Soares Fernanda S, Amaral Flávia C, Silva Natália L C, Valente Matheus R, Santos Lorena K R, Yamashiro Lívia H, Scheffer Mara C, Castanheira Fernanda V E S, Ferreira Raphael G, Gehrke Laura, Alves-Filho José C, Silva Luciano P, Báfica André, Spiller Fernando
Laboratory of Immunobiology, Federal University of Santa Catarina (UFSC), Florianópolis, Brazil.
Microbiology Laboratory, University Hospital, Federal University of Santa Catarina (UFSC), Florianópolis, Brazil.
Front Immunol. 2017 Dec 22;8:1890. doi: 10.3389/fimmu.2017.01890. eCollection 2017.
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 into the blood stream. Induction of AP in mice with guts that were enriched with recapitulated the increased mortality rate observed in the meropenem-pretreated AP mice. Furthermore, naïve mice challenged with a mouse or a clinical strain of 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.
尽管抗生素诱导的菌群失调已被证明会加剧肠道炎症，但有人提出抗生素预防在某些临床情况下可能有益，如急性胰腺炎（AP）。然而，美罗培南等广谱抗生素在重症急性胰腺炎期间是否会影响多重耐药（MDR）细菌的传播尚未得到研究。在本研究中，采用梗阻性重症急性胰腺炎小鼠模型来研究美罗培南预处理对细菌传播和疾病结局的影响。正如预期的那样，接受胆胰管梗阻的动物发生了重症急性胰腺炎。令人惊讶的是，与生理盐水预处理的急性胰腺炎小鼠（生存中位数为7天）相比，美罗培南预处理加速了急性胰腺炎小鼠的死亡（生存中位数为2天）。早期死亡与多重耐药菌株的易位有关，主要是易位到血流中。在肠道富含[具体细菌名称未给出]的小鼠中诱导急性胰腺炎，重现了在美罗培南预处理的急性胰腺炎小鼠中观察到的死亡率增加。此外，用小鼠或临床菌株[具体细菌名称未给出]攻击的未感染小鼠通过涉及Toll样受体2的机制死于感染。这些结果证实，广谱抗生素在炎症性疾病期间可能会导致间接有害影响，并揭示了一种与小鼠梗阻性急性胰腺炎期间美罗培南预处理相关的肠道致病共生菌。
