High frequency of azole resistant Candida spp. colonization among presumptive multidrug resistant tuberculosis (MDR-TB) patients

Abstract

Background Tuberculosis is one of the major causes of death globally. The problems become even more complicated with the rise in prevalence of multidrug resistant tuberculosis (MDR-TB). Many diseases have been reported to occur with tuberculosis making it more difficult to manage. Candida spp., which are yeast-like fungi and a constituent of normal flora in humans, are notoriously reported to be one of the most common opportunistic nosocomial infections. This study aimed to measure the proportion of presumptive MDR-TB patients colonized with Candida spp. and to characterize its susceptibility against azole group antifungal agents. Methods Sputum from presumptive MDR-TB patients were collected and examined for the presence of Mycobacterium tuberculosis and its rifampicin resistant status using GeneXpert. It was further cultured on Sabouroud’s Dextrose Agar (SDA) to isolate the Candida spp. The Candida species were determined using HiCrome™ Candidal Differential Agar. Antifungal susceptibility was tested using microbroth dilution methods. Checkerboard microdilution assays were performed to measure the interaction between rifampicin and fluconazole to C. albicans. Results There were 355 presumptive MDR-TB patients enrolled. A total of 101 (28.4%) patients were confirmed to have M. tuberculosis. There were 113 (31.8%) sputum positive for Candida spp., which corresponded to 149 Candida spp. isolates. Candida albicans was the most frequent (53.7%) species isolated from all patients. The susceptibility of Candida spp. against fluconazole, itraconazole, and ketoconazole were 38.3%, 1.3%, and 10.7% respectively. There was significant association between rifampicin exposure history and susceptibility of Candida albicans against fluconazole (Odds Ratio: 9.96; 95% CI: 1.83–54.19; p <0.01), but not for ketoconazole and itraconazole. The checkerboard microdilution assays showed that rifampicin decreased the fungicidal activity of fluconazole to C. albicans in a dose-dependent manner. Conclusion There was high frequency of azole resistant Candida spp. isolates colonizing the respiratory tract of presumptive MDR-TB patients. This presence might indicate the association of chronic exposure to rifampicin, the main drug for tuberculosis therapy, with the induction of azole resistance.