GenoType MTBDRsf Line Probe Assay Shortens Time to Diagnosis of Extensively Drug-Resistant Tuberculosis in a High-Throughput Diagnostic Laboratory

摘要

Rationale. Conventional culture-based drug susceptibility testing (DST) for the second-line antituberculosis drugs is slow, leading to diagnostic delay with associated exacerbation of transmission, amplification of resistance, and increased mortality. Objectives: To assess the diagnostic performance of the GenoType MTBDRs/ line probe assay (LPA) for the rapid detection of mutations conferring resistance to ofloxacin (OFX), amikacin (AMK), and eth-ambutol and to determine the impact of implementation on the turnaround time in a high-throughput diagnostic laboratory. Methods: Six hundred and fifty-seven direct patient acid-fast bacilli smear-positive specimens resistant to isoniazid, rifampin, or both according to the GenoType MTBDRplus assay were consecutively tested, using the GenoType MTBDRs/ LPA. The diagnostic performance was assessed relative to the "gold standard" culture-based method, and the laboratory turnaround times for both methods were determined. Measurements and Main Results: A total of 516 of 657 patient specimens had valid results for both tests. The sensitivity for detecting OFX, AMK, and extensive drug resistance, using the GenoType MTBDRs/ LPA, was 90.7% (95% confidence interval [CI], 80.1-96.0%), 100% (95% Cl, 91.8-100%), and 92.3% (95% Cl, 75.9-97.9%), respectively, and the specificity for detection was 98.1% (95% CI, 96.3-99.0%), 99.4% (95% Cl, 98.2-99.8%), and 99.6% (95% CI, 98.5-99.9%), respectively. Implementation of this test significantly reduced the turnaround time by 93.3% (P < 0.001), calculated from the date that the specimen was received at the laboratory to reporting second-line results. In addition, a significant increase in diagnostic yield of 20.1% and 19.3% (P < 0.001) for OFX and AMK resistance, respectively, was obtained for isolates that were either contaminated or had lost viability. Conclusions: The GenoType MTBDRs/ LPA is a rapid and reliable DST that can be easily incorporated into the diagnostic algorithm. This assay significantly improved diagnosticyield (P < 0.001) while simultaneously decreasing diagnostic delay for reporting second-line DST. The rapid dissemination of second-line DST results will guide initiation of appropriate treatment, thereby reducing transmission and improving treatment outcome.