Detection of pneumonia associated pathogens using a prototype multiplexed pneumonia test in hospitalized patients with severe pneumonia

PLoS One. 2014 Nov 14;9(11):e110566. doi: 10.1371/journal.pone.0110566. eCollection 2014.

Abstract

Severe pneumonia remains an important cause of morbidity and mortality. Polymerase chain reaction (PCR) has been shown to be more sensitive than current standard microbiological methods--particularly in patients with prior antibiotic treatment--and therefore, may improve the accuracy of microbiological diagnosis for hospitalized patients with pneumonia. Conventional detection techniques and multiplex PCR for 14 typical bacterial pneumonia-associated pathogens were performed on respiratory samples collected from adult hospitalized patients enrolled in a prospective multi-center study. Patients were enrolled from March until September 2012. A total of 739 fresh, native samples were eligible for analysis, of which 75 were sputa, 421 aspirates, and 234 bronchial lavages. 276 pathogens were detected by microbiology for which a valid PCR result was generated (positive or negative detection result by Curetis prototype system). Among these, 120 were identified by the prototype assay, 50 pathogens were not detected. Overall performance of the prototype for pathogen identification was 70.6% sensitivity (95% confidence interval (CI) lower bound: 63.3%, upper bound: 76.9%) and 95.2% specificity (95% CI lower bound: 94.6%, upper bound: 95.7%). Based on the study results, device cut-off settings were adjusted for future series production. The overall performance with the settings of the CE series production devices was 78.7% sensitivity (95% CI lower bound: 72.1%) and 96.6% specificity (95% CI lower bound: 96.1%). Time to result was 5.2 hours (median) for the prototype test and 43.5 h for standard-of-care. The Pneumonia Application provides a rapid and moderately sensitive assay for the detection of pneumonia-causing pathogens with minimal hands-on time.

Trial registration: Deutsches Register Klinischer Studien (DRKS) DRKS00005684.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bacteria / genetics
  • Bacteria / isolation & purification*
  • Female
  • Hospitalization
  • Humans
  • Male
  • Middle Aged
  • Multiplex Polymerase Chain Reaction / methods*
  • Pneumonia / microbiology*
  • Young Adult

Associated data

  • DRKS/DRKS00005684

Grant support

The devices, CRO, and conventional microbial testing were funded by Curetis (www.curetis.com). Local study personnel were funded by their institutions (University Hospital Jena, University Hospital Tubingen, University Hospital of the Ruhr-University Bochum, Université Libre de Bruxelles, Hospital Clinic of Barcelona). This work was supported by the European Union Seventh Framework Program [grant agreement number 241446 to Jan Weile, Ruhr-University Bochum], and the BMBF Innovation Award Medical Technology [grant agreement number EZ1113B to Jan Weile]. M.W.P. was supported by a grant from the German Ministry of Education and Research (Bundesministerium für Bildung und Forschung), grant number 01KI1204. The funder Curetis was involved in study design, data collection and analysis, as well as in the decision to publish. Curetis staff (see authors' affiliations) was involved in manuscript preparation.