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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.
Chowdhary, Anuradha; Prakash, Anupam; Sharma, Cheshta; Kordalewska, Milena; Kumar, Anil; Sarma, Smita; Tarai, Bansidhar; Singh, Ashutosh; Upadhyaya, Gargi; Upadhyay, Shalini; Yadav, Priyanka; Singh, Pradeep K; Khillan, Vikas; Sachdeva, Neelam; Perlin, David S; Meis, Jacques F.
Afiliación
  • Chowdhary A; Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India.
  • Prakash A; Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India.
  • Sharma C; Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India.
  • Kordalewska M; Public Health Research Institute, Rutgers Biomedical and Health Sciences, Newark, NJ, USA.
  • Kumar A; Department of Microbiology, Amrita Institute of Medical Sciences and Research Center, Amrita University, Ponekkara, Cochin, India.
  • Sarma S; Department of Microbiology, Medanta-The Medcity, Gurgaon, Haryana, India.
  • Tarai B; Department of Microbiology, Max hospital, New Delhi, India.
  • Singh A; Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India.
  • Upadhyaya G; Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India.
  • Upadhyay S; Department of Microbiology, Medanta-The Medcity, Gurgaon, Haryana, India.
  • Yadav P; Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India.
  • Singh PK; Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India.
  • Khillan V; Department of Microbiology, Institute of Liver & Biliary Sciences, New Delhi, India.
  • Sachdeva N; Department of Microbiology, Rajiv Gandhi Cancer Institute & Research Center, Delhi, India.
  • Perlin DS; Public Health Research Institute, Rutgers Biomedical and Health Sciences, Newark, NJ, USA.
  • Meis JF; Department of Medical Microbiology and Infectious Diseases, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands.
J Antimicrob Chemother ; 73(4): 891-899, 2018 04 01.
Article en En | MEDLINE | ID: mdl-29325167
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Azoles / Candida / Candidiasis / Proteínas Fúngicas / Farmacorresistencia Fúngica / Equinocandinas / Antifúngicos Tipo de estudio: Clinical_trials Límite: Female / Humans / Male / Middle aged País/Región como asunto: Asia Idioma: En Revista: J Antimicrob Chemother Año: 2018 Tipo del documento: Article País de afiliación: India Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Azoles / Candida / Candidiasis / Proteínas Fúngicas / Farmacorresistencia Fúngica / Equinocandinas / Antifúngicos Tipo de estudio: Clinical_trials Límite: Female / Humans / Male / Middle aged País/Región como asunto: Asia Idioma: En Revista: J Antimicrob Chemother Año: 2018 Tipo del documento: Article País de afiliación: India Pais de publicación: Reino Unido