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Aims:To examine the effect on the leakage of low molecular weight cytoplasmic constituents from Staphylococcus aureus using phenolics singly and in combination, and to see if the observations could be modelled using a non-linear dose response. Methods and Results: The rate of potassium, phosphate and adenosine triphosphate leakage was examined in the presence of chlorocresol and m-cresol. Individually, leakage was observed only at long contact times or high concentrations. Combined at these ineffective concentrations, the cytoplasmic pool of all constituents studied was released within minutes. Both chlorocresol and m-cresol were shown to have non-linear dose responses. A rate model for the combinations, which takes account of these non-linear responses, accurately predicted the observations. Conclusions: Antimicrobials, which when used alone exhibit a non-linear dose response, will also give a nonlinear dose response in combination. The simple linear-additive model ignores the concept of the dilution coefficient and will always describe the phenomenon of synergy for combinations where one or more of the components has a dilution coefficient greater than one. This has been borne out by examination of the purported prime lesion of chlorocresol and m-cresol, alone and in combination. Significance and Impact of the Study: Studies aimed at producing synergistic mixtures of antimicrobials, which ignore the non-linear additive effect, may waste valuable research effort looking for a physiological explanation for an apparent synergy, where none, in-fact, exists. Patents granted on the basis of analyses using the linear-additive model for combinations of compounds with non-linear dose responses may no longer be supportable.

M BE RT . 2000. Disinfection kinetic studies of sodium dodecyl sulphate, benzalkonium chloride and sodium hypochlorite against Staphylococcus aureus revealed that when a higher inoculum level of Staph. aureus than normal was used (approximately 1 log higher), the efficacy of disinfection was severely attenuated. Kinetic analysis using the Hom model for experiments carried out on tests using 3 × 10 8 organisms ml −1 were unable to account for the large increase in disinfection power observed when smaller inoculum levels were used. Since the inoculum was the same in every way except for the numbers used, the large variations in the log reduction/time curves could not be explained by a variation in the resistance of the population to the biocide, as identical log reduction-time curves should have resulted. The level of disinfection achieved for a given concentration of biocide was found to be approximately linearly related to the cell number ml −1 of test solution and not to the log number. The variation observed is believed to occur due to intrinsic self-quenching of the biocide by the microbes during the course of the disinfection test. As the level of free biocide decreases, the rate of reaction decreases, giving the tails of the log reduction/time curves. Such intrinsic self-quenching could explain the large variations known to occur in the legally required disinfection suspension tests.