Quantitative measurement of drug susceptibility of Mycobacterium tuberculosis for monitoring chemotherapy response.

ABSTRACT

Changes in the degree of drug susceptibility of the bacterial population in tuberculosis patients during chemotherapy can be monitored by testing Mycobacterium tuberculosis isolates against various concentrations of drugs in 7H12 broth to determine radiometrically the minimal inhibitory concentration (MIC). The MICs were determined for multiple cultures isolated from 13 patients, of whom nine responded to chemotherapy within a few months, and four failed to respond at all. No changes in MICs were observed with the isolates obtained from the patients with a favorable response to chemotherapy. Determination of the MICs indicated that the failure in two cases out of four was associated with a steady increase in the degree of resistance of the patients' bacterial population. In two other failure cases, lack of change in the MIC values for multiple cultures suggests that the failure was associated with factors other than drug resistance. During the period of chemotherapy, quantitation of the degree of drug susceptibility in terms of broth-determined MICs may help to identify promptly those patients whose bacterial population is becoming resistant to the administered antimicrobial agents. For those patients who do not respond to chemotherapy, lack of change in the degree of resistance of their bacterial population may alert the physician to attempt to identify causes other than drug resistance for the chemotherapy failure.