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Re-evaluation of the critical concentration of isoniazid and rifampicin among M. tuberculosis strains isolated from patients using wild-type MIC distribution

Implementing Organization

National Institute for Research in Tuberculosis (NIRT) Visit
Principal Investigator
Dr. V. N. Azger Dusthackeer
Scientist, National Institute for Research in Tuberculosis (NIRT), Chennai
CO-Principal Investigator
Dr. Geetha Ramachandran
National Institute for Research in Tuberculosis (NIRT), Chennai, Dr. Hemanth Kumar, National Institute for Research in Tuberculosis (NIRT), Chennai

Project Overview

Wild type MIC distribution of Isoniazid and Rifampicin was determined using 276 isolates of M. tuberculosis isolated from the sputum specimens of tuberculosis patients before the start of treatment in Middle brooke 7H10 agar plate. The critical concentration was determined to be same for RMP in both solid and liquid media (1.0mg/L). But critical concentration for INH in MGIT960 was higher than that recommended by WHO1. In this study in a sample size of 96 it was found to be 0.25 mg/L as against 0.1 mg/L as recommended by WHO1. With available PK results performed in these patients the optimal level of the PD indices which should be above 10 and 100 for the ratios Cmax/MIC and AUC/MIC respectively2 the PD levels for RMP was found to be below the expected level, but for INH it is well above the required ratios for Cmax/MIC and AUC/MIC. More over for 8 of the patients who are MICs of the infecting M.tuberculosis isolate results as well as their serum levels were available and the PD indices were calculated individually. RMP levels were subtherapeutic in 5 out of 8 of these patients. With the smaller sample size of the study a foregone conclusion cannot be arrived based on this sample size, but the unexpected result of the subtherapeutic levels found in majority of these patients with respect to RMP, one of the important anti-TB drugs in the regimen to treat tuberculosis implicates the importance of such a study in larger sample size.
Funding Organization
Funding Organization
Indian Council of Medical Research (ICMR), New Delhi
Quick Information
Area of Research
Medical Sciences
Focus Area
Tuberculosis and chest diseases
Start Date
2015
End Date
2016
Status
Completed
Contact
azger@nirt.res.in;umadevi.r@nirt.res.in;akhemanth20@gmail.com
Output
No. of Research Paper
00
Technologies (If Any)
00
No. of PhD Produced
00
Publications
00
No. of Patents
Filed : 00
Grant : 00
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