Impact Of Antimicrobial Agents Research Articles

Mathematical modelling of resistance emergence

Sir, We read with great interest the article by Magee 1 and the associated correspondence. We would like to add to the discussion from our perspective. Using mathematical modelling and simulations, the study by Magee has offered us insights on resistance emergence from the global societal viewpoint (resistance epidemiology). 1 If these models are predictive, they are powerful research tools that would allow us to have a glimpse of the future as a result of any intervention (or the lack of) in public healthcare policy. Similar approaches have been used to evaluate the effectiveness of various treatment protocols to prevent the spread of antimicrobial resistance. 2,3 However, these models generally use assumed model parameter values (as opposed to values derived from collected data) to make predictions with respect to qualitative intervention(s), and many times the computer simulations could not be validated prospectively. Our group and others have been working on modelling of antimicrobial resistance at a different scale (experimental therapeutics). Using a mathematical modelling approach to understand the relationship between the antimicrobial exposure in a single patient and the likelihood of resistance emergence, we strive to rationally design dosing regimens that suppress (delay) the emergence of resistance. Such efforts can be evidenced by a selected list of our work published recently. 4–6 While the mathematical structures of these models may differ somewhat, the model parameter estimates are almost invariably derived from actual experimental data, and in most cases the model predictions are supported by prospective validation. We are hopeful that dosing regimens for new (and existing) antimicrobial agents will be designed more scientifically in the future, with the objective of long-term resistance suppression in mind, in addition to clinical cure of the patients and toxicity avoidance. It is our vision that the work of both groups of researchers could be combined in the future to provide a more robust assessment of the impact of antimicrobial agents’ utilization on the emergence of resistance.

Antimicrobial drug delivery in food animals and microbial food safety concerns: an overview of in vitro and in vivo factors potentially affecting the animal gut microflora

This review provides an overview of considerations particular to the delivery of antimicrobial agents to food animals. Antimicrobial drugs are used in food animals for a variety of purposes. These drugs may have therapeutic effects against disease agents, or may cause changes in the structure and/or function of systems within the target animal. Routes of administration, quantity, duration, and potency of an antimicrobial drug are all important factors affecting their action(s) and success. Not only might targeted pathogens be affected, but also bacteria residing in (or on) the treated food animals, especially in the intestines (gastrointestinal tract microflora). Resistance to antimicrobial agents can occur through a number of mechanisms. The extent to which resistance develops is greatly affected by the amount of drug [or its metabolite(s)] a bacterium is exposed to, the duration of exposure, and the interaction between an individual antimicrobial agent and a particular bacterium. The impact of antimicrobial agents on the emergence of resistance in vitro and in vivo may not readily correlate.

Antibiotic resistance: a current perspective.

Antibiotic resistance: a current perspective.

Impact of antimicrobial agents on the gastrointestinal microflora and the risk of infections

The most common and significant cause of disturbances in the normal gastrointestinal microflora is the administration of antimicrobial agents. The microflora can be influenced by antimicrobial agents because of incomplete absorption of any orally administered antimicrobial agent, secretion of an antimicrobial agent by the salivary glands and in the bile, or secretion from the intestinal mucosa. In most cases the influence is not beneficial to the patient because suppression of the indigenous microorganisms often permits potential pathogens to overgrow and cause septic conditions, diarrhea, or colitis. Antimicrobial agents that influence the normal microflora also promote the emergence of antimicrobial-resistant strains. The authors' experience on the impact of different betalactams, erythromycin, clindamycin, tetracycline, and nitroimidazoles on the gastrointestinal microflora and the risk of infections when these agents are used is reviewed.