Performance of PCR/Electrospray Ionization-Mass Spectrometry on Whole Blood for Detection of Bloodstream Microorganisms in Patients with Suspected Sepsis

Kristoffer Strålin, Richard E. Rothman, Volkan Özenci, Kieron Barkataki, David Brealey, Neelam Dhiman, Lara Poling, Michael C. Kurz, Ajit P. Limaye, Frank LoVecchio, Kristin Lowery, Loren G. Miller, Gregory J. Moran, J. Scott Overcash, Amisha Parekh, W. Frank Peacock, Emanuel P. Rivers, Matthew Sims, Amy M. Stubbs, Martin SundqvistMåns Ullberg, Karen C. Carroll

Research output: Contribution to journalArticlepeer-review

Abstract

Blood culture (BC) often fails to detect bloodstream microorganisms in sepsis. However, molecular diagnostics hold great potential. The molecular method PCR/electrospray ionization-mass spectrometry (PCR/ESI-MS) can detect DNA from hundreds of different microorganisms in whole blood. The aim of the present study was to evaluate the performance of this method in a multicenter study including 16 teaching hospitals in the United States (n = 13) and Europe (n = 3). First, on testing of 2,754 contrived whole blood samples, with or without spiked microorganisms, PCR/ESI-MS produced 99.1% true-positive and 97.2% true-negative results. Second, among 1,460 patients with suspected sepsis (sepsis-2 definition), BC and PCR/ESI-MS on whole blood were positive in 14.6% and 25.6% of cases, respectively, with the following result combinations: BC positive and PCR/ESI-MS negative, 4.3%; BC positive and PCR/ESI-MS positive, 10.3%; BC negative and PCR/ESI-MS positive, 15.3%; and BC negative and PCR/ESI-MS negative, 70.1%. Compared with BC, PCR/ESI-MS showed the following sensitivities (coagulase-negative staphylococci not included): Gram-positive bacteria, 58%; Gram-negative bacteria, 78%; and Candida species, 83%. The specificities were 94% for all individual species. Patients who had received prior antimicrobial medications (n = 603) had significantly higher PCR/ESI-MS positivity rates than patients without prior antimicrobial treatment—31% versus 22% (P 0.0001)—with pronounced differences for Gram-negative bacteria and Candida species. In conclusion, PCR/ESI-MS showed excellent performance on contrived samples. On clinical samples, it showed high specificities, moderately high sensitivities for Gram-negative bacteria and Candida species, and elevated positivity rates during antimicrobial treatment. These promising results encourage further development of molecular diagnostics to be used with whole blood for detection of bloodstream microorganisms in sepsis.

Original languageEnglish (US)
Article numbere01860
JournalJournal of clinical microbiology
Volume58
Issue number9
DOIs
StatePublished - Sep 2020
Externally publishedYes

Keywords

  • Bacteremia
  • Direct detection
  • PCR/ESI-MS
  • Sepsis

ASJC Scopus subject areas

  • Microbiology (medical)

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