INDUCTION OF THE ANTIGEN-85 COMPLEX OF MYCOBACTERIUM-TUBERCULOSIS IN SPUTUM - A DETERMINANT OF OUTCOME IN PULMONARY TUBERCULOSIS TREATMENT

Sputum quantitative culture, acid-fast smear, days-to-positive by BACT EC, and Mycobacterium tuberculosis antigen 85 complex were monitored d uring therapy in 42 patients with pulmonary tuberculosis (TB). By BACT EC, 4 patients were persistently positive on days 90-180, and treatmen t ultimately failed in 2 of these. Antigen 85 expression increased in subjects in whom disease persisted (persisters) from days 0 to 14 when the difference between persisters and nonpersisters was statistically significant (P = .002). Only antigen 85 complex values at day 14 sugg ested TB persistence at or after day 90. All subjects with day 14 anti gen 85 complex values <60 pg/mL responded rapidly to treatment and wer e cured. Of those with values >60 pg/mL, in 33% TB persisted at or aft er day 90 and treatment failed in 17%. Biologic factors expressed earl y in therapy, not related to compliance or resistance, may exert a sub stantial influence on outcome. The antigen 85 complex is critical in c ell wall biosynthesis and is induced by isoniazid in vitro, I:ts induc tion may represent an adaptive transition to a persistent state during therapy.