{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:30:17Z","timestamp":1787016617897,"version":"build-2736575974"},"reference-count":33,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2006,1,1]],"date-time":"2006-01-01T00:00:00Z","timestamp":1136073600000},"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":[[2006,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Whether or not flucytosine should be administered to patients infected with\n                    <jats:italic>Cryptococcus neoformans<\/jats:italic>\n                    isolates found to be resistant to flucytosine in vitro remains a controversial issue. Thus, the efficacy of amphotericin B and flucytosine in combination was investigated by mortality and fungal burden studies in a murine model of disseminated cryptococcosis using two clinical isolates of\n                    <jats:italic>Cryptococcus neoformans<\/jats:italic>\n                    , one susceptible and one resistant (i.e., 64 \u03bcg\/ml) to flucytosine. Amphotericin B was given intraperitoneally at 0.25 or 0.5 mg\/kg\/day, while flucytosine was given at 100 or 250 mg\/kg\/day orally. Treatment was started 24 h or day 6 after inoculation and continued for 5 days in fungal burden and mortality studies, respectively. The combination of amphotericin B at 0.5 mg\/kg\/day and flucytosine at 250 mg\/kg\/day was significantly more effective than monotherapies for reducing fungal burden in brain, spleen, and lungs after infection by the flucytosine-susceptible isolate and in brain and spleen for the flucytosine-resistant isolate. For the flucytosine-resistant isolate, the combination of amphotericin B at 0.5 mg\/kg\/day with flucytosine at 100 mg\/kg\/day was significantly better than monotherapies for reducing the fungal burden in the brain. Survival obtained after the combination of amphotericin B at 0.5 mg\/kg\/day and flucytosine at 250 mg\/kg\/day increased compared to that obtained with monotherapies for both isolates, but the difference was statistically significant only for the flucytosine-susceptible isolate. Antagonism was never observed. This study demonstrates the beneficial effect of the addition of flucytosine to amphotericin B against experimental disseminated cryptococcal infection even when the\n                    <jats:italic>C. neoformans<\/jats:italic>\n                    isolate is resistant to flucytosine.\n                  <\/jats:p>","DOI":"10.1128\/aac.50.1.113-120.2006","type":"journal-article","created":{"date-parts":[[2005,12,23]],"date-time":"2005-12-23T05:07:51Z","timestamp":1135314471000},"page":"113-120","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":65,"title":["Efficacy of Amphotericin B in Combination with Flucytosine against Flucytosine-Susceptible or Flucytosine-Resistant Isolates of\n                    <i>Cryptococcus neoformans<\/i>\n                    during Disseminated Murine Cryptococcosis"],"prefix":"10.1128","volume":"50","author":[{"given":"Patrick","family":"Schwarz","sequence":"first","affiliation":[{"name":"Centre National de Re\u0301fe\u0301rence Mycologie et Antifongiques, Unite\u0301 de Mycologie Mole\u0301culaire, CNRS FRE2849, Institut Pasteur, 75724 Paris Cedex 15, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franc\u0327oise","family":"Dromer","sequence":"additional","affiliation":[{"name":"Centre National de Re\u0301fe\u0301rence Mycologie et Antifongiques, Unite\u0301 de Mycologie Mole\u0301culaire, CNRS FRE2849, Institut Pasteur, 75724 Paris Cedex 15, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Lortholary","sequence":"additional","affiliation":[{"name":"Centre National de Re\u0301fe\u0301rence Mycologie et Antifongiques, Unite\u0301 de Mycologie Mole\u0301culaire, CNRS FRE2849, Institut Pasteur, 75724 Paris Cedex 15, France"},{"name":"Universite\u0301 Paris Descartes, Faculte\u0301 de Me\u0301decine, AP-HP, Ho\u0302pital Necker-Enfants-Malades, Service des Maladies Infectieuses et Tropicales, 75743 Paris Cedex 15, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Dannaoui","sequence":"additional","affiliation":[{"name":"Centre National de Re\u0301fe\u0301rence Mycologie et Antifongiques, Unite\u0301 de Mycologie Mole\u0301culaire, CNRS FRE2849, Institut Pasteur, 75724 Paris Cedex 15, France"},{"name":"Universite\u0301 Paris Descartes, Faculte\u0301 de Me\u0301decine, AP-HP, Ho\u0302pital Europe\u0301en Georges Pompidou, Unite\u0301 de Parasitologie-Mycologie, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.4.938-942.2000"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197907193010303"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.11.3065-3069.2001"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)16301-0"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1086\/341564"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/PL00011265"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.3.528"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.7.1589"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-200402200-00024"},{"key":"e_1_3_1_11_2","first-page":"331","volume":"47","year":"1995","unstructured":"Greco, W. 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