title: Successful treatment of Cryptococcal meningitis with a combination of liposomal amphotericin B, flucytosine and posaconazole: two case reports.
abstract: Cryptococcus neoformans CNS infection frequently affects HIV-infected patients and is often lethal, despite antifungal therapy. The most recent treatment guidelines for Cryptococcal meningitis recommend therapy with lyposomal amphotericin B and possible association with flucitosine. However, clinical response rates in HIV-infected patients are not satisfactory, with a persistent high mortality rate and long term therapy is affected by a high risk of major side effects. Posaconazole, the latest broad-spectrum azole, with both in vitro- and in vivo-documented potent activity against C. neoformans, clearly showed no antagonism with amphotericin B, echinocandins or flucytosine and it has both in vitro and in vivo agonistic activity with flucytosine against C. neoformans. We report two cases of successful salvage therapy based on the addition of posaconazole to a standard treatment based on liposomal amphotericin B and Flucytosine. In addition we used posaconazole also in a maintenance therapeutic regimen with no evidence of recurrences in the follow up of these patients. Our report confirms that posaconazole has clinical activity in the CNS against C. neoformans infection. In addition posaconazole showed no antagonism with any other currently available antifungal agent, and was in fact synergistic to some of them (flucytosine); consequently, it seems to be an ideal candidate for antimicrobial combination salvage therapies. Finally posaconazole represents a good alternative to parenteral therapy and an ideal candidate for long-term maintenance therapy due to its competent toxicity profile and oral bioavailability.
authors.affiliation: III U.O. di Malattie Infettive A.O. Cotugno, Via T. Tasso, Napoli, Italy. esposvin@libero.it
authors.forename: V
authors.initials: V
authors.lastname: Esposito
authors.forename: R
authors.initials: R
authors.lastname: Viglietti
authors.forename: M
authors.initials: M
authors.lastname: Gargiulo
authors.forename: R
authors.initials: R
authors.lastname: Parrella
authors.forename: M
authors.initials: M
authors.lastname: Onofrio
authors.forename: V
authors.initials: V
authors.lastname: Sangiovanni
authors.forename: D
authors.initials: D
authors.lastname: Ambrosino
authors.forename: A
authors.initials: A
authors.lastname: Chirianni
mesh_terms: D000328:Adult; D000666:Amphotericin B / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005437:Flucytosine / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D016919:Meningitis, Cryptococcal / Q000188:drug therapy*; D008875:Middle Aged; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D000935:Antifungal Agents; D014230:Triazoles; C068538:liposomal amphotericin B; C101425:posaconazole; D000666:Amphotericin B; D005437:Flucytosine