Punnee PitisuttithumRicardo NegroniJohn R. GraybillBeatriz BustamantePeter PappasStanley ChapmanRoberta S. HareCatherine J. HardaloMahidol UniversityHospital de Infecciosas Francisco Javier MunizUniversity of Texas Health Science Center at San AntonioHospital Nacional Cayetano HerediaUniversity of Alabama at BirminghamUniversity of Mississippi Medical CenterMerck & Co., Inc.2018-06-212018-06-212005-10-01Journal of Antimicrobial Chemotherapy. Vol.56, No.4 (2005), 745-75514602091030574532-s2.0-27144459842https://repository.li.mahidol.ac.th/handle/20.500.14594/16816Objectives: A multinational, multicentre, open-label clinical trial was conducted to evaluate the safety and efficacy of posaconazole, an extended-spectrum triazole antifungal agent, in subjects with invasive fungal infections who had refractory disease or who were intolerant of standard antifungal therapy. In this subanalysis, we report on those subjects in this trial who had a fungal infection that involved the CNS. Methods: Subjects received posaconazole oral suspension 800 mg/day in divided doses for up to 1 year; however, subjects could receive additional therapy as part of a treatment-use extension protocol. A blinded, third-party data review committee determined subject eligibility and outcome. Results: Of the 330 subjects who enrolled in the study, 53 had infections of the CNS, of which 39 were considered evaluable for efficacy. Most had refractory disease (37 of 39) and underlying HIV infection (29 of 39). Twenty-nine subjects had cryptococcal infections, and 10 had infections caused by other fungal pathogens [Aspergillusspp. (four), Pseudallescheria boydii (two), Coccidioides immitis (one), Histoplasma capsulatum (one), Ramichloridium mackenziei (one), and Apophysomyces elegans plus a Basidiomycetessp. (one)]. Successful outcomes were observed in 14 of 29 (48%) subjects with cryptococcal meningitis and five of 10 (50%) subjects with CNS infections due to other fungal pathogens. Posaconazole was well tolerated. Conclusions: These data suggest that posaconazole, as an oral medication, has clinical activity against fungal infections of the CNS and may provide a valuable alternative to parenteral therapy in patients failing existing antifungal agents. © The Author 2005. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.Mahidol UniversityMedicinePharmacology, Toxicology and PharmaceuticsArticleSCOPUS10.1093/jac/dki288