FcMBL magnetic bead-based MALDI-TOF MS rapidly identifies paediatric blood stream infections from positive blood cultures

PLoS One. 2022 Nov 22;17(11):e0276777. doi: 10.1371/journal.pone.0276777. eCollection 2022.

Abstract

Rapid identification of potentially life-threatening blood stream infections (BSI) improves clinical outcomes, yet conventional blood culture (BC) identification methods require ~24-72 hours of liquid culture, plus 24-48 hours to generate single colonies on solid media suitable for identification by mass spectrometry (MS). Newer rapid centrifugation techniques, such as the Bruker MBT-Sepsityper® IVD, replace culturing on solid media and expedite the diagnosis of BCs but frequently demonstrate reduced sensitivity for identifying clinically significant Gram-positive bacterial or fungal infections. This study introduces a protocol that utilises the broad-range binding properties of an engineered version of mannose-binding lectin linked to the Fc portion of immunoglobulin (FcMBL) to capture and enrich pathogens combined with matrix-assisted laser desorption-ionisation time-of-flight (MALDI-TOF) MS for enhanced infection identification in BCs. The FcMBL method identified 94.1% (64 of 68) of clinical BCs processed, with a high sensitivity for both Gram-negative and Gram-positive bacteria (94.7 and 93.2%, respectively). The FcMBL method identified more patient positive BCs than the Sepsityper® (25 of 25 vs 17 of 25), notably with 100% (3/3) sensitivity for clinical candidemia, compared to only 33% (1/3) for the Sepsityper®. Additionally, during inoculation experiments, the FcMBL method demonstrated a greater sensitivity, identifying 100% (24/24) of candida to genus level and 9/24 (37.5%) top species level compared to 70.8% (17/24) to genus and 6/24 to species (25%) using the Sepsityper®. This study demonstrates that capture and enrichment of samples using magnetic FcMBL-conjugated beads is superior to rapid centrifugation methods for identification of BCs by MALDI-TOF MS. Deploying the FcMBL method therefore offers potential clinical benefits in sensitivity and reduced turnaround times for BC diagnosis compared to the standard Sepsityper® kit, especially for fungal diagnosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacteremia* / diagnosis
  • Bacteremia* / microbiology
  • Bacteriological Techniques / methods
  • Blood Culture
  • Child
  • Gram-Positive Bacteria
  • Humans
  • Magnetic Phenomena
  • Sepsis*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods

Grants and funding

K.A.K. and N.K. received funding from The BENECARE Foundation, Liechtenstein who have financially supported this work with a donation. T.J.E. was supported by the Imperial College Borland Fellowship in Mathematics. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.