Indomethacin increases severity of Clostridium difficile infection in mouse model

Juan Muñoz-Miralles, Bruno C. Trindade, Pablo Castro-Córdova, Ingrid L. Bergin, Leslie A. Kirk, Fernando Gil, David M. Aronoff, Daniel Paredes-Sabja

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1271-1281
Number of pages11
JournalFuture Microbiology
Volume13
Issue number11
DOIs
Publication statusPublished - 1 Sept 2018

Keywords

  • Prostaglandins

ASJC Scopus subject areas

  • Microbiology
  • Microbiology (medical)

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