Molecular characterisation of Candida auris isolates from immunocompromised patients in a tertiary-care hospital in Kuwait reveals a novel mutation in FKS1 conferring reduced susceptibility to echinocandins

Mohammad Asadzadeh 1, Eiman Mokaddas 1 2, Suhail Ahmad 1, Aneesa A Abdullah 2, Theun de Groot 3, Jacques F Meis 3 4 5, Shama A Shetty 2

Affiliations

01 March 2022

-

doi: 10.1111/myc.13419

Abstract

Background: Candida auris is an emerging, potentially multidrug-resistant pathogen that exhibits clade-specific resistance to fluconazole and also develops resistance to echinocandins and amphotericin B easily. This study analysed 49 C auris isolates for alterations in hotspot-1 and hotspot-2 of FKS1 for the detection of mutations conferring reduced susceptibility to echinocandins.

Methods: C auris isolates (n = 49) obtained from 18 immunocompromised patients during June 2016-December 2018 were analysed. Antifungal susceptibility testing was performed by Etest and broth microdilution-based MICRONAUT-AM assay. Mutations in hotspot-1 and hotspot-2 regions of FKS1 were detected by PCR sequencing and fingerprinting of the isolates was done by short tandem repeat typing.

Results: The patients had multiple comorbidities/risk factors for Candida spp. infection including cancer/leukaemia/lymphoma/myeloma (n = 16), arterial/central line (n = 17), urinary catheter (n = 17), mechanical ventilation (n = 14) and major surgery (n = 9) and received antifungal drugs as prophylaxis and/or empiric treatment. Seven patients developed C auris candidemia/breakthrough candidemia, nine patients had candiduria with/without candidemia and four patients developed surgical site/respiratory infection. Resistance to fluconazole and amphotericin B was detected in 44 and four isolates, respectively. Twelve C auris isolates from eight patients showed reduced susceptibility to echinocandins. Seven isolates contained hostspot-1 mutations and three isolates from a candidemia patient contained R1354H mutation in hotspot-2 of FKS1. Ten patients died, five were cured, two were lost to follow-up and treatment details for one patient were not available.

Conclusions: Our findings describe development of a novel mutation in FKS1 conferring reduced susceptibility to echinocandins in one patient during treatment and unfavourable clinical outcome for many C auris-infected patients.

Keywords: C auris; Immunocompromised patients; breakthrough candidemia; echinocandin resistance; hotspot-2 FKS1 mutation; infection.

