An Association of an eBURST Group With Triazole Resistance of Candida tropicalis Blood Isolates

Tulyaprawat, Orawan; Pharkjaksu, Sujiraphong; Chongtrakool, Piriyaporn; Ngamskulrungroj, Popchai

doi:10.3389/fmicb.2020.00934

Cited by 15 publications

(16 citation statements)

References 43 publications

(64 reference statements)

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“…C. tropicalis was the most common cause of candidemia, followed by C. albicans , C. glabrata , and C. parapsilosis . This is consistent with previous studies, including a report that C. tropicalis was the most frequent species isolated from blood samples in the same geographic area of Thailand [ 12 , 13 , 14 , 15 ]. Although several studies identified C. albicans as the most common fungus isolated from blood samples, more recent studies reported a decreasing frequency of C. albicans -associated candidemia and an increasing frequency of candidemia associated with NAC [ 16 , 17 , 18 ].…”

Section: Discussionsupporting

confidence: 93%

“…MLST can clarify the genetic diversity among isolates and characterize the fluconazole susceptibility pattern [ 46 ]. The genetic diversity observed in this study was comparable to that of a previous study in Thailand [ 12 ] but higher than that in other countries [ 47 ]. CC1, a major cluster associated with azole resistance in this study, is a large fluconazole-non-susceptible group found in Taiwan and China [ 46 , 48 ].…”

Section: Discussionsupporting

confidence: 85%

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Species Distribution, Antifungal Susceptibility, and Molecular Epidemiology of Candida Species Causing Candidemia in a Tertiary Care Hospital in Bangkok, Thailand

Boonsilp

Homkaew

Phumisantiphong

et al. 2021

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Candida species represent a common cause of bloodstream infection (BSI). Given the emergence of non-albicans Candida (NAC) associated with treatment failure, investigations into the species distribution, fungal susceptibility profile, and molecular epidemiology of pathogens are necessary to optimize the treatment of candidemia and explore the transmission of drug resistance for control management. This study evaluated the prevalence, antifungal susceptibility, and molecular characteristics of Candida species causing BSI in a tertiary-level hospital in Bangkok, Thailand. In total, 54 Candida isolates were recovered from 49 patients with candidemia. C. tropicalis was the most prevalent species (33.3%), followed by C. albicans (29.6%). Most Candida species were susceptible to various antifungal agents, excluding C. glabrata and C. tropicalis, which had increased rates of non-susceptibility to azoles. Most C. glabrata isolates were non-susceptible to echinocandins, especially caspofungin. The population structure of C. albicans was highly diverse, with clade 17 predominance. GoeBURST analysis of C. tropicalis revealed associations between genotype and fluconazole resistance in a particular clonal complex. The population structure of C. glabrata appeared to have a low level of genetic diversity in MLST loci. Collectively, these data might provide a fundamental database contributing to the development of novel antifungal agents and diagnostic tests.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 85%

Species Distribution, Antifungal Susceptibility, and Molecular Epidemiology of Candida Species Causing Candidemia in a Tertiary Care Hospital in Bangkok, Thailand

Boonsilp

Homkaew

Phumisantiphong

et al. 2021

JoF

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“…The proportion of C. tropicalis among Candida species causing candidaemia are relatively high in tropical Asia and Latin America compared to other continents [2,3]. Azole-resistant C. tropicalis clinical isolates have emerged worldwide [4][5][6][7][8][9][10][11]. This has become particularly problematic in the Asia-Pacific region since 2010 [4,5,7,10,11].…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of Azole Resistance and Trailing in Candida tropicalis Bloodstream Isolates

Chen

Chuang

et al. 2021

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Objectives: Azole-resistant Candida tropicalis has emerged in Asia in the context of its trailing nature, defined by residual growth above minimum inhibitory concentrations (MICs). However, limited investigations in C. tropicalis have focused on the difference of genotypes and molecular mechanisms between these two traits. Methods: Sixty-four non-duplicated C. tropicalis bloodstream isolates collected in 2017 were evaluated for azole MICs by the EUCAST E.def 7.3.1 method, diploid sequence type (DST) by multilocus sequencing typing, and sequences and expression levels of genes encoding ERG11, its transcription factor, UPC2, and efflux pumps (CDR1, CDR2 and MDR1). Results: Isavuconazole showed the highest in vitro activity and trailing against C. tropicalis, followed by voriconazole and fluconazole (geometric mean [GM] MIC, 0.008, 0.090, 1.163 mg/L, respectively; trailing GM, 27.4%, 20.8% and 19.5%, respectively; both overall p < 0.001). Fourteen (21.9%) isolates were non-WT to fluconazole/voriconazole, 12 of which were non-WT to isavuconazole and clustered in clonal complex (CC) 3. Twenty-five (39.1%) isolates were high trailing WT, including all CC2 isolates (44.0%) (containing DST140 and DST98). All azole non-WT isolates carried the ERG11 mutations A395T/W and/or C461T/Y, and most carried the UPC2 mutation T503C/Y. These mutations were not identified in low and high trailing WT isolates. Azole non-WT and high trailing WT isolates exhibited the highest expression levels of ERG11 and MDR1, 3.91- and 2.30-fold, respectively (both overall p < 0.01). Conclusions: Azole resistance and trailing are phenotypically and genotypically different in C. tropicalis. Interference with azole binding and MDR1 up-regulation confer azole resistance and trailing, respectively.

