Development and evaluation of a multiplex quantitative polymerase chain reaction assay for detecting bacteria associated with lower respiratory tract infection

Int J Infect Dis. 2022 Sep:122:202-211. doi: 10.1016/j.ijid.2022.05.052. Epub 2022 May 26.

Abstract

Objectives: This study aimed to establish a multiplex quantitative polymerase chain reaction (MQ-PCR) assay for 12 bacterial pathogens found in lower respiratory tract infection (LRTI) and to evaluate its performance in a cohort of 211 patients with LRTI.

Methods: The study was divided into two stages: a pilot study to establish the methodology and a clinical validation study to evaluate its performance. In the pilot study, we established the MQ-PCR and analyzed its performance regarding limits of detection, reproducibility, specificity, and efficiency. In the clinical validation study, we obtained 211 sputum and/or bronchoalveolar lavage fluid (BALF) samples and detected pathogens by MQ-PCR. The MQ-PCR time was 3 h from sample collection to complete pathogen detection.

Results: The limit of detection was 1000 copies/ml, and the maximum efficiency was >95%. When cutoffs of ≥105 copies/ml in sputum and ≥104 copies/ml in BALF were applied, the sensitivity, specificity, and positive and negative predictive values of the MQ-PCR were 77% (95% confidence interval [CI] 67-88%), 94% (95% CI 93-95%), 25% (95% CI 19-31%), and 99% (95% CI 99-100%), respectively.

Conclusions: This study demonstrates that the new MQ-PCR assay is time-saving, more effective and sensitive, and brings us closer to mainstream adoption of quantitative molecular detection of bacteria.

Keywords: Bacterial load; Bacterial pathogens; Lower respiratory tract infection; MQ-PCR.

MeSH terms

  • Bacteria / genetics
  • Humans
  • Multiplex Polymerase Chain Reaction* / methods
  • Pilot Projects
  • Reproducibility of Results
  • Respiratory Tract Infections* / diagnosis
  • Respiratory Tract Infections* / microbiology
  • Sensitivity and Specificity