Comparison of Human and Soil Candida tropicalis Isolates with Reduced Susceptibility to Fluconazole

PLOS ONE, Dec 2019

Infections caused by treatment-resistant non-albicans Candida species, such as C. tropicalis, has increased, which is an emerging challenge in the management of fungal infections. Genetically related diploid sequence type (DST) strains of C. tropicalis exhibiting reduced susceptibility to fluconazole circulated widely in Taiwan. To identify the potential source of these wildly distributed DST strains, we investigated the possibility of the presence in soil of such C. tropicalis strains by pulsed field gel electrophoresis (PFGE) and DST typing methods. A total of 56 C. tropicalis isolates were recovered from 26 out of 477 soil samples. Among the 18 isolates with reduced susceptibility to fluconazole, 9 belonged to DST149 and 3 belonged to DST140. Both DSTs have been recovered from our previous studies on clinical isolates from the Taiwan Surveillance of Antimicrobial Resistance of Yeasts (TSARY) program. Furthermore, these isolates were more resistant to agricultural azoles. We have found genetically related C. tropicalis exhibiting reduced susceptibility to fluconazole from the human hosts and environmental samples. Therefore, to prevent patients from acquiring C. tropicalis with reduced susceptibility to azoles, prudent use of azoles in both clinical and agricultural settings is advocated.

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Comparison of Human and Soil Candida tropicalis Isolates with Reduced Susceptibility to Fluconazole

et al. (2012) Comparison of Human and Soil Candida tropicalis Isolates with Reduced Susceptibility to Fluconazole. PLoS ONE 7(4): e34609. doi:10.1371/journal.pone.0034609 Comparison of Human and Soil Candida tropicalis Isolates with Reduced Susceptibility to Fluconazole Yun-Liang Yang 0 Chih-Chao Lin 0 Te-Pin Chang 0 Tsai-Ling Lauderdale 0 Hui-Ting Chen 0 Ching-Fu Lee 0 Chih-Wen Hsieh 0 Pei-Chen Chen 0 Hsiu-Jung Lo 0 Kirsten Nielsen, University of Minnesota, United States of America 0 1 Department of Biological Science and Technology, National Chiao Tung University , Hsinchu, Taiwan , 2 Institute of Molecular Medicine and Bioengineering, National Chiao Tung University , Hsinchu, Taiwan , 3 National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan, 4 Department of Applied Science, National Hsinchu University of Education, Hsinchu, Taiwan, 5 School of Dentistry, China of Medical University , Taichung , Taiwan Infections caused by treatment-resistant non-albicans Candida species, such as C. tropicalis, has increased, which is an emerging challenge in the management of fungal infections. Genetically related diploid sequence type (DST) strains of C. tropicalis exhibiting reduced susceptibility to fluconazole circulated widely in Taiwan. To identify the potential source of these wildly distributed DST strains, we investigated the possibility of the presence in soil of such C. tropicalis strains by pulsed field gel electrophoresis (PFGE) and DST typing methods. A total of 56 C. tropicalis isolates were recovered from 26 out of 477 soil samples. Among the 18 isolates with reduced susceptibility to fluconazole, 9 belonged to DST149 and 3 belonged to DST140. Both DSTs have been recovered from our previous studies on clinical isolates from the Taiwan Surveillance of Antimicrobial Resistance of Yeasts (TSARY) program. Furthermore, these isolates were more resistant to agricultural azoles. We have found genetically related C. tropicalis exhibiting reduced susceptibility to fluconazole from the human hosts and environmental samples. Therefore, to prevent patients from acquiring C. tropicalis with reduced susceptibility to azoles, prudent use of azoles in both clinical and agricultural settings is advocated. - Funding: This study was supported by 99A1-ID-PP-04-014 and 00A 1-ID-PP-04-014 from National Health Research Institutes and NSC 99-2320-B-400-006-MY3 and NSC 99-2320-B-009-001-MY3 from National Science Council in Taiwan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. Due to the elevated number of risk populations, the prevalence of fungal infections has increased significantly in past two decades. Candida species are the most frequently isolated fungal pathogens causing morbidity and mortality in seriously immunocompromised hosts. Although Candida albicans is the most prevalent species in hospitalized individuals and in nosocomial infections, there has been a shift toward the more treatment-resistant non-albicans Candida species [1,2,3,4,5]. This has become an emerging issue in the management of fungal infection. The prevalence of these species differed significantly in various geographic areas [4,5,6,7,8,9,10]. Candida glabrata was the most frequently isolated species in Western countries [4,11,12], whereas C. tropicalis predominated in Asia [5,13,14,15]. For the treatment, azoles, echinocandins, polyenes, and 5-flucytosine are the four major classes of antifungal drugs. Due to low cost and less side effects, fluconazole has become one of the most commonly prescribed drugs. Among the phenomena associated with azole resistance, trailing describes the reduced but persistent growth that some isolates exhibit at drug concentrations above the minimum inhibitory concentrations (MICs) in broth dilution tests [16]. When the MIC of an isolate measured after 48 hours (h) incubation is approximately 4-fold higher than that at the 24 h point [17], the isolate is defined to have trailing growth. Thus, in the present study, isolates with fluconazole MICs$64 mg/L or voriconazole MICs$4 mg/L after 48 h incubation were considered to have reduced susceptibility to azole drugs. In order to monitor the trends of species distribution and drug susceptibilities of yeast pathogens, the Taiwan Surveillance of Antimicrobial Resistance of Yeasts (TSARY) program was initiated in 1999 [18]. Subsequently, two more rounds of TSARY were conducted in 2002 and 2006. Previously, we found 23 of the 162 C. tropicalis isolates collected from TSARY in 1999 with fluconazole MICs$64 mg/L to be closely related despite being collected from different hospitals throughout Taiwan [19,20]. Furthermore, 5 of the 23 isolates exhibiting reduced susceptibility to fluconazole were from hospital N4 and all belonged to the same diploid sequence typ (...truncated)


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Yun-Liang Yang, Chih-Chao Lin, Te-Pin Chang, Tsai-Ling Lauderdale, Hui-Ting Chen, Ching-Fu Lee, Chih-Wen Hsieh, Pei-Chen Chen, Hsiu-Jung Lo. Comparison of Human and Soil Candida tropicalis Isolates with Reduced Susceptibility to Fluconazole, PLOS ONE, 2012, Volume 7, Issue 4, DOI: 10.1371/journal.pone.0034609