Two Closely Related Fluconazole-Resistant <i>Candida tropicalis</i> Clones Circulating in Taiwan from 1999 to 2006

Li, Shuying; Yang, Yun-Liang; Lin, Yu-Hsin; Ko, Hui-Ching; Wang, An-Huei; Chen, Kuo-Wei; Wang, Chih‐Wei; Chi, Hsin; Lo, Hsiu‐Jung

doi:10.1089/mdr.2009.0915

Cited by 22 publications

(16 citation statements)

References 13 publications

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“…The four clusters comprised 48.7% of the fluconazole non-susceptible isolates overall. Previous studies in Taiwan also observed regional dissemination of genetically close-related fluconazole-resistant C. tropicalis isolates (Chou et al, 2007; Li et al, 2009). Therefore, continuous monitoring of the fluconazole non-susceptible C. tropicalis isolates assisted by molecular typing assays is warranted.…”

Section: Discussionmentioning

confidence: 71%

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

et al. 2017

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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.

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Section: Discussionmentioning

confidence: 71%

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

et al. 2017

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“…On the other hand, we did not find the Y132F and S145F substitutions in our isolates. Because increased resistance of C. tropicalis to fluconazole and outbreaks of infection caused by fluconazole-resistant C. tropicalis have been recognized in some hospitals (5,25,26), C. tropicalis isolates with the ERG11 mutation should be genotyped to investigate the transmission of particular clones. Although overexpression of ERG11 associated with missense mutations has been described as the mechanism of azole resistance in clinical isolates of C. tropicalis (7,8), in the present study, only two FNS isolates harbored ERG11 mutations, suggesting that gene overexpression, rather than ERG11 mutation, is the main mechanism of azole resistance in C. tropicalis isolates from Korean hospitals.…”

Section: Discussionmentioning

confidence: 99%

Resistance Mechanisms and Clinical Features of Fluconazole-Nonsusceptible Candida tropicalis Isolates Compared with Fluconazole-Less-Susceptible Isolates

Choi

Won

Shin

et al. 2016

Antimicrob Agents Chemother

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eWe investigated the azole resistance mechanisms and clinical features of fluconazole-nonsusceptible (FNS) isolates of Candida tropicalis recovered from Korean surveillance cultures in comparison with fluconazole-less-susceptible (FLS) isolates. Thirtyfive clinical isolates of C. tropicalis, comprising 9 FNS (fluconazole MIC, 4 to 64 g/ml), 12 FLS (MIC, 1 to 2 g/ml), and 14 control (MIC, 0.125 to 0.5 g/ml) isolates, were assessed. CDR1, MDR1, and ERG11 expression was quantified, and the ERG11 and UPC2 genes were sequenced. Clinical features of 16 patients with FNS or FLS bloodstream isolates were analyzed. Both FNS and FLS isolates had >10-fold higher mean expression levels of CDR1, MDR1, and ERG11 genes than control isolates (P values of <0.02 for all). When FNS and FLS isolates were compared, FNS isolates had 3.4-fold higher mean ERG11 expression levels than FLS isolates (P ‫؍‬ 0.004), but there were no differences in those of CDR1 or MDR1. Of all 35 isolates, 4 (2 FNS and 2 FLS) and 28 (8 FNS, 11 FLS, and 9 control) isolates exhibited amino acid substitutions in Erg11p and Upc2p, respectively. Both FNS and FLS bloodstream isolates were associated with azole therapeutic failure (3/4 versus 4/7) or uncleared fungemia (4/6 versus 4/10), but FNS isolates were identified more frequently from patients with previous azole exposure (6/6 versus 3/10; P ‫؍‬ 0.011) and immunosuppression (6/6 versus 3/10; P ‫؍‬ 0.011). These results reveal that the majority of FNS C. tropicalis isolates show overexpression of CDR1, MDR1, and ERG11 genes, and fungemia develops after azole exposure in patients with immunosuppression. Candida tropicalis has become an important cause of bloodstream infections (BSIs) in seriously ill patients (1-3). Although C. tropicalis is usually susceptible to azole antifungals, 7 to 40% of clinical isolates have recently been reported to be resistant to azoles, particularly fluconazole (2-5). The mechanisms responsible for acquired azole resistance are well-characterized in Candida albicans and include mutations in the ERG11 gene, which encodes the drug target enzyme (lanosterol 14␣-demethylase), overexpression of ERG11, and overexpression of genes encoding efflux pumps (6). In C. tropicalis, overexpression of ERG11 associated with missense mutations has been described as the most frequent azole resistance mechanism in clinical isolates (7,8). However, the azole resistance mechanisms of C. tropicalis remain a matter of debate, and only five studies have been reported to date (7-11). In addition, there is a lack of substantial research on mutations in the transcription factor Upc2p of C. tropicalis, which can induce ERG11 overexpression and contribute to the development of fluconazole resistance in C. albicans (12)(13)(14).Fluconazole MIC distributions of wild-type C. tropicalis ranged from 0.125 to 64 g/ml following 24 h of incubation using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution (BMD) methods, and their modal MIC values were 0.125 to 0.5 g/ml (6). Recently, the CLSI es...

