Abstract
A recent large outbreak of fungal infections by Exserohilum rostratum from contaminated compounding solutions has highlighted the need to rapidly screen available pharmaceuticals that could be useful in therapy. The present study utilized two newly-developed high throughput assays to screen approved drugs and pharmaceutically active compounds for identification of potential antifungal agents. Several known drugs were found that have potent effects against E. rostratum including the triazole antifungal posaconazole. Posaconazole is likely to be effective against infections involving septic joints and may provide an alternative for refractory central nervous system infections. The anti-E. rostratum activities of several other drugs including bithionol (an anti-parasitic drug), tacrolimus (an immunosuppressive agent) and floxuridine (an antimetabolite) were also identified from the drug repurposing screens. In addition, activities of other potential antifungal agents against E. rostratum were excluded, which may avoid unnecessary therapeutic trials and reveals the limited therapeutic alternatives for this outbreak. In summary, this study has demonstrated that drug repurposing screens can be quickly conducted within a useful time-frame. This would allow clinical implementation of identified alternative therapeutics and should be considered as part of the initial public health response to new outbreaks or rapidly-emerging microbial pathogens.
Highlights
Unusual or highly antibiotic resistant organisms may subject large numbers of individuals to unexpected infectious diseases due to greater globalization that brings more widespread distribution networks and potential threats such as bioterrorism
A large outbreak of fungal infections has been caused by the widespread distribution of contaminated preservative-free methylprednisolone acetate prepared by a single compounding pharmacy [1,2,3,4]
Exserohilum rostratum, a dermatiaceous fungus commonly found on plants, in soil and in households, has been identified as one of the predominant pathogens in the current multistate outbreak of fungal meningitis and other infections associated with contaminated steroid injections
Summary
Unusual or highly antibiotic resistant organisms may subject large numbers of individuals to unexpected infectious diseases due to greater globalization that brings more widespread distribution networks and potential threats such as bioterrorism. Exserohilum rostratum, a dermatiaceous fungus commonly found on plants, in soil and in households, has been identified as one of the predominant pathogens in the current multistate outbreak of fungal meningitis and other infections associated with contaminated steroid injections. It rarely causes infections in healthy people, infections of skin and corneal tissues as well as more disseminated infections in immunocompromised populations have been reported [6,7,8]
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