Pharmacokinetics of colistin in the gastrointestinal tract of poultry following dosing via drinking water, and the bactericidal impact on enteric E. coli.

Abstract

Colistin, a last line antibiotic of major importance in veterinary medicine and critical importance in human medicine, is authorised to treat gastrointestinal (enteric) infections caused by non-invasive E. coli in multiple veterinary species including poultry. Its use in veterinary medicine has been implicated in the widespread prevalence of mobilised colistin resistance. The objectives of this study were to determine the intestinal content reached in broiler chickens during 72 h treatment with colistin, evaluate the associated impact on intestinal E. coli, and selection of less susceptible E. coli populations. In this study, 94 broiler chickens were administered a dose of 75 000 IU/kg/day via drinking water. Luminal intestinal content was assessed for colistin content by UHPLC-MS/MS, E. coli were isolated and enumerated on UriSelect agar™, and minimum inhibitory concentration was determined to assess susceptibility. Intestinal samples were collected pre-, during- and post-dosing.
Colistin content increased during treatment to a maximum of 5.09 mg/kg. During this time the total population of E. coli showed an almost 1000-fold reduction. An apparent increase in the relative abundance of E. coli with a phenotypically lower susceptibility, either mcr-negative (6.25 – 10.94%) or mcr-1-positive (4.16 – 31.25%) was observed, although this susceptibility shift was not maintained post-treatment. Elimination of colistin (LOQ = 1.1 mg/kg), following cessation of dosing, was achieved within 4 hours and a significant drop in minimum inhibitory concentration was observed following this period. Mcr-negative and mcr-1-positive isolates, with a lower susceptibility, were observed at the end of the study period indicating maintained sub-populations in the chicken gut. However, the results of this study show limited impact on long-term maintenance of less susceptible E. coli populations as a direct result of colistin treatment, in individual birds and the environment.