title: Activity of sertraline against Cryptococcus neoformans: in vitro and in vivo assays.
abstract: Cryptococcus neoformans infection is an important cause of meningitis in HIV/AIDS endemic regions. Antifungals for its management include amphotericin B, flucytosine, and fluconazole. Recently, treatment of this mycosis with sertraline has been studied with variable clinical outcomes. The aim of the study was to assess the in vitro antifungal effect of sertraline against clinical isolates of Cryptococcus spp. as well as its in vivo activity in a murine model of cryptococcal meningoencephalitis. The in vitro susceptibility to fluconazole, amphotericin B, voriconazole and sertraline of 153 Cryptococcus spp. strains were evaluated according to CLSI procedures. Fungal tissue burden, serum antigenaemia and histopathology, together with the therapeutic efficacy of amphotericin B (3 mg/kg), fluconazole (15 mg/kg), and sertraline (3, 10, and 15 mg/kg) were evaluated in mice intracranially inoculated with one isolate of Cryptococcus neoformans. All strains were susceptible to the antifungals studied and exhibited growth inhibition with sertraline at clinically relevant concentrations. Sertraline at a dose of 15 mg/kg reduced the fungal burden in the brain and spleen with an efficacy comparable to that of fluconazole. In conclusion, sertraline exhibited an excellent in vitro-in vivo anti-cryptococcal activity, representing a possible new alternative for the clinical management of meningeal cryptococcosis.
authors.affiliation: Department of Microbiology, School of Medicine, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico.
authors.forename: Rogelio de J
authors.initials: Rde J
authors.lastname: Treviño-Rangel
authors.affiliation: Department of Internal Medicine, Infectology Service, University Hospital "Dr. José E. González", Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico.
authors.forename: Hiram
authors.initials: H
authors.lastname: Villanueva-Lozano
authors.affiliation: Department of Internal Medicine, Infectology Service, University Hospital "Dr. José E. González", Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico.
authors.forename: Pedro
authors.initials: P
authors.lastname: Hernández-Rodríguez
authors.affiliation: Department of Internal Medicine, Infectology Service, University Hospital "Dr. José E. González", Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico.
authors.forename: Michel F
authors.initials: MF
authors.lastname: Martínez-Reséndez
authors.affiliation: Department of Histology, School of Medicine, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico.
authors.forename: Jaime
authors.initials: J
authors.lastname: García-Juárez
authors.affiliation: Department of Histology, School of Medicine, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico.
authors.forename: Humberto
authors.initials: H
authors.lastname: Rodríguez-Rocha
authors.affiliation: Department of Microbiology, School of Medicine, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico gmglez@yahoo.com.mx.
authors.forename: Gloria M
authors.initials: GM
authors.lastname: González
mesh_terms: D000825:Animal Structures / Q000382:microbiology; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D015169:Colony Count, Microbial; D003453:Cryptococcosis / Q000188:drug therapy* / Q000382:microbiology* / Q000473:pathology; D003455:Cryptococcus neoformans / Q000187:drug effects* / Q000302:isolation & purification; D004195:Disease Models, Animal; D016469:Fungemia / Q000382:microbiology; D006651:Histocytochemistry; D006801:Humans; D008297:Male; D051379:Mice; D020280:Sertraline / Q000008:administration & dosage* / Q000494:pharmacology*; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D020280:Sertraline
keywords: Cryptococcus neoformans; antifungal efficacy study; antifungal in vitro susceptibility; cryptococcal meningoencephalitis; sertraline