TY - JOUR

T1 - Detection of Mycobacterium tuberculosis complex in pulmonary and extrapulmonary samples with the FluoroType MTBDR assay

AU - Svensson, Erik

AU - Folkvardsen, Dorte Bek

AU - Rasmussen, Erik Michael

AU - Lillebaek, Troels

PY - 2021

Y1 - 2021

N2 - ObjectivesRifampicin (RIF) and isoniazid (INH) are the two most effective first-line antibiotic drugs for the treatment of tuberculosis (TB). The new FluoroType MTBDR (FT-MTBDR) real-time PCR is intended to detect INH and RIF resistance mutations as a second step following a primary Mycobacterium tuberculosis complex (MTBC) PCR. Here we evaluate the feasibility of the FT-MTBDR assay to detect simultaneously MTBC-specific DNA as well as to detect potential INH and RIF resistance through analysing inhA promotor, katG and rpoB sequences in one PCR reaction.MethodsWe analysed 3885 consecutive primary samples with FT-MTBDR and compared the results with microscopy and culture: 978 were from sputum, 2007 from other respiratory tract locations plus gastric lavages, and 875 from extrapulmonary locations, respectively.ResultsOverall, 176 samples were MTBC culture positive and 139 FT-MTBDR positive, providing a FT-MTBDR sensitivity of 0.714 (95% confidence interval 0.640–0.779) and specificity of 0.996 (0.994–0.998), respectively. For the 978 sputum, 96 were MTBC culture positive and 89 FT-MTBDR positive, sensitivity 0.854 (0.764–0.915) and specificity 0.992 (0.983–0.997). Of the 139 MTBC positive, 99 (71%) had interpretable genotypic resistance results for at least one drug, 92 (66%) for both drugs.DiscussionThe ability of FT-MTBDR to detect MTBC is adequate with the significant added feature of simultaneous genotypic resistance detection of both INH and RIF in a single PCR reaction.

AB - ObjectivesRifampicin (RIF) and isoniazid (INH) are the two most effective first-line antibiotic drugs for the treatment of tuberculosis (TB). The new FluoroType MTBDR (FT-MTBDR) real-time PCR is intended to detect INH and RIF resistance mutations as a second step following a primary Mycobacterium tuberculosis complex (MTBC) PCR. Here we evaluate the feasibility of the FT-MTBDR assay to detect simultaneously MTBC-specific DNA as well as to detect potential INH and RIF resistance through analysing inhA promotor, katG and rpoB sequences in one PCR reaction.MethodsWe analysed 3885 consecutive primary samples with FT-MTBDR and compared the results with microscopy and culture: 978 were from sputum, 2007 from other respiratory tract locations plus gastric lavages, and 875 from extrapulmonary locations, respectively.ResultsOverall, 176 samples were MTBC culture positive and 139 FT-MTBDR positive, providing a FT-MTBDR sensitivity of 0.714 (95% confidence interval 0.640–0.779) and specificity of 0.996 (0.994–0.998), respectively. For the 978 sputum, 96 were MTBC culture positive and 89 FT-MTBDR positive, sensitivity 0.854 (0.764–0.915) and specificity 0.992 (0.983–0.997). Of the 139 MTBC positive, 99 (71%) had interpretable genotypic resistance results for at least one drug, 92 (66%) for both drugs.DiscussionThe ability of FT-MTBDR to detect MTBC is adequate with the significant added feature of simultaneous genotypic resistance detection of both INH and RIF in a single PCR reaction.

KW - Early resistance detection

KW - FluoroType

KW - Isoniazid

KW - Mutation analysis

KW - Mycobacterium tuberculosis

KW - PCR

KW - Resistance

KW - Rifampicin

U2 - 10.1016/j.cmi.2020.12.020

DO - 10.1016/j.cmi.2020.12.020

M3 - Journal article

C2 - 33421581

VL - 27

SP - 1514.e1-1514.e4

JO - Clinical Microbiology and Infection

JF - Clinical Microbiology and Infection

SN - 1198-743X

IS - 10

ER -