Evaluation of Direct Nitrate Reductase Assay for Culture and Susceptibility Testing of Mycobacterium Tuberculosis to Four Primary Antitubercular Drugs

Abstract

Rapid, simple drug susceptibility tests applicable in developing countries would allow earlier treatment of patients with multi-drug resistant Mycobacterium tuberculosis infections. To evaluate the performance and feasibility of a Direct Nitrate Reductase Assay for detecting the drug-resistant tuberculosis directly in microscopy-positive samples, this prospective study comparing the sensitivity and specificity of the Direct Nitrate Reductase Assay with the gold standard Lowenstein Jensen proportion method was carried out at National TB and SAARC TB and HIV/AIDS Centre, Thimi, Bhaktapur, Nepal from June 2008 to March 2009. Out of 302 sputum samples taken, 144 (47.68%) sputum samples those showing positive for Acid Fast Bacilli were tested by Direct Nitrate Reductase Assay method and the test was completed on 121 (84%) specimens. Of the 23 specimen for which the test was not completed, 12 (8.33%) were culture-negative and 11 (7.63%) were contaminated on culture. The sensitivity and specificity of the Direct Nitrate Reductase Assay were studied in 121 specimens and were 100% and 91% for isoniazid, 100% and 98.95% for rifampicin, 96% and 91.66% for streptomycin, and 100% and 98% for ethambutol respectively. Of the 121 samples tested for drug susceptibility, 72.72% (88) were sensitive to all four drugs and 27.28% (33) were resistant to one or more drugs with 19% (23) multi-drug resistant. The Direct Nitrate Reductase Assay is sensitive and specific enough for the detection of multi-drug resistant tuberculosis and is also easy to perform, rapid and inexpensive, making it suitable for developing countries. However, its usefulness for national drug resistance surveys should be assessed. Key words: sensitivity, specificity, gold standard, multi-drug resistant