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References

  1.  
    1. Richardson M, Lass-Flörl C. Changing epidemiology of systemic fungal infections. Clin Microbiol Infect. 2008;14:5-24.
  2.  
    1. Sprute R, Cornely OA, Chen SC, Seidel D, Schuetz AN, Zhang SX. All you need to know and more about the diagnosis and management of rare yeast infections. MBio. 2021;12:e0159421.
  3.  
    1. Calley JL, Warris A. Recognition and diagnosis of invasive fungal infections in neonates. J Infect. 2017;74:S108-S113.
  4.  
    1. McCarty TP, Pappas PG. Invasive candidiasis. Infect Dis Clin North Am. 2016;30:103-124.
  5.  
    1. Pappas PG, Kauffman CA, Andes DR, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;62:e1-e50.
  6.  
    1. Arendrup MC, Patterson TF. Multidrug-resistant Candida: epidemiology, molecular mechanisms, and treatment. J Infect Dis. 2017;216(Suppl_3):S445-S451.
  7.  
    1. Jenks JD, Cornely OA, Chen SC, Thompson GR 3rd, Hoenigl M. Breakthrough invasive fungal infections: Who is at risk? Mycoses. 2020;63:1021-1032.
  8.  
    1. Borjian Boroujeni Z, Shamsaei S, Yarahmadi M, et al. Distribution of invasive fungal infections: Molecular epidemiology, etiology, clinical conditions, diagnosis and risk factors: A 3-year experience with 490 patients under intensive care. Microb Pathog. 2021;152:104616.
  9.  
    1. Barchiesi F, Orsetti E, Mazzanti S, et al. Candidemia in the elderly: What does it change? PLoS One. 2017;12:e0176576.
  10.  
    1. Zatta M, Di Bella S, Giacobbe DR, et al. Clinical features and mortality of nosocomial candidemia in very old patients: A multicentre Italian study. Gerontology. 2020;66:532-541.
  11.  
    1. Bretagne S, Desnos-Ollivier M, Sitbon K, et al. No impact of fluconazole to echinocandins replacement as first-line therapy on the epidemiology of yeast fungemia (Hospital-Driven Active Surveillance, 2004-2017, Paris, France). Front Med (Lausanne). 2021;8: 641965.
  12.  
    1. Ahmad S, Khan Z. Invasive candidiasis: a review of nonculture-based laboratory diagnostic methods. Indian J Med Microbiol. 2012;30:264-269.
  13.  
    1. Clancy CJ, Nguyen MH. Diagnosing invasive candidiasis. J Clin Microbiol. 2018;56:e01909-e1917.
  14.  
    1. Arensman K, Miller JL, Chiang A, et al. Clinical outcomes of patients treated for Candida auris infections in a multisite health system, Illinois, USA. Emerg Infect Dis. 2020;26:876-880.
  15.  
    1. Chen XC, Xu J. Wu DP Clinical characteristics and outcomes of breakthrough candidemia in 71 hematologic malignancy patients and/or allogeneic hematopoietic stem cell transplant recipients: A single-center retrospective study from China, 2011-2018. Clin Infect Dis. 2020;71(Suppl 4):S394-S399.
  16.  
    1. Posteraro B, De Carolis E, Criscuolo M, et al. Candidaemia in haematological malignancy patients from a SEIFEM study: Epidemiological patterns according to antifungal prophylaxis. Mycoses. 2020;63:900-910.
  17.  
    1. Schroeder M, Weber T, Denker T, et al. Epidemiology, clinical characteristics, and outcome of candidemia in critically ill patients in Germany: a single-center retrospective 10-year analysis. Ann Intensive Care. 2020;10:142. 10.1186/s13613-020-00755-8
  18.  
    1. Zeng Z, Ding Y, Tian G, et al. A seven-year surveillance study of the epidemiology, antifungal susceptibility, risk factors and mortality of candidaemia among paediatric and adult inpatients in a tertiary teaching hospital in China. Antimicrob Resist Infect Control. 2020;9:133.
  19.  
    1. Kato H, Hagihara M, Shibata Y, et al. Comparison of mortality between echinocandins and polyenes for an initial treatment of candidemia: A systematic review and meta-analysis. J Infect Chemother. 2021;27:1562-1570.
  20.  
    1. Diekema D, Arbefeville S, Boyken L, Kroeger J, Pfaller M. The changing epidemiology of healthcare-associated candidemia over three decades. Diagn Microbiol Infect Dis. 2012;73:45-48.
