Skip to main content
NCBI home page
Medline Book to support NIHPA logoLink to Medline Book to support NIHPA
. 2025 Oct 8:1–19. doi: 10.3310/GJRM3321

Rapid diagnostic tests to inform clinical decision-making for antifungal stewardship in the ICU: a qualitative study with NHS staff, patients, and their legal representatives.

Chikomborero Cynthia Mutepfa, Jana Suklan, Jennifer Bell, Mary Guiney, William Jones, John Simpson, Ronan McMullan
PMCID: PMC12683465  PMID: 41081795

Abstract

BACKGROUND

Invasive candidiasis is a fungal infection of the blood or organs that is associated with high morbidity and mortality in critically ill patients. Current diagnosis is based on blood culture, which typically takes 2 days to confirm the presence of Candida, and longer for differentiating the species and sensitivities to antifungal drugs. Administration of antifungal treatment is time-critical, hence critically ill patients considered 'at-risk' of Candida infection are often started on antifungal treatment pending test results. However, many of these patients may not have empirical treatment stopped when test results become available because of concerns about the sensitivity of blood culture. The Antifungal STewardship Opportunities study is a multisite national diagnostic test accuracy study investigating the use of rapid tests in the intensive care unit that have the potential to influence decision-making.

OBJECTIVE(S), STUDY DESIGN, SETTINGS AND PARTICIPANTS

Our aim is to understand patient and physician risk preferences for using the Antifungal STewardship Opportunities testing strategy to discontinue empirical antifungal therapy using semi-structured interviews. An a priori sample size of 30 National Health Service staff and 10 patient interviews was selected to elicit information relating to the aims. Interview schedules were developed, and all interviews were conducted via video or teleconferencing between December 2021 and December 2022 and lasted between 10 and 60 minutes. Interviews were recorded, transcribed and subjected to thematic analysis.

FINDINGS

Semi-structured interviews were conducted with 21 National Health Service clinicians and seven patients and legal representatives. National Health Service staff were risk-averse to stopping empirical antifungal therapy, especially if the patient was improving, while patients were risk-neutral. Although there is a clear unmet need for new rapid testing strategy, clinical confidence in its accuracy, clinical utility, cost-effectiveness and usability were strong factors for its consideration for use in decision-making and adoption. Patients did not exhibit strong feelings towards stopping empirical antifungal treatment as they expressed reliance on clinical judgement.

LIMITATIONS

There was a potential for selection bias as interview participants being from participating sites. The target recruitment numbers of patients and their legal representatives was not achieved due to low retention rates.

CONCLUSIONS

If found to have high accuracy and cost-effectiveness, the potential of the Antifungal STewardship Opportunities diagnostic strategy to aid decision-making on antifungal prescribing could change intensive care unit clinicians practice, as they are risk-averse to stopping empirical antifungal treatment. However, consideration of the resources needed including staff, and lab facilities, adequate training as well as established guidelines to facilitate its adoption is required.

FUTURE WORK

Our next aim is to use Antifungal STewardship Opportunities results to inform the update of National Institute for Health and Care Excellence guidelines and explore schemes such as the Accelerated Access Collaborative and MedTech funding mandate to propel the adoption of this testing strategy.

FUNDING

This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 15/116/03.

Plain language summary

Invasive candidiasis is a serious fungal infection of the blood or other organs which can lead to death, especially in critically ill patients. Diagnosing this infection involves a lengthy process which takes up to 2 days or more. Due to the risks of starting treatment late, doctors often start treatment with antifungal medications before having results available. Faster diagnosis is crucial for efficient antimicrobial stewardship and to reduce unnecessary use of potentially toxic and costly drugs. Antifungal STewardship Opportunities study is investigating the use of rapid tests to improve how we diagnose invasive candidiasis in the United Kingdom. ‘Stewardship’ is about responsible use of medications that fight off infections. It is believed that these tests will help physicians make the decision on whether antifungal drugs are needed in a timelier way. Our objective was to understand the risk preferences of patients and physicians in using the Antifungal STewardship Opportunities testing strategy for stopping or modifying medications prescribed before test results were available. The study involved interviews with 21 National Health Service staff members and seven patients or their legal representatives, conducted between December 2021 and December 2022. The results of the interviews indicated that National Health Service clinicians were generally reluctant to take the risks of stopping the use of antifungal medications if the patient’s health conditions improved. Patients trusted their physicians in their decision to continue or stop the treatment. All agreed that there is the need for a quicker, cost-effective, reliable and easy-to-use test. These factors would increase the likelihood for the test to be adopted. To assess the potential of the test, National Health Service needs to have staff and lab capacity to deliver on faster turnaround times. If the Antifungal STewardship Opportunities diagnostic strategy is proven effective, the development of guidelines to support its implementation in National Health Service will follow.

