Angen, Ø.

Christiansen, L.

Damborg, Peter

Folkesson, Sven Anders

Græsbøll, Kaare

Larsen, I.

Mellerup, Anders

Nielsen, J. P.

Nielsen, Søren Saxmose

Olsen, J. E.

Zachariasen, C.

A Danish research project, MINIRESIST, investigated the consequences of varying doses and treatment strategies for oxytetracycline treatment of Lawsonia intracellularis diarrhea in nursery pigs. Batches of nursery pigs in five herds were randomly allocated to one of five treatment protocols (batch treatment orally with high, normal and low doses; penwise treatment with normal dose and injection treatment with normal dose). Outcomes, in terms of reduction of L. intracellularis determined by qPCR, growth rate and fecal dry matter content (determined on 30 pigs per batch in 61 batches), and levels of tetracyclineresistant coliforms, and quantification of resistance genes in intestinal content (determined on 15 pigs per batch in 80 batches), were determined and analyzed statistically. These studies were supplemented with in silico simulation of phenotypic resistance development in the intestine based on in vitro determined growth characteristics of porcine commensal E. coli in the presence of tetracycline, Low-dose batch-treatment did not differ significantly from normal and high dose treatment in terms of reduction of L. intracellularis, and phenotypic resistance levels under field conditions also did not differ statistically depending on dosing levels. qPCR results were shown to add to phenotypic resistance-determination with information on selected genes. Injection treatment resulted in the lowest number of resistant bacteria, but also in the lowest overall cure rate, probably because treatment was based on fecal scores, which have low sensitivity for diarrhea. Simulation studies suggested that resistance development was mostly dependent on the duration of the treatment and the total amount of oxytetracycline used per pig. Ongoing field testing has been initiated to confirm this conclusion, since no field experimentation has yet been performed with variation of duration of treatment. In conclusion, batch treatment with the lowest dose was recommended from both a disease and a resistance point of view

