Correlation between the BACTEC MGIT 960 culture system with Genotype MTBDRplus and TB-SPRINT in multidrug resistant Mycobacterium tuberculosis clinical isolates from Brazil

Abstract

BACKGROUNDThe accurate detection of multidrug-resistant tuberculosis (MDR-TB) is critical for the application of appropriate patient treatment and prevention of transmission of drug-resistant Mycobacterium tuberculosis isolates. The goal of this study was to evaluate the correlation between phenotypic and molecular techniques for drug-resistant tuberculosis diagnostics. Molecular techniques used were the line probe assay genotype MTBDRplus and the recently described tuberculosis-spoligo-rifampin-isoniazid typing (TB-SPRINT) bead-based assay. Conventional drug susceptibility testing (DST) was done on a BACTECTM MGIT 960 TB.METHODWe studied 80 M. tuberculosis complex (MTC) clinical isolates from Minas Gerais state, of which conventional DST had classified 60 isolates as MDR and 20 as drug susceptible.FINDINGSAmong the 60 MDR-TB isolates with MGIT as a reference, sensitivity, specificity, accuracy, and kappa for rifampicin (RIF) resistance using TB-SPRINT and MTBDRplus, were 96.7% versus 93.3%, 100.0% versus 100.0%, 97.5% versus 95.0% and 0.94 versus 0.88, respectively. Similarly, the sensitivity, specificity, accuracy, and kappa for isoniazid (INH) resistance were 85.0% and 83.3%, 100.0% and 100.0%, 88.8% and 87.5% and 0.74 and 0.71 for both tests, respectively. Finally, the sensitivity, specificity, accuracy, and kappa for MDR-TB were 85.0% and 83.3%, 100.0% and 100.0%, 88.8% and 87.5% and 0.74 and 0.71 for both tests, respectively.MAIN CONCLUSIONSBoth methods exhibited a good correlation with the conventional DST. We suggest estimating the cost-effectiveness of MTBDRplus and TB-SPRINT in Brazil.

Speeding up the diagnosis of multidrug-resistant tuberculosis in a high-burden region with the use of a commercial line probe assay

“…Our findings are in agreement with a review 24 that estimated pooled sensitivities and specificities for resistance prediction to RIF (91.3% and 97.1%) and INH (89.4% and 98.9%). Regarding the data from Brazil using the MTBDR plus in clinical isolates, our findings are comparable with a study 25 in the State of Minas Gerais, showing sensitivities of 93.3% for RIF, 83.3% for MDR or INH resistance detection, and 100% specificity for both drugs. A study on MDR-TB patients in Ribeirão Preto (SP), revealed 100% and 80% sensitivity in detecting RIF and INH resistance, respectively 26 …”

“…In this study, rpo B Ser531Leu and kat G Ser315Thr mutations predominated, as in other settings 25 28 ) Identifying the specific mutation associated with drug resistance, which is not possible by phenotypic methods, may provide additional information on the category of resistance and guide therapeutic decision, as to the choice of the treatment regimen 29 .…”

Molecular Diagnosis of Drug-Resistant Tuberculosis; A Literature Review

“…GenoType MTBDR plus VER2.0 shows good accuracy for the detection of MDR isolates in smear-positive specimens (sensitivity between 83.3 and 96.4%, and specificity between 98.6 and 100%) (Bai et al, 2016; Nathavitharana et al, 2016; Dantas et al, 2017; Meaza et al, 2017). The Nipro NTM+MDRTB strips also show high specificity (between 97 and 100%) for INH and RIF resistance screening in cultured isolates and clinical (sputum) samples, but sensitivity varies between studies (from 50 to 95%) (Mitarai et al, 2012; Ruesch-Gerdes and Ismail, 2015; Nathavitharana et al, 2016).…”

Multicenter evaluation of TB-SPRINT 59-Plex Beamedex®: accuracy and cost analysis

“…This technique is a microbead-based assay developed to run on Luminex® devices (Luminex Corp., Austin, TX, USA) for the simultaneous spoligotyping and detection of rpoB , katG , and inhA mutations associated with resistance to RIF and INH. It has also been successfully used in previous studies and performed well when compared to the MTBDR plus [9–11] . However, no data on its accuracy and costs have been gathered from a multicenter laboratory study considering all components of the cost chain.…”