title: Fluconazole and amphotericin B susceptibility testing of Cryptococcus neoformans: results of minimal inhibitory concentrations against 265 isolates from HIV-positive patients before and after two or more months of antifungal therapy.
abstract: Cryptococcosis, a fatal disease without appropriate treatment, is still one of the major opportunistic mycoses in AIDS patients in Argentina despite the availability of high active anti-retroviral therapy (HAART). Over the last decade, drugs employed in the treatment of disseminated cryptococcosis at Infectious Diseases Hospital "F.J. Muñiz" included amphotericin B (AMB) followed by fluconazole (FCZ), due to the fact that flucytosine was not available in Argentina during this period. A considerable number of patients did not negativize cultures after 2-3 weeks of treatment as it was expected, and in some of them the isolation of Cryptococcus neoformans in different samples was still possible after 2 or more months of adequate therapy and even in cases with clinical improvement. The aim of this study was to establish the susceptibility profile of C. neoformans clinical isolates to those antifungals and to investigate whether there were any changes after at least 2 months of treatment. A total of 265 strains were studied (116 obtained from patients at diagnosis and 149 corresponding to the same individuals 2 months or more after receiving therapy). Susceptibility patterns before treatment to AMB showed MICs < or =1 microg/ml for all the strains, and no increase was seen after treatment. All the strains were susceptible to FCZ (MIC< or =8 microg/ml) at diagnosis; but in a group with relapses or those who did not negativize cultures, one isolate became resistant after therapy (MIC> or =64 microg/ml) and other four showed dose-dependent susceptibility (MIC 16-32 microg/ml). There was no relation between these results and clinical outcome as it was pointed out in other publications.
authors.affiliation: Mycology Unit, Hospital of Infectious Diseases F.J.Muñiz, Uspallata 2272, (1282) Buenos Aires, Argentina. aarechavala@intramed.net
authors.forename: Alicia Irene
authors.initials: AI
authors.lastname: Arechavala
authors.forename: María Eugenia
authors.initials: ME
authors.lastname: Ochiuzzi
authors.forename: María Daniela
authors.initials: MD
authors.lastname: Borgnia
authors.forename: Gabriela María
authors.initials: GM
authors.lastname: Santiso
mesh_terms: D000328:Adult; D000666:Amphotericin B / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D003453:Cryptococcosis / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology*; D003455:Cryptococcus neoformans / Q000187:drug effects* / Q000302:isolation & purification; D005260:Female; D015725:Fluconazole / Q000494:pharmacology*; D006679:HIV Seropositivity / Q000150:complications / Q000382:microbiology*; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D013997:Time Factors
chemical_list: D000935:Antifungal Agents; D000666:Amphotericin B; D015725:Fluconazole