Systematic review and meta-analysis of the nitrate reductase assay for drug susceptibility testing of Mycobacterium tuberculosis and the detection limits in liquid medium

Miri Kwak, Won Kyu Lee, Young Ju Lim, Seung Heon Lee, Sungweon Ryoo

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Recently, the need for rapid, reliable, and low-cost drug susceptibility testing (DST) methods has increased due to the emergence of multidrug-resistant Mycobacterium tuberculosis. Colorimetric methods of DST provide results more quickly than standard culture methods and are inexpensive than molecular methods. Thus, colorimetric methods, such as the nitrate reductase assay (NRA), are being recommended. We searched Medline PubMed for reports on the NRA for DST of M. tuberculosis written in English and published within the last five years. We selected 20 reports on six major anti-TB drugs and conducted a meta-analysis using Meta-Disc software. The pooled sensitivities for isoniazid, rifampicin, streptomycin, ethambutol, ofloxacin, and kanamycin were 95.4%, 96.4%, 91.5%, 93.1%, 99.3%, and 88.4%, and the pooled specificities were 98.5%, 99.2%, 92.9%, 97.8%, 97.4%, and 99.4%, respectively. The area under the summary receiver operator curve for all drugs was 0.9723–0.9952. The time to results (TTR) for the direct and indirect NRAs was 7–28 days and 6–15 days, respectively. Quality assessments were conducted using the quality of diagnostic accuracy studies tool (QUADAS-2) items, and most reports showed good performance. However, ethambutol, streptomycin, and kanamycin showed relatively low sensitivity. We performed a quantitative NRA in liquid media at various inoculum concentrations. The TTR at 4.94 × 106, 1.67 × 104, and 2.27 × 102 CFU/mL was 4, 14, and 14 days, respectively. The minimum absorbance and nitrite concentration for positive samples were 0.8 and 168 μM, respectively. We propose a quantitative standard to determine sample positivity to address the problems with the current standard NRA which is much less expensive than the conventional assay conducted on solid medium.

Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalJournal of Microbiological Methods
Volume141
DOIs
Publication statusPublished - 2017 Oct 1

Fingerprint

Nitrate Reductase
Mycobacterium tuberculosis
Limit of Detection
Meta-Analysis
Ethambutol
Kanamycin
Pharmaceutical Preparations
Streptomycin
Multidrug-Resistant Tuberculosis
Drug Costs
Ofloxacin
Isoniazid
Rifampin
Nitrites
PubMed
Software

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology
  • Microbiology (medical)

Cite this

@article{3aa339ebdd774ad8958b0d09ba9d7a98,
title = "Systematic review and meta-analysis of the nitrate reductase assay for drug susceptibility testing of Mycobacterium tuberculosis and the detection limits in liquid medium",
abstract = "Recently, the need for rapid, reliable, and low-cost drug susceptibility testing (DST) methods has increased due to the emergence of multidrug-resistant Mycobacterium tuberculosis. Colorimetric methods of DST provide results more quickly than standard culture methods and are inexpensive than molecular methods. Thus, colorimetric methods, such as the nitrate reductase assay (NRA), are being recommended. We searched Medline PubMed for reports on the NRA for DST of M. tuberculosis written in English and published within the last five years. We selected 20 reports on six major anti-TB drugs and conducted a meta-analysis using Meta-Disc software. The pooled sensitivities for isoniazid, rifampicin, streptomycin, ethambutol, ofloxacin, and kanamycin were 95.4{\%}, 96.4{\%}, 91.5{\%}, 93.1{\%}, 99.3{\%}, and 88.4{\%}, and the pooled specificities were 98.5{\%}, 99.2{\%}, 92.9{\%}, 97.8{\%}, 97.4{\%}, and 99.4{\%}, respectively. The area under the summary receiver operator curve for all drugs was 0.9723–0.9952. The time to results (TTR) for the direct and indirect NRAs was 7–28 days and 6–15 days, respectively. Quality assessments were conducted using the quality of diagnostic accuracy studies tool (QUADAS-2) items, and most reports showed good performance. However, ethambutol, streptomycin, and kanamycin showed relatively low sensitivity. We performed a quantitative NRA in liquid media at various inoculum concentrations. The TTR at 4.94 × 106, 1.67 × 104, and 2.27 × 102 CFU/mL was 4, 14, and 14 days, respectively. The minimum absorbance and nitrite concentration for positive samples were 0.8 and 168 μM, respectively. We propose a quantitative standard to determine sample positivity to address the problems with the current standard NRA which is much less expensive than the conventional assay conducted on solid medium.",
author = "Miri Kwak and Lee, {Won Kyu} and Lim, {Young Ju} and Lee, {Seung Heon} and Sungweon Ryoo",
year = "2017",
month = "10",
day = "1",
doi = "10.1016/j.mimet.2017.07.001",
language = "English",
volume = "141",
pages = "1--9",
journal = "Journal of Microbiological Methods",
issn = "0167-7012",
publisher = "Elsevier",

