Synergistic effect of rifampin, streptomycin, ethionamide, and ethambutol on Mycobacterium intracellulare

Abstract

A method of quantitative estimation to determine the interaction of antituberculosis drugs is suggested. The design of experiments, performed on 7H11 agar plates, is adjusted to the following statistical treatment by combined use of probit analysis and isobologram methods. By plotting the values reflecting the inhibition of 75% of the bacterial population (ED75) with their confidence limits on the isobologram, it was found that the clearest results proving synergism between the drugs could be obtained. Six 2-drug combinations and 6 3-drug combinations were tested against strains of Mycobacterium intracellulare (serovar 8), and a synergistic effect was demonstrated in most of them. These were various combinations of rifampin, streptomycin, ethambutol, and ethionamide. The application of probit analysis to the data derived from testing single drugs can provide a quantitative estimation of the actual drug resistance of the M. intracellulare strains.