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Comparative Study
. 2017 Dec 28;17(1):795.
doi: 10.1186/s12879-017-2898-3.

Comparison of line probe assay to BACTEC MGIT 960 system for susceptibility testing of first and second-line anti-tuberculosis drugs in a referral laboratory in South Africa

Nontuthuko E Maningi  1 , Lesibana A Malinga  2 , John F Antiabong  3 , Ruth M Lekalakala  4 , Nontombi M Mbelle  3   4
Affiliations
Comparative Study

Comparison of line probe assay to BACTEC MGIT 960 system for susceptibility testing of first and second-line anti-tuberculosis drugs in a referral laboratory in South Africa

Nontuthuko E Maningi et al. BMC Infect Dis. .

Abstract

Background: The incidence of multidrug-resistant tuberculosis (MDR-TB) is increasing and the emergence of extensively drug-resistant tuberculosis (XDR-TB) is a major challenge. Controlling resistance, reducing transmission and improving treatment outcomes in MDR/XDR-TB patients is reliant on susceptibility testing. Susceptibility testing using phenotypic methods is labour intensive and time-consuming. Alternative methods, such as molecular assays are easier to perform and have a rapid turn-around time. The World Health Organization (WHO) has endorsed the use of line probe assays (LPAs) for first and second line diagnostic screening of MDR/XDR-TB.

Methods: We compared the performance of LPAs to BACTEC MGIT 960 system for susceptibility testing of bacterial resistance to first-line drugs: rifampicin (RIF), isoniazid (INH), ethambutol (EMB), and second-line drugs ofloxacin (OFL) and kanamycin (KAN). One hundred (100) consecutive non-repeat Mycobacterium tuberculosis cultures, resistant to either INH or RIF or both, as identified by BACTEC MGIT 960 were tested. All isoniazid resistant cultures (n = 97) and RIF resistant cultures (n = 90) were processed with Genotype®MTBDRplus and Genotype®MTBDRsl line probe assays (LPAs). The agar proportion method was employed to further analyze discordant LPAs and the MGIT 960 isolates.

Results: The Genotype ®MTBDRplus (version 2) sensitivity, specificity, PPV and NPV from culture isolates were as follows: RIF, 100%, 87.9, 58.3% and 100%; INH, 100%, 94.4%, 93.5% and 100%. The sensitivity, specificity PPV and NPV for Genotype ® MTBDRsl (version 1 and 2) from culture isolates were as follows: EMB, 60.0%, 89.2%, 68.2% and 85.3%; OFL, 100%, 91.4%, 56.2% and 100%; KAN, 100%, 97.7%, 60.0% and 100%. Line probe assay showed an excellent agreement (k = 0.93) for INH susceptibility testing when compared to MGIT 960 system while there was good agreement (k = 0.6-0.7) between both methods for RIF, OFL, KAN testing and moderate agreement for EMB (k = 0.5). A high RIF mono-resistance (MGIT 960 33/97 and LPA 43/97) was observed.

Conclusion: LPAs are an efficient and reliable rapid molecular DST assay for rapid susceptibility screening of MDR and XDR-TB. Using LPAs in high MDR/XDR burden countries allows for appropriate and timely treatment, which will reduce transmission rates, morbidity and improve treatment outcomes in patients.

Keywords: Drug-resistance; Ethambutol; Isoniazid; Kanamycin; Line-probe assay; MGIT 960 system; Mycobacterium tuberculosis; Ofloxacin; Rifampicin.

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Conflict of interest statement

Ethics approval and consent to participate

Ethical approval was obtained from the Faculty of Health Science Research Ethics, University of Pretoria with protocol number 318/2013 and preceded experimental work.

Consent for publication

Not Applicable.

Competing interests

The authors declare that they have no competing interests.

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Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Flow diagram of MGIT 960 cultures for laboratory evaluation of LPA DST compared to MGIT 960 DST. MGIT-Mycobacterium Growth Indicator Tube, LPA-Line Probe Assay, ZN-Zeihl Nelson
See this image and copyright information in PMC

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