Antifungal Pharmacodynamics of Fluconazole Against Cryptococcus neoformans Isolates from Companion Animals in Lagos State

Cryptococcal disease in companion animals, principally caused by Cryptococcus neoformans var. grubii, causes severe meningoencephalitis, pulmonary infiltration, and ocular disease particularly in immunocompromised hosts. Lagos State, South West Nigeria, with its dense human and animal populations, elevated pigeon density, and growing companion animal community, represents a significant ecological setting for Cryptococcus transmission. Antifungal treatment relies heavily on fluconazole, yet pharmacodynamic data for C. neoformans isolates from Nigerian companion animals are absent from the literature. This study isolated C. neoformans from cerebrospinal fluid, nasal exudate, and bronchoalveolar lavage of companion animals including cats, dogs, and rabbits with confirmed cryptococcal disease at veterinary hospitals in Lagos over a 24-month period. Twenty-five isolates were recovered and subjected to fluconazole susceptibility testing by broth microdilution following EUCAST standards. Time-kill kinetics were characterised at 0.5x, 1x, 2x, and 4x MIC concentrations. Capsule morphology and melanin production were characterised for virulence profiling. Fluconazole MIC values ranged from 1 to 16 micrograms per millilitre, with 76 percent of isolates classified as susceptible. Four isolates showed intermediate susceptibility and two showed resistance at MIC above 16 micrograms per millilitre. Time-kill studies demonstrated fungistatic rather than fungicidal activity across all isolates at therapeutic concentrations. High-capsule-producing isolates showed significantly higher MIC values. These findings provide first pharmacodynamic reference data for C. neoformans from Nigerian companion animals, supporting fluconazole as first-line therapy while highlighting the need for MIC-guided treatment in refractory cases. Keywords: Cryptococcus neoformans, fluconazole, pharmacodynamics, companion animals, Lagos.