title: Bacteriophage assays for rifampicin resistance detection in Mycobacterium tuberculosis: updated meta-analysis.
abstract: OBJECTIVE
  To update a previously reported meta-analysis of evidence regarding the diagnostic accuracy and performance characteristics of commercial and non-commercial phage-based assays for the detection of rifampicin (RMP) resistant tuberculosis (TB). DESIGN AND OUTCOMES: We conducted a systematic review and meta-analysis of test accuracy using bivariate random effects regression and hierarchical summary receiver operating characteristics (HSROC) analysis. Tests included the commercial FASTPlaque assays, luciferase reporter phage (LRP) assays, and in-house phage amplification tests. Sensitivity and specificity for RMP resistance were the main outcomes.
  
  
  RESULTS
  By updating previous literature searches, a total of 31 studies (with 3085 specimens) were included in this meta-analysis. Evaluations of commercial phage amplification assays yielded more variable estimates of sensitivity (range 81-100%) and specificity (range 73-100%) compared to evaluations of in-house amplification assays (sensitivity range 88-100%, specificity range 84-100%). LRP evaluations yielded the most consistent estimates of diagnostic accuracy, with seven of eight studies reporting 100% sensitivity and four of eight reporting 100% specificity. Estimates of accuracy failed to capture a major failing of the commercial assay, i.e., the rate of contaminated and indeterminate results. These ranged from 3% to 36% in studies looking at direct detection of RMP resistance from patient specimens (mean 20%).
  
  
  CONCLUSIONS
  Phage-based assays will require further development to maximise interpretable results and reduce technical failures. Once technical issues are resolved, impact on patient-important outcomes and cost-effectiveness need to be determined to inform policy for widespread use.
authors.affiliation: Department of Epidemiology, McGill University, Montreal, Quebec, Canada. madhukar.pai@mcgill.ca
authors.forename: J
authors.initials: J
authors.lastname: Minion
authors.forename: M
authors.initials: M
authors.lastname: Pai
mesh_terms: D000904:Antibiotics, Antitubercular / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D006801:Humans; D009160:Mycobacteriophages / Q000502:physiology*; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000821:virology*; D012293:Rifampin / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis* / Q000382:microbiology
chemical_list: D000904:Antibiotics, Antitubercular; D012293:Rifampin