Species-Specific Immunoassay Aids Identification of Pathogen and Tracks Infectivity in Foot Infection.

Abstract

Conventional bacterial cultures frequently fail to identify the dominant pathogen in polymicrobial foot infections, in which <i>Staphylococcus aureus</i> is the most common infecting pathogen. Previous work has shown that species-specific immunoassays may be able to identify the main pathogen in musculoskeletal infections. We sought to investigate the clinical applicability of a <i>S. aureus</i> immunoassay to accurately identify the infecting pathogen and monitor its infectivity longitudinally in foot infection. We hypothesized that this species-specific immunoassay could aid in the diagnosis of <i>S. aureus</i> and track the therapeutic response in foot infections. From July 2015 to July 2019, 83 infected foot ulcer patients undergoing surgical intervention (debridement or amputation) were recruited and blood was drawn at 0, 4, 8, and 12 weeks. Whole blood was analyzed for <i>S. aureus</i>-specific serum antibodies (mix of historic and new antibodies) and plasmablasts were isolated and cultured to quantify titers of newly synthesized antibodies (NSAs). Anti-<i>S. aureus</i> antibody titers were compared with culture results to assess their concordance in identifying <i>S. aureus</i> as the pathogen. The NSA titer changes at follow-ups were compared with wound healing status to evaluate concordance between evolving host immune response and clinically resolving or relapsing infection. Analysis of serum for anti-<i>S. aureus</i> antibodies showed significantly increased titers of 3 different anti-<i>S. aureus</i> antibodies, IsdH (<i>P</i> = .037), ClfB (<i>P</i> = .025), and SCIN (<i>P</i> = .005), in <i>S. aureus</i> culture-positive patients compared with culture-negative patients. Comparative analysis of combining antigens for <i>S. aureus</i> infection diagnosis increased the concordance further. During follow-up, changes of NSA titers against a single or combination of <i>S. aureus</i> antigens significantly correlated with clinically resolving or recurring infection represented by wound healing status. In the management of foot infection, the use of <i>S. aureus</i>-specific immunoassay may aid in diagnosis of the dominant pathogen and monitoring of the host immune response against a specific pathogen in response to treatment. Importantly, this immunoassay could detect recurrent foot infection, which may guide a surgeon's decision to intervene. Level II, prospective comparative study.