1887

Abstract

The increasing prevalence and growing resistance of fungi present a significant peril to public health. There are only four classes of antifungal medicines available today, and few candidates are in clinical trials.

Rapid and sensitive diagnostic techniques are lacking for most fungal pathogens, and those that do exist are expensive or hard to obtain.

This study aimed to evaluate the feasibility of a novel automated antifungal susceptibility testing system, Fungus AST, in comparison to the broth microdilution method (BMD) recommended by the Clinical and Laboratory Standards Institute (CLSI).

A total of 101 clinical spp. isolates were collected from the Zengcheng Branch of Nanfang Hospital and subjected to antifungal susceptibility testing. Antifungal susceptibility was assessed using the Fungus AST method and the BMD.

In this study, we introduce a novel automated antifungal susceptibility testing system, Fungus AST, which detects the turbidity and/or colour intensity of microdilution wells using a four-wavelength detection technology in real time and is designed to match the growth characteristics of strains over time. Based on our analysis, all reportable ranges of Fungus AST were suitable for clinical fungal isolates in PR China. Within ±twofold dilutions, reproducibility was 100 %. Considering the BMD as a referenced method, ten antifungal agents (anidulafungin, caspofungin, micafungin, fluconazole, voriconazole, posaconazole, itraconazole, amphotericin B, 5-flucytosine and nystatin) showed an essential agreement of >95 %. The category agreement of five antifungal agents (anidulafungin, caspofungin, micafungin, fluconazole and voriconazole) was excellent at >90 %. One isolate and voriconazole showed a major error (ME) (1.7 %), and no other ME or very ME agents were found.

Given the above, it can be argued that the utilization of Fungus AST is a discretionary automated approach. More improvements are needed in Fungus AST compared to the BMD system for a wider range of clinical isolates, including different types of fungi.

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.001811
2024-03-05
2024-04-22
Loading full text...

Full text loading...

