Candida auris in various hospitals across Kuwait and their susceptibility and molecular basis of resistance to antifungal drugs

Suhail Ahmad 1, Ziauddin Khan 1, Noura Al-Sweih 1, Wadha Alfouzan 1, Leena Joseph 1

Affiliations

01 January 2020

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doi: 10.1111/myc.13022

Abstract

Background: Candida auris, a multidrug-resistant species, has the propensity of nosocomial transmission despite normal decontamination procedures. Here, we describe the isolation of C auris from patients in various hospitals in Kuwait during 2014-2018. Susceptibility to antifungal drugs and molecular basis of resistance to fluconazole, voriconazole and micafungin were also studied.

Methods: Candida auris (n = 314) obtained from 126 patients in eight hospitals were studied. All isolates were identified by PCR amplification and/or PCR-sequencing of ribosomal DNA (rDNA). Antifungal susceptibility was determined by Etest. Molecular basis of resistance to fluconazole and micafungin was studied by PCR-sequencing of ERG11 and FKS1 genes, respectively.

Findings: Bloodstream (n = 58), urine (n = 124), respiratory (n = 98) and other (n = 34) specimens yielded 314 C auris isolates. The proportion of bloodstream C auris among all yeast isolates was higher (42 of 307, 13.7%) in 2018 as compared to 2014-2017 (16 of 964, 1.7%) (P = .001). More bloodstream isolates (42 of 139) were cultured in 2018 than during 2014-2017 (16 of 175) (P = .001). Resistance to amphotericin B, fluconazole, voriconazole and micafungin was detected in 27.1%, 100%, 41.1% and 1.7% isolates, respectively. Fluconazole-resistant isolates contained either Y132F or K143R mutation in ERG11. Isolates with K143R mutation were additionally resistant to voriconazole. Micafungin-resistant isolates contained S639F mutation in hot spot 1 of FKS1.

Conclusions: Our study highlights spreading of C auris in major hospitals across Kuwait and its increasing role as a bloodstream pathogen in 2018. Cross-resistance to voriconazole was also seen in isolates with K143R mutation in ERG11, while micafungin-resistant isolates harboured S639F mutation in hot spot 1 of FKS1.

Keywords: Candida auris; Kuwait hospitals; antifungal susceptibility; bloodstream infections; resistance mechanism.

