Recent studies have illustrated the impact <i>Cryptosporidium</i> and <i>Shigella </i>infection place on the lives of malnourished children and immunocompromised individuals. For the treatment of cryptosporidiosis, the only FDA approved therapeutic, nitazoxanide, lacks efficacy against the protozoan parasite in the populations the carry the largest burden of disease. Unlike cryptosporidiosis, treatment options for shigellosis are not limited by a lack of intrinsically efficacious therapeutics. Over the past half century, plenty of antibiotics have demonstrated microbiological and clinical efficacy against shigellosis. Instead, therapeutic options continue to diminish as widespread resistance emerges to many first- and second-line therapeutics. While new therapeutics are desperately needed for the treatment of both cryptosporidiosis and shigellosis, drug development efforts for both diseases are complicated by a lack of in vitro and in vivo models to evaluate potential therapeutics. Furthermore, there are unresolved questions about the ideal pharmacokinetic characteristics of new anti Cryptosporidium and anti Shigella therapeutics. Specifically, should drug developers optimize drug candidates and formulations to increase drug exposure in the gastrointestinal lumen, enterocytes, or systemic circulation? In addition, how should researchers interpret data suggesting their therapeutic is a drug efflux transporter substrate? Through the development of novel in vitro and in vivo models, we have identified new therapeutic opportunities for both the treatment of cryptosporidiosis and shigellosis. In addition, we are starting to gain a better understanding of the drug physicochemical properties associated with efficacy in the treatment of both diseases.

Identification and characterization of novel therapeutics for the treatment of cryptosporidiosis and shigellosis

2019 Fall National Meeting

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