References

  1. Bassetti M, Vena A, Bouza E, Peghin M, Muñoz P et al. Antifungal susceptibility testing in Candida, Aspergillus and Cryptococcus infections: are the MICs useful for clinicians?. Clin Microbiol Infect 2020; 26:1024–1033 [View Article] [PubMed]
    [Google Scholar]
  2. Fisher MC, Alastruey-Izquierdo A, Berman J, Bicanic T, Bignell EM et al. Tackling the emerging threat of antifungal resistance to human health. Nat Rev Microbiol 2022; 20:557–571 [View Article] [PubMed]
    [Google Scholar]
  3. Yu J, He C, Wang T, Zhang G, Li J et al. Rapid automated antifungal susceptibility testing system for yeasts based on growth characteristics. Front Cell Infect Microbiol 2023; 13:1153544 [View Article] [PubMed]
    [Google Scholar]
  4. Berkow EL, Lockhart SR, Ostrosky-Zeichner L. Antifungal susceptibility testing: current approaches. Clin Microbiol Rev 2020; 33:e00069-19 [View Article] [PubMed]
    [Google Scholar]
  5. Espinel-Ingroff A. Commercial methods for antifungal susceptibility testing of yeasts: strengths and limitations as predictors of resistance. J Fungi 2022; 8:309 [View Article] [PubMed]
    [Google Scholar]
  6. Clinical and Laboratory Standards Institute "Performance standards for antifungal susceptibility testing of yeasts,” in Approved standard. In CLSI Supplement M27M44S, 3rd. edn Wayne, PA: Clinical and Laboratory Standards Institute; 2022
    [Google Scholar]
  7. The European Committee on Antimicrobial Susceptibility Testing “Overview of antifungal ECOFFs and clinical breakpoints for yeasts, moulds and dermatophytes using the EUCAST E.Def 7.4, E.Def 9.4 and E.Def 11.0 procedures,” in Approved standard; 2023 http://www.eucast.org/astoffungi/clinicalbreakpointsforantifungals/ accessed 14 August 2023
  8. Clinical and Laboratory Standards Institute “Epidemiological cutoff values for antifungal susceptibility testing,” in Approved standard. In CLSI Supplement M57S, 4th. edn Wayne, PA: Clinical and Laboratory Standards Institute; 2022
    [Google Scholar]
  9. International Organization for standardization “Clinical Laboratory Testing and in Vitro Diagnostic Test Systems – Susceptibility Testing of Infectious Agents and Evaluation of Performance of Antimicrobial Susceptibility Test Devices – Part 1: Reference Method for Testing the in Vitro Activity of Antimicrobial Agents against Rapidly Growing Aerobic Bacteria Involved in Infectious Diseases.” 2006 p ISO 20776-1
    [Google Scholar]
  10. Philips S, Van Hoecke F, De Laere E, Vervaeke S, De Smedt R et al. Comparison of two commercial colorimetric broth microdilution tests for Candida susceptibility testing: sensititre yeastone versus MICRONAUT-AM. J Fungi 2021; 7:356 [View Article] [PubMed]
    [Google Scholar]
  11. Alastruey-Izquierdo A, Melhem MSC, Bonfietti LX, Rodriguez-Tudela JL. Susceptibility test for fungi: clinical and laboratorial correlations in medical mycology. Rev Inst Med Trop Sao Paulo 2015; 57:57–64 [View Article] [PubMed]
    [Google Scholar]
  12. Durand C, Maubon D, Cornet M, Wang Y, Aldebert D et al. Can we improve antifungal susceptibility testing?. Front Cell Infect Microbiol 2021; 11:720609 [View Article] [PubMed]
    [Google Scholar]
  13. Midani FS, Collins J, Britton RA. AMiGA: software for automated analysis of microbial growth assays. mSystems 2021; 6:e0050821 [View Article] [PubMed]
    [Google Scholar]
  14. Mayerhöfer TG, Pahlow S, Popp J. The bouguer-beer-lambert law: shining light on the obscure. Chemphyschem 2020; 21:2029–2046 [View Article] [PubMed]
    [Google Scholar]
  15. Clinical and Laboratory Standards Institute “Reference method for broth dilution antifungal susceptibility testing of yeasts,” in Approved standard. In CLSI Supplement M27, 4th. edn Wayne, PA: Clinical and Laboratory Standards Institute; 2017
    [Google Scholar]
  16. Clark RB, Lewinski MA, Loeffelholz MJ, Tibbetts RJ. Cumitech 31A: verification and validation of procedures in the clinical microbiology laboratory. Am Soc Microbiol 2009ISBN 978-1-55581-530-1
    [Google Scholar]
  17. Clinical and Laboratory Standards Institute “Verification of commercial microbial identification and antimicrobial susceptibility testing systems”, in Approved standard. In CLSI Guideline M52, 1st. edn Wayne, PA: Clinical and Laboratory Standards Institute; 2015
    [Google Scholar]
  18. Clemons KV, Espiritu M, Parmar R, Stevens DA. Assessment of the paradoxical effect of caspofungin in therapy of candidiasis. Antimicrob Agents Chemother 2006; 50:1293–1297 [View Article] [PubMed]
    [Google Scholar]
  19. Wagener J, Loiko V. Recent insights into the paradoxical effect of echinocandins. J Fungi 2017; 4:5 [View Article] [PubMed]
    [Google Scholar]
  20. Sousa F, Nascimento C, Ferreira D, Reis S, Costa P. Reviving the interest in the versatile drug nystatin: a multitude of strategies to increase its potential as an effective and safe antifungal agent. Adv Drug Deliv Rev 2023; 199:114969 [View Article] [PubMed]
    [Google Scholar]
  21. Worth Health Organization “WHO fungal priority pathogens list to guide research, development and public health action.” Antimicrobial Resistance Division, Global Coordination and Partnership; 2022 https://www.who.int/publications/i/item/9789240060241
  22. Richard F, Cubeddu LX. Antifungal Drugs, Lippincott’s Illustrated Reviews: Pharmacology, 4th. edn Lippincott Williams & Wilkins; 2009
    [Google Scholar]
  23. Worth Health Organization WHO Model List of Essential Medicines – 22nd List 2021
    [Google Scholar]
  24. Scheibler E, Garcia MCR, Medina da Silva R, Figueiredo MA, Salum FG et al. Use of nystatin and chlorhexidine in oral medicine: properties, indications and pitfalls with focus on geriatric patients. Gerodontology 2017; 34:291–298 [View Article] [PubMed]
    [Google Scholar]
  25. Korting HC, Ollert M, Georgii A, Fröschl M. In vitro susceptibilities and biotypes of Candida albicans isolates from the oral cavities of patients infected with human immunodeficiency virus. J Clin Microbiol 1988; 26:2626–2631 [View Article] [PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.001811
Loading
/content/journal/jmm/10.1099/jmm.0.001811
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error