A novel method for evaluating the antimicrobial activity of tuberculosis treatment regimens

OBJECTIVE: To evaluate the clinical response to anti-tuberculosis chemotherapy rapidly. METHOD: Sputum viable counts from a previously published clinical trial comparing a standard regimen and one containing isoniazid, rifampicin and ciprofloxacin were re-evaluated using an exponential decay model. The results were fitted to a one or two phase exponential decline. The decline in viable counts followed a curve described by a single-phase exponential decay model. From these data the time taken to reduce the viable count by 50% (vt₅₀) was calculated to estimate the bactericidal effect of the regimens. RESULTS AND CONCLUSION: This method shows promise as a means for early identification of patients who are responding poorly as a result of resistance or poor immune response and for comparing anti-tuberculosis regimens in clinical trials. The failure to show a two-phase exponential decay curve suggested that either the sputum does not contain bacteria upon which only drugs with a sterilising activity act or that they are not present in sufficient numbers to have a significant impact on the total viable count. Further studies are required to understand the physiological state of organisms being sampled in sputum.