Predicting the outcome of therapy for pulmonary tuberculosis.

Patients vary considerably in their response to treatment of pulmonary tuberculosis. Although several studies have indicated that adverse outcomes are more likely in those patients with delayed sputum sterilization, few tools are available to identify those patients prospectively. In this study, multivariate models were developed to predict the response to therapy in a prospectively recruited cohort of 42 HIV-uninfected subjects with drug-sensitive tuberculosis. The cohort included 2 subjects whose initial response was followed by drug-sensitive relapse. The total duration of culture positivity was best predicted by a model that included sputum M. tuberculosis antigen 85 concentration on Day 14 of therapy, days-to-positive in BACTEC on Day 30, and the baseline radiographic extent of disease (R = 0.63). A model in which quantitative AFB microscopy replaced BACTEC also performed adequately (R = 0.58). Both models predicted delayed clearance of bacilli in both relapses (> 85th percentile of all subjects) using information collected during the first month of therapy. Stratification of patients according to anticipated response to therapy may allow TB treatment to be individualized, potentially offering superior outcomes and greater efficiency in resource utilization, and aiding in the conduct of clinical trials.

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 BACTEC, and Mycobacterium tuberculosis antigen 85 complex were monitored during therapy in 42 patients with pulmonary tuberculosis (TB). By BACTEC, 4 patients were persistently positive on days 90-180, and treatment 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 suggested TB persistence at or after day 90. All subjects with day 14 antigen 85 complex values < 60 pg/mL responded rapidly to treatment and were cured. Of those with values > 60 pg/mL, in 33% TB persisted at or after day 90 and treatment failed in 17%. Biologic factors expressed early in therapy, not related to compliance or resistance, may exert a substantial influence on outcome. The antigen 85 complex is critical in cell wall biosynthesis and is induced by isoniazid in vitro. Its induction may represent an adaptive transition to a persistent state during therapy.