Post-weaning diarrhea (PWD) is one of the most serious threats for the swine industry worldwide. It is commonly associated with the proliferation of enterotoxigenic Escherichia coli in the pig intestine. Colistin, a cationic antibiotic, is widely used in swine for the oral treatment of intestinal infections caused by E. coli, and particularly of PWD. However, despite the effectiveness of this antibiotic in the treatment of PWD, several studies have reported high rates of colistin resistant E. coli in swine. Furthermore, this antibiotic is considered of very high importance in humans, being used for the treatment of infections due to multidrug-resistant (MDR) Gram-negative bacteria (GNB). Moreover, the recent discovery of the mcr-1 gene encoding for colistin resistance in Enterobacteriaceae on a conjugative stable plasmid has raised great concern about the possible loss of colistin effectiveness for the treatment of MDR-GNB in humans. Consequently, it has been proposed that the use of colistin in animal production should be considered as a last resort treatment only. Thus, to overcome the economic losses, which would result from the restriction of use of colistin, especially for prophylactic purposes in PWD control, we believe that an understanding of the factors contributing to the development of this disease and the putting in place of practical alternative strategies for the control of PWD in swine is crucial. Such alternatives should improve animal gut health and reduce economic losses in pigs without promoting bacterial resistance. The present review begins with an overview of risk factors of PWD and an update of colistin use in PWD control worldwide in terms of quantities and microbiological outcomes. Subsequently, alternative strategies to the use of colistin for the control of this disease are described and discussed. Finally, a practical approach for the control of PWD in its various phases is proposed.

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.

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BackgroundIn animal models, the impact of social and environmental manipulations on chronic pain have been investigated in short term studies where enrichment was implemented prior to or concurrently with the injury. The focus of this study was to evaluate the impact of environmental enrichment or impoverishment in mice three months after induction of chronic neuropathic pain.MethodsThirty-four CD-1 seven to eight week-old male mice were used. Mice underwent surgery on the left leg under isoflurane anesthesia to induce the spared nerve injury model of neuropathic pain or sham condition. Mice were then randomly assigned to one of four groups: nerve injury with enriched environment (n = 9), nerve injury with impoverished environment (n = 8), sham surgery with enriched environment (n = 9), or sham surgery with impoverished environment (n = 8). The effects of environmental manipulations on mechanical (von Frey filaments) heat (hot plate) and cold (acetone test) cutaneous hypersensitivities, motor impairment (Rotarod), spontaneous exploratory behavior (open field test), anxiety-like behavior (elevated plus maze) and depression-like phenotype (tail suspension test) were assessed in neuropathic and control mice 1 and 2 months post-environmental change. Finally, the effect of the environment on spinal expression of the pro-nociceptive neuropeptides substance P and CGRP form the lumbar spinal cord collected at the end of the study was evaluated by tandem liquid chromatography mass spectrometry.ResultsEnvironmental enrichment attenuated nerve injury-induced hypersensitivity to mechanical and cold stimuli. In contrast, an impoverished environment exacerbated mechanical hypersensitivity. No antidepressant effects of enrichment were observed in animals with chronic neuropathic pain. Finally, environmental enrichment resulted lower SP and CGRP concentrations in neuropathic animals compared to impoverishment. These effects were all observed in animals that had been neuropathic for several months prior to intervention.ConclusionsThese results suggest that environmental factors could play an important role in the rehabilitation of chronic pain patients well after the establishment of chronic pain. Enrichment is a potentially inexpensive, safe and easily implemented non-pharmacological intervention for the treatment of chronic pain.

OBJECTIVE To evaluate pharmacokinetics of bupivacaine after IP administration to cats undergoing ovariohysterectomy. ANIMALS 8 healthy cats. PROCEDURES Anesthesia was induced with propofol and maintained with isoflurane. Buprenorphine (0.02 mg/kg, IV) and meloxicam (0.2 mg/kg, SC) were administered. A 20-gauge catheter was inserted into a jugular vein for blood sample collection. A ventral midline incision was made, and a solution of 0.5% bupivacaine (2 mg/kg) diluted with an equal volume of saline (0.9% NaCl) solution (final concentration, 0.25% bupivacaine) was injected into the peritoneal space over the right and left ovarian pedicles and caudal aspect of the uterus before ovariohysterectomy. Cats were monitored for signs of bupivacaine toxicosis. Venous blood samples (2 mL) were collected before (time 0) and 2, 5, 10, 15, 20, 30, 60, 120, and 240 minutes after bupivacaine administration. Plasma bupivacaine concentrations were determined with a liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters were determined by data plotting followed by analysis with a noncompartmental model. RESULTS No signs of bupivacaine toxicosis were observed. Maximum bupivacaine plasma concentration was 1,030 ± 497.5 ng/mL at a mean ± SD value of 30 ± 24 minutes after administration. Mean elimination half-life was 4.79 ± 2.7 hours. Mean clearance indexed by bioavailability and volume of distribution indexed by bioavailability were 0.35 ± 0.18 L•h/kg and 2.10 ± 0.84 L/kg, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Intraperitoneal administration of bupivacaine resulted in concentrations that did not cause observable toxicosis. Studies to investigate analgesic effects for this technique in cats are warranted.

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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.