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References

  1.  
    1. Chowdhary A, Sharma C, Meis JF Candida auris: A rapidly emerging cause of hospital-acquired multidrug-resistant fungal infections globally. PLoS Pathog. 2017;13:e1006290.
  2.  
    1. Jeffery-Smith A, Taori SK, Schelenz S, Jeffery K, Johnson EM, Borman A Candida auris Incident management Team, Manuel R, Brown CS Candida auris: a Review of the Literature. Clin Microbiol Rev. 2017;31:e00029-e117.
  3.  
    1. Khan Z, Ahmad S Candida auris: an emerging multidrug-resistant pathogen of global significance. Curr Med Res Pract. 2017;7:240-248.
  4.  
    1. Satoh K, Makimura K, Hasumi Y, Nishiyama Y, Uchida K, Yamaguchi H Candida auris sp. nov., a novel ascomycetous yeast isolated from the external ear canal of an inpatient in a Japanese hospital. Microbiol Immunol. 2009;53:41-44.
  5.  
    1. Lee WG, Shin JH, Uh Y, et al. First three reported cases of nosocomial fungemia caused by Candida auris. J Clin Microbiol. 2011;49:3139-3142.
  6.  
    1. Kim MN, Shin JH, Sung H, et al. Candida haemulonii and closely related species at 5 university hospitals in Korea: identification, antifungal susceptibility, and clinical features. Clin Infect Dis. 2009;48:e57-e61.
  7.  
    1. Shin JH, Kim MN, Jang SJ, et al. Detection of amphotericin B resistance in Candida haemulonii and closely related species by use of the Etest, Vitek-2 yeast susceptibility system, and CLSI and EUCAST broth microdilution methods. J Clin Microbiol. 2012;50:1852-1855.
  8.  
    1. Sarma S, Kumar N, Sharma S, et al. Candidemia caused by amphotericin B and fluconazole resistant Candida auris. Indian J Med Microbiol. 2013;31:90-91.
  9.  
    1. Chowdhary A, Sharma C, Duggal S, et al. New clonal strain of Candida auris, Delhi, India. Emerg Infect Dis. 2013;19:1670-1673.
  10.  
    1. Chowdhary A, Anil Kumar V, Sharma C, et al. Multidrug-resistant endemic clonal strain of Candida auris in India. Eur J Clin Microbiol Infect Dis. 2014;33:919-926.
  11.  
    1. Rudramurthy SM, Chakrabarti A, Paul RA, et al. Candida auris candidaemia in Indian ICUs: Analysis of risk factors. J Antimicrob Chemother. 2017;72:1794-1801.
  12.  
    1. de Cássia Orlandi Sardi J, Silva DR, Soares Mendes-Giannini MJ, Rosalen PL. Candida auris: Epidemiology, risk factors, virulence, resistance, and therapeutic options. Microb Pathog. 2018;125:116-121.
  13.  
    1. Khan Z, Ahmad S, Benwan K, et al. Invasive Candida auris infections in Kuwait hospitals: epidemiology, antifungal treatment and outcome. Infection. 2018;46:641-650.
  14.  
    1. Lockhart SR, Etienne KA, Vallabhaneni S, et al. Simultaneous emergence of multidrug-resistant Candida auris on 3 continents confirmed by whole-genome sequencing and epidemiological analyses. Clin Infect Dis. 2017;64:134-140.
  15.  
    1. Muñoz JF, Gade L, Chow NA, et al. Genomic insights into multidrug-resistance, mating and virulence in Candida auris and related emerging species. Nat Commun. 2018;9:5346.
  16.  
    1. Rhodes J, Abdolrasouli A, Farrer RA, et al. Genomic epidemiology of the UK outbreak of the emerging human fungal pathogen Candida auris. Emerg Microbes Infect. 2018;7:43.
  17.  
    1. Emara M, Ahmad S, Khan Z, et al. Candida auris candidemia in Kuwait, 2014. Emerg Infect Dis. 2015;21:1091-1092.
  18.  
    1. Khan ZU, Ahmad S, Al-Sweih N, Joseph L, Alfouzan F, Asadzadeh M. Increasing prevalence, molecular characterization and antifungal drug susceptibility of serial Candida auris isolates in Kuwait. PLoS ONE. 2018;13:e0195743.
  19.  
    1. Asadzadeh M, Ahmad S, Al-Sweih N, Khan Z. Molecular fingerprinting studies do not support intrahospital transmission of Candida albicans among candidemia patients in Kuwait. Front Microbiol. 2017;8:247.
  20.  
