Capacity of Abbott RealTime MTB RIF/INH to detect rifampicin- and isoniazid-resistant tuberculosis.

Abbott RealTime MTB RIF/INH Resistance (RT RIF/INH) is a new assay for the detection of resistance to rifampicin (RIF) and isoniazid (INH) in tuberculosis (TB) patients. To evaluate the capacity of RT RIF/INH to detect resistance-associated mutations in target genes. A total of 311 Mycobacterium tuberculosis strains that had been pre-characterised using genotypic methods (GenoType® MTBDRplus, Sanger sequencing) and phenotypic drug susceptibility testing were subjected to DNA extraction on Abbott m2000sp and analysed using RT RIF/INH. Detection of heteroresistant mutations was studied with artificial mixtures of wild-type and mutant DNA. Overall sensitivity and specificity values of RT RIF/INH to detect resistance were respectively 87.2% and 98.4% for RIF and respectively 90.1% and 99.2% for INH. The capacity of RT RIF/INH to detect specific mutations was 100% for katG, inhA and frequent rpoB mutations, and 76% for rare rpoB mutations. Among the latter, two rare mutations were not consistently detected. With heteroresistant samples, RT RIF/INH reported resistance if samples contained at least 75-90% of mutant DNA. RT RIF/INH is a reliable high-throughput assay for the detection of RIF and INH resistance markers. The ability to detect INH resistance also may be of benefit in areas with high rates of INH-resistant, non-multidrug-resistant TB. .

Diagnostic accuracy of the Xpert® MTB/RIF cycle threshold level to predict smear positivity: a meta-analysis.

SETTING: Xpert® MTB/RIF is the most widely used molecular assay for rapid diagnosis of tuberculosis (TB). The number of polymerase chain reaction cycles after which detectable product is generated (cycle threshold value, CT) correlates with the bacillary burden.OBJECTIVE To investigate the association between Xpert CT values and smear status through a systematic review and individual-level data meta-analysis. DESIGN: Studies on the association between CT values and smear status were included in a descriptive systematic review. Authors of studies including smear, culture and Xpert results were asked for individual-level data, and receiver operating characteristic curves were calculated. RESULTS: Of 918 citations, 10 were included in the descriptive systematic review. Fifteen data sets from studies potentially relevant for individual-level data meta-analysis provided individual-level data (7511 samples from 4447 patients); 1212 patients had positive Xpert results for at least one respiratory sample (1859 samples overall). ROC analysis revealed an area under the curve (AUC) of 0.85 (95%CI 0.82-0.87). Cut-off CT values of 27.7 and 31.8 yielded sensitivities of 85% (95%CI 83-87) and 95% (95%CI 94-96) and specificities of 67% (95%CI 66-77) and 35% (95%CI 30-41) for smear-positive samples. CONCLUSION: Xpert CT values and smear status were strongly associated. However, diagnostic accuracy at set cut-off CT values of 27.7 or 31.8 would not replace smear microscopy. How CT values compare with smear microscopy in predicting infectiousness remains to be seen.