Abstract
With the widespread use of long-term fluconazole prophylaxis and suppressive treatment, the potential development of fluconazole resistance poses a threat to the management of cryptococcal disease. Interpretive breakpoints for the in vitro antifungal susceptibility testing of C. neoformans have not been established and it is unclear whether the fluconazole minimum inhibitory concentration (MIC) is clinically relevant. To gain insight into the management of patients with cryptococcosis who fail fluconazole therapy, we conducted a PubMed literature search for cases of fluconazole-resistant cryptococcosis reported from 1991 to 2011. A total of 20 such cases were identified in which most patients had AIDS and 30% had never had prior exposure to fluconazole. Fluconazole failure in patients with cryptococcal disease cannot be fully attributed to emerging resistance of the etiologic agent and heteroresistance is a potential alternative mechanism. There is a need to refine the definition of fluconazole-resistant cryptococcosis and additional studies of such patients will improve treatment strategies and outcomes.
Declaration of interest: J McCormack has received funding for research and travel grants from Pfizer. The authors report no conflicts of interest. The authors alone are responsible for the content and the writing of the paper.
This paper was first published online on Early Online on 21 September 2012.