AMPLIFICATION OF RIBOSOMAL-RNA FOR ASSESSMENT OF TREATMENT RESPONSE OF PULMONARY TUBERCULOSIS PATIENTS DURING ANTIMICROBIAL THERAPY

The time course of persistence of Mycobacterium tuberculosis as measur ed by detection of rRNA, acid-fast bacillus (AFB) smear, and culture w as determined for pulmonary tuberculosis patients during antimicrobial therapy, Twenty-three patients who were initially AFB smear positive and who subsequently completed a course of antimicrobial therapy were selected for the study, Sequential specimens were tested by AFB smear, culture, and rRNA amplification (Gen-Probe Amplified Mycobacterium Tu berculosis Direct Test [MTD]). The initial diagnostic specimens of all patients were positive by culture; those of 22 patients (96%) also we re positive by MTD. Overall, MTD results remained positive longer than both smear and culture results. The median times to the last positive test result were 9 days for AFB smear, 26 days for culture, and 30 da ys for MTD. The last positive test result was the AFB smear result in 4% of cases, the culture result in 22%, and the MTD result in 52%. Fif ty-six percent of patients had a period of shedding of noncultivable M , tuberculosis which was detected by MTD after culture results had con verted to negative, This noncultivable period lasted 7 to 245 days. Al l three tests became reproducibly negative before the end of therapy a nd remained negative during follow-up for up to 1 year. These results indicate that during successful antimicrobial therapy, M, tuberculosis is eliminated in sputum samples as measured by amplification of rRNA, as well as by AFB smear and culture. No long-term rRNA carrier state was detected. While the time course of clearance of M. tuberculosis me asured by rRNA overall was longer than with the two traditional tests, the rRNA test results allow sensitive and precise measurement of the clearance of noncultivable M. tuberculosis from respiratory specimens. This attribute may allow rRNA testing to be useful in clarifying pati ent response to antimicrobial therapy.