Predicting the outcome of therapy for pulmonary tuberculosis

Abstract

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.

Figures

Figure 1

Frequency distributions of day of last rapidly positive culture in BACTEC (indicating mycobacterial growth within 20 d of inoculation (left panel) and that of the day of last positive culture on solid medium (right panel). Subjects from Uganda are indicated in gray; those from Brazil are indicated in black. The two rightmost subjects in both graphs represent relapses.

Figure 2

The relationship between the predicted and observed day of last rapidly positive BACTEC culture, using the multivariate models shown in Table 1. Two relapses are indicated as black squares. The dotted lines indicate equality. The right hand model does not require mycobacterial culture. Predicted values are not shown for those subjects with incomplete data.