Therapeutic efficacy of posaconazole against isolates of Candida albicans with different susceptibilities to fluconazole in a vaginal model.
A battery of 34 vaginal isolates of Candida albicans was tested against posaconazole (POS) and fluconazole (FLU) to determine their in vitro susceptibilities and to obtain FLU-susceptible and FLU-resistant strains for the murine in vivo studies. FLU-resistant strains were chosen on the basis of their 48-h MICs. The 48-h geometric mean MICs for all isolates tested were 0.016 and 0.656 microg/ml for POS and FLU, respectively. The treatment regimens for the vaginal murine infection model were POS or FLU at 10 or 20 mg/kg of body weight/day and 20 mg/kg twice a day. All regimens with POS were effective in reducing fungal burden of both the fluconazole-susceptible and resistant isolates of C. albicans. All FLU regimens were effective against infection induced by the fluconazole-susceptible strain. While FLU at 10 mg/kg was ineffective against fungal burden of the resistant strain, treatment with FLU at 20 mg/kg once or twice a day was effective against this strain. Both POS and FLU at 20 mg/kg twice a day were able to clear C. albicans from vaginas of mice infected with the fluconazole-susceptible strain. POS displayed a more effective in vivo activity than FLU in the treatment of murine C. albicans vaginitis produced by isolates with different susceptibilities to FLU.
González
Gloria M
GM
Departamento de Microbiología, Facultad de Medicina, Universidad Autónoma de Nuevo León, México. gmglez@yahoo.com.mx
Robledo
Efrén
E
Saldívar
Donato
D
González
Gerardo
G
Bosques
Francisco
F
Garza
Elvira
E
D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000302:isolation & purification; D002181:Candidiasis, Vulvovaginal / Q000188:drug therapy* / Q000382:microbiology*; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D025141:Drug Resistance, Fungal; D005260:Female; D015725:Fluconazole / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology*; D014621:Vagina / Q000382:microbiology
D000935:Antifungal Agents; D014230:Triazoles; C101425:posaconazole; D015725:Fluconazole