Martin Bradley discusses new targets for antifungal stewardship, which offer the potential for improved patient care, but miss opportunities for cost savings
Antimicrobial stewardship is a healthcare system-wide approach to promoting and monitoring the judicious use of antimicrobials, such as antifungals, to preserve their future effectiveness.1 Such programmes aim to optimise therapy for individual patients, prevent overuse and misuse of these medicines, and minimise the development of resistance.1 A variety of activities can be undertaken in an antimicrobial stewardship programme, but these generally include monitoring and evaluating antimicrobial prescribing and how this relates to local resistance patterns, providing regular feedback to individual prescribers in all care settings about their antimicrobial prescribing, and audit.2
Compelling data confirm that antimicrobial stewardship programmes are effective at reducing inappropriate antimicrobial use and decreasing length of hospital stay.3,4 In 2015, NICE published guidance for organisations on implementing antimicrobial stewardship programmes,2 and these programmes are now accepted practice in NHS secondary care organisations.5 More recent research has shown that additional specific antifungal stewardship programmes can ensure the appropriate use of antifungal agents, improve the quality of patient care, and reduce costs,6–8 but as of 2017, only 11% of trusts had specific antifungal stewardship programmes in place.5
The benefits of antifungal stewardship
In addition to the clinical benefits of general stewardship programmes, the potential for cost savings is a significant aspect of antifungal stewardship: until recently, most antifungal agents were high-cost, and stewardship contributes to their more judicious use. Several antifungal drugs are excluded from the national tariff, and NHS England has commissioning responsibility for them. The overall spend by NHS England on antifungals exceeds £80 million per annum,9 and a 6-year antifungal stewardship programme at a London teaching hospital demonstrated that 25% of the antifungal drug spend can be saved by such a scheme.6 One of the main drivers for saving was the de‑escalation or cessation of treatment when empirical treatment was found to be unnecessary by specialist review.6
Because there has been a lack of formal antifungal stewardship in hospitals in England to date, and antifungal stewardship offers significant potential for savings and improved patient care, NHS England has included antifungal stewardship as one of the triggers for the Medicines Optimisation Commissioning for Quality and Innovation (CQUIN) indicator for
2019–2021.9 NHS England anticipates that there is an opportunity to save £4–8 million per annum nationally through improved antifungal stewardship.9 The precise details of the CQUIN indicator are to be negotiated locally between providers and regional specialised commissioning.
Aims of the CQUIN indicator on antifungal stewardship
Antifungal stewardship is one of five triggers of the CQUIN indicator for 2019–2021, and organisations that sign up to the antifungal stewardship scheme will receive 20% of the CQUIN funding associated with that trigger.9 There are four main drivers for improvement in the antifungal stewardship trigger in the CQUIN scheme: implementation of evidence‑based guidance, formation of antifungal stewardship teams, diagnostic gap analysis, and Bluteq approval for isavuconazole.10
Implementation of evidence-based guidance
Trusts are required to demonstrate that they have up-to-date, evidence‑based antifungal prescribing guidelines for the prophylaxis and treatment of invasive fungal infections. A prophylaxis risk table for drug choice should be included to help standardise the approach to management within the organisation. The guidance should have been approved by the appropriate trust committee (e.g. the Drug and Therapeutics Committee), and shared with NHS England by the end of quarter 1 of 2019/20.
Antifungal stewardship teams, and antifungal reviews
Commissioners are expecting that an antifungal stewardship team will be set up within each trust signing up to the scheme; as a minimum, this team should consist of a consultant microbiologist or infectious diseases physician and a pharmacist.10 The antifungal stewardship team will need to undertake targeted therapeutic reviews of patients initiated on antifungal treatment, and will be required to discuss therapy choices with senior members of the clinical team that prescribed the treatment. The team should ensure that antifungal therapy is reviewed 48–72 hours after initiation, and every 7 days thereafter.10 One of the functions of the 48–72-hour review is to elucidate whether the appropriate diagnostic interventions had been arranged within the first 24 hours. In order to facilitate improved diagnostic processes, the antifungal stewardship team will ideally also review patients at 24 hours after the initiation of antifungal agents. Reviews are intended to highlight patients appropriate for de-escalation or cessation of therapy, inform recommendations on duration of therapy, identify patients suitable for switching from intravenous to oral treatment, and prompt additional investigations and therapeutic drug monitoring.
Trusts should have identified members and processes within their antifungal stewardship teams by the end of quarter 2 of 2019/20, and audits of antifungal stewardship activities are to be reported to NHS England by the end of quarter 4. An audit template has been provided, available at www.england.nhs.uk/publication/pss1-meds-optimisation-pss-cquin-indicator/,11 and trusts are required to report on various parameters (e.g. initial choice of treatment and antifungal advice given) of the 24-hour, 48–72-hour, and 7-day reviews. Data from a maximum of 20 patients—or 30% of patients receiving antifungals, whichever is the smaller figure—are required for the audit.10
Diagnostic gap analysis
A significant problem with the current management of fungal infection is that suboptimal diagnostic tools can drive overuse of antifungal agents. Improving diagnostic facilities and procedures should assist with this medicines optimisation drive. The British Society of Medical Mycology (BSMM) recently developed best practice guidance for the diagnosis of serious fungal diseases, consisting of 43 recommendations on aspects of antifungal treatment including best practice for serological and molecular, histopathological, and radiological testing.12 Many organisations are likely to lack some of the facilities required to adhere to these recommendations; therefore, the initial step is a gap analysis (due by the end of quarter 3 of 2019/2020),9 and it is expected that trusts will progress towards having facilities and processes in place to deliver the BSMM guidelines.
