Indomethacin increases severity of Clostridium difficile infection in mouse model

Future Microbiol. 2018 Sep;13(11):1271-1281. doi: 10.2217/fmb-2017-0311. Epub 2018 Sep 21.

Abstract

Aim: To evaluate the effect on the nonsteroidal anti-inflammatory drug indomethacin on Clostridium difficile infection (CDI) severity.

Materials & methods: Indomethacin was administered in two different mouse models of antibiotic-associated CDI in two different facilities, using a low and high dose of indomethacin.

Results: Indomethacin administration caused weight loss, increased the signs of severe infection and worsened histopathological damage, leading to 100% mortality during CDI. Indomethacin-treated, antibiotic-exposed mice infected with C. difficile had enhanced intestinal inflammation with increased expression of KC, IL-1β and IL-22 compared with infected mice unexposed to indomethacin.

Conclusion: These results demonstrate a negative impact of nonsteroidal anti-inflammatory drugs on antibiotic-associated CDI in mice and suggest that targeting the synthesis or signaling of prostaglandins might be an approach to ameliorating the severity of CDI.

Keywords: C. difficile infection severity; NSAID; antibiotic-associated CDI; indomethacin; prostaglandins.

Publication types

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

MeSH terms

  • Animals
  • Anti-Bacterial Agents / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Clostridioides difficile*
  • Clostridium Infections / drug therapy*
  • Clostridium Infections / pathology*
  • Disease Models, Animal
  • Indomethacin / administration & dosage
  • Indomethacin / adverse effects*
  • Interleukin-1beta / metabolism
  • Interleukin-22
  • Interleukins / metabolism
  • Intestines / drug effects
  • Intestines / pathology*
  • Mice
  • Mice, Inbred C57BL
  • Prostaglandin Antagonists / adverse effects
  • Prostaglandins / biosynthesis
  • Risk Factors
  • Severity of Illness Index*
  • Weight Loss

Substances

  • Anti-Bacterial Agents
  • Anti-Inflammatory Agents, Non-Steroidal
  • IL1B protein, mouse
  • Interleukin-1beta
  • Interleukins
  • Prostaglandin Antagonists
  • Prostaglandins
  • Indomethacin