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Downloaded from orbit.dtu.dk on: Nov 08, 2017Effect of variation in oxytetracycline treatment of Lawsonia intracellularis diahrea innursery pigs on treatment-efficacy and resistance developmentLarsen, I.; Mellerup, Anders; Zachariasen, C.; Nielsen, Søren Saxmose; Folkesson, Anders; Angen, Ø.;Christiansen, L.; Græsbøll, Kaare; Damborg, Peter; Nielsen, J. P.; Olsen, J. E.Published in:Safepork 2015 Proceedings Book: Epidemiology and control of hazards in pork production chainPublication date:2015Document VersionPublisher's PDF, also known as Version of recordLink back to DTU OrbitCitation (APA):Larsen, I., Mellerup, A., Zachariasen, C., Nielsen, S. S., Folkesson, S. A., Angen, Ø., ... Olsen, J. E. (2015).Effect of variation in oxytetracycline treatment of Lawsonia intracellularis diahrea in nursery pigs on treatment-efficacy and resistance development. In Safepork 2015 Proceedings Book: Epidemiology and control of hazardsin pork production chain : SAFEPORK, One health approach under a concept of farm to fork (pp. 135-135)Safepork 2015 Conference Epidemiology and control of hazards in pork production chain – SAFEPORKOne health approach under a concept of farm to fork135134 Antimicrobials in swine production, antimicrobial resistance, alternative  strategies to antimicrobial useAntimicrobials in swine production, antimicrobial resistance, alternative strategies to antimicrobial useTable 1: Feed conversion and average daily weight gain in weaners after initiation of the antibiotic free pigs   project. Weaned pigs Yearly average AB free period DifferenceAverage daily weight gain 504 538 + 34 g/dayFE/kg gain 1,84 1,69 - 0,15 FE/kgThe combination of lowered antibiotic consumption with improved production figures highlights the advantage of prophylaxis compared to treatment. Vaccination protects the pigs from onset of disease, thereby preventing damage to the intestinal mucosa, resulting in an increased growth rate of the vaccinated pigs compared to non-vaccinates (Bak and Rathkjen, 2009). Hence, vaccinated pigs perform better compared to non-vaccinated pigs, even if the non-vaccinated pigs receive antibiotic treatments after an outbreak of diarrhoea.ConclusionPreliminary results from the project are positive, indicating that it will be possible to produce at least 50% of the pigs without use of antibiotics. This is possible with herd relevant vaccination programs, including PCV2, Mycoplasma hyopneumoniae and Lawsonia intracellularis, and with continuous focus on caretaking and hygiene.References• ECDC/EFSA/EMA (2015): ECDC/EFSA/EMA first joint report on the integrated analysis of the consumption of antimicrobial agents and occurrence of antimicrobial resistance in bacteria from humans and food-producing animals. EFSA Journal 2015;13(1):4006, 114 pp.• DANMAP (2013): Use of antimicrobial agents and occurrence of antimicrobial resistance in bacteria from food animals, food and humans in Denmark. ISSN 1600-2032, p 92.• Danish Food and Medicines Agency (2015): Action plan for combating MRSA in food producing animals (in Danish). http://fvm.dk/nyheder/nyhed/nyhed/handlingsplan-til-bekaempelse-af-husdyr-mrsa-1/• Hardge et al. (2004): Prevention of Porcine Proliferative Enteropathy by vaccination – efficacy and economics in European farms. The Pig Journal 54, pp 17-34.• Bak and Rathkjen (2009): Strategy to reduce antibiotic use in Danish nurseries and finishing units. Proceedings of the 8th Safepork Symposium, Quebec, Canada, Sept 30- Oct 2 2009.  • Bundgaard et al. (2012): Vaccination significantly reduces use of antibiotics. Pig Progress; Alternative Growth Promotion Special, pp 2-3.• Bak and Rathkjen (2009): Reduced use of antimicrobials after vaccination of pigs against• porcine proliferative enteropathy in a Danish SPF herd. Acta Veterinaria Scandinavia 51:1.(1) Boehringer-Ingelheim, Copenhagen, Denmark. (2)Klintebygård, Nexø, Denmark *corresponding author: hanne.bak@boehringer-ingelheim.comEffect of variation in oxytetracycline treatment of Lawsonia intracellularis diahrea in nursery pigs on treatment-efficacy and resistance developmentLarsen, I.1; Mellerup, A.2; Zachariasen, C.3; Saxmose Nielsen, S4.; Folkesson, A.2; Angen, Ø.5; Christiansen, L.6;  Græsbøl, K.7; Damborg, P3.; Nielsen, J. P.4; Olsen, J. E.3A Danish research project, MINIRESIST, investigated the consequences of varying doses and treatment strategies for oxytetracycline treatment of Lawsonia intracellularis diarrhea in nursery pigs. Batches of nursery pigs in five herds were randomly allocated to one of five treatment protocols (batch treatment orally with high, normal and low doses; penwise treatment with normal dose and injection treatment with normal dose). Outcomes, in terms of reduction of L. intracellularis determined by qPCR, growth rate and fecal dry matter content (determined on 30 pigs per batch in 61 batches), and levels of tetracycline-resistant coliforms, and quantification of resistance genes in intestinal content (determined on 15 pigs per batch in 80 batches), were determined and analyzed statistically. These studies were supplemented with in silico simulation of phenotypic resistance development in the intestine based on in vitro determined growth characteristics of porcine commensal E. coli in the presence of tetracycline, Low-dose batch-treatment did not differ significantly from normal and high dose treatment in terms of reduction of L. intracellularis, and phenotypic resistance levels under field conditions also did not differ statistically depending on dosing levels. qPCR results were shown to add to phenotypic resistance-determination with information on selected genes. Injection treatment resulted in the lowest number of resistant bacteria, but also in the lowest overall cure rate, probably because treatment was based on fecal scores, which have low sensitivity for diarrhea. Simulation studies suggested that resistance development was mostly dependent on the duration of the treatment and the total amount of oxytetracycline used per pig. Ongoing field testing has been initiated to confirm this conclusion, since no field experimentation has yet been performed with variation of duration of treatment. In conclusion, batch treatment with the lowest dose was recommended from both a disease and a resistance point of view.  1Department of Large Animal Science, University of Copenhagen;2National Veterinary Institute, Danish Technical University;3Department of Veterinary Disease Biology, University of Copenhagen;4Department of Large Animal Sciences, University of Copenhagen;5National Veterinary Institute, Norway;6Department of Applied Mathematics and Computer Science, Danish Technical University;7Department of Applied Mathematics and Computer Science, Danish Techical University

Effect of variation in oxytetracycline treatment of Lawsonia intracellularis diahrea in nursery pigs on treatment-efficacy and resistance development

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Effect of variation in oxytetracycline treatment of Lawsonia intracellularis diahrea in nursery pigs on treatment-efficacy and resistance development

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