    1. Asadzadeh M, Ahmad S, Hagen F, Meis JF, Al-Sweih N, Khan Z. Simple, low-cost detection of Candida parapsilosis complex isolates and molecular fingerprinting of Candida orthopsilosis strains in Kuwait by ITS region sequencing and amplified fragment length polymorphism analysis. PLoS ONE. 2015;10:e0142880.
  21.  
    1. Ahmad S, Mustafa AS, Khan Z, Al-Rifaiy AI, Khan ZU. PCR-enzyme immunoassay of rDNA in the diagnosis of candidemia and comparison with amplicon detection by agarose gel electrophoresis. Int J Med Microbiol. 2004;294:45-51.
  22.  
    1. Khan ZU, Ahmad S, Mokaddas E, Chandy R, Cano J, Guarro J Actinomucor elegans var. kuwaitiensis isolated from the wound of a diabetic patient. Antonie van. Leeuwoenhoek. 2008;94:343-352.
  23.  
    1. Khan ZU, Ahmad S, Hagen F, et al. Cryptococcus randhawai sp. nov., a novel anamorphic basidiomycetous yeast isolated from tree trunk hollow of Ficus religiosa (peepal tree) from New Delhi, India. Antonie Van Leeuwenhoek. 2010;97(3):253-259.
  24.  
    1. Asadzadeh M, Al-Sweih NA, Ahmad S, Khan ZU. Antifungal susceptibility of clinical Candida parapsilosis isolates in Kuwait. Mycoses. 2008;51:318-323.
  25.  
    1. Kathuria S, Singh PK, Sharma C, et al. Multidrug-resistant Candida auris misidentified as Candida haemulonii: characterization by matrix-assisted laser desorption ionization-time of flight mass spectrometry and DNA sequencing and its antifungal susceptibility profile variability by Vitek 2, CLSI broth microdilution, and Etest method. J Clin Microbiol. 2015;53:1823-1830.
  26.  
    1. Center for Disease Control and Prevention. Candida auris. Atlanta, GA. Updated August 21, 2017. https://www.cdc.gov/fungal/candida-auris/recommendations.html.
  27.  
    1. 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;73:891-899.
  28.  
    1. Healey KR, Kordalewska M, Jiménez Ortigosa C, et al. Limited ERG11 mutations identified in isolates of Candida auris directly contribute to reduced azole susceptibility. Antimicrob Agents Chemother. 2018;62:e01427-e1518.
  29.  
    1. Ahmad S, Joseph L, Parker JE, et al. ERG6 and ERG2 are major targets conferring reduced susceptibility to amphotericin B in clinical Candida glabrata isolates in Kuwait. Antimicrob Agents Chemother. 2019;63:e01900-e1918.
  30.  
    1. Kordalewska M, Lee A, Park S, et al. Understanding echinocandin resistance in the emerging pathogen Candida auris. Antimicrob Agents Chemother. 2018;62:e00238-e318.
  31.  
    1. Khan Z, Ahmad S, Mokaddas E, et al. Development of echinocandin resistance in Candida tropicalis following short-term exposure to caspofungin for empiric therapy. Antimicrob Agents Chemother. 2018;62:e01926-e2017.
  32.  
    1. Welsh RM, Bentz ML, Shams A, et al. Survival, persistence, and isolation of the emerging multidrug-resistant pathogenic yeast Candida auris on a plastic health care surface. J Clin Microbiol. 2017;55:2996-3005.
  33.  
    1. Kean R, Sherry L, Townsend E, et al. Surface disinfection challenges for Candida auris: an in-vitro study. J Hosp Infect. 2018;98:433-436.
  34.  
    1. Ruiz-Gaitán A, Moret AM, Tasias-Pitarch M, et al. An outbreak due to Candida auris with prolonged colonisation and candidaemia in a tertiary care European hospital. Mycoses. 2018;61:498-505.
  35.  
    1. Kordalewska M, Zhao Y, Lockhart SR, Chowdhary A, Berrio I, Perlin DS. Rapid and accurate molecular identification of the emerging multidrug resistant pathogen Candida auris. J Clin Microbiol. 2017;55:2445-2452.
  36.  
    1. Mizusawa M, Miller H, Green R, et al. Can Multidrug-Resistant Candida auris be reliably identified in clinical microbiology laboratories? J Clin Microbiol. 2017;55:638-640.
  37.  
