The role of antifungal stewardship in improving IFI outcomes

The need for antifungal stewardship

The global burden of invasive and severe fungal diseases is massive, with over 3 million chronic severe infections globally and an annual incidence of at least 1.9 million acute invasive fungal infections (IFIs).¹ IFIs mostly affect immunosuppressed or critically ill individuals, and are associated with significant morbidity, mortality and increased healthcare costs.^2,3

Timely initiation and the judicious use of appropriate antifungal therapy are crucial to the successful management of IFI. At present, up to half of antifungal prescriptions are unnecessary or inappropriate,³ in part due to the limited sensitivity of fungal diagnostics. Additionally, the choice of antifungal therapy in many institutions is often limited by their cost, toxicity profile or their availability. The lack of effective and timely fungal diagnostic tools could lead to significant delays in targeted treatment, which inadvertently increases the risk of overexposure to potentially toxic agents, antifungal resistance and poor patient outcomes.² Together, these factors outline the importance of multidisciplinary antifungal stewardship (AFS), which is increasingly being recognized in the pursuit of optimizing antifungal therapy and improving the outcomes of patients with IFI.²

AFS refers to coordinated interventions to monitor and direct the appropriate use of antifungal agents with the aim of achieving optimal clinical outcomes, minimizing selective pressure and reducing the occurrence of adverse events.^2,4 AFS is an emerging component of antimicrobial stewardship (AMS), with which it shares goals and principles for guiding therapy. However, AFS faces a number of unique challenges, such as^2,4:

• difficulties in diagnosis, eg, poor sensitivity of culture-based microbiologic tests and non-specific clinical manifestations of IFIs (in immunocompromised patients);
• the lack of consensus on management and de-escalation methodologies; and
• limited antifungal resistance reporting 

Core elements of AFS 

An international consensus panel developed a set of core elements of any AMS (and AFS) program, which includes³:

1. Engagement of the senior hospital management leadership towards AFS, including accountability and dedicated resources to support AFS activities
2. Accountability and responsibilities of a highly functioning, experienced multidisciplinary AFS team, including infectious disease (ID) physicians, ID-trained pharmacists and other key healthcare personnel managing these diseases
3. Available expertise on infection management, including access to timely conventional and non-culture-based diagnostic testing for Candida and Aspergillus species
4. Education and practical training through targeted programs to address knowledge gaps
5. Actions aiming at responsible antimicrobial use, such as ID consultation for patients with IFI and development of treatment bundles or guidelines
6. Monitoring, surveillance and reporting of fungal infections with access to timely antifungal susceptibility testing
7. Reporting and feedback mechanisms to track antifungal drug use

To have a successful AFS program, establishing a core set of metrics/performance measures that reflect the impact of the program is important; data-driven approaches have been shown to aid stewardship programs in optimizing antimicrobial use (Table 1).^2,3

Table 1. Proposed metrics for measuring the impact of AFS^2,3

Outcome	Examples of metrics
Antifungal consumption	DDD/1,000 patient days Days of therapy/1,000 patient days Length of therapy
Antifungal prescribing quality	Number of antifungal prescriptions reviewed Number of treatment modifications recommended Appropriate choice of antifungal agent
Diagnosis	Appropriate diagnostic test used Turnaround time for results Follow-up cultures until negative result
Microbiological	Causative organisms/species Antifungal resistance Time to microbiological clearance
Clinical	Incidence of IFI IFI-related mortality Hospital length of stay
Cost	Antifungal prescription cost Diagnostic cost Other AFS implementation cost

AFS, antifungal stewardship; DDD, defined daily dose; IFI, invasive fungal infections

Conclusion

As the populations at risk for IFIs continue to expand, the need for AFS programs to monitor and prevent severe fungal infection becomes even more pressing. An effective AFS program, backed by core elements and data-driven measures, can help optimize antifungal prescribing and IFI management.

References

1. Bongomin F, et al. J Fungi (Basel) 2017;3:57.
2. Chakrabarti A, et al. Open Forum Infect Dis 2022;9:ofac234.
3. Johnson MD, et al. J Infect Dis 2020;222(Suppl 3):S175-S198.
4. Khanina A, et al. Intern Med J 2021;51(Suppl 7):18-36.