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Colistin sulfate (CS) is used in Canada for the treatment of post weaning diarrhea (PWD), to overcome conventional therapeutic antibiotics failures. The aim of the present study was to determine the effect of a conventional oral regimen of CS for the treatment of PWD, on the development of E. coli CS resistance and to evaluate the effect of ETEC: F4 infection on CS intestinal absorption. A total of 48 pigs were used, challenge was carried out by oral administration of 10 9 CFU of a hemolytic ETEC: F4 strain resistant to nalidixic acid. CS was administered at a dose of 50.000 UI/kg twice a day for 5 days. Feces were examined clinically and bacteriologically before and after challenge to evaluate presence of diarrhea and E. coli fecal excretion. ETEC: F4 virulence factors were monitored and CS plasma concentrations were quantified by an HPLC-MS/MS. From one until six days after CS administration, a significant reduction in the fecal excretion of ETEC: F4, total E. coli, ETEC: F4 virulence factors and in diarrhea scores was observed in the challenged treated group compared to the challenged untreated group (p 0.71). A significant selection pressure on E. coli total population was observed following CS treatment (p

Colistin sulfate (CS), a polymyxin antibiotic, is used in Canada for the treatment of post-weaning diarrhea in pigs as an alternative to neomycin. The aim of the present study was to evaluate some pharmacokinetics parameters of CS and its effect on the evolution of the intestinal Escherichia coli population in pigs challenged with enterotoxigenic E. coli (ETEC): F4. A total of 14 weaned piglets were divided into two groups, a non-challenged, treated group (n=7) and a challenged, treated group (n=7). Both groups received a single oral dose of CS at 50,000 IU/Kg. Challenge was carried out by oral administration of 10 9 CFU of a hemolytic ETEC: F4 strain resistant to nalidixic acid. Blood samples were taken at 30 min and 1, 2, 4, 6, 8, 12, 24, 36 and 48 hours post treatment from each pig and CS quantification was performed by LC-MS/MS. In the challenged group, severity of diarrhea was monitored and the presence of the ETEC:F4 strain in the feces was enumerated using 5% bovine blood agar plates containing nalidixic acid. In both groups, total E. coli counts were carried out using Petrifilm E. coli/Coliform count plates. In both groups, the plasma concentration of CS was below the lower limit of quantification (20 ng/ml). Following CS treatment, a decrease in the total E. coli and ETEC: F4 fecal counts were observed at 24 h post treatment. The fecal consistency was not affected by CS treatment. For the first time, a study of some CS pharmacokinetics parameters with a highly sensitive method showed that CS levels are not detectable in systemic circulation following oral administration, and concurrent oral challenge with an ETEC strain did not affect CS absorption. A single dose of CS resulted in reduced bacterial counts of the total E. coli and ETEC: F4 populations in the feces.