Use of mycobacteriophage quantitative PCR on MGIT broths for a rapid tuberculosis antibiogram

J Clin Microbiol. 2014 May;52(5):1523-8. doi: 10.1128/JCM.03637-13. Epub 2014 Feb 26.

Abstract

Phenotypic culture-based drug susceptibility testing (DST) for Mycobacterium tuberculosis is a valuable tool to identify four to six active drugs for individualized multidrug-resistant (MDR) tuberculosis (TB) regimens. Current culture-based methods are slow, however; therefore, we evaluated a rapid mycobacteriophage-based quantitative PCR (qPCR) assay for use directly on M. tuberculosis-positive MGIT broths. We compared phage qPCRs, using a simple cutoff of 3 for the ΔCq value (where Cq is quantification cycle, and ΔCq is calculated as the Cq of starting phage minus the Cq of TB isolates in drug-containing medium), on 325 clinical M. tuberculosis MGIT broth cultures versus the respective subcultured isolates tested by agar proportion. The median accuracy for the 13 drugs/concentrations tested was 98%, with most discrepancies being false-resistant results. Evaluation of phage qPCR on greater numbers of resistant strains of 393 isolates grown on Löwenstein-Jensen medium showed similar findings, with a median accuracy, sensitivity, and specificity of 97%, 90%, and 99%, respectively. This rapid culture-based DST methodology can be performed for any drug on TB-positive MGIT broths, with a specimen-to-antibiogram turnaround time of approximately 23.9 days, compared with waiting 58.6 days for isolate growth on solid medium followed by agar proportion DST.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antitubercular Agents / pharmacology
  • Culture Media / metabolism
  • Humans
  • Microbial Sensitivity Tests / methods*
  • Mycobacteriophages / drug effects
  • Mycobacteriophages / genetics*
  • Mycobacterium tuberculosis / drug effects
  • Mycobacterium tuberculosis / virology*
  • Polymerase Chain Reaction / methods
  • Sensitivity and Specificity
  • Tuberculosis, Multidrug-Resistant / drug therapy
  • Tuberculosis, Multidrug-Resistant / microbiology
  • Tuberculosis, Multidrug-Resistant / virology

Substances

  • Antitubercular Agents
  • Culture Media