Correlation of In Vitro Azole Susceptibility with In Vivo Response in a Murine Model of Cryptococcal Meningitis

Abstract

Correlations between in vitro susceptibility and in vivo responses to fluconazole were sought in a mouse model of cryptococcal meningitis. Twenty clinical isolates were used. Two distinct populations were noted. Eight high-virulence isolates had an LD50 of < or = 252 cfu of Cryptococcus neoformans. Twelve low-virulence isolates had an LD50 of > 252 cfu. For 7 low-virulence isolates, the LD50 was > 20,000 cfu. C. neoformans also had a broad range of in vitro susceptibilities (MICs of 1.25 to > 80 micrograms/mL) at 24 h. A correlation was found between the MIC and the minimum effective dose of fluconazole in mice. This was observed with both survival and tissue counts as parameters of efficacy. This study documents for the first time the in vivo relevance of in vitro susceptibility to an azole antifungal for C. neoformans.