Predicted PK/PD inadequacy of amoxicillin delivered in drinking water against respiratory pathogens in post-weaning piglets: can time-restricted dosing improve animals’ exposure and potential treatment efficacy?

Collective treatments via drinking water allow rapid and targeted treatment of many animals as soon as disease is detected, but inter-animal variability in drinking behaviour can lead to over- or under-exposure. We therefore developed a pharmaco-statistical model integrating real-time individual water consumption to simulate amoxicillin plasma concentrations and assess actual treatment efficacy. One hundred fifty piglets received amoxicillin (10 mg/kg/day, 2.5-3 days) via drinking water under continuous, daytime, or night-time treatment, and water and blood samples were collected. Using individual drinking profiles and pharmacokinetic parameters, we simulated plasma concentrations in a virtual population of 5000 piglets per modality to compared with the obtained actual plasma concentrations. We then estimated the proportion of adequately treated animals by comparing modelled plasma concentrations with MICs for five major respiratory pathogens. Amoxicillin treatment was effective in at least 80% of piglets only for one of the five targeted pathogens, Streptococcus suis. These findings suggest that it may be necessary to evaluate other antibiotics using the same modelling approach to improve treatment of Glaesserella parasuis, Actinobacillus pleuropneumoniae, Pasteurella multocida, and Bordetella bronchiseptica. This strategy could also be extended to other species treated collectively via drinking water, such as poultry.