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. 2017 Mar 22:8:464.
doi: 10.3389/fmicb.2017.00464. eCollection 2017.

Notable Increasing Trend in Azole Non-susceptible Candida tropicalis Causing Invasive Candidiasis in China (August 2009 to July 2014): Molecular Epidemiology and Clinical Azole Consumption

Xin Fan  1 , Meng Xiao  2 , Kang Liao  3 , Timothy Kudinha  4 , He Wang  2 , Li Zhang  2 , Xin Hou  2 , Fanrong Kong  5 , Ying-Chun Xu  2
Affiliations

Notable Increasing Trend in Azole Non-susceptible Candida tropicalis Causing Invasive Candidiasis in China (August 2009 to July 2014): Molecular Epidemiology and Clinical Azole Consumption

Xin Fan et al. Front Microbiol. .

Abstract

Objectives: To report the notable increasing trends of C. tropicalis antifungal resistance in the past 5 years, and explore molecular epidemiology, and the relationship between clinical azoles consumption and increased resistance rate. Methods: Between August 2009 and July 2014, 507 non-duplicated C. tropicalis isolates causing invasive candidiasis were collected from 10 hospitals in China. The in vitro antifungal susceptibility of nine common agents was determined by Sensititre YeastOne™ using current available species-specific clinical breakpoint (CBPs) or epidemiological cut-off values (ECVs). A high discriminatory three-locus (ctm1, ctm3, and ctm24) microsatellite scheme was used for typing of all isolates collected. Clinical consumption of fluconazole and voriconazole was obtained and the Defined Daily Dose measurement units were assigned to the data. Results: Overall, 23.1 and 20.7% of isolates were non-susceptible to fluconazole and voriconazole, respectively. And over 5 years, the non-susceptible rate of C. tropicalis isolates to fluconazole and voriconazole continuously increased from 11.2 to 42.7% for fluconazole (P < 0.001), and from 10.4 to 39.1% for voriconazole (P < 0.001). Four genotype clusters were observed to be associated with fluconazole non-susceptible phenotype. However, the increase in azole non-susceptible rate didn't correlate with clinical azole consumption. Conclusions: The rapid emergence of azole resistant C. tropicalis strains in China is worrying, and continuous surveillance is warranted and if the trend persists, empirical therapeutic strategies for C. tropicalis invasive infections should be modified.

Keywords: Candida tropicalis; China; antifungal susceptibility; azole resistance; genotyping; invasive candidiasis.

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Figures

Figure 1
Figure 1
Geographic distribution of the 10 surveillance centers involved in this study, number of isolates collected, and change of fluconazole non-susceptible rate from the first to the last surveillance year in each center.
Figure 2
Figure 2
Trends of susceptibility (including susceptible or wild-type rate, and MIC50, MIC90, and GM MIC values) of 507 C. tropicalis isolates to four azoles (A), fluconazole; (B), voriconazole; (C), itraconazole; (D), posaconazole, over 5 years. S, susceptible; SDD, susceptible dose-dependent; R, resistant; WT, wild-type; NWT, non-wild-type; MIC, minimum inhibitory concentration; GM, geometric mean.
Figure 3
Figure 3
The minimum spanning tree (MST) draw by three-locus microsatellite genotyping results of 507 C. tropicalis isolates. Panel (A) and four genotype clusters associated with fluconazole non-susceptible phenotypes (B–E). Each circle corresponds to a microsatellite genotype, and the size of circle represents number of isolates for each genotype. Different colors in the circle represents different fluconazole susceptibility categories. The lines between circles indicate the similarity between profiles.
Figure 4
Figure 4
Trends of fluconazole and voriconazole susceptibilities and clinical consumption of these two drugs over the 5-year surveillance period.
See this image and copyright information in PMC

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