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Information on how to access prescribing information and adverse event reporting can be found at the bottom of the page.

Diagnostics

Despite progress in treatment and management, invasive fungal infections remain a significant cause of morbidity and mortality in a wide range of patients.1–3

Effective management relies on early classification and diagnosis but identifying pathogens in time continues to be a challenge.4,5 For example, only 50% of invasive mould infections are diagnosed before death, in part due to issues with diagnostic test availability and turnaround time.3,5

The future of invasive fungal infection management is in your hands – take the lead with antifungal stewardship and diagnostics in your Trust.

Bridging the gap

In 2015, the British Society for Medical Mycology (BSMM) developed best-practice guidance for the diagnosis of serious fungal disease.2 Putting measures in place today could help to protect tomorrow. NHS AFS guidance reiterates this; one of their 5 key improvement principles is a diagnostic gap analysis.6 Reporting the results of the analysis to the relevant Trust committee (drug and therapeutics or antimicrobial stewardship) will help them take appropriate action.6

For more information on the NHS improvement principles, visit AFS in practice.

Diagnostic tools

Some of the current approaches for the diagnosis of invasive fungal infections include:2

A diagnostic-driven approach

Given the time-pressured, life-threatening nature of invasive fungal infections, prophylaxis and empiric treatment (without a confirmed pathogen) are commonly used in at-risk patients.11–13 However, over the last 20 years prophylactic antifungal agents have been overused. Inappropriate antifungal prophylaxis can lead to toxicity, DDIs, high costs and the emergence of antifungal resistance, even delaying the initiation of effective antifungal therapy.13,14

For more than a third of patients prescribed posaconazole, itraconazole and voriconazole as prophylaxis, the antifungal strategy has been deemed 'inappropriate'.15 Prophylaxis is associated with significant costs and potential disadvantages, including those related to toxicity and drug-drug interactions.16 Repeated, long-term or prophylactic antifungal therapy is associated with increased resistance.17

The true cost of inadequate invasive fungal infection prophylaxis

Treating fungal infections can be expensive. Prophylaxis has an 'ecological cost' due to the impact of inappropriate treatment on resistance rates and individual patient burden.18 Usefulness and cost-benefit should be evaluated per patient. It's important to consider whether the substantial cost of prophylaxis could be more appropriately spent on an effective diagnostic-driven approach to treatment.

In an economic comparison based on a decision-analytic model, total costs per patient over five months were 32% lower using a diagnostic-driven vs empirical strategy, in part due to reduced incidence of adverse events and decreased use of antifungal therapy:11,a

Total cost per patient of diagnostic-driven vs. empiric strategy11,a

It’s time to pioneer a diagnostic-driven approach, which has been shown to improve chances of survival, as well as ensuring timely treatment.19,20 For example, early use of diagnostic assays can help to accurately identify invasive aspergillosis patients and assist with selecting an appropriate choice of treatment.11

An earlier diagnosis and targeted therapy, thereby eliminating unnecessary antifungals, can help to reduce costs and breakthrough infections, and improve outcomes.11,21 Act now for the future of invasive fungal infection management, with a diagnostic-driven approach.

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a. Economic comparison of an empirical versus diagnostic-driven strategy for treating invasive fungal infections in immunocompromised patients. Diagnostic driven strategy: patients began antifungal therapy when they were suspected of having an invasive fungal infection based on characteristic lesions on CT scan, Aspergillus species colonization, and/or positive ELISA results for galactomannan antigen (GM) and/or positive results for Aspergillus species on PCR assay. Patients were treated with C-AmB, L-AmB, or voriconazole. Empirical strategy: patients began antifungal therapy when they had persistent or recurrent neutropenic fevers that failed to defervesce despite broad-spectrum antibacterial therapy for 72 to 96 hours, with no invasive fungal infection identified. Patients were treated with C-AmB, L-AmB, or caspofungin.11

ABS, antibacterial stewardship; AFS, antifungal stewardship; AmB, amphotericin B; AMS, antimicrobial stewardship; BDG, 1,3-β-D-glucan; BSMM, British Society for Medical Mycology; CRAG, cryptococcal antigen; CQUIN, Commissioning for Quality and Innovation; CT, computerised tomography; DDI, drug-drug interaction; GM, galactomannan; MRI, magnetic resonance imaging; NHS, National Health Service; PCR, polymerase chain reaction.

Prescribing Information:

Click here for CRESEMBA® (isavuconazole) and Vfend (voriconazole) prescribing information

References

Enoch DA et al. Methods Mol Biol 2017;1508:17–65.Schelenz S et al. Lancet Infect Dis 2015;15(4):461–474.Talento AF et al. J Fungi 2021;7:801. https://doi.org/10.3390/jof7100801.Drgona l et al. Eur J Clin Microbiol Infect Dis 2014;33:7–21.Dignani MC. F1000Prime Rep 2014;6:81.NHS England Antifungal Stewardship Implementation Pack. Available at: https://www.england.nhs.uk/wp-content/uploads/2019/03/PSS1-meds-optimisation-trigger-5-antifungal-stewardship-implementation-pack-v7.pdf. Accessed August 2022.Skiada A et al. J Fungi (Basel) 2020;6(4):265.Jenks JD et al. Curr Fungal Infect Rep 2020;14:378–383.Heldt S and Hoenigl M. Curr Fungal Infect Rep 2017;11:45–51.Mercier T et al. Crit Care 2020;24:642.Barnes R et al. Clin Ther 2015;37(6):1317–1328.Mercier T and Maertens J. J Antimicrob Chemother 2017;72(suppl_1):i29–i38.de Kort EA et al. Medical Mycology 2019;57:S267–S273.Ko BS et al. J Microbiol Immunol Infect 2018;51(3):287–301.Nivoix Y et al. J Antimicrob Chemother 2012;67:2506–2513.Coussement J et al. Curr Opin Infect Dis 2021;34(4):297–306.Perlin OS et al. Lancet Infect Dis 2017;17(12):S1473–S3099(17).Cataldo MA and Petrosillo N. Ther Clin Risk Manag 2011;7:13–20.Rogers TR et al. Br J Haematol. 2011;153(6):681–697.Freemantle N et al. J Antimicrob Chemother 2011;66(Suppl 1):i25–35.Hamdy RF et al. Virulence 2017;8(6):658–672.
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