PARAMETERIZATION OF INOCULUM EFFECT VIA MATHEMATICAL-MODELING - AMINOGLYCOSIDES AGAINST STAPHYLOCOCCUS-AUREUS AND ESCHERICHIA-COLI

Inoculum effect describes the inoculum size dependent changes in minim um inhibitory concentrations (MIC) exhibited by antibiotic-bacterium c ombinations demonstrating such effect. Traditionally, inoculum effect has been loosely defined based on the extent of increase in the MIC wi th respect to the increase in inoculum size. In most studies, assessme nt of MIC data has relied on the arbitrary selection of a point of ref erence for both baseline MIC and inoculum size. More importantly, this conventional method of assessment does not permit information conveye d in a complete MIC versus inoculum size profile to be fully explored. To undertake these issues, a mathematical model was developed for the description of the entire inoculum effect profile. With the employmen t of three key parameter estimates, i.e., the baseline MIG, the thresh old inoculum size at which the increase in MIC commences, and the rate of increase in MIC with respect to inoculum size, both the shape and location of the profile could be adequately defined. To verify the app lication of this model, a series of four aminoglycosides were tested a gainst standard strains of E. coli and S. aureus. Results showed a goo d degree of organism specificity and antibiotic class dependency of th e inoculum effect profiles. Analysis of the parameter estimates obtain ed provided further support for these observations. In conclusion, the mathematical model developed in the present study adequately describe d the inoculum effect exhibited by the various aminoglycoside-bacteriu m combinations tested. The parameter estimates generated by the modeli ng approach allowed comparison and quantitative analysis of the inocul um effect profiles with minimal difficulties.