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.There is substantial variability in the response to therapy for pulmonary tuberculosis, even in those patients with fully drug sensitive isolates. In some patients, bacilli are killed rapidly and cleared quickly from sputum. In others, viable organisms persist for many weeks or months, despite multidrug treatment. In yet others, bacilli are cleared, only to reappear after therapy is stopped. These observations form the basis for the definitions of treatment failure and relapse, respectively. The causes of this phenomenon are not well understood, but they may involve mycobacterial and host biologic factors as well as host behavioral factors.The search for tools to monitor tuberculosis therapy and predict outcome is made particularly complex by the observation that mycobacterial killing is not a single uniform process. Most actively replicating bacilli are killed rapidly during the first 1 to 2 wk of therapy. This phase of treatment can be measured by quantitative sputum culture (early
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Author Manuscript Author ManuscriptAuthor Manuscript Author Manuscript bactericidal activity or EBA) (1-5). There is, however, no known relationship between EBA and the outcome of treatment. Prolonged treatment is required to eradicate persisting organisms with reduced or otherwise altered metabolic activity. Nonreplicating bacilli show reduced susceptibility to the bactericidal activities of antimycobacterial drugs (6, 7). This later, sterilizing phase of therapy appears to be distinct from the first, based in part on the differential activities of antimycobacterial drugs during the two phases.Two studies indicate that, in contrast to EBA, the time to sterilization is an important determinant of outco...