title: Pyrosequencing for the rapid detection of rifampicin resistance in Mycobacterium tuberculosis: a meta-analysis.
abstract: BACKGROUND
  Multidrug-resistant tuberculosis is a major threat to the control of tuberculosis and to public health. Whereas most conventional methods of drug susceptibility testing (DST) are precise but time consuming, pyrosequencing is a rapid, high-throughput technique.
  
  
  OBJECTIVE
  To conduct a meta-analysis to evaluate the overall accuracy of pyrosequencing for the detection of rifampicin (RMP) resistance.
  
  
  METHODS
  We searched PubMed, Web of Science, Elsevier and BIOSIS databases according to a written protocol and explicit study selection criteria. A summary receiver operating characteristic curve (SROC) and Cochrane (Q*) index were calculated to perform this meta-analysis using Meta-Disc software.
  
  
  RESULTS
  Twelve studies involving 594 specimens with RMP resistance and 793 RMP-susceptible specimens met the inclusion criteria. Of these, 11 were based on Mycobacterium tuberculosis clinical isolates. The overall sensitivity and specificity were estimated at respectively 0.94 (95%CI 0.92-0.96) and 0.98 (95%CI 0.97-0.99). The area under the SROC curve was 0.99 and the Cochrane (Q*) index was 0.96. For clinical specimens, the overall sensitivity and specificity estimates were respectively 0.89 (range 0.52-1.00) and 0.99 (range 0.95-1.00).
  
  
  CONCLUSIONS
  This meta-analysis shows that pyrosequencing is a highly sensitive and specific tool for the detection of RMP resistance in M. tuberculosis. The pyrosequencing assay is conducted in a high-throughput format, with a turnaround time of <2 h, making it substantially faster than conventional DST methods. We propose that pyrosequencing applied directly to clinical specimens instead of M. tuberculosis isolates could be of greater clinical value.
authors.affiliation: Tongji University School of Medicine, Shanghai, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Guo
authors.forename: R-J
authors.initials: RJ
authors.lastname: Zheng
authors.forename: C-T
authors.initials: CT
authors.lastname: Zhu
authors.forename: L-L
authors.initials: LL
authors.lastname: Zou
authors.forename: J-F
authors.initials: JF
authors.lastname: Xiu
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: Z-Y
authors.initials: ZY
authors.lastname: Hu
mesh_terms: D000904:Antibiotics, Antitubercular / Q000494:pharmacology; D024881:Drug Resistance, Bacterial; D057166:High-Throughput Screening Assays / Q000379:methods; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods*; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D012293:Rifampin / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D013997:Time Factors
chemical_list: D000904:Antibiotics, Antitubercular; D012293:Rifampin