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


BACKGROUND
Deutsches Register Klinischer Studien (DRKS) DRKS00005684.
Institute of Medical Microbiology and Hygiene, University of Tübingen, Tübingen, Germany; German Centre for Infection Research (DZIF), partner site Tübingen, Tübingen, Germany.
Berit
B
Schulte
Heart and Diabetes Center North Rhine-Westphalia, Institute for Laboratory- and Transfusion Medicine, University Hospital of the Ruhr-University Bochum, Bad Oeynhausen, Germany; Heart and Diabetes Center North Rhine-Westphalia, Clinic for Thoracic and Cardiovascular Surgery, University Hospital of the Ruhr-University Bochum, Bad Oeynhausen, Germany.
Holm
H
Eickmeyer
German Centre for Infection Research (DZIF), partner site Tübingen, Tübingen, Germany; Department of Anesthesiology and Intensive Care Medicine, Tübingen University Hospital, Tübingen, Germany.
Alexandra
A
Heininger
University Hospital Jena, Institute of Medical Microbiology, Jena, Germany.
Stephanie
S
Juretzek
University Hospital Jena, Institute of Medical Microbiology, Jena, Germany.
Matthias
M
Karrasch
Université Libre de Bruxelles, Laboratory of Microbiology, Bruxelles, Belgium.
Olivier
O
Denis
Université Libre de Bruxelles, Laboratory of Microbiology, Bruxelles, Belgium.
Sandrine
S
Roisin
University Hospital Jena, Center for Infectious Diseases and Infection Control, and Center for Sepsis Care and Control, Jena, Germany.
Mathias W
MW
Pletz
Curetis AG, Holzgerlingen, Germany.
Matthias
M
Klein
Curetis AG, Holzgerlingen, Germany.
Sandra
S
Barth
Curetis AG, Holzgerlingen, Germany.
Gerd H
GH
Lüdke
Curetis AG, Holzgerlingen, Germany.
Anne
A
Thews
Department of Pneumology, Institut Clinic del Tórax, Hospital Clinic of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona (UB) - Ciber de Enfermedades Respiratorias (Ciberes), Barcelona, Spain.
Antoni
A
Torres
Department of Pneumology, Institut Clinic del Tórax, Hospital Clinic of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona (UB) - Ciber de Enfermedades Respiratorias (Ciberes), Barcelona, Spain.
Catia
C
Cillóniz
University Hospital Jena, Institute of Medical Microbiology, Jena, Germany; University Hospital Jena, Center for Infectious Diseases and Infection Control, and Center for Sepsis Care and Control, Jena, Germany.
Eberhard
E
Straube
Institute of Medical Microbiology and Hygiene, University of Tübingen, Tübingen, Germany; German Centre for Infection Research (DZIF), partner site Tübingen, Tübingen, Germany.
Ingo B
IB
Autenrieth
University Hospital Jena, Institute of Medical Microbiology, Jena, Germany; University Hospital Jena, Center for Infectious Diseases and Infection Control, and Center for Sepsis Care and Control, Jena, Germany.
Peter M
PM
Keller
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001419:Bacteria / Q000235:genetics / Q000302:isolation & purification*; D005260:Female; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction / Q000379:methods*; D011014:Pneumonia / Q000382:microbiology*; D055815:Young Adult