Full text of this article can be found in Bookshelf.

References

  1. Calandra T, Roberts JA, Antonelli M, Bassetti M, Vincent JL. Diagnosis and management of invasive candidiasis in the ICU: an updated approach to an old enemy. Crit Care 2016;20:125. doi: 10.1186/s13054-016-1313-6. [DOI] [PMC free article] [PubMed]
  2. Sobel J, Revankar S. Systemic candidiasis – symptoms, diagnosis and treatment. BMJ Best Practice 2021.
  3. de Pascale G, Tumbarello M. Fungal infections in the ICU: advances in treatment and diagnosis. Curr Opin Crit Care 2015;21:421–9. doi: 10.1097/MCC.0000000000000230. [DOI] [PubMed]
  4. Harrison D, Muskett H, Harvey S, Grieve R, Shahin J, Patel K, et al. Development and validation of a risk model for identification of non-neutropenic, critically ill adult patients at high risk of invasive Candida infection: the Fungal Infection Risk Evaluation (FIRE) Study. Health Technol Assess 2013;17:1–156. doi: 10.3310/hta17030. [DOI] [PMC free article] [PubMed]
  5. Bassetti M, Azoulay E, Kullberg BJ, Ruhnke M, Shoham S, Vazquez J, et al. EORTC/MSGERC definitions of invasive fungal diseases: summary of activities of the intensive care unit working group. Clin Infect Dis 2021;72:S121–7. doi: 10.1093/cid/ciaa1751. [DOI] [PubMed]
  6. Bassetti M, Righi E, Ansaldi F, Merelli M, Scarparo C, Antonelli M, et al. A multicenter multinational study of abdominal candidiasis: epidemiology, outcomes and predictors of mortality. Intensive Care Med 2015;41:1601–10. doi: 10.1007/s00134-015-3866-2. [DOI] [PubMed]
  7. Gill CM, Kenney RM, Hencken L, Mlynarek ME, Alangaden GJ, Samuel LP, Davis SL. T2 Candida versus beta-D-glucan to facilitate antifungal discontinuation in the intensive care unit. Diagn Microbiol Infect Dis 2019;95:162–5. doi: 10.1016/j.diagmicrobio.2019.04.016. [DOI] [PubMed]
  8. Auzinger G, Playford EG, Graham CN, Knox HN, Weinstein D, Kantecki M, et al. Cost-effectiveness analysis of anidulafungin for the treatment of candidaemia and other forms of invasive candidiasis. BMC Infect Dis 2015;15:463. doi: 10.1186/s12879-015-1143-1. [DOI] [PMC free article] [PubMed]
  9. Tabah A, Koulenti D, Laupland K, Misset B, Valles J, Bruzzi De Carvalho F, et al. Characteristics and determinants of outcome of hospital-acquired bloodstream infections in intensive care units: the EUROBACT International Cohort Study. Intensive Care Med 2012;38:1930–45. doi: 10.1007/s00134-012-2695-9. [DOI] [PubMed]
  10. PHE. Laboratory Surveillance of Candidaemia in England: 2020. Vol. 15, Health Protection TReport. London: Public Health England; 2021.
  11. Chun K, Syndergaard C, Damas C, Trubey R, Mukindaraj A, Qian S, et al. Sepsis pathogen identification. J Lab Autom 2015;20:539–61. doi: 10.1177/2211068214567345. [DOI] [PubMed]
  12. Logan C, Martin-Loeches I, Bicanic T. Invasive candidiasis in critical care: challenges and future directions. Intensive Care Med 2020;46:2001–14. doi: 10.1007/s00134-020-06240-x. [DOI] [PubMed]
  13. Avni T, Leibovici L, Paul M. PCR diagnosis of invasive candidiasis: systematic review and meta-analysis. J Clin Microbiol 2011;49:665–70. doi: 10.1128/JCM.01602-10. [DOI] [PMC free article] [PubMed]
  14. McMullan R, McAuley D, Clarke M, Walsh T, Dark P, Perkins G, et al. Antifungal stewardship opportunities with rapid tests for fungal infection in critically-ill patients (The A-Stop Study) – NIHR Funding and Awards. 2017.
  15. Wright WF, Overman SB, Ribes JA. (1–3)-β-D-Glucan assay: a review of its laboratory and clinical application. Lab. Med 2011;42:679–85.
