Development of Resistance to 5-Fluorocytosine in Candida parapsilosis during Therapy

Abstract

After an initially favorable response, infective endocarditis caused by Candida parapsilosis recurred on day 37 of treatment with 5-fluorocytosine. Development of resistance of the organism to 5-fluorocytosine during therapy was documented by in vitro tests (MIC, 6.5 µg/ml initially, > 129 µg/ml after relapse). Although strains isolated before treatment and after relapse were able to incorporate exogenous uracil into RNA and were susceptible to 5-fluorouracil, the isolate found after relapse differed from the one isolated before treatment in being unable to incorporate exogenous cytosine and resistant to 5-fluorocytosine. The enzymatic basis of this resistance was identified as a virtual lack of cytosine deaminase activity in the strain isolated after relapse.