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A multicentre study of antifungal susceptibility patterns among 350 Candida auris isolates (2009-17) in India: role of the ERG11 and FKS1 genes in azole and echinocandin resistance.
J Antimicrob Chemother 2018; 73(4):891-899JA

Abstract

Background

Candida auris has emerged globally as an MDR nosocomial pathogen in ICU patients.

Objectives

We studied the antifungal susceptibility of C. auris isolates (n = 350) from 10 hospitals in India collected over a period of 8 years. To investigate azole resistance, ERG11 gene sequencing and expression profiling was conducted. In addition, echinocandin resistance linked to mutations in the C. auris FKS1 gene was analysed.

Methods

CLSI antifungal susceptibility testing of six azoles, amphotericin B, three echinocandins, terbinafine, 5-flucytosine and nystatin was conducted. Screening for amino acid substitutions in ERG11 and FKS1 was performed.

Results

Overall, 90% of C. auris were fluconazole resistant (MICs 32 to ≥64 mg/L) and 2% and 8% were resistant to echinocandins (≥8 mg/L) and amphotericin B (≥2 mg/L), respectively. ERG11 sequences of C. auris exhibited amino acid substitutions Y132 and K143 in 77% (n = 34/44) of strains that were fluconazole resistant whereas WT genotypes, i.e. without substitutions at these positions, were observed in isolates with low fluconazole MICs (1-2 mg/L) suggesting that these substitutions confer a phenotype of resistance to fluconazole similar to that described for Candida albicans. No significant expression of ERG11 was observed, although expression was inducible in vitro with fluconazole exposure. Echinocandin resistance was linked to a novel mutation S639F in FKS1 hot spot region I.

Conclusions

Overall, 25% and 13% of isolates were MDR and multi-azole resistant, respectively. The most common resistance combination was azoles and 5-flucytosine in 14% followed by azoles and amphotericin B in 7% and azoles and echinocandins in 2% of isolates.

Authors+Show Affiliations

Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India.Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India.Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India.Public Health Research Institute, Rutgers Biomedical and Health Sciences, Newark, NJ, USA.Department of Microbiology, Amrita Institute of Medical Sciences and Research Center, Amrita University, Ponekkara, Cochin, India.Department of Microbiology, Medanta-The Medcity, Gurgaon, Haryana, India.Department of Microbiology, Max hospital, New Delhi, India.Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India.Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India.Department of Microbiology, Medanta-The Medcity, Gurgaon, Haryana, India.Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India.Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India.Department of Microbiology, Institute of Liver & Biliary Sciences, New Delhi, India.Department of Microbiology, Rajiv Gandhi Cancer Institute & Research Center, Delhi, India.Public Health Research Institute, Rutgers Biomedical and Health Sciences, Newark, NJ, USA.Department of Medical Microbiology and Infectious Diseases, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands. Centre of Expertise in Mycology Radboudumc/CWZ, Nijmegen, The Netherlands.

Pub Type(s)

Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29325167

Citation

Chowdhary, Anuradha, et al. "A Multicentre Study of Antifungal Susceptibility Patterns Among 350 Candida Auris Isolates (2009-17) in India: Role of the ERG11 and FKS1 Genes in Azole and Echinocandin Resistance." The Journal of Antimicrobial Chemotherapy, vol. 73, no. 4, 2018, pp. 891-899.
Chowdhary A, Prakash A, Sharma C, et al. A multicentre study of antifungal susceptibility patterns among 350 Candida auris isolates (2009-17) in India: role of the ERG11 and FKS1 genes in azole and echinocandin resistance. J Antimicrob Chemother. 2018;73(4):891-899.
Chowdhary, A., Prakash, A., Sharma, C., Kordalewska, M., Kumar, A., Sarma, S., ... Meis, J. F. (2018). A multicentre study of antifungal susceptibility patterns among 350 Candida auris isolates (2009-17) in India: role of the ERG11 and FKS1 genes in azole and echinocandin resistance. The Journal of Antimicrobial Chemotherapy, 73(4), pp. 891-899. doi:10.1093/jac/dkx480.
Chowdhary A, et al. A Multicentre Study of Antifungal Susceptibility Patterns Among 350 Candida Auris Isolates (2009-17) in India: Role of the ERG11 and FKS1 Genes in Azole and Echinocandin Resistance. J Antimicrob Chemother. 2018 04 1;73(4):891-899. PubMed PMID: 29325167.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A multicentre study of antifungal susceptibility patterns among 350 Candida auris isolates (2009-17) in India: role of the ERG11 and FKS1 genes in azole and echinocandin resistance. AU - Chowdhary,Anuradha, AU - Prakash,Anupam, AU - Sharma,Cheshta, AU - Kordalewska,Milena, AU - Kumar,Anil, AU - Sarma,Smita, AU - Tarai,Bansidhar, AU - Singh,Ashutosh, AU - Upadhyaya,Gargi, AU - Upadhyay,Shalini, AU - Yadav,Priyanka, AU - Singh,Pradeep K, AU - Khillan,Vikas, AU - Sachdeva,Neelam, AU - Perlin,David S, AU - Meis,Jacques F, PY - 2017/07/28/received PY - 2017/11/18/accepted PY - 2018/1/13/pubmed PY - 2019/5/21/medline PY - 2018/1/12/entrez SP - 891 EP - 899 JF - The Journal of antimicrobial chemotherapy JO - J. Antimicrob. Chemother. VL - 73 IS - 4 N2 - Background: Candida auris has emerged globally as an MDR nosocomial pathogen in ICU patients. Objectives: We studied the antifungal susceptibility of C. auris isolates (n = 350) from 10 hospitals in India collected over a period of 8 years. To investigate azole resistance, ERG11 gene sequencing and expression profiling was conducted. In addition, echinocandin resistance linked to mutations in the C. auris FKS1 gene was analysed. Methods: CLSI antifungal susceptibility testing of six azoles, amphotericin B, three echinocandins, terbinafine, 5-flucytosine and nystatin was conducted. Screening for amino acid substitutions in ERG11 and FKS1 was performed. Results: Overall, 90% of C. auris were fluconazole resistant (MICs 32 to ≥64 mg/L) and 2% and 8% were resistant to echinocandins (≥8 mg/L) and amphotericin B (≥2 mg/L), respectively. ERG11 sequences of C. auris exhibited amino acid substitutions Y132 and K143 in 77% (n = 34/44) of strains that were fluconazole resistant whereas WT genotypes, i.e. without substitutions at these positions, were observed in isolates with low fluconazole MICs (1-2 mg/L) suggesting that these substitutions confer a phenotype of resistance to fluconazole similar to that described for Candida albicans. No significant expression of ERG11 was observed, although expression was inducible in vitro with fluconazole exposure. Echinocandin resistance was linked to a novel mutation S639F in FKS1 hot spot region I. Conclusions: Overall, 25% and 13% of isolates were MDR and multi-azole resistant, respectively. The most common resistance combination was azoles and 5-flucytosine in 14% followed by azoles and amphotericin B in 7% and azoles and echinocandins in 2% of isolates. SN - 1460-2091 UR - https://www.unboundmedicine.com/medline/citation/29325167/A_multicentre_study_of_antifungal_susceptibility_patterns_among_350_Candida_auris_isolates__2009_17__in_India:_role_of_the_ERG11_and_FKS1_genes_in_azole_and_echinocandin_resistance_ L2 - https://academic.oup.com/jac/article-lookup/doi/10.1093/jac/dkx480 DB - PRIME DP - Unbound Medicine ER -