Evaluation of the ability of colistin, amoxicillin (components of Potencil^®), and fluoroquinolones to attenuate bacterial endotoxin‐ and Shiga exotoxin‐mediated cytotoxicity—In vitro studies

Abstract

Escherichia coli is one of the major pathogens in humans and animals causing localized and systemic infections, which often lead to acute inflammation, watery diarrhea, and hemorrhagic colitis. Bacterial lipopolysaccharide (LPS) and Shiga exotoxins (Stx) are mostly responsible for such clinical signs. Therefore, highly effective treatment of E. coli infections should include both eradication of bacteria and neutralization of their toxins. Here, for the first time, we compared the in vitro ability of common antibiotics to decrease LPS- and Stx-mediated cytotoxicity: colistin, amoxicillin (used separately or combined), enrofloxacin, and its metabolite ciprofloxacin. Three experimental scenarios were realized as follows: (a) the direct effect of antibiotics on endotoxin, (b) the effect of antibiotic treatment on LPS-mediated cytotoxicity in an experiment mimicking "natural infection," (c) the effect of antibiotics to decrease Stx2e-mediated cytotoxicity. Two cell lines, A549 and Vero cells, were used to perform cytotoxic assays with the methyl tetrazolium (MTT) and lactate dehydrogenase leakage (LDH) methods, respectively. Colistin and amoxicillin, especially used in combination, were able to attenuate LPS toxic effect, which was reflected by increase in A549 cell viability. In comparison with other antibiotics, the combination of colistin and amoxicillin exhibited the highest boster or additive effect in protecting cells against LPS- and Stx2e-induced toxicity. In summary, in comparison with fluoroquinolones, the combination of colistin and amoxicillin at concentrations similar to those achieved in plasma of treated animals exhibited the highest ability to attenuate LPS- and Stx2e-mediated cytotoxicity.

Human gut microbiota evaluation and comparation after the separate or combined antibiotics exposure using the simulator of human intestinal microbial ecosystem (SHIME)

“…The phenomena of microbiota shift shown in our research are identical to several in vivo studies on intestinal microbiota; however, Proteobacteria phylum such as Enterobacter and Bacteroides were most predominantly detected following AMX administration [52,67,68]. Furthermore, the percentage of Escherichia-Shigella was decreased after POL treatment found in this study was further supported by earlier reports that con rmed the eradication ability of POL on Escherichia and its cytotoxicity [23,64]. Some studies have also discovered a trend toward increasing taxonomic diversity after AMX treatment and a signi cant effect on the beta diversity pursued by POL exposure [23,69].…”

“…For instance, a study con rmed that combination of colistin-polymyxin B or tigecycline with a carbapenem therapy is superior to monotherapy for carbapenemase-producing Klebsiella pneumoniae [63]. Besides, the combination of AMX and POL therapy would effectively attenuate bacterial endotoxin-and Shiga exotoxin-mediated cytotoxicity and reduce mortality from peritonitis [25,64]. However, excessive use of combinations should be avoided because it might be associated with increased risk for the toxicity and super-infections [41].…”

Clinical and Pathological Characteristics of Amoxicillin Associated Hemorrhagic Colitis

“…con rmed AAC cases, in whichtwowere caused byK.oxytoca,twowere caused by C.di cile, whereas no existing pathogens were observed for the remaining 8 cases. E.coliis a foodborne pathogen42 that can cause watery diarrhea and hemorrhagic colitis43,44 . In addition, AAHC may also be associated with clostridium perfringens infection45 .AAHC is self-limiting, and its treatment should be discontinued rst, with supportive treatment as the main method, focusing on uid rehydration and electrolyte correction46 .In severe cases, short course intravenous hormone therapy is available.…”