. Ali N. Lewis L. L. Whitcomb T. O. Marshall D. J. Pizzo P. A. Fungemia in children infected with the human immunodeficiency virus: new epidemiologic patterns, emerging pathogens, and improved outcome with antifungal therapy. Clin. Infect. Dis. 20 1995 900 906","journal-title":"Clin. Infect. Dis."},{"key":"e_1_3_1_25_2","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/978-1-4615-2490-8_8","article-title":"Fungal infections in the immunocompromised host","volume":"3","author":"Wheat L. J.","year":"1994","unstructured":"Wheat L. J. Fungal infections in the immunocompromised host Clinical approach to infection in the immunocompromised host Rubin R. H. Young L. S. 3 1994 211 237 Plenum Publishing Corporation New York, N.Y","journal-title":"Clinical approach to infection in the immunocompromised host"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.44.9.2310-2318.2000","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.44.9.2310-2318.2000","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T16:43:20Z","timestamp":1645461800000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.44.9.2310-2318.2000"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,9]]},"references-count":24,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2000,9]]}},"alternative-id":["10.1128\/AAC.44.9.2310-2318.2000"],"URL":"https:\/\/doi.org\/10.1128\/aac.44.9.2310-2318.2000","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,9]]},"assertion":[{"value":"1999-11-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2000-06-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2000-09-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}