    1. Snayd M, Dias F, Ryan RW, Clout D, Banach DB. Misidentification of Candida auris by RapID Yeast Plus, a commercial, biochemical enzyme-based manual rapid identification system. J Clin Microbiol. 2018;56:e00080-e118.
  38.  
    1. Forsberg K, Woodworth K, Walters M, et al. Candida auris: The recent emergence of a multidrug-resistant fungal pathogen. Med Mycol. 2019;57:1-12.
  39.  
    1. Kenters N, Kiernan M, Chowdhary A, et al. Control of Candida auris in healthcare institutions: outcome of an International Society for Antimicrobial Chemotherapy expert meeting. Int J Antimicrob Agents. 2019;54:400-406.
  40.  
    1. Lone SA, Ahmad A Candida auris - the growing menace to global health. Mycoses. 2019;62:620-637. https://doi.org/10.1111/myc.12904.
  41.  
    1. Chow NA, de Groot T, Badali H, Abastabar M, Chiller TM, Meis JF. Potential Fifth Clade of Candida auris, Iran, 2018. Emerg Infect Dis. 2019;25:1780-1781.
  42.  
    1. Biswal M, Rudramurthy SM, Jain N, et al. Controlling a possible outbreak of Candida auris infection: lessons learnt from multiple interventions. J Hosp Infect. 2017;97:363-370.
  43.  
    1. Abastabar M, Haghani I, Ahangarkani F, et al. Candida auris otomycosis in Iran and review of recent literature. Mycoses. 2019;62:101-105.
  44.  
    1. Choi HI, An J, Hwang JJ, Moon SY, Son JS. Otomastoiditis caused by Candida auris: Case report and literature review. Mycoses. 2017;60:488-492.
  45.  
    1. Schelenz S, Hagen F, Rhodes JL, et al. First hospital outbreak of the globally emerging Candida auris in a European hospital. Antimicrob Resist Infect Control. 2016;5:35.
  46.  
    1. Ruiz Gaitán AC, Moret A, López Hontangas JL, et al. Nosocomial fungemia by Candida auris: First four reported cases in continental Europe. Rev Iberoam Micol. 2017;34:23-27.
  47.  
    1. Abdolrasouli A, Armstrong-James D, Ryan L, Schelenz S In vitro efficacy of disinfectants utilised for skin decolonisation and environmental decontamination during a hospital outbreak with Candida auris. Mycoses. 2017;60:758-763.
  48.  
    1. Singh R, Kaur M, Chakrabarti A, Shankarnarayan SA, Rudramurthy SM. Biofilm formation by Candida auris isolated from colonising sites and candidemia cases. Mycoses. 2019;62:706-709.
  49.  
    1. van Schalkwyk E, Mpembe RS, Thomas J, et al. Epidemiologic shift in candidemia driven by Candida auris, South Africa, 2016-2017. Emerg Infect Dis. 2019;25:1698-1707.
  50.  
    1. Chakrabarti A, Sood P, Rudramurthy SM, et al. Incidence, characteristics and outcome of ICU-acquired candidemia in India. Intensive Care Med. 2015;41:285-295.
  51.  
    1. Mathur P, Hasan F, Singh PK, Malhotra R, Walia K, Chowdhary A. Five-year profile of candidaemia at an Indian trauma centre: high rates of Candida auris blood stream infections. Mycoses. 2018;61:674-680.
  52.  
    1. Welsh RM, Bentz ML, Shams A, et al. Survival, persistence, and isolation of the emerging multidrug-resistant pathogenic yeast Candida auris on a plastic healthcare surface. J Clin Microbiol. 2017;55:2996-3005.
  53.  
    1. Tsay S, Kallen A, Jackson BR, Chiller TM, Vallabhaneni S. Approach to the investigation and management of patients with Candida auris, an emerging multidrug-resistant yeast. Clin Infect Dis. 2018;66:306-311.
  54.  
    1. Eyre DW, Sheppard AE, Madder H, et al. Candida auris outbreak and its control in an intensive care setting. N Engl J Med. 2018;379:1322-1331.
  55.  
    1. de Groot T, Chowdhary A, Meis JF, Voss A. Killing of Candida auris by UV-C: importance of exposure time and distance. Mycoses. 2019;62:408-412.
  56.  
    1. Escandón P, Chow NA, Caceres DH, et al. Molecular epidemiology of Candida auris in Colombia reveals a highly related, countrywide colonization with regional patterns in amphotericin B resistance. Clin Infect Dis. 2019;68:15-21.

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