1. Evaluation of a multiplex-qPCR for paediatric pleural empyema-An observational study in hospitalised children.
- Author
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Jacobson J, Fabri L, Osowicki J, Shanthikumar S, Costa AM, Ortika B, Wee-Hee A, Pragassen M, Gatt C, Gonis G, Nguyen C, Rozen T, Teague W, Buttery J, Clifford V, Mulholland K, Steer A, Ranganathan S, Daley A, Dunne E, and Satzke C
- Subjects
- Humans, Child, Preschool, Male, Female, Child, Haemophilus influenzae genetics, Haemophilus influenzae isolation & purification, Staphylococcus aureus genetics, Staphylococcus aureus isolation & purification, Staphylococcus aureus drug effects, Streptococcus pneumoniae genetics, Streptococcus pneumoniae isolation & purification, Streptococcus pyogenes genetics, Streptococcus pyogenes isolation & purification, Infant, Hospitalization, Anti-Bacterial Agents therapeutic use, Sensitivity and Specificity, DNA, Bacterial genetics, Empyema, Pleural microbiology, Empyema, Pleural drug therapy, Empyema, Pleural diagnosis, Multiplex Polymerase Chain Reaction methods
- 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., Competing Interests: CS, EM, SR, CN and JJ are investigators on a Merck Investigator Studies Program grant funded by MSD on pneumococcal serotype epidemiology in children with empyema. CS, ED, CDN and EM are investigators on a clinical research collaboration with Pfizer unrelated to this work. ED is currently employed by Pfizer. The other authors declare that they have no competing interests., (Copyright: © 2024 Jacobson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2024
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