Abstract
Candida glabrata is an increasingly important cause of invasive candidiasis. In China, relatively little is known of the molecular epidemiology of C. glabrata and of its antifungal susceptibility patterns. Here we studied 411 non-duplicate C. glabrata isolates from 411 patients at 11 hospitals participating in the National China Hospital Invasive Fungal Surveillance Net program (CHIF-NET; 2010-2014). Genotyping was performed using multilocus sequence typing (MLST) employing six genetic loci and by microsatellite analysis. Antifungal susceptibility testing was performed using Sensititre YeastOne™ YO10 methodology. Of 411 isolates, 35 sequence types (ST) were identified by MLST and 79 different genotypes by microsatellite typing; the latter had higher discriminatory power than MLST in the molecular typing of C. glabrata. Using MLST, ST7 and ST3 were the most common STs (66.4 and 9.5% of all isolates, respectively) with 24 novel STs identified; the most common microsatellite types were T25 (30.4% of all isolates) and T31 (12.4%). Resistance to fluconazole (MIC > 32 μg/mL) was seen in 16.5% (68/411) of isolates whilst MICs of >0.5 μg/mL for voriconazole, >2 μg/mL for itraconazole and >2 μg/mL for posaconazole were seen for 28.7, 6.8, and 7.3% of isolates, respectively; 14.8% of all isolates cross-resistant/non-wide-type to fluconazole and voriconazole. Fluconazole resistant rates increased 3-fold over the 5-year period whilst that of isolates with non-WT MICs to voriconazole, 7-fold. All echinocandins exhibited >99% susceptibility rates against all isolates but notably one isolate exhibited multi-drug resistance to the azoles and echinocandins. The study has provided a global picture of the molecular epidemiology and drug resistance rates of C. glabrata in China during the period of the study.
Highlights
Candida species are the most common opportunistic fungal pathogens in debilitated or immunecompromised hosts with high rates of mortality (Hajjeh et al, 2004; Wisplinghoff et al, 2004; Kullberg and Arendrup, 2015; Pappas et al, 2016)
Of 411 isolates, 163 (39.7%) were from patients admitted in the Intensive care unit (ICU), 29.7% (122/411) from patients in the Surgery Department, 18.2% (75/411) from the Medical Department, 4.9% (20/411) from the Emergency Department and 7.5% (31/411) from other departments
multilocus sequence typing (MLST) analysis revealed a low degree of genetic diversity within C. glabrata the six-locus based MLST scheme showed a large number of STs overall—it allowed for the differentiation of 35 sequence types (STs) among 411 isolates, including 24 novel STs (PU 1-PU 24)
Summary
Candida species are the most common opportunistic fungal pathogens in debilitated or immunecompromised hosts with high rates of mortality (up to 40%) (Hajjeh et al, 2004; Wisplinghoff et al, 2004; Kullberg and Arendrup, 2015; Pappas et al, 2016). The majority of cases of invasive candidiasis (IC) are attributed to Candida albicans, globally, there are increasing rates of infection by non-C. albicans species (Kullberg and Arendrup, 2015; Xiao et al, 2015; Pappas et al, 2016). E.g., pulse field gel electrophoresis (PFGE), multilocus sequence typing (MLST) assays and microsatellite analysis have been established to determine genetic relatedness of C. glabrata (Dodgson et al, 2003; Foulet et al, 2005; Lin et al, 2007; Brisse et al, 2009; EnacheAngoulvant et al, 2010; Abbes et al, 2012). Microsatellite marker analysis is another rapid, reliable technique with several multilocus microsatellite systems proposed (Foulet et al, 2005; Brisse et al, 2009; EnacheAngoulvant et al, 2010; Abbes et al, 2012)
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