Butaye, Patrick

Croubels, Siska

Daeseleire, Els

Devreese, Mathias

Dewulf, Jeroen

Haesebrouck, Freddy

Heyndrickx, Marc

Peeters, Laura

English

Ghent University Academic Bibliography

CODA CERVA Veterinary and Agrochemical Research Center  - Groeselenberg ,99    B-1180  BRUSSELS phone : +32(0)2 379 04 00    www.var.fgov.beDay1 to D6 D7 D8 D9 D10 D11 D12 D13 D14 D15 D16 D17 D18Acclimatisation Experimental period= manure sampling = euthanasia and sampling of caecum and colon contentConcentrations of selected antimicrobials in caecum, colon and manure of pigs due to a 3 % cross-contamination of the feedL. Peeters1, E. Daeseleire4, M. Devreese3, J. Dewulf5, M. Heyndrickx2, 4, F. Haesebrouck2, P. Butaye1, 2 and S. Croubels31: Veterinary and Agrochemical Research centre, Department of General Bacteriology, Brussels, Belgium;2: Ghent University, Department of Pathology, Bacteriology and Avian Diseases, Merelbeke, Belgium;3: Ghent University, Department of Pharmacology, Toxicology and Biochemistry, Merelbeke, Belgium;4: Institute for Agricultural and Fisheries Research (ILVO), Technology and Food Science Unit, Melle, Belgium; 5: Ghent University, Department of Reproduction, Obstetrics and Herd health, Merelbeke, BelgiumConclusionsIntroduction Materials and methodsPig feed may contain up to 3% carry-over of the recommended therapeutic concentrations ofantimicrobials1 as a result of contamination between medicated and non-medicated feed. Gutconcentrations due to this cross-contamination with chlortetracycline, doxycycline andsulfadiazine-trimethoprim were investigated.1Based on the EU guideline regarding coccidiostats or histomonostats (2009/8/EG). Since 2013, limits of 1% ofminimal therapeutic concentrations are applied in Belgium.ResultsThese data show that the poor oral bioavailabilities of tetracyclines may result in rather high concentrations in caecum, colon and manure, even at 3% cross-contamination of the feed. As expected, the high oral bioavailabilities of sulfadiazine and trimethoprim appear to result in very low gut concentrations. Researchon the effects of these concentrations on the gut flora is ongoing.Antimicrobial concentrations in manureAntimicrobial concentrations in caecum and colon content Concentration chlortetracycline in caecum and colon contentSampling siteend colonmiddle coloncaecum begin colonConc. chlortetracycline (mg/kg)Concentration doxycycline in caecum and colon contentSampling siteend colonmiddle coloncaecum begin colonConc. doxycycline (mg/kg)Concentration sulfadiazine in caecum and colon contentSampling siteend colonmiddle coloncaecum begin colon02468101214Day 0 Day 2 Day 4 Day 6 Day 8 Day 10conc. chlortetracycline (mg/kg)Mean concentration chlortetracycline in manure0123456Day 0 Day 2 Day 4 Day 6 Day 8 Day 10conc. doxycycline (mg/kg)Mean concentration doxycycline in manure0100200300400500600700800900Day 0 Day 2 Day 4 Day 6 Day 8 Day 10Conc. sulfadiazine (µg/kg)Mean concentration sulfadiazine in manureHomogeneity of the experimental feed0510152025301 2 3 4 5 6 7 8 9 10Conc. doxycycline (mg/kg)Sample no.Concentration doxycycline in feedtheoretical conc. (6.76mg/kg)error margin (-20%)error margin (+10%)05101520251 2 3 4 5 6 7 8 9 10Conc. chlortetracycline (mg/kg)Sample no.Concentration chlortetracycline in feedtheoreticalconc.(9.29mg/kg)error margin (-20%)error margin (+20%)0123451 2 3 4 5 6 7 8 9 10conc. trimethoprim (mg/kg)Sample no.Concentration trimethoprim in feedtheoretical conc.: 2.38 mg/kg024681012141618201 2 3 4 5 6 7 8 9 10Conc. sulfadiazine (mg/kg)Sample no.Concentration sulfadiazine in feedtheoretical conc.: 11.9 mg/kg+ chlortetracycline+ doxycycline + sulfadiazine-trimethoprim3%1 432 765 10981. Preparation of 3 batches of experimental feed with a 3%carry-over level of the recommended therapeutic dose of followingantimicrobials: doxycycline, sulfadiazine-trimethoprim andchlortetracycline. For each batch, 10 samples were analysed using in-house developed and validated LC-MS/MS methods.2. Animal experimentTwenty-four pigs were equallydivided into one control group andthree experimental groupsreceiving experimental feedduring 10 days. Every two days,individual manure samples weretaken and individual colon andcaecum content was sampled onday 11. Samples were analysedusing in-house developed andvalidated LC-MS/MS methods.Average antimicrobial concentrations in all 3batches approached the intended concentrations.However, high variations between differentsamples were found.Mean concentrations (+/- SD) of each antimicrobial rose to a steady state on day 4 of:4 mg/kg wet weight (w.w.) for doxycycline10 mg/kg w.w. for chlortetracycline500-700 µg/kg w.w. for sulfadiazineTrimethoprim: all values were below the limit of detection, no quantificationTransfer ratio’s (TR)- Mean concentration of 6 observations/sampling site- CI 95% Antimicrobial TR Caecum / colon  contentTR ManureBAChlortetracycline 82% 92% 6%Doxycycline 39% 52% 20%Sulfadiazine 4.1% 4.5% 80-100%Trimethoprim ND ND 60-80%Transfer ratio (TR) of antimicrobials compared to their oral bioavailability (BA) in pigs - Mean concentration end colon ~ mean concentration manure for all antimicrobials tested- Tetracycline concentrations are relatively high in general and highest concentrations are found in end colon- Sulfadiazine concentrations are relatively low in general and highest concentrations are found in middle colon- Trimethoprim: all values were below the limit of detection, no quantificationTR manure =  𝑀𝑒𝑎𝑛 𝑐𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛 𝑚𝑎𝑛𝑢𝑟𝑒 (∗)𝑀𝑒𝑎𝑛 𝑐𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛 𝑖𝑛 𝑓𝑒𝑒𝑑(*) day 2 – day 10 of experimental periodTR caecum and colon content = 𝑀𝑒𝑎𝑛 𝑐𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛 𝑐𝑎𝑒𝑐𝑢𝑚 𝑎𝑛𝑑 𝑐𝑜𝑙𝑜𝑛 𝑐𝑜𝑛𝑡𝑒𝑛𝑡𝑀𝑒𝑎𝑛 𝑐𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛 𝑖𝑛 𝑓𝑒𝑒𝑑This study was funded by the Federal Public Service of Health, Food chain Safety and Environment (contract RT 12/03 CROSSCONTAM)

Concentrations of selected antimicrobials in caecum, colon and manure of pigs due to a 3% cross-contamination of the feed

https://biblio.ugent.be/publication/4410126/file/4410127.pdf

Concentrations of selected antimicrobials in caecum, colon and manure of pigs due to a 3% cross-contamination of the feed

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