Evaluation of a multiplex-qPCR for paediatric pleural empyema-An observational study in hospitalised children

PLoS One. 2024 Jun 25;19(6):e0304861. doi: 10.1371/journal.pone.0304861. eCollection 2024.

Abstract

Pleural empyema is a serious complication of pneumonia in children. Negative bacterial cultures commonly impede optimal antibiotic therapy. To improve bacterial identification, we developed a molecular assay and evaluated its performance compared with bacterial culture. Our multiplex-quantitative PCR to detect Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus and Haemophilus influenzae was assessed using bacterial genomic DNA and laboratory-prepared samples (n = 267). To evaluate clinical performance, we conducted the Molecular Assessment of Thoracic Empyema (MATE) observational study, enrolling children hospitalised with empyema. Pleural fluids were tested by bacterial culture and multiplex-qPCR, and performance determined using a study gold standard. We determined clinical sensitivity and time-to-organism-identification to assess the potential of the multiplex-qPCR to reduce the duration of empiric untargeted antibiotic therapy. Using spiked samples, the multiplex-qPCR demonstrated 213/215 (99.1%) sensitivity and 52/52 (100%) specificity for all organisms. During May 2019-March 2023, 100 children were enrolled in the MATE study; median age was 3.9 years (IQR 2-5.6). A bacterial pathogen was identified in 90/100 (90%) specimens by multiplex-qPCR, and 24/100 (24%) by bacterial culture (P <0.001). Multiplex-qPCR identified a bacterial cause in 68/76 (90%) culture-negative specimens. S. pneumoniae was the most common pathogen, identified in 67/100 (67%) specimens. We estimate our multiplex-qPCR would have reduced the duration of untargeted antibiotic therapy in 61% of cases by a median 20 days (IQR 17.5-23, range 1-55). Multiplex-qPCR significantly increased pathogen detection compared with culture and may allow for reducing the duration of untargeted antibiotic therapy.

Publication types

  • Observational Study

MeSH terms

  • Anti-Bacterial Agents / therapeutic use
  • Child
  • Child, Preschool
  • DNA, Bacterial / genetics
  • Empyema, Pleural* / diagnosis
  • Empyema, Pleural* / drug therapy
  • Empyema, Pleural* / microbiology
  • Female
  • Haemophilus influenzae / genetics
  • Haemophilus influenzae / isolation & purification
  • Hospitalization
  • Humans
  • Infant
  • Male
  • Multiplex Polymerase Chain Reaction* / methods
  • Sensitivity and Specificity
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / genetics
  • Staphylococcus aureus / isolation & purification
  • Streptococcus pneumoniae / genetics
  • Streptococcus pneumoniae / isolation & purification
  • Streptococcus pyogenes / genetics
  • Streptococcus pyogenes / isolation & purification

Substances

  • Anti-Bacterial Agents
  • DNA, Bacterial

Grants and funding

Support for this work included funding from the Murdoch Children’s Research Institute. The Murdoch Children’s Research Institute was supported by the Victorian Government’s Operational Infrastructure Support Program. The funders had no role in study design, collection, analysis and interpretation of data, or manuscript preparation.