Determination of ansamycin MICs for Mycobacterium avium complex in liquid medium by radiometric and conventional methods

Abstract

A radiometric method to determine the MIC of ansamycin (LM427) for Mycobacterium avium complex clinical isolates has been developed. It is based on a comparison of the conventional growth curve determination and the radiometric detection of growth (growth index) in the same liquid medium (7H12 broth). This new method requires less time and labor than does a conventional determination of MIC in liquid medium (CFU). Other advantages of this method include relatively short periods of exposure of the drug to 37 degrees C and the composition of 7H12 broth, which has practically no substrates which could absorb or bind the drug. Thus, a more accurate estimation of the MIC in this medium can be expected than by the conventional agar dilution (proportion) method. The MICs of ansamycin appeared to be higher in agar plates than in 7H12 broth. More than 70% of the isolates had a broth-determined MIC one to three times lower than the average peak concentration of ansamycin achieved in sera of patients. The wide range of MICs suggests the importance of testing susceptibility in broth with many concentrations in addition to, or rather than in, agar plates with concentrations of 2.0 or 1.0 micrograms/ml only. Taking into account relatively low levels of ansamycin in sera of patients, it would be appropriate to compare the MICs with the levels in serum to make the outcome of chemotherapy more predictable.