  21.  
    1. Guinea J. Global trends in the distribution of Candida species causing candidemia. Clin Microbiol Infect. 2014;20(Suppl 6):5-10.
  22.  
    1. Lamoth F, Lockhart SR, Berkow EL, Calandra T. Changes in the epidemiological landscape of invasive candidiasis. J Antimicrob Chemother. 2018;73(suppl_1):i4-i13.
  23.  
    1. Song Y, Chen X, Yan Y, Wan Z, Liu W, Li R. Prevalence and antifungal susceptibility of pathogenic yeasts in China: A 10-year retrospective study in a teaching hospital. Front Microbiol. 2020;11:1401.
  24.  
    1. Kim EJ, Lee E, Kwak YG, et al. Trends in the epidemiology of candidemia in intensive care units from 2006 to 2017: Results from the Korean National Healthcare-Associated Infections Surveillance System. Front Med (Lausanne). 2020;7:606976.
  25.  
    1. Alobaid K, Ahmad S, Asadzadeh M, et al. Epidemiology of candidemia in Kuwait: A nationwide, population-based study. J Fungi (Basel). 2021;7:673.
  26.  
    1. Khan ZU, Al-Sweih NA, Ahmad S, et al. Outbreak of fungemia among neonates caused by Candida haemulonii resistant to amphotericin B, itraconazole, and fluconazole. J Clin Microbiol. 2007;45:2025-2027.
  27.  
    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.
  28.  
    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.
  29.  
    1. Pfaller MA, Diekema DJ, Turnidge JD, Castanheira M, Jones RN. Twenty Years of the SENTRY Antifungal Surveillance Program: Results for Candida Species from 1997-2016. Open Forum Infect Dis. 2019;6(Suppl 1):S79-S94.
  30.  
    1. Khan Z, Ahmad S, Al-Sweih N, Khan S, Joseph L Candida lusitaniae in Kuwait: prevalence, antifungal susceptibility and role in neonatal fungemia. PLoS One. 2019;14:e0213532.
  31.  
    1. Ahmad S, Khan Z, Al-Sweih N, Alfouzan W, Joseph L, Asadzadeh M Candida kefyr in Kuwait: prevalence, antifungal drug susceptibility and genotypic heterogeneity. PLoS One. 2020;15:e0240426.
  32.  
    1. Sfeir MM, Jiménez-Ortigosa C, Gamaletsou MN, et al. Breakthrough Bloodstream Infections Caused by Echinocandin-Resistant Candida tropicalis: An Emerging Threat to Immunocompromised Patients with Hematological Malignancies. J Fungi (Basel). 2020;6:20.
  33.  
    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.
  34.  
    1. Nobrega de Almeida J Jr, Brandão IB, Francisco EC, et al. Axillary digital thermometers uplifted a multidrug-susceptible Candida auris outbreak among COVID-19 patients in Brazil. Mycoses. 2021;64:1062-1072.
  35.  
    1. Ahmad S, Alfouzan W Candida auris: Epidemiology, diagnosis, pathogenesis, antifungal susceptibility and infection control measures to combat the spread of infections in healthcare facilities. Microorganisms. 2021;9:807.
  36.  
    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.
  37.  
    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.
  38.  
    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 ERG11 and FKS1 genes in azole and echinocandin resistance. J Antimicrob Chemother. 2018;73:891-899.
  39.  
    1. Chaabane F, Graf A, Jequier L, Coste AT. Review on antifungal resistance mechanisms in the emerging pathogen Candida auris. Front Microbiol. 2019;10:2786.
  40.  
    1. Kordalewska M, Lee A, Park S, et al. Understanding echinocandin resistance in the emerging pathogen Candida auris. Antimicrob Agents Chemother. 2018;62:e00238-18.
  41.  
    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.
  42.  
    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.
  43.  
    1. Alfouzan W, Ahmad S, Dhar R, et al. Molecular epidemiology of Candida auris outbreak in a major secondary-care hospital in Kuwait. J Fungi (Basel). 2020;6:30.
  44.  
    1. Centers for Disease Control and Prevention. Treatment and management of infections and colonization: Recommendations for treatment of Candida auris infections. 2019. Available online: https://www.cdc.gov/fungal/candida-auris/c-auris-treatment.html (accessed on 15 November 2021)
