Rapid Diagnosis of Infection in the Critically Ill, a Multicenter Study of Molecular Detection in Bloodstream Infections, Pneumonia, and Sterile Site Infections.
OBJECTIVE
Early identification of causative microorganism(s) in patients with severe infection is crucial to optimize antimicrobial use and patient survival. However, current culture-based pathogen identification is slow and unreliable such that broad-spectrum antibiotics are often used to insure coverage of all potential organisms, carrying risks of overtreatment, toxicity, and selection of multidrug-resistant bacteria. We compared the results obtained using a novel, culture-independent polymerase chain reaction/electrospray ionization-mass spectrometry technology with those obtained by standard microbiological testing and evaluated the potential clinical implications of this technique.


METHODS
Observational study.


METHODS
Nine ICUs in six European countries.


METHODS
Patients admitted between October 2013 and June 2014 with suspected or proven bloodstream infection, pneumonia, or sterile fluid and tissue infection were considered for inclusion.


METHODS
None.


RESULTS
We tested 616 bloodstream infection, 185 pneumonia, and 110 sterile fluid and tissue specimens from 529 patients. From the 616 bloodstream infection samples, polymerase chain reaction/electrospray ionization-mass spectrometry identified a pathogen in 228 cases (37%) and culture in just 68 (11%). Culture was positive and polymerase chain reaction/electrospray ionization-mass spectrometry negative in 13 cases, and both were negative in 384 cases, giving polymerase chain reaction/electrospray ionization-mass spectrometry a sensitivity of 81%, specificity of 69%, and negative predictive value of 97% at 6 hours from sample acquisition. The distribution of organisms was similar with both techniques. Similar observations were made for pneumonia and sterile fluid and tissue specimens. Independent clinical analysis of results suggested that polymerase chain reaction/electrospray ionization-mass spectrometry technology could potentially have resulted in altered treatment in up to 57% of patients.


CONCLUSIONS
Polymerase chain reaction/electrospray ionization-mass spectrometry provides rapid pathogen identification in critically ill patients. The ability to rule out infection within 6 hours has potential clinical and economic benefits.
1Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium. 2Division of Critical Care, University College London Hospitals NIHR Biomedical Research Centre and Bloomsbury Institute of Intensive Care Medicine, University College Hospital, London, United Kingdom. 3Department of Anesthesiology and Critical Care, Val de Grâce Military Hospital, Paris, France. 4Intensive Care Unit, Department of Anesthesiology, Pharmacology and Intensive Care, University Hospitals of Geneva, Geneva, Switzerland. 5Barts and The London School of Medicine and Dentistry, Queen Mary University of London and Barts Health NHS Trust, London, United Kingdom. 6Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Frankfurt, Frankfurt am Main, Germany. 71st Clinic of Anaesthesia and Intensive Care of Warsaw Medical University, Warsaw, Poland. 8Genomic Research Laboratory, Department of Internal Medicine, Service of Infectious Diseases, University of Geneva Hospitals, Geneva, Switzerland. 9Department of Microbiology, Saint Louis University Hospital, Paris, France. 10Abbott GmbH & Co. KG, Wiesbaden, Germany. 11Ibis Biosciences, Abbott, Carlsbad, CA.
Jean-Louis
JL
Vincent
David
D
Brealey
Nicolas
N
Libert
Nour Elhouda
NE
Abidi
Michael
M
O'Dwyer
Kai
K
Zacharowski
Malgorzata
M
Mikaszewska-Sokolewicz
Jacques
J
Schrenzel
François
F
Simon
Mark
M
Wilks
Marcus
M
Picard-Maureau
Donald B
DB
Chalfin
David J
DJ
Ecker
Rangarajan
R
Sampath
Mervyn
M
Singer
D000328:Adult; D000368:Aged; D016470:Bacteremia / Q000175:diagnosis / Q000382:microbiology*; D017848:Blood-Borne Pathogens / Q000302:isolation & purification*; D001826:Body Fluids / Q000382:microbiology; D003422:Critical Care / Q000379:methods; D016638:Critical Illness; D042241:Early Diagnosis; D005060:Europe; D005260:Female; D006090:Gram-Negative Bacteria / Q000302:isolation & purification; D006094:Gram-Positive Bacteria / Q000302:isolation & purification; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D018410:Pneumonia, Bacterial / Q000175:diagnosis / Q000382:microbiology*; D016133:Polymerase Chain Reaction / Q000379:methods*; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D013048:Specimen Handling; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*