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      Role of posaconazole in the management of oropharyngeal and esophageal candidiasis

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          Abstract

          Mucocutaneous candidiasis (MC) is one of the first signs of human immunodeficiency virus (HIV) infection. Over 90% of patients with AIDS will eventually develop oropharyngeal candidiasis (OPC) at some time during their illness, and an additional 10% will develop esophageal candidiasis (EC). Although numerous antifungal agents are available, azoles, both topical (clotrimazole) and systemic (fluconazole, itraconazole), have replaced older topical antifungals (gentian violet and nystatin) in the management of MC in these patients. The systemic azoles, itraconazole and fluconazole, are generally safe and effective agents in HIV-infected patients with MC. A concern in these patients is the clinical relapse, which appears to be dependent on degree of immunosuppression and is more common following clotrimazole and ketoconazole than with fluconazole or itraconazole. Posaconazole is a new extended-spectrum triazole recently approved for the management of OPC. In vitro, posaconazole possesses potent activity against numerous Candida species, including strains that are resistant to fluconazole. Recent clinical trials demonstrate that posaconazole is as efficacious as fluconazole in producing a successful clinical response in HIV-infected patients with OPC/EC. In addition, posaconazole was safe and more effective in sustaining clinical success after treatment was discontinued. Posaconazole appears to be an effective alternative in the management of MC in this difficult- to-treat population.

          Most cited references101

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          Posaconazole is effective as salvage therapy in zygomycosis: a retrospective summary of 91 cases.

          To evaluate the activity of posaconazole for treatment of zygomycosis, a disease for which therapeutic options are limited, we conducted a retrospective study including 91 patients with zygomycosis (proven zygomycosis, 69 patients; probable zygomycosis, 22 patients). Patients had infection that was refractory to prior antifungal treatment (n=81) or were intolerant of such treatment (n=10) and participated in the compassionate-use posaconazole (800 mg/day) program. The rate of success (i.e., either complete or partial response) at 12 weeks after treatment initiation was 60%, and 21% of patients had stable disease. The overall high success and survival rates reported here provide encouraging data regarding posaconazole as an alternative therapy for zygomycosis.
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            In vitro activities of posaconazole, fluconazole, itraconazole, voriconazole, and amphotericin B against a large collection of clinically important molds and yeasts.

            The in vitro activity of the novel triazole antifungal agent posaconazole (Noxafil; SCH 56592) was assessed in 45 laboratories against approximately 19,000 clinically important strains of yeasts and molds. The activity of posaconazole was compared with those of itraconazole, fluconazole, voriconazole, and amphotericin B against subsets of the isolates. Strains were tested utilizing Clinical and Laboratory Standards Institute broth microdilution methods using RPMI 1640 medium (except for amphotericin B, which was frequently tested in antibiotic medium 3). MICs were determined at the recommended endpoints and time intervals. Against all fungi in the database (22,850 MICs), the MIC(50) and MIC(90) values for posaconazole were 0.063 microg/ml and 1 mug/ml, respectively. MIC(90) values against all yeasts (18,351 MICs) and molds (4,499 MICs) were both 1 mug/ml. In comparative studies against subsets of the isolates, posaconazole was more active than, or within 1 dilution of, the comparator drugs itraconazole, fluconazole, voriconazole, and amphotericin B against approximately 7,000 isolates of Candida and Cryptococcus spp. Against all molds (1,702 MICs, including 1,423 MICs for Aspergillus isolates), posaconazole was more active than or equal to the comparator drugs in almost every category. Posaconazole was active against isolates of Candida and Aspergillus spp. that exhibit resistance to fluconazole, voriconazole, and amphotericin B and was much more active than the other triazoles against zygomycetes. Posaconazole exhibited potent antifungal activity against a wide variety of clinically important fungal pathogens and was frequently more active than other azoles and amphotericin B.
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              Guidelines for treatment of candidiasis.

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                Author and article information

                Journal
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                1176-6336
                1178-203X
                August 2007
                August 2007
                : 3
                : 4
                : 533-542
                Affiliations
                Division of Infectious Diseases, Henry Ford Hospital, Microbiology and Infectious Disease Translational Research Center, Wayne State University School of Medicine Detroit, MI, USA
                Author notes
                Correspondence: Jose A Vazquez Division of Infectious Diseases, Henry Ford Hospital, 2799 West Grand Boulevard, CFP-202, Detroit, MI, 48202, USA Tel +1 313 916 6298 Fax +1 313 916 3797 Email jvazque1@ 123456hfhs.org
                Article
                2374940
                18472974
                33e697c1-e8af-4fba-86cf-a604ce918e47
                © 2007 Dove Medical Press Limited. All rights reserved
                History
                Categories
                Review

                Medicine
                hiv-infected,posaconazole,oropharyngeal and esophageal candidiasis
                Medicine
                hiv-infected, posaconazole, oropharyngeal and esophageal candidiasis

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