  45.  
    1. Perlin DS. Resistance to echinocandin-class antifungal drugs. Drug Resist Update. 2007;10:121-130.
  46.  
    1. Sanguinetti M, Posteraro B, Lass-Flörl C. Antifungal drug resistance among Candida species: mechanisms and clinical impact. Mycoses. 2015;58:2-13.
  47.  
    1. Kurtz MB, Abruzzo G, Flattery A, et al. Characterization of echinocandin-resistant mutants of Candida albicans: genetic, biochemical, and virulence studies. Infect Immun. 1996;64:3244-3251.
  48.  
    1. Ben-Ami R, Garcia-Effron G, Lewis RE, et al. Fitness and virulence costs of Candida albicans FKS1 hot spot mutations associated with echinocandin resistance. J Infect Dis. 2011;204:626-635.
  49.  
    1. Ben-Ami R, Kontoyiannis DP. Resistance to echinocandins comes at a cost: the impact of FKS1 hotspot mutations on Candida albicans fitness and virulence. Virulence. 2012;3:95-97.
  50.  
    1. Khan ZU, Ahmad S, Al-Sweih N, Joseph L, Alfouzan W, Asadzadeh M. Increasing prevalence, molecular characterization and antifungal drug susceptibility of serial Candida auris isolates in Kuwait. PLoS One. 2018;13:e0195743.
  51.  
    1. Khan Z, Ahmad S, Al-Sweih N, et al. Changing trends in epidemiology and antifungal susceptibility patterns of six bloodstream Candida species isolates over a 12-year period in Kuwait. PLoS One. 2019;14:e0216250.
  52.  
    1. Jamal WY, Ahmad S, Khan ZU, Rotimi VO. Comparative evaluation of two matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) systems for the identification of clinically significant yeasts. Int J Infect Dis. 2014;26:167-170.
  53.  
    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.
  54.  
    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;97:253-259.
  55.  
    1. Centers for Disease Control and Prevention. Antifungal susceptibility testing and interpretation. https://www.cdc.gov/fungal/candida-auris/c-auris-antifungal.html (last accessed on October 12, 2021).
  56.  
    1. Ahmad S, Khan Z, Al-Sweih N, Alfouzan W, Joseph L Candida auris in various hospitals across Kuwait and their susceptibility and molecular basis of resistance to antifungal drugs. Mycoses. 2020;63:104-112.
  57.  
    1. De Groot T, Puts Y, Barrio I, Chowdhary A, Meis JF. Development of Candida auris short tandem repeat typing and its application to a global collection of isolates. MBio. 2020;11:e02971-19.
  58.  
    1. Asadzadeh M, Ahmad S, Al-Sweih N, Hagen F, Meis JF, Khan Z. High-resolution fingerprinting of Candida parapsilosis isolates suggests persistence and transmission of infections among neonatal intensive care unit patients in Kuwait. Sci Rep. 2019;9:1340.
  59.  
    1. Al Maani A, Paul H, Al-Rashdi A, et al. Ongoing challenges with healthcare-associated Candida auris outbreaks in Oman. J Fungi (Basel). 2019;5:101.
  60.  
    1. Cortegiani A, Misseri G, Fasciana T, Giammanco A, Giarratano A, Chowdhary A. Epidemiology, clinical characteristics, resistance, and treatment of infections by Candida auris. J Intensive Care. 2018;6:69.
  61.  
    1. Mulet Bayona JV, Tormo Palop N, Salvador García C, et al. Characteristics and management of candidaemia episodes in an established Candida auris outbreak. Antibiotics (Basel). 2020;9:E558.
  62.  
    1. Shastri PS, Shankarnarayan SA, Oberoi J, Rudramurthy SM, Wattal C, Chakrabarti A Candida auris candidaemia in an intensive care unit-prospective observational study to evaluate epidemiology, risk factors, and outcome. J Crit Care. 2020;57:42-48.
  63.  
    1. Cornely OA, Hoenigl M, Lass-Flörl C, et al. Defining breakthrough invasive fungal infection-Position paper of the mycoses study group education and research consortium and the European Confederation of Medical Mycology. Mycoses. 2019;62:716-729.
  64.  
