Journal
FUTURE MICROBIOLOGY
Volume 13, Issue 11, Pages 1271-1281Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/fmb-2017-0311
Keywords
antibiotic-associated CDI; C; difficile infection severity; indomethacin; NSAID; prostaglandins
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Funding
- Fondo Nacional de Ciencia y Tecnologia de Chile (FONDECYT) [1151025]
- Fondo de Fomento al Desarrollo Cientifico y Tecnologico (FONDEF) [ID16|10038]
- NIH [TR001723, AI121796]
- Vanderbilt Digestive Diseases Research Center NIH [DK058404]
- CAPES [BEX 9179/11-9]
- [CONICYT 21161395]
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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-1 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.
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