@article{5674b0b8ea7b4164aed1dcf24c1b3179,
title = "Moderate positive predictive value of a multiplex real-time PCR on whole blood for pathogen detection in critically ill patients with sepsis",
abstract = "A novel multiplex real-time PCR for bloodstream infections (BSI-PCR) detects pathogens directly in blood. This study aimed at determining the positive predictive value (PPV) of BSI-PCR in critically ill patients with sepsis. We included consecutive patients with presumed sepsis upon admission to the intensive care unit (ICU). The multiplexed BSI-PCR included 17 individual PCRs for a broad panel of species- and genus-specific DNA targets. BSI-PCR results were compared with a reference diagnosis for which plausibility of infection and causative pathogen(s) had been prospectively assessed by trained observers, based on available clinical and microbiological evidence. PPV and false positive proportion (FPP) were calculated. Clinical plausibility of discordant positive results was adjudicated by an expert panel. Among 325 patients, infection likelihood was categorized as confirmed, uncertain, and ruled out in 210 (65%), 88 (27%), and 27 (8%) subjects, respectively. BSI-PCR identified one or more microorganisms in 169 (52%) patients, of whom 104 (61%) had at least one detection in accordance with the reference diagnosis. Discordant positive PCR results were observed in 95 patients, including 30 subjects categorized as having an {"}unknown{"} pathogen. Based on 5525 individual PCRs yielding 295 positive results, PPV was 167/295 (57%) and FPP was 128/5525 (2%). Expert adjudication of the 128 discordant PCR findings resulted in an adjusted PPV of 68% and FPP of 2%. BSI-PCR was all-negative in 156 patients, including 79 (51%) patients in whom infection was considered ruled out. BSI-PCR may complement conventional cultures and expedite the microbiological diagnosis of sepsis in ICU patients, but improvements in positive predictive value of the test are warranted before its implementation in clinical practice can be considered.",
keywords = "Diagnostic research, Pathogen detection, Sepsis, Intensive care, Multiplex real-time PCR, INFECTIONS",
author = "{van de Groep}, Kirsten and Bos, {Martine P.} and Varkila, {Meri R. J.} and Savelkoul, {Paul H. M.} and Ong, {David S. Y.} and Derde, {Lennie P. G.} and Juffermans, {Nicole P.} and Bonten, {Marc J. M.} and Cremer, {Olaf L.} and {de Beer}, {Friso M.} and Bos, {Lieuwe D. J.} and Glas, {Gerie J.} and Hoogendijk, {Arie J.} and {van Hooijdonk}, {Roosmarijn T. M.} and Janneke Horn and Huson, {Mischa A.} and {van der Poll}, Tom and Schouten, {Laura R. A.} and Brendon Scicluna and Schultz, {Marcus J.} and Marleen Straat and {van Vught}, {Lonneke A.} and Luuk Wieske and Wiewel, {Maryse A.} and Esther Witteveen and Frencken, {Jos F.} and Klouwenberg, {Peter M. C. Klein} and Koster-Brouwer, {Maria E.} and Varkila, {Meri R. J.} and Verboom, {Diana M.} and {MARS Consortium}",
note = "Funding Information: We thank the MARS consortium, including participating ICUs and (research) nurses for their logistical support and help in data acquisition for this project. We thank Anna Rubenjan and Christel Gazenbeek for sample processing and performing all BSI-PCR assays. Members of the MARS Consortium: Amsterdam University Medical Centers, University of Amsterdam (NL): Friso M. de Beer, MD; Lieuwe D. J. Bos, MD, PhD; Gerie J. Glas, MD; Arie J. Hoogendijk, PhD; Roosmarijn T. M. van Hooijdonk, MD, PhD; Janneke Horn MD, PhD; Mischa A. Huson, MD, PhD; Nicole P. Juffermans, MD, PhD; Tom van der Poll, MD, PhD; Laura R. A. Schouten, MD; Brendon Scicluna, PhD; Marcus J. Schultz, MD, PhD; Marleen Straat, MD, PhD; Lonneke A. van Vught, MD, PhD; Luuk Wieske, MD, PhD; Maryse A. Wiewel, MD, PhD; Esther Witteveen, MD, PhD. University Medical Center Utrecht, Utrecht University (NL) : Marc J.M. Bonten, MD, PhD; Olaf L. Cremer, MD, PhD; Jos F. Frencken, MD, PhD; K. van de Groep, MD; Peter M.C. Klein Klouwenberg, MD, PharmD, PhD; Maria E. Koster-Brouwer, MSc; David S.Y. Ong, MD, PharmD, PhD; Meri R.J. Varkila MD; Diana M. Verboom, MD. Work package ?Pathogen Detection? : Microbiome, Amsterdam (NL): Martine P. Bos, PhD; Paul H.M. Savelkoul, PhD; Arnold Catsburg. Biocartis, Mechelen (BE): Bart van Meerbergen, PhD; Sarah Berghmans, BSc. Radboud University Nijmegen (NL): Dimitri Diavatopoulos, PhD; Marrit Habets, MSc; Eveline Snelders, PhD; Jan Zoll, PhD. Checkpoints, Wageningen (NL): Pieter Vos, PhD; Aneta Karczmarek, PhD; Philips, Eindhoven (NL) : Sigi Neerken, PhD; Paul van de Wiel, PhD. Publisher Copyright: {\textcopyright} 2019, The Author(s).",
year = "2019",
month = oct,
doi = "10.1007/s10096-019-03616-w",
language = "English",
volume = "38",
pages = "1829--1836",
journal = "European Journal of Clinical Microbiology & Infectious Diseases",
issn = "0934-9723",
publisher = "Springer, Cham",
number = "10",
}