1. Indomethacin increases severity of Clostridium difficile infection in mouse model.
- Author
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Muñoz-Miralles J, Trindade BC, Castro-Córdova P, Bergin IL, Kirk LA, Gil F, Aronoff DM, and Paredes-Sabja D
- Subjects
- Animals, Anti-Bacterial Agents adverse effects, Anti-Inflammatory Agents, Non-Steroidal administration & dosage, Disease Models, Animal, Indomethacin administration & dosage, Interleukin-1beta metabolism, Interleukins metabolism, Intestines drug effects, Mice, Mice, Inbred C57BL, Prostaglandin Antagonists adverse effects, Prostaglandins biosynthesis, Risk Factors, Weight Loss, Interleukin-22, Anti-Inflammatory Agents, Non-Steroidal adverse effects, Clostridioides difficile, Clostridium Infections drug therapy, Clostridium Infections pathology, Indomethacin adverse effects, Intestines pathology, Severity of Illness Index
- 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.
- Published
- 2018
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