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Deciphering Candida auris Paradoxical Growth Effect (Eagle Effect) in Response to Echinocandins

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Candida auris

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2517))

Abstract

The paradoxical growth effect (PGE; also known as Eagle effect) is an in vitro phenomenon observed during antifungal susceptibility testing (AFST). In PGE, some fungal isolates grow in medium containing high concentrations of an echinocandin, above the minimal inhibitory concentration (MIC), despite being fully susceptible at lower concentrations. The presence of PGE complicates the assignment of isolates to susceptible or resistant category, especially in the case of newly emerged pathogens like Candida auris, for which susceptibility breakpoints are not established.

Here we describe a protocol aiding in the determination of whether a given C. auris isolate is echinocandin-resistant or echinocandin-susceptible but exhibiting paradoxical growth.

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References

  1. Perlin DS (2015) Mechanisms of echinocandin antifungal drug resistance. Ann N Y Acad Sci 1354:1–11. https://doi.org/10.1111/nyas.12831

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Barchiesi F, Spreghini E, Tomassetti S, Arzeni D, Giannini D, Scalise G (2005) Comparison of the fungicidal activities of caspofungin and amphotericin B against Candida glabrata. Antimicrob Agents Chemother 49(12):4989–4992. https://doi.org/10.1128/AAC.49.12.4989-4992.2005

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Ernst EJ, Klepser ME, Ernst ME, Messer SA, Pfaller MA (1999) In vitro pharmacodynamic properties of MK-0991 determined by time-kill methods. Diagn Microbiol Infect Dis 33(2):75–80. https://doi.org/10.1016/s0732-8893(98)00130-8

    Article  PubMed  CAS  Google Scholar 

  4. Pappas PG, Kauffman CA, Andes DR, Clancy CJ, Marr KA, Ostrosky-Zeichner L, Reboli AC, Schuster MG, Vazquez JA, Walsh TJ, Zaoutis TE, Sobel JD (2016) Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis 62(4):e1–e50. https://doi.org/10.1093/cid/civ933

    Article  PubMed  Google Scholar 

  5. Chowdhary A, Prakash A, Sharma C, Kordalewska M, Kumar A, Sarma S, Tarai B, Singh A, Upadhyaya G, Upadhyay S, Yadav P, Singh PK, Khillan V, Sachdeva N, Perlin DS, Meis JF (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. J Antimicrob Chemother 73(4):891–899. https://doi.org/10.1093/jac/dkx480

    Article  PubMed  CAS  Google Scholar 

  6. Kordalewska M, Lee A, Park S, Berrio I, Chowdhary A, Zhao Y, Perlin DS (2018) Understanding echinocandin resistance in the emerging pathogen Candida auris. Antimicrob Agents Chemother 62(6):e00238-00218. https://doi.org/10.1128/AAC.00238-18

    Article  Google Scholar 

  7. Berkow EL, Lockhart SR (2018) Activity of CD101, a long-acting echinocandin, against clinical isolates of Candida auris. Diagn Microbiol Infect Dis 90(3):196–197. https://doi.org/10.1016/j.diagmicrobio.2017.10.021

    Article  PubMed  CAS  Google Scholar 

  8. Woodworth MH, Dynerman D, Crawford ED, Doernberg SB, Ramirez-Avila L, Serpa PH, Nichols A, Li LM, Lyden A, Tato CM, Miller S, Derisi JL, Langelier C (2019) Sentinel case of Candida auris in the Western United States following prolonged occult colonization in a returned traveler from India. Microb Drug Resist 25(5):677–680. https://doi.org/10.1089/mdr.2018.0408

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. CLSI (ed) (2017) Reference method for broth dilution antifungal susceptibility testing of yeast, CLSI Standard M27, 4th edn. Clinical and Laboratory Standards Institute, Wayne

    Google Scholar 

  10. Arendrup MC, Meletiadis J, Mouton JW, Lagrou K, Hamal P, Guinea J, the Subcommittee on Antifungal Susceptibility Testing (AFST) of the ESCMID European Committee for Antimicrobial Susceptibility Testing (EUCAST) (2020) EUCAST definitive document E.DEF 7.3.2 Method for the determination of broth dilution minimum inhibitory concentrations of antifungal agents for yeasts

    Google Scholar 

  11. Vanstraelen K, Lagrou K, Maertens J, Wauters J, Willems L, Spriet I (2013) The Eagle-like effect of echinocandins: what’s in a name? Expert Rev Anti-Infect Ther 11(11):1179–1191. https://doi.org/10.1586/14787210.2013.841543

    Article  PubMed  CAS  Google Scholar 

  12. Stevens DA, Espiritu M, Parmar R (2004) Paradoxical effect of caspofungin: reduced activity against Candida albicans at high drug concentrations. Antimicrob Agents Chemother 48(9):3407–3411. https://doi.org/10.1128/AAC.48.9.3407-3411.2004

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Marine M, Pastor FJ, Sahand IH, Ponton J, Quindos G, Guarro J (2009) Paradoxical growth of Candida dubliniensis does not preclude in vivo response to echinocandin therapy. Antimicrob Agents Chemother 53(12):5297–5299. https://doi.org/10.1128/AAC.00980-09

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Kathuria S, Singh PK, Sharma C, Prakash A, Masih A, Kumar A, Meis JF, Chowdhary A (2015) 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 53(6):1823–1830. https://doi.org/10.1128/JCM.00367-15

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Espinel-Ingroff A, Arendrup MC, Pfaller MA, Bonfietti LX, Bustamante B, Canton E, Chryssanthou E, Cuenca-Estrella M, Dannaoui E, Fothergill A, Fuller J, Gaustad P, Gonzalez GM, Guarro J, Lass-Florl C, Lockhart SR, Meis JF, Moore CB, Ostrosky-Zeichner L, Pelaez T, Pukinskas SR, St-Germain G, Szeszs MW, Turnidge J (2013) Interlaboratory variability of caspofungin MICs for Candida spp. using CLSI and EUCAST methods: should the clinical laboratory be testing this agent? Antimicrob Agents Chemother 57(12):5836–5842. https://doi.org/10.1128/AAC.01519-13

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. CLSI (ed) (2020) Performance standards for antifungal susceptibility testing of yeasts, CLSI Supplement M60, 2nd edn. Clinical and Laboratory Standards Institute, Wayne

    Google Scholar 

  17. Brillowska-Dabrowska A, Nielsen SS, Nielsen HV, Arendrup MC (2010) Optimized 5-hour multiplex PCR test for the detection of tinea unguium: performance in a routine PCR laboratory. Med Mycol 48(6):828–831. https://doi.org/10.3109/13693780903531579

    Article  PubMed  CAS  Google Scholar 

  18. Centers for Disease Control and Prevention (2020) Candida auris. Information for laboratorians and health professionals. Antifungal susceptibility testing and interpretation. https://www.cdc.gov/fungal/candida-auris/c-auris-antifungal.html. Accessed 23 Apr 2021

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Correspondence to Milena Kordalewska or David S. Perlin .

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Kordalewska, M., Perlin, D.S. (2022). Deciphering Candida auris Paradoxical Growth Effect (Eagle Effect) in Response to Echinocandins. In: Lorenz, A. (eds) Candida auris. Methods in Molecular Biology, vol 2517. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2417-3_6

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  • DOI: https://doi.org/10.1007/978-1-0716-2417-3_6

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-2416-6

  • Online ISBN: 978-1-0716-2417-3

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