| Autor: |
Soares FS; Laboratory of Immunobiology, Federal University of Santa Catarina (UFSC), Florianópolis, Brazil., Amaral FC; Laboratory of Immunobiology, Federal University of Santa Catarina (UFSC), Florianópolis, Brazil., Silva NLC; Laboratory of Immunobiology, Federal University of Santa Catarina (UFSC), Florianópolis, Brazil., Valente MR; Laboratory of Immunobiology, Federal University of Santa Catarina (UFSC), Florianópolis, Brazil., Santos LKR; Laboratory of Immunobiology, Federal University of Santa Catarina (UFSC), Florianópolis, Brazil., Yamashiro LH; Laboratory of Immunobiology, Federal University of Santa Catarina (UFSC), Florianópolis, Brazil., Scheffer MC; Microbiology Laboratory, University Hospital, Federal University of Santa Catarina (UFSC), Florianópolis, Brazil., Castanheira FVES; Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil., Ferreira RG; Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil., Gehrke L; Laboratory of Immunobiology, Federal University of Santa Catarina (UFSC), Florianópolis, Brazil., Alves-Filho JC; Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil., Silva LP; Embrapa Genetic Resources and Biotechnology, Brasilia, Brazil.; Institute of Biological Sciences, University of Brasilia, Brasilia, Brazil., Báfica A; Laboratory of Immunobiology, Federal University of Santa Catarina (UFSC), Florianópolis, Brazil.; Department of Microbiology, Immunology and Parasitology, Federal University of Santa Catarina (UFSC), Florianópolis, Brazil., Spiller F; Laboratory of Immunobiology, Federal University of Santa Catarina (UFSC), Florianópolis, Brazil.; Department of Pharmacology, Federal University of Santa Catarina (UFSC), Florianópolis, Brazil. |
| Abstrakt: |
Although antibiotic-induced dysbiosis has been demonstrated to exacerbate intestinal inflammation, it has been suggested that antibiotic prophylaxis may be beneficial in certain clinical conditions such as acute pancreatitis (AP). However, whether broad-spectrum antibiotics, such as meropenem, influence the dissemination of multidrug-resistant (MDR) bacteria during severe AP has not been addressed. In the currently study, a mouse model of obstructive severe AP was employed to investigate the effects of pretreatment with meropenem on bacteria spreading and disease outcome. As expected, animals subjected to biliopancreatic duct obstruction developed severe AP. Surprisingly, pretreatment with meropenem accelerated the mortality of AP mice (survival median of 2 days) when compared to saline-pretreated AP mice (survival median of 7 days). Early mortality was associated with the translocation of MDR strains, mainly Enterococcus gallinarum into the blood stream. Induction of AP in mice with guts that were enriched with E. gallinarum recapitulated the increased mortality rate observed in the meropenem-pretreated AP mice. Furthermore, naïve mice challenged with a mouse or a clinical strain of E. gallinarum succumbed to infection through a mechanism involving toll-like receptor-2. These results confirm that broad-spectrum antibiotics may lead to indirect detrimental effects during inflammatory disease and reveal an intestinal pathobiont that is associated with the meropenem pretreatment during obstructive AP in mice. |
