Amixicile Reduces Severity of Cryptosporidiosis but Does Not Have In Vitro Activity against Cryptosporidium

Antimicrob Agents Chemother. 2018 Nov 26;62(12):e00718-18. doi: 10.1128/AAC.00718-18. Print 2018 Dec.

Abstract

Cryptosporidium species cause significant morbidity in malnourished children. Nitazoxanide (NTZ) is the only approved treatment for cryptosporidiosis, but NTZ has diminished effectiveness during malnutrition. Here, we show that amixicile, a highly selective water-soluble derivative of NTZ diminishes Cryptosporidium infection severity in a malnourished mouse model despite a lack of direct anticryptosporidial activity. We suggest that amixicile, by tamping down anaerobes associated with intestinal inflammation, reverses weight loss and indirectly mitigates infection-associated pathology.

Keywords: Cryptosporidium; amixicile; environmental enteropathy; malnutrition; nitazoxanide.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiprotozoal Agents / pharmacology
  • Benzamides / pharmacology*
  • Cryptosporidiosis / drug therapy*
  • Cryptosporidiosis / etiology
  • Cryptosporidium parvum / drug effects*
  • Cryptosporidium parvum / pathogenicity
  • Disease Models, Animal
  • Mice, Inbred C57BL
  • Nitro Compounds
  • Pyruvate Synthase / antagonists & inhibitors
  • Pyruvate Synthase / metabolism
  • Thiazoles / pharmacology*
  • Weight Loss / drug effects

Substances

  • Antiprotozoal Agents
  • Benzamides
  • Nitro Compounds
  • Thiazoles
  • amixicile
  • Pyruvate Synthase
  • nitazoxanide