The impact of the fluconazole trailing effect on the persistence of Candida albicans bloodstream infection when treated with fluconazole

Objectives The trailing effect of Candida species is a phenomenon characterized by reduced but persistent growth at antifungal concentrations above the minimal inhibitory concentration (MIC). We assessed the impact of trailing growth on the persistence of Candida albicans candidemia in patients receiving fluconazole therapy. Methods We retrospectively investigated candidemia isolates at three hospitals in southern Taiwan between 2013 and 2020. Patients treated with fluconazole for fluconazole-susceptible C. albicans candidemia were enrolled. The degree of trailing was determined as the average growth above the MIC divided by the measured growth at the lowest drug concentration using the EUCAST method and classified into four categories, residual (0.1-5%), slight (6-10%), moderate (11-15%), and heavy trailers (>15%). Results Among isolates from 190 patients, the proportions of heavy trailers at 24 h, 48 h, and 72 h were 63.7% (121/190), 63.2% (120/190), and 74.7% (142/190), respectively. Persistent candidemia was observed in 17 (8.9 %) patients. The proportion of persistent C. albicans candidemia in heavy trailing isolates at 48 h was higher than in isolates without heavy trailing (13.3% [16/120] vs. 1.4% [1/70], p=0.007). A multivariate analysis showed that immunosuppression (odds ratio [OR] = 7.92; 95% confidence interval [CI]: 2.38-26.39, p=0.001), hospitalization days after the index date of C. albicans identification (OR=1.03; 95% CI: 1.01-1.05, p=0.011) and heavy trailing isolates at 48 h (OR=10.04; 95% CI: 1.27-79.88, p=0.029) were independent factors for persistent candidemia. Conclusions The current study revealed that heavy trailing in C. albicans isolates is associated with persistent candidemia in patients receiving fluconazole treatment.