Nitrate Reductase Assay for Rapid Detection of Isoniazid, Rifampin, Ethambutol, and Streptomycin Resistance in Mycobacterium tuberculosis: a Systematic Review and Meta-Analysis

Abstract

Colorimetric phenotypic tests recently gained interest because traditional primary drug susceptibility testing of Mycobacterium tuberculosis isolates takes a long time. We used meta-analysis techniques to review the reliability and accuracy of the nitrate reductase assay (NRA), which is one of the most popular colorimetric methods to detect resistance to first-line drugs. Medline, PubMed, ISI Web, Web of Science, and Google Scholar were used to search for studies enrolled in the meta-analysis. The analysis included 35 studies for isoniazid (INH), 38 for rifampin (RIF), and 22 for ethambutol (EMB) and streptomycin (STR). Summary receiver operating characteristic (SROC) curves were applied to summarize diagnostic accuracy. The meta-analyses were performed by the use of Meta-DiSc software (version 1.4) and were focused on sensitivity and specificity values for measurements of accuracy. The pooled sensitivities were 96% for INH, 97% for RIF, 90% for EMB, and 82% for STR. The pooled specificities for INH, RIF, EMB, and STR were 99%, 100%, 98%, and 96%, respectively. The times required to obtain results were between 5 and 28 days by the direct NRA and between 5 and 14 days by the indirect test. In conclusion, the present meta-analysis showed that the NRA is a reliable low-cost rapid colorimetric susceptibility test that can be used for the detection of multidrug-resistant (MDR) tuberculosis, including detection of EMB resistance. However, the test appears to have a relatively low sensitivity for STR and needs further improvement.