Statin Use and Aspergillosis Risk—More than Meets the Eye?

To theEditor—I read with interest the significant work by Villalobos APC et al recently published in Clinical Infectious Diseases [1]. The work is important as it provides human data derived from a highly immunosuppressed patient population and supports a significant body of work that has accumulated for the last 25 years demonstrating the activity of statins against a variety of opportunistic fungi [2]. As the authors correctly point out, in addition to their antifungal activity, statins display an array of other immunomodulating activity and synergize with other downstream inhibitors of ergosterol pathway such as the azoles [2]. In that context, I would like to point out some additional nuanced questions coming from this work and the research of the impact statins on Aspergillus biology, clinical severity, diagnostics, and Aspergillus species distribution in invasive aspergillosis (IA). First, as statins are commonly used in the context of metabolic syndrome, statin use could be a surrogate marker of a better concomitant dysglycemia control that affects fungal risk [3, 4]. Although the impact of statins on mortality could not be addressed in this work due to the relatively small number of IA events, as preclinical studies have shown that statins can impact the biology of molds in a variety of ways that could limit their virulence [5], it would be of interest to see if there was an imbalance in the site of infection (Aspergillus pneumonia vs tracheobronchitis/anastomotic infections) as a reflection of severity of infection between the two groups. In this respect, it is also important to understand if statin use was associated with less frequently with culture or galactomannan-documented IA to rule-out misclassification bias. As statins can impair growth of A. fumigatus [6], it would be of interest to know if the percentage of possible aspergillosis cases were higher in the statin group. Finally, as some statins (lovastatin) are produced by some Aspergillus species, specifically Aspergillus terreus [7], and the possibility of feedback loops in inhibition of metabolic gene clusters has been described in Aspergillus [8], the distribution of Aspergillus species in the statin vs non-statin IA groups would be of interest for future studies.

Note

Potential conflicts of interest. The author reports honoraria and research support from Gilead Sciences and Astellas Pharma. He received consultant fees from Astellas Pharma, Merck, and Gilead Sciences, and is a member of the Data Review Committee of Cidara Therapeutics, AbbVie, and the Mycoses Study Group. He also reports grants from Merck, Astellas, T2 Biosystems, and Pfizer; and personal fees from Amplyx, Scynexis, and Jazz Pharmaceuticals.

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