Colistin (Polymyxin E) is one of the few cationic antimicrobial peptides commercialized in both human and veterinary medicine. For several years now, colistin has been considered the last line of defense against infections caused by multidrug-resistant Gram-negative such as Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Colistin has been extensively used orally since the 1960s in food animals and particularly in swine for the control of Enterobacteriaceae infections. However, with the recent discovery of plasmid-mediated colistin resistance encoded by the mcr-1 gene and the higher prevalence of samples harboring this gene in animal isolates compared to other origins, livestock has been singled out as the principal reservoir for colistin resistance amplification and spread. Co-localization of the mcr-1 gene and Extended-Spectrum-β-Lactamase genes on a unique plasmid has been also identified in many isolates from animal origin. The use of colistin in pigs as a growth promoter and for prophylaxis purposes should be banned, and the implantation of sustainable measures in pig farms for microbial infection prevention should be actively encouraged and financed. The scientific research should be encouraged in swine medicine to generate data helping to reduce the exacerbation of colistin resistance in pigs and in manure. The establishment of guidelines ensuring a judicious therapeutic use of colistin in pigs, in countries where this drug is approved, is of crucial importance. The implementation of a microbiological withdrawal period that could reduce the potential contamination of consumers with colistin resistant bacteria of porcine origin should be encouraged. Moreover, the management of colistin resistance at the human-pig-environment interface requires the urgent use of the One Health approach for effective control and prevention. This approach needs the collaborative effort of multiple disciplines and close cooperation between physicians, veterinarians, and other scientific health and environmental professionals. This review is an update on the chemistry of colistin, its applications and antibacterial mechanism of action, and on Enterobacteriaceae resistance to colistin in pigs. We also detail and discuss the One Health approach and propose guidelines for colistin resistance management.
Enterotoxigenic Escherichia coli (ETEC: F4) associated with post-weaning diarrhea (PWD) in pigs has developed resistance against several antimicrobial families, leading to increased use of colistin sulfate (CS) for the treatment of this disease. The objective of this study was to determine the efficacy of oral CS treatment in experimental PWD due to ETEC: F4 challenge and determine the effect of this challenge on CS intestinal absorption. In this study, 96 pigs were divided into two trials based on CS dose (100 000 or 50 000 IU/kg). Fecal shedding of ETEC: F4, total E. coli, and CS-resistant E. coli, diarrhea scores, and weight changes were evaluated. Colistin sulfate plasma concentrations were determined by HPLC–MS/MS. Regardless of the dose, CS treatment resulted in a reduction of fecal ETEC: F4 and total E. coli shedding, and in diarrhea scores but only during the treatment period. However, CS treatment resulted in a slight increase in fecal shedding of CS resistant E. coli and did not prevent weight loss in challenged pigs. In addition, challenge with ETEC: F4 resulted in an increase of CS intestinal absorption. Our study is among the first to demonstrate that under controlled conditions, CS was effective in reducing fecal shedding of ETEC: F4 and total E. coli in experimental PWD. However, CS treatment was associated with a slight selection pressure on E. coli and did not prevent pig weight loss. Further studies are needed in field conditions, to better characterize CS therapeutic regimen efficacy and bacterial resistance dissemination.Electronic supplementary materialThe online version of this article (doi:10.1186/s13567-016-0344-y) contains supplementary material, which is available to authorized users.
The aim of the present study was to investigate the in vitro gastric stability of colistin sulfate (CS) and its antimicrobial activity against Escherichia coli and to study the impact of ETEC O149: F4 (K88) infection in pigs on CS intestinal absorption. The stability profile of CS was evaluated in a simulated gastric fluid (SGF). Antimicrobial activity of CS and its degradation products were examined in a 96-well polystyrene microplate model. The effect of experimental infection with ETEC O149: F4 on CS intestinal absorption was determined by quantification of CS systemic concentration using a validated LC-MS/MS method. A rapid degradation of CS accompanied by an increase in CS antimicrobial activity by comparison with non-degraded CS (P<0.0001) was observed in SGF. Additionally, CS levels were not quantifiable in systemic circulation using a highly sensitive method and concurrent oral challenge did not affect CS absorption in an induction model of subclinical post-weaning diarrhea (PWD).
Tail-biting (TB) in pigs is a serious behavioral disorder. It is an important challenge in swine production as it impacts animal welfare and health and the economics and safety of the pork meat supply chain. To prevent TB, approaches including enrichment material and tail docking are proposed but none are optimal. Nutrition appears to be an important factor in TB behavior, perhaps by modulating the intestinal microbiota (IM). Our aim was to assess the association between TB behavior and IM in pigs through comparisons of IM in groups of biter, bitten and non-biter/non-bitten pigs. Each group composed of 12 pigs was formed at the beginning of the growing/finishing phase based on a target behavior analysis centered on TB behavior for the biter group and a score of damages caused to the tail for the bitten group. Blood and fecal samples were collected from each pig during a TB episode, at time 0, t0, and when the TB episode was considered finished, 4 weeks later, at time 1, t1. Serum cortisol level was determined by ELISA and used as an indicator of stress. The pig's fecal microbiota was analyzed from DNA extracted from freshly collected fecal matter using amplicon sequencing of the V4 hypervariable region of the 16S rRNA gene. Serum cortisol levels were significantly higher in either the biter or bitten pig groups compared to the negative control group (p = 0.02 and p = 0.01, respectively). The microbiota alpha-diversity was not significantly different between all groups, biter, bitten and negative control. Analyses of beta-diversity, however, revealed a significant difference between either the biter or the bitten group in comparison to the non-biter/non-bitten negative control group in terms of structure and composition of the microbiota. Lactobacillus were significantly more abundant in the negative control group compared to the two other groups (p = 0.001). No significant difference was revealed between the biter and bitten groups. Quantitative real-time PCR (qPCR) confirmed that lactobacilli were more abundant in the negative control group. Our study indicates that TB behavior is associated with the IM composition in pigs.
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