91做厙

This project aims to evaluate the impact of colistin use on antimicrobial resistance and rationalise dosing through a combination of in vivo pharmacokinetic (PK) dose studies, in vitro pharmacodynamic (PD) and antimicrobial susceptibility testing, and advanced in silico PK/PD modelling.

Challenge

Colistin (polymyxin E) is categorised as a highest priority critically important antimicrobial by the World Health Organisation (WHO) and a veterinary critically important antimicrobial by the World Organisation for Animal Health (OIE), indicating the essential nature of this antimicrobial in both human and veterinary medicine.

Antimicrobial resistance (AMR) is a leading cause of global death, with 1.27 million deaths directly attributable to AMR in 2019 (Murray et al., 2022). Colistin is a last-line antibiotic to treat multidrug resistant gram-negative infections in humans. In veterinary medicine colistin is used to treat infections caused by Enterobacteriaceae in pigs, poultry, and cattle, such as enterocolitis and colibacillosis. To maintain this antibiotic for human use, with consideration to the recent discovery of mobilised colistin resistance (MCR) and its global prevalence in bacteria from both humans and animals, the European Medicines Agency (EMA) advocated a reduction in colistin sales and usage in animals. The poultry sector is one of the largest global livestock industries, with more than 23 billion chickens worldwide (Mottet and Tempio, 2017), indicating the extent of potential animal welfare issues and production losses associated with the reduction of colistin use, which remains an almost irreplaceable veterinary antimicrobial for intestinal E. coli infections in poultry.

To maintain colistin as an essential antimicrobial for both human and veterinary use, recent and reliable data regarding the pharmacokinetics (PK) and pharmacodynamics (PD) at the clinical dose in poultry, and its impact on the potential selection of resistance is required to inform application and policy.