Use of pharmacodynamic principles to optimise dosage regimens for antibacterial agents in the elderly.

Throughout most of the world we are witnessing an ever increasing number of aged people as a percentage of the general population. In the coming years, the unique spectrum of infections presented by an elderly population, particularly those in long-term care facilities, will challenge our ability to maintain an effective battery of antibacterials. The pharmacokinetic parameters of most antibacterial agents are altered when assessed in the elderly due in part to non-pathological physiological changes. The inability to clear a drug from the body due to declining lung, kidney/bladder, gastrointestinal and circulatory efficiency can cause accumulation in the body of drugs given in standard dosages. While this may have the potential benefit of achieving therapeutic concentrations at a lower dose, there is also a heightened risk of attaining toxic drug concentrations and an increased chance of unfavourable interactions with other medications. Pharmacodynamic issues in the elderly are related to problems that arise from treating elderly patients who may have a history of previous antibacterial treatment and exposure to resistant organisms from multiple hospitalisations. Furthermore, the elderly often acquire infections in tandem with other common disease states such as diabetes mellitus and heart disease. Thus, it is essential that optimised dosage strategies be designed specifically for this population using pharmacodynamic principles that take into account the unique circumstances of the elderly. Rational and effective dosage and administration strategies based on pharmacodynamic breakpoints and detailed understanding of the pharmacokinetics of antibacterials in the elderly increase the chances of achieving complete eradication of an infection in a timely manner. In addition, this strategy helps prevent selection of drug-resistant bacteria and minimises the toxic effects of antibacterial therapy in the elderly patient.