Breakthrough candidaemias during empirical therapy with fluconazole in non-cancer and non-HIV adults caused by in vitro-susceptible Candida spp.: Report of 33 cases

The objective of this study was to assess risk factors and the outcome of breakthrough fungaemias (BFs) occurring during fluconazole (FLU) therapy in non-cancer and non-HIV individuals. Thirty-three fungaemias occurring during therapy with FLU among a total of 310 fungaemias observed within a 10-y national survey were analysed. The agar disk diffusion method was used for antifungal susceptibility testing and the Vitek system for species identification. Univariate and multivariate analysis was performed to determine risk factors for BF. All BFs were due to species known to be susceptible to FLU: Candida albicans (25/33), C. parapsilosis (6/33) and C. guillermondii (2/33). The mean number of positive blood cultures per episode was 2.4. The MIC of Candida spp. to FLU was 0.5-8 mg/ml (all strains were susceptible in vitro). Neonatal age ( < 4 weeks), very low birth weight, prior surgery, central venous catheter placement, artificial ventilation, total parenteral nutrition and C. parapsilosis were significantly related to BF in univariate analysis, but only central venous catheter placement was significantly related in multivariate analysis. However, the outcome of BFs and non-BFs was similar. All BFs occurred in non-HIV patients who were not previously treated with azoles, and were caused by in vitro FLU-susceptible species (C. albicans and C. tropicalis). Thus factors other than in vitro susceptibility play a role in BFs.