Preliminary Exploration on the Serum Biomarkers of Bloodstream Infection with Carbapenem-resistant Klebsiella Pneumoniae Based on Mass Spectrometry

Background: Carbapenem-resistant K. pneumoniae (CRKP) bloodstream infections (BSI) must be rapidly identified to improve patient survival rates. This study investigated a new mass spectrometry-based method for improving the identification of CRKP BSI and explored potential biomarkers that could differentiate CRKP BSI from sensitive.

Methods: Mouse models of BSI were first established. MALDI-TOF MS was then used to profile serum peptides in CRKP BSI versus normal samples before applying BioExplorer software to establish a diagnostic model to distinguish CRKP from normal. The diagnostic value of the model was then tested against 32 clinical CRKP BSI and 27 healthy serum samples. Finally, the identities of the polypeptides used to establish the diagnostic model were determined by secondary mass spectrometry.

Results: 107 peptide peaks were shared between the CRKP and normal groups, with 18 peaks found to be differentially expressed. Five highly expressed peptides in the CRKP group (m/z 1349.8, 2091.3, 2908.2, 4102.1, and 8129.5) were chosen to establish a diagnostic model. The accuracy, specificity and sensitivity of the model were determined as 79.66%, 81.48%, and 78.12%, respectively. Secondary mass spectrometry identified the Fibrinogen alpha chain (FGA), Inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) and Serum amyloid A-2 protein (SAA2) as the source of the 5 serum peptides.

Conclusions: We successfully established a serum peptide-based diagnostic model that distinguished clinical CRKP BSI samples from normal healthy controls. The application of MALDI-TOF MS to measure serum peptides, therefore, represents a promising approach for early BSI diagnosis of BSI, especially for multidrug-resistant bacteria where identification is urgent.