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“…To understand the association between azole use and the emergence of ANS C. tropicalis isolates, we analyzed the clinical history of respective patients (20/127; 15.7%) and found that 50% of them were azole-naïve, which is similar to the results obtained for patients infected with Candida parapsilosis ( Tóth et al, 2019 ) and C. auris ( Jeffery-Smith et al, 2018 ). Recent studies from Iran ( Arastehfar et al, 2020a ), Taiwan ( Chen et al, 2019 ), and Japan ( Chong et al, 2012 ) have reported the same phenomenon, which could be the driving force behind the replacement of C. albicans as the first leading cause of candidemia with C. tropicalis documented in Taiwan ( Tulyaprawat et al, 2020 ). We also found an association between fluconazole resistance and genotypes, which may account for the dramatic increase in the number and persistence of ANS isolates in clinical settings since the previous candidemia study in Turkey ( Arikan-Akdagli et al, 2019 ), hypothetically because azole-resistant isolates may possess a higher mutagenesis potential allowing them to thrive in conditions when fluconazole is heavily used ( Healey et al, 2016 ).…”

Section: Discussionmentioning

confidence: 74%

Recent Increase in the Prevalence of Fluconazole-Non-susceptible Candida tropicalis Blood Isolates in Turkey: Clinical Implication of Azole-Non-susceptible and Fluconazole Tolerant Phenotypes and Genotyping

et al. 2020

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Candida tropicalis is the fourth leading cause of candidemia in Turkey. Although C. tropicalis isolates from 1997 to 2017 were characterized as fully susceptible to antifungals, the increasing global prevalence of azole-non-susceptible (ANS) C. tropicalis and the association between high fluconazole tolerance (HFT) and fluconazole therapeutic failure (FTF) prompted us to re-evaluate azole susceptibility of C. tropicalis in Turkey. In this study, 161 C. tropicalis blood isolates from seven clinical centers were identified by ITS rDNA sequencing, genotyped by multilocus microsatellite typing, and tested for susceptibility to five azoles, two echinocandins, and amphotericin B (AMB); antifungal resistance mechanisms were assessed by sequencing of ERG11 and FKS1 genes. The results indicated that C. tropicalis isolates, which belonged to 125 genotypes grouped into 11 clusters, were fully susceptible to echinocandins and AMB; however, 18.6% of them had the ANS phenotype but only two carried the ANS-conferring mutation (Y132F). HFT was recorded in 52 isolates, 10 of which were also ANS. Large proportions of patients infected with ANS and HFT isolates (89 and 40.7%, respectively) showed FTF. Patients infected with azole-susceptible or ANS isolates did not differ in mortality, which, however, was significantly lower for those infected with HFT isolates ( P = 0.007). There were significant differences in mortality ( P = 0.02), ANS ( P = 0.012), and HFT ( P = 0.007) among genotype clusters. The alarming increase in the prevalence of C. tropicalis blood isolates with ANS and HFT in Turkey and the notable FTF rate should be a matter of public health concern.

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An Association of an eBURST Group With Triazole Resistance of Candida tropicalis Blood Isolates

Cited by 15 publications

References 43 publications

Species Distribution, Antifungal Susceptibility, and Molecular Epidemiology of Candida Species Causing Candidemia in a Tertiary Care Hospital in Bangkok, Thailand

Species Distribution, Antifungal Susceptibility, and Molecular Epidemiology of Candida Species Causing Candidemia in a Tertiary Care Hospital in Bangkok, Thailand

Mechanisms of Azole Resistance and Trailing in Candida tropicalis Bloodstream Isolates

Recent Increase in the Prevalence of Fluconazole-Non-susceptible Candida tropicalis Blood Isolates in Turkey: Clinical Implication of Azole-Non-susceptible and Fluconazole Tolerant Phenotypes and Genotyping

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