A novel method for evaluating the antimicrobial activity of tuberculosis treatment regimens.
OBJECTIVE
To evaluate the clinical response to antituberculosis chemotherapy rapidly.


METHODS
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.


CONCLUSIONS
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.
Gillespie
S H
SH
Department of Medical Microbiology, University College London, London, United Kingdom. stepheng@rfc.ucl.ac.uk
Charalambous
B M
BM
D000995:Antitubercular Agents / Q000008:administration & dosage*; D002470:Cell Survival; D002939:Ciprofloxacin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage; D008826:Microbial Sensitivity Tests; D015233:Models, Statistical; D012293:Rifampin / Q000008:administration & dosage; D013183:Sputum / Q000382:microbiology*; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000382:microbiology
D000995:Antitubercular Agents; D002939:Ciprofloxacin; D007538:Isoniazid; D012293:Rifampin