}

TY - JOUR

T1 - Systematic review and meta-analysis of the nitrate reductase assay for drug susceptibility testing of Mycobacterium tuberculosis and the detection limits in liquid medium

AU - Kwak, Miri

AU - Lee, Won Kyu

AU - Lim, Young Ju

AU - Lee, Seung Heon

AU - Ryoo, Sungweon

PY - 2017/10/1

Y1 - 2017/10/1

N2 - Recently, the need for rapid, reliable, and low-cost drug susceptibility testing (DST) methods has increased due to the emergence of multidrug-resistant Mycobacterium tuberculosis. Colorimetric methods of DST provide results more quickly than standard culture methods and are inexpensive than molecular methods. Thus, colorimetric methods, such as the nitrate reductase assay (NRA), are being recommended. We searched Medline PubMed for reports on the NRA for DST of M. tuberculosis written in English and published within the last five years. We selected 20 reports on six major anti-TB drugs and conducted a meta-analysis using Meta-Disc software. The pooled sensitivities for isoniazid, rifampicin, streptomycin, ethambutol, ofloxacin, and kanamycin were 95.4%, 96.4%, 91.5%, 93.1%, 99.3%, and 88.4%, and the pooled specificities were 98.5%, 99.2%, 92.9%, 97.8%, 97.4%, and 99.4%, respectively. The area under the summary receiver operator curve for all drugs was 0.9723–0.9952. The time to results (TTR) for the direct and indirect NRAs was 7–28 days and 6–15 days, respectively. Quality assessments were conducted using the quality of diagnostic accuracy studies tool (QUADAS-2) items, and most reports showed good performance. However, ethambutol, streptomycin, and kanamycin showed relatively low sensitivity. We performed a quantitative NRA in liquid media at various inoculum concentrations. The TTR at 4.94 × 106, 1.67 × 104, and 2.27 × 102 CFU/mL was 4, 14, and 14 days, respectively. The minimum absorbance and nitrite concentration for positive samples were 0.8 and 168 μM, respectively. We propose a quantitative standard to determine sample positivity to address the problems with the current standard NRA which is much less expensive than the conventional assay conducted on solid medium.

AB - Recently, the need for rapid, reliable, and low-cost drug susceptibility testing (DST) methods has increased due to the emergence of multidrug-resistant Mycobacterium tuberculosis. Colorimetric methods of DST provide results more quickly than standard culture methods and are inexpensive than molecular methods. Thus, colorimetric methods, such as the nitrate reductase assay (NRA), are being recommended. We searched Medline PubMed for reports on the NRA for DST of M. tuberculosis written in English and published within the last five years. We selected 20 reports on six major anti-TB drugs and conducted a meta-analysis using Meta-Disc software. The pooled sensitivities for isoniazid, rifampicin, streptomycin, ethambutol, ofloxacin, and kanamycin were 95.4%, 96.4%, 91.5%, 93.1%, 99.3%, and 88.4%, and the pooled specificities were 98.5%, 99.2%, 92.9%, 97.8%, 97.4%, and 99.4%, respectively. The area under the summary receiver operator curve for all drugs was 0.9723–0.9952. The time to results (TTR) for the direct and indirect NRAs was 7–28 days and 6–15 days, respectively. Quality assessments were conducted using the quality of diagnostic accuracy studies tool (QUADAS-2) items, and most reports showed good performance. However, ethambutol, streptomycin, and kanamycin showed relatively low sensitivity. We performed a quantitative NRA in liquid media at various inoculum concentrations. The TTR at 4.94 × 106, 1.67 × 104, and 2.27 × 102 CFU/mL was 4, 14, and 14 days, respectively. The minimum absorbance and nitrite concentration for positive samples were 0.8 and 168 μM, respectively. We propose a quantitative standard to determine sample positivity to address the problems with the current standard NRA which is much less expensive than the conventional assay conducted on solid medium.

UR - http://www.scopus.com/inward/record.url?scp=85025091990&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85025091990&partnerID=8YFLogxK

U2 - 10.1016/j.mimet.2017.07.001

DO - 10.1016/j.mimet.2017.07.001

M3 - Article

C2 - 28694139

AN - SCOPUS:85025091990

VL - 141

SP - 1

EP - 9

JO - Journal of Microbiological Methods

JF - Journal of Microbiological Methods

SN - 0167-7012

ER -