5 years ago

Why Is Antibiotic Treatment Not Enough for Sepsis Resolution? An Evaluation in an Experimental Animal Model.

Sepsis remains a major health problem at the level of mortality, morbidity and economic burden to the healthcare system, a condition that is aggravated by the development of secondary conditions, such as septic shock and multiple organ failure. Our current understanding of the etiology of human sepsis has advanced, at least in part, due to the use of experimental animal models, particularly the model of cecum ligation and puncture (CLP). Antibiotic treatment has been commonly used in this model to closely mirror the treatment of human septic patients. However, it is questionable whether their use may obscure the elucidation of the cellular and molecular mechanisms involved in the septic response. The objective of the present study was to determine the effect of antibiotic treatment in the outcome of a fulminant model of CLP. Various dosing strategies were used for the administration of imipenem that has a broad-spectrum coverage of enteric bacteria. No statistically significant differences in survival were observed between the different antibiotic dosing strategies and untreated mice, suggesting that live bacteria may not be the only factor inducing septic shock. To further investigate this hypothesis, mice were challenged with sterilized or unsterilized cecal contents. We found that exposure of mice to sterilized cecal contents also resulted in a high mortality rate. Therefore, it is possible that bacterial debris, apart from bacterial proliferation, triggers a septic response and contributes to mortality in this model, suggesting that additional factors are involved in the development of septic shock.

Publisher URL: http://doi.org/10.1128/IAI.00664-17

DOI: 10.1128/IAI.00664-17

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