Methods for Improving Drug Treatments in Mammals

Abstract

An improved method for identifying the size, shape and duration of drug exposure necessary to improve drug treatment in a subject with a bacterial infection. In addition, an improved method for identification of new dosing strategies which optimize the probability of positive treatment outcomes in subjects using resistance inhibitory concentration (RIC), wherein the subject has a bacterial infection caused by a bacterium with a propensity for heteroresistance. Further, an improved method for decreasing the potential for on-therapy drug resistance by determining a patient's RIC prior to administration of fosfomycin treatment, wherein RIC is utilized to differentiate the parameter which is best related to the driver or index of fosfomycin efficacy for the resistant subpopulation present and the required inhibitory concentration of those mutants.

1 . A method for treating a subject with a bacterial infection that includes infection with a “resistant” mutant subpopulation of  E. coli,  the method comprising administering fosfomycin to a subject according to an optimum dosing interval consistent with the resistance inhibitory concentration (RIC) of fosfomycin required to inhibit the “resistant” mutant subpopulations of  E. coli,  wherein bacterial density is effectively reduced and the “resistant” mutant subpopulation is inhibited.