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“…Chou et al (27) also reported an association between the DSTs and the C. tropicalis trailing phenomenon. Additionally, Li et al (36) described several alleles associated with low MICs of fluconazole (alleles 3 of ICL1, 9 of MDR1, 1 of SAPT2, 3, 6, and 10 of SAPT4, 48 of XYR1, and 7 of ZWF1a). In our study, we found no isolate with DST 140, and there was an association of allele 48 (XYR1) and allele 6 (SAPT4) with fluconazole-susceptible and fluconazole-resistant isolates, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…MLST has been used to establish the relationship between the DSTs with susceptibility profile to fluconazole and the trailing phenomenon (27,32,36). In Brazil, fluconazole is an effective systemic antifungal drug against most isolates of C. tropicalis (24).…”

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confidence: 99%

Multilocus Sequence Typing of Candida tropicalis Shows the Presence of Different Clonal Clusters and Fluconazole Susceptibility Profiles in Sequential Isolates from Candidemia Patients in São Paulo, Brazil

et al. 2013

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fThe profiles of 61 Candida tropicalis isolates from 43 patients (28 adults and 15 children) diagnosed with candidemia at two teaching hospitals in São Paulo, Brazil, were characterized by multilocus sequence typing (MLST). For the 14 patients who had bloodstream infections, 32 isolates were serially collected from their blood and/or catheters. Thirty-nine diploid sequence types (DSTs) were differentiated. According to the C. tropicalis MLST database (http://pubmlst.org/ctropicalis/), 36 DSTs and 23 genotypes identified from the 61 isolates had not previously been described. This report represents the first study to characterize sequential isolates of C. tropicalis from candidemia cases in South America. Microvariation in a single gene was found in the sequential isolates from 7 patients. The main polymorphisms occurred in the alleles of the XYR1 gene, specifically at nucleotide positions 215, 242, and 344. Macrovariation in six gene fragments was detected in the isolates from 3 patients. eBURST analysis added two new groups to this study (groups 6 and 18). Additionally, susceptibility tests indicate that 3 isolates were resistant to fluconazole. No correlation was found between the DSTs and susceptibility to fluconazole and/or selective antifungal pressure. Two patients were sequentially infected with resistant and susceptible strains. MLST is an important tool for studying the genetic diversity of multiple/sequential isolates of patients with candidemia, allowing the comparison of our data with those from other regions of the world, as well as allowing an analysis of the genetic relationship among several clones in sequential isolates from the same or different candidemia patient sites (blood or catheter).

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Two Closely Related Fluconazole-Resistant Candida tropicalis Clones Circulating in Taiwan from 1999 to 2006

Cited by 22 publications

References 13 publications

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

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

Resistance Mechanisms and Clinical Features of Fluconazole-Nonsusceptible Candida tropicalis Isolates Compared with Fluconazole-Less-Susceptible Isolates

Multilocus Sequence Typing of Candida tropicalis Shows the Presence of Different Clonal Clusters and Fluconazole Susceptibility Profiles in Sequential Isolates from Candidemia Patients in São Paulo, Brazil

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