RT Journal Article
SR Electronic
T1 GenoType MTBDRsl performance on clinical samples with diverse genetic background
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP erj01641-2011
DO 10.1183/09031936.00164111
A1 P. Miotto
A1 A.M. Cabibbe
A1 P. Mantegani
A1 E. Borroni
A1 L. Fattorini
A1 E. Tortoli
A1 G.B. Migliori
A1 D.M. Cirillo
YR 2012
UL http://erj.ersjournals.com/content/early/2012/01/19/09031936.00164111.abstract
AB Individualized regimen for MDR-tuberculosis requires data on the sensitivity to second-line drugs. The direct detection of gene mutations known to be associated with drug resistance is the only available rapid method for prediction of resistances.We evaluate the performance of the GenoType MTBDRsl (Hain Lifescience) for the detection of second-line resistant TB and we correlate the frequency of mutations to different M. tuberculosis genotypes.We tested 175 strains and 59 clinical specimens interpreting the results according to the STARD recommendations. All the strains were also investigated by spoligotyping and MIRU-VNTR.The performances of the MTBDRsl in detecting resistance to fluoroquinolones (FQ), second-line injectable drugs (SLID), and ethambutol (EMB) on clinical isolates were similar (specificity: ∼99%; sensitivity: ∼70%; PPV: ∼99%).Of the 59 respiratory specimens, 3 samples were classified as “indeterminate”. The specificity in detecting resistances was similar for FQs and EMB (100%, CI 92.7–100; 100%, CI 83.9–100, respectively), with a PPV of 100% (CI 64.6–100) and 100% (CI 87.9–100), respectively. Detection of SLID showed a specificity of 89.1% (CI 77.0–95.3) and a PPV of 58.3% (CI 32.0–80.7). Sensitivity for FQ-resistance detection was 100% (CI 64.6–100), whereas for SLID and EMB was 89.1% (CI 77.0–95.3) and 86.1% (CI 71.3–93.9), respectively. We detected a significant association between mutations in the rrs genes and Beijing lineage.Due to the high PPV and specificity, the MTBDRsl can be used to “rule in” XDR-TB in high risk group; the low sensitivity and NPV make confirmation by conventional DST mandatory when mutations are not identified. NPV for SLIDs is higher in Beijing strains, showing that the predictive values of the molecular tests is related to the genetic background.