Clinical pharmacology of antimicrobial use in humans and animals

Veterinary public health is a frontier in the fight against human disease, charged to control and eradicate zoonotic diseases that are naturally transmitted between vertebrate animals and man. Currently there is a need for clinical pharmacologists and all health care givers to limit the development of bacterial resistance in humans to contain the increased health care expenditures related to morbidity and mortality associated with the use of antimicrobials. The development of resistance predates the use of antibiotics and will always be a problem to the successful treatment of patients. Ongoing discussion debates the extent to which antibiotic use in animals contributes to the development of antibiotic resistance in humans. The veterinary use ofantibiotics as antimicrobial growth promoters is thought to influence the prevalence of resistance in animal bacteria and to be a risk factor for the emergence of antibiotic resistance in human pathogens. Transfer of antibiotic resistant bacteria from animals to humans may occur via contact, including occupational exposure and via the food chain. Resistance genes may transferfrom bacteria of animals to human pathogens in the intestinal flora of humans. Prevention of the development of resistance in humans necessitates good animal husbandry and hygienic measures to prevent cross contamination and a decrease in the use of antibiotics. Appropriate use of antibiotics for food animals will preserve the long-term efficacy of existing antibiotics, support animal health and welfare, and limit the risk of transfer of antibiotic resistance to humans. Investigators must also develop new antimicrobial agents. Poole (J Pharmacy Pharmacol 2001;53:283) recommends targeting the three predominate mechanisms of development of resistance by antimicrobials (i.e., antibiotic inactivation, target site modification, and altered uptake via restricted entry and/or enhanced efflux) to specifically complement the development of novel agents with novel bacterial targets. Bacterial resistance and its selection may be evaluated by comparing the relationship to antibiotic pharmacokinetic (PK) values obtained from serum concentrations and organism MICs (minimum inhibitory concentrations; concentration-dependent killing) to reveal culture and sensitivity tests in patients. Pharmacodynamic (PD) models may be developed to identify factors associated with the probability that bacterial resistance will develop. Thomas et al (Antimicrobial Agents Chemotherapy 1998;42:521) used this combined approach of PK/PD and MICs to examine data retrospectively. The role of clinical pharmacology is to work with PK/PD models such as these to determine the best use of antibiotics in humans to minimize the development of resistance. The role of any regulatory body responsible for the protection of the public health and food safety for consumers is to assess risk and to then communicate and manage the risk. Scientific uncertainty must be interpreted to propose sound policy options. The conversion of sound science into an appropriate regulatory policy to protect the public health is most important.