Optimized dosing regimens for the combinations of sulfonamides and trimethoprim in veterinary medicine

Antibiotics are routinely used in both human and animal medicine to treat many serious bacterial diseases. Their use in animals is highly regulated, and ensures better health and welfare of animals. Unfortunately, use of antibiotics over many decades has led to bacteria becoming resistant to these treatments, with antimicrobial resistance being one of the biggest future health risks for humanity.
The European Medicines Agency advocates the use of specific antibiotics for veterinary medicine. These are drugs which are classed as not critically important for human health. Unfortunately, since these drugs were often registered decades ago, with less requirements in terms of dose selection, it is highly probable that the dosage regimens fail to achieve optimal efficacy.
Our team are cross-European specialists in veterinary clinical microbiology and pharmacology and our project is focused on optimizing dosing levels; i.e. using the correct dose at the correct time, for the correct duration, of two drugs in combination: trimethoprim and sulfonamides in seven different animal species. The use of these drugs in an optimal way will both increase the likelihood of successful treatment in animals and reduce the risk of developing further antimicrobial resistance.
This project will lead to better future usage of these drugs in veterinary medicine. The use of accurate treatments will also result in lower reliance on other antibiotics which may be vital for use in human medicine.

Due to the pending constraints for veterinarians to use antibiotics critically important for human health in Europe, the relative use of first-line antibiotics such as the combination of trimethoprim (TMP) and sulfonamides (S) will increase in all animal species in coming years. Unfortunately, for these old drugs, the selection of the doses does not have a solid scientific basis. For TMP and S, the dose ratio of 1:5 found in veterinary formulations is a direct transposition of the ratio of the human drug and has not been established by considering the pharmacokinetics (PK) of the drugs in each animal species, suggesting that the doses are likely suboptimal.

To fill the gaps related to the PK of TMP and S, and to the pharmacodynamics (PD) of their interaction on veterinary pathogens, we have built a consortium of 6 partners recognized as European specialists in veterinary clinical microbiology and pharmacology. Our group will carry out PK studies in dogs, horses, pigs, cattle, goats, poultry and fish and extensive PD studies on most relevant pathogens. By integrating the generated data in PK/PD models, we will be able to compare the expected efficacy of the current dosing regimens of TMP combined with different S, and to identify the needed adjustments to ensure efficacy in all studied species.

Our project will contribute to a responsible and prudent use of TMP/S combinations in veterinary medicine and will benefit human and environmental health by avoiding inefficacious treatments and by limiting the recourse to second-line antibiotics more critical for human health.