  16. Wilson NM, Alangaden G, Tibbetts RJ, Samuel LP, Davis SL, Kenney RM. T2 magnetic resonance assay improves timely management of candidemia. Open Forum Infect Dis 2017;3.
  17. Fungiplex® Candida. Bruker [Internet]. URL: www.bruker.com/en/products-and-solutions/molecular-diagnostics/assays/fungal-infections/fungiplex-candida.html (accessed 9 June 2022).
  18. Braun V, Clarke V. Thematic Analysis: A practical guide. London: SAGE; 2022.
  19. Wheeldon J, Åhlberg M. Visualizing Social Science Research: Maps, Methods, & Meaning. Los Angeles: Sage Publications; 2012.
  20. Fusch PI, Ness LR. Are we there yet? Data saturation in qualitative research. Qual Rep 2015;20:1408–16.
  21. Tissot F, Agrawal S, Pagano L, Petrikkos G, Groll AH, Skiada A, et al. ECIL-6 guidelines for the treatment of invasive candidiasis, aspergillosis and mucormycosis in leukemia and hematopoietic stem cell transplant patients. Haematologica 2017;102:433–44. doi: 10.3324/haematol.2016.152900. [DOI] [PMC free article] [PubMed]
  22. Pappas PG, Kauffman CA, Andes DR, Clancy CJ, Marr KA, Ostrosky-Zeichner L, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the infectious diseases society of America. Clin Infect Dis 2016;62:e1–50. doi: 10.1093/cid/civ933. [DOI] [PMC free article] [PubMed]
  23. Cornely OA, Bassetti M, Calandra T, Garbino J, Kullberg BJ, Lortholary O, et al.; ESCMID Fungal Infection Study Group. ESCMID* guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients. Clin Microbiol Infect 2012;18:19–37. doi: 10.1111/1469-0691.12039. [DOI] [PubMed]
  24. de Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, et al.; European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis 2008;46:1813–21. doi: 10.1086/588660. [DOI] [PMC free article] [PubMed]
  25. Joint Formulary Committee. Antifungals, Systemic Use | Treatment Summaries | BNF | NICE. British National Formulary. 2022. URL: https://bnf.nice.org.uk/treatment-summaries/antifungals-systemic-use/ (accessed 12 June 2025).
  26. Lewis RE. Current concepts in antifungal pharmacology. Mayo Clin Proc 2011;86:805–17. doi: 10.4065/mcp.2011.0247. [DOI] [PMC free article] [PubMed]
  27. Antifungal Agents. EMCrit Project. URL: https://emcrit.org/ibcc/antifungal/ (accessed 12 June 2025).
  28. Baumgarten M, Poulsen I. Patients’ experiences of being mechanically ventilated in an ICU: a qualitative metasynthesis. Scand J Caring Sci 2015;29:205–14. doi: 10.1111/scs.12177. [DOI] [PubMed]
  29. McKeating C, White PL, Posso R, Palmer M, Johnson E, McMullan R. Diagnostic accuracy of fungal PCR and β-d-glucan for detection of candidaemia: a preliminary evaluation. J Clin Pathol 2018;71:420–4. doi: 10.1136/jclinpath-2017-204692. [DOI] [PubMed]
  30. Martin-Loeches I, Antonelli M, Cuenca-Estrella M, Dimopoulos G, Einav S, de Waele JJ, et al. ESICM/ESCMID task force on practical management of invasive candidiasis in critically ill patients. Intensive Care Med 2019;45:789–805. doi: 10.1007/s00134-019-05599-w. [DOI] [PubMed]
  31. Wong CA, Song WB, Jiao M, O’Brien E, Ubel P, Wang G, Scales CD. Strategies for research participant engagement: a synthetic review and conceptual framework. Clin Trials 2021;18:457–65. doi: 10.1177/17407745211011068. [DOI] [PubMed]
  32. NHS England. MedTech Funding Mandate policy 2022/23: Guidance for NHS Commissioners and Providers of NHS-Funded Care. 2022. URL: www.england.nhs.uk/publication/medtech-funding-mandate-policy-2022-23-guidance-for-nhs-commissioners-and-providers-of-nhs-funded-care/ (accessed 12 June 2025).

RESOURCES