    1. Breda GL, Tuon FF, Meis JF, et al. Breakthrough candidemia after the introduction of broad spectrum antifungal agents: A 5-year retrospective study. Med Mycol. 2018;56:406-415.
  65.  
    1. Garcia-Bustos V, Salavert M, Ruiz-Gaitán AC, Cabañero-Navalon MD, Sigona-Giangreco IA, Pemán J. A clinical predictive model of candidaemia by Candida auris in previously colonized critically ill patients. Clin Microbiol Infect. 2020;26:1507-1513.
  66.  
    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.
  67.  
    1. Chen J, Tian S, Han X, et al. Is the superbug fungus really so scary? A systematic review and meta-analysis of global epidemiology and mortality of Candida auris. BMC Infect Dis. 2020;20:827.
  68.  
    1. Luzzati R, Cavinato S, Deiana ML, Rosin C, Maurel C, Borelli M. Epidemiology and outcome of nosocomial candidemia in elderly patients admitted prevalently in medical wards. Aging Clin Exp Res. 2015;27:131-137.
  69.  
    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:e01900-18.
  70.  
    1. Vanstraelen K, Lagrou K, Maertens J, Wauters J, Willems L, Spriet I. The Eagle-like effect of echinocandins: what's in a name? Expert Rev Anti Infect Ther. 2013;11:1179-1191.
  71.  
    1. Ruiz-Gaitán AC, Cantón E, Fernández-Rivero ME, Ramírez P, Pemán J. Outbreak of Candida auris in Spain: A comparison of antifungal activity by three methods with published data. Int J Antimicrob Agents. 2019;53:541-546.
  72.  
    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.
  73.  
    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.
  74.  
    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:e01427-18.
  75.  
    1. Rybak JM, Muñoz JF, Barker KS, et al. Mutations in TAC1B: a novel genetic determinant of clinical fluconazole resistance in Candida auris. MBio. 2020;11:e00365-20.
  76.  
    1. Rybak J, Barker KS, Munoz JF, et al. In vivo emergence of high-level resistance during treatment reveals the first identified mechanism of amphotericin B resistance in Candida auris. Clin Microbiol Infect. 2021;10.1016/j.cmi.2021.11.024
  77.  
    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:e01926-17.
  78.  
    1. Al-Baqsami Z, Ahmad S, Khan Z. Antifungal drug susceptibility, molecular basis of resistance to echinocandins and molecular epidemiology of fluconazole resistance among clinical Candida glabrata isolates in Kuwait. Sci Rep. 2020;10:6238.
  79.  
    1. Alexander BD, Johnson MD, Pfeiffer CD, et al. Increasing echinocandin resistance in Candida glabrata: clinical failure correlates with presence of FKS mutations and elevated minimum inhibitory concentrations. Clin Infect Dis. 2013;56:1724-1732.
  80.  
    1. Sharma D, Paul RA, Rudramurthy SM, et al. Impact of FKS1 genotype on echinocandin in-vitro susceptibility in Candida auris and in vivo response in a murine model of infection. Antimicrob Agents Chemother. 2021. 10.1128/AAC.01652-21. Posted Online 15 November
  81.  
    1. Arendrup MC, Pfaller MA. Danish Fungaemia Study Group. Caspofungin Etest susceptibility testing of Candida species: Risk of misclassification of susceptible isolates of C glabrata and C krusei when adopting the revised CLSI caspofungin breakpoints. Antimicrob Agents Chemother. 2012;56:3965-3968.
  82.  
    1. Pfaller MA, Messer SA, Diekema DJ, Jones RN, Castanheira M. Use of micafungin as a surrogate marker to predict susceptibility and resistance to caspofungin among 3,764 clinical isolates of Candida by use of CLSI methods and interpretive criteria. J Clin Microbiol. 2014;52:108-114.
  83.  
    1. Perlin DS. Echinocandin resistance in Candida. Clin Infect Dis. 2015;61(Suppl 6):S612-S617.
  84.  
    1. Aldejohann AM, Herz M, Martin R, Walther G, Kurzai O. Emergence of resistant Candida glabrata in Germany. JAC Antimicrob Resist 2021;3:dlab122.

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