Bluteq approval for isavuconazole
Isavuconazole is a new, high-cost antifungal agent that was licensed in November 2015 for invasive aspergillosis and in mucormycosis in patients for whom amphotericin B is inappropriate. NHS England has commissioned this treatment since it was licensed, but there are no agreed formal criteria for its use. The Bluteq prior approval process is intended to restrict isavuconazole for use only where there are no alternatives, e.g. voriconazole.
Patent expiries—a missed opportunity revealed
Several previously expensive antifungal drugs have recently been made available as generic agents at considerably lower prices than those of the original branded medications. Anidulafungin, micafungin, caspofungin, and voriconazole have recently come off patent, and are commonly used in the management of fungal infections; therefore, considerable savings in antifungal spend are anticipated from these patent expiries, irrespective of whether the CQUIN indicator is employed. Many of the savings detailed in early literature on antifungal stewardship were related to the de‑escalation or cessation of these specific antifungal agents (where clinically appropriate). Drug expenditure savings from antifungal stewardship activities will therefore be less significant than the literature predicted; had the initiative been implemented a few years earlier, considerable savings in drug spend would have been possible for those financial years. However, improved diagnostics and more appropriate use of antifungals can be expected to deliver some savings, improve patient care, and help reduce antifungal resistance.
Three antifungal drugs remain high-cost: liposomal amphotericin B, posaconazole, and isavuconazole. As described earlier, Bluteq prior approval is expected to limit the use of isavuconazole to scenarios in which it is absolutely necessary. However, the patent for posaconazole will expire by the end of the year, and as of early 2020, generic versions of this agent are likely to become available, equating to considerable savings for the NHS regardless of the activities of antifungal stewardship programmes.
Antimicrobial stewardship programmes promote the prudent use of antibiotics, and there is strong evidence that they improve patient outcomes.1–4 Consequently, they have become ubiquitous in secondary care organisations in the UK. Specific antifungal stewardship measures have an evolving evidence base, and studies have shown that they also can considerably reduce drug spend; however, very few organisations have adopted a formal antifungal stewardship strategy. Given the opportunity for improved patient care and savings, NHS England has included antifungal stewardship in the national Medicines Optimisation CQUIN indicator for 2019–2021,9 and has outlined specific recommendations for the composition and activities of antifungal stewardship teams, although the specifics are being negotiated at a local level.
Many antifungal agents have recently become available as generic agents, so the potential savings conferred by their more judicious use are lower than would have been the case had the initiative been introduced in previous years. Despite this, antifungal stewardship remains a laudable project to preserve the clinical effectiveness of these medicines, improve patient care, and enhance diagnostic processes.
- Davies S. Annual report of the Chief Medical Officer. Volume Two, 2011. Infections and the rise of antimicrobial resistance. London: DH, 2013.
Available at: assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/138331/CMO_Annual_Report_Volume_2_2011.pdf (accessed 7 November 2019).
- NICE. Antimicrobial stewardship: systems and processes for effective antimicrobial medicine use. NICE Guideline 15. NICE, 2015. Available at: www.nice.org.uk/ng15
- Schuts E, Hulscher M, Mouton J et al. Current evidence on hospital antimicrobial stewardship objectives: a systematic review and meta-analysis. Lancet Infect Dis 2016; 16: 847–856.
- Davey P, Marwick C, Scott C et al. Interventions to improve antibiotic prescribing practices for hospital inpatients. Cochrane Database Syst Rev 2017; (2): CD003543.
- Micallef C, Ashiru-Oredope D, Hansraj S et al. An investigation of antifungal stewardship programmes in England. J Med Microbiol 2017; 66 (11): 1581–1589.
- Whitney L, Al-Ghusein H, Glass S. Effectiveness of an antifungal stewardship programme at a London teaching hospital 2010-2016. J Antimicrob Chemother 2019; 74: 234–241.
- Valerio M, Rodriguez-Gonzalez C, Muñoz P et al. Evaluation of antifungal use in a tertiary care institution: antifungal stewardship urgently needed. J Antimicrob Chemother 2014; 69 (7): 1993–1999.
- Mondain V, Lieutier F, Hasseine L et al. A 6-year antifungal stewardship programme in a teaching hospital. Infection 2013; 41: 621–628.
- NHS England. PSS1 Medicines optimisation and stewardship PSS CQUIN indicator. London: NHS England, 2019. Available at: www.england.nhs.uk/publication/pss1-meds-optimisation-pss-cquin-indicator/
- NHS England. Improving value in specialised services. Antifungal stewardship implementation pack. London: NHS England, 2019. Available at: www.england.nhs.uk/wp-content/uploads/2019/03/PSS1-meds-optimisation-trigger-5-antifungal-stewardship-implementation-pack-v7.pdf
- NHS England. PSS1 Medicines Optimisation national reporting template. London: NHS England, 2019. Available at: www.england.nhs.uk/wp-content/uploads/2019/10/PSS1-mo-national-reporting-template-v3.xlsx
- Schelenz S, Barnes R, Barton R. British Society for Medical Mycology best practice recommendations for the diagnosis of serious fungal diseases. Lancet Infect Dis 2015; 15 (4) 461–474.