Do We Need Modification of Recent IDSA & ECIL Guidelines while Managing Patients in Asia?

Dr Louis Chai
Senior Consultant and Associate Professor
University Medicine Cluster
National University Health System
Singapore

Guidelines are very important in the management of fungal infections. They play a crucial role in summarizing the current evidence base, standardizing care and improving outcomes. However, there are many reasons why clinicians in Asia (or, indeed, elsewhere in the world) might want to deviate from recommendations:

• The importance of individualized clinical judgment over generic pathways;
• Differences between trial data and ‘real-life’ practice;
• Local epidemiology and resistance patterns;
• Varying patient demographics;
• Drug intolerance; and
• Cost concerns.

Invasive candidiasis

According to both the Infectious Diseases Society of America (IDSA) and the European Conference on Infections in Leukemia (ECIL), echinocandins are now the recommended initial therapy for candidemia in both neutropenic and non-neutropenic patients.^1,2 There remains an allowance for the use of azoles and liposomal amphotericin B in some circumstances.

However, in an Asian context, local circumstances may dictate some divergence from guidelines. In particular, epidemiology may differ substantially in this region compared with North America and Europe – most notably in a higher incidence of Candida tropicalis and a lower incidence of C. glabrata.^3,4

In addition, cost is a concern. A recent Asian study assessed the cost-effectiveness of individual echinocandins (caspofungin, micafungin and anidulafungin) versus non-echinocandins for C. albicans and non-albicans spp., taking into account the probability of treatment success, mortality rates, adverse drug events, etc.⁵ Importantly, the study found that echinocandins – particularly anidulafungin – were cost-effective compared with other therapies.

Invasive aspergillosis

In recent guidance from IDSA and ECIL, recommendations for the primary therapy of invasive aspergillosis (IA) were based largely around voriconazole and isavuconazole.^1,6 ECIL-6 recommends against first-line use of amphotericin B deoxycholate on the grounds of low efficacy and high toxicity.⁶

However, the reality of IA management may come down to whether or not a given center can take a diagnosis-driven approach, based on the latest tools and rapid diagnostic turnaround times. For many centers in Asia, this is not yet possible because the capacity to investigate the underlying etiology is limited. Instead, an empiric approach must be taken, based on the treatment of a presumed fungal infection, triggered by persistent fever in a high-risk (neutropenic) patient. The choice of empiric therapy may include agents such as voriconazole, fluconazole, liposomal amphotericin B and caspofungin.

References

1. Pappas PG, et al. Clin Infect Dis 2016;62:e1-e50.
2. Tissot F, et al. Haematologica 2017;102:433-444.
3. Falagas ME, et al. Int J Infectious Dis 2010;14:e954-e966.
4. Pfaller MA, et al. J Clin Microbiol 2011;49:396-399.
5. Ou HT, et al. BMC Infect Dis 2017;17:481.
6. Patterson TF, et al. Clin Infect Dis 2016;63:e1-e60.