Theory of antimicrobial combinations: biocide mixtures - synergy or addition?

Abstract

Aims:To demonstrate the effect that non-linear dose responses have on the appearance of synergy in mixtures of antimicrobials. Methods and Results: A mathematical model, which allows the prediction of the efficacy of mixtures of antimicrobials with non-linear dose responses, was produced. The efficacy of antimicrobial mixtures that would be classified as synergistic by time-kill methodology was shown to be a natural consequence of combining antimicrobials with non-linear dose responses. Conclusions: The effectiveness of admixtures of biocides and other antimicrobials with non-linear dose responses can be predicted. If the dose response (or dilution coefficient) of any biocidal component, in a mixture, is other than one, then the time-kill methodology used to ascertain the existence of synergy in antimicrobial combinations is flawed. Significance and Impact of the Study: The kinetic model developed allows the prediction of the efficacy of antimicrobial combinations. Combinations of known antimicrobials, which reduce the time taken to achieve a specified level of microbial inactivation, can be easily assessed once the kinetic profile of each component has been obtained. Most patented cases of antimicrobial synergy have not taken into account the possible effect of non-linear dose responses of the component materials. That much of the earlier literature can now be predicted, suggests that future cases will require more thorough proof of the alleged synergy.

In vitro efficacy of synergistic antibiotic combinations in imipenem resistant Pseudomonas aeruginosa strains

“…Combination antibiotic treatment provide larger spectrum antimicrobial effect, prevent the rapid emergence of resistance strains, decrease dose-related toxicity by using reduced dose of both drugs, enhanced inhibition of microorganisms. 3 The aim of this study was to determine the in vitro effects of some antimicrobial drug combinations on imipenem resistant P. aeruginosa.…”

Evaluation of the best method to assess antibiotic potentiation by phytochemicals against Staphylococcus aureus

“…Indeed, the biological system is less able to compensate for the action of 2 or more drugs simultaneously (Zimmermann et al, 2007). Also, the cost of developing a new antimicrobial versus the cost of finding a combination between known ones is an easy justification for research into drug potentiation (Lambert et al, 2003).…”

The New Metall-Beta-Lactamase’s Inhibitor Efficacy in a Model System in Vitro

“…Кроме того, есть ряд работ по оценке наличия синергизма или антагонизма антибиотика и антимик робных агентов из групп четвертичных аммониевых со-единений, ЭДТА [21,31,32,39].…”