Pathogen-specific and Prognosis of S. aureus infection in Orthopaedic Surgery

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Abstract S. aureus is the major pathogens in periprosthetic joint infection (>50%) and diabetic foot ulcers (DFU) (46- 68%). Most infected foot ulcer patients undertake initial pursuit of foot salvage therapy, a strategy that features debridement followed by 6 weeks long intravenous antibiotic treatment. With this approach, some patients will retain their feet while others will be placed at higher risk of further spread of infection. Currently, there is no sensitive and specific diagnostic tool for monitoring a pathogen’s ongoing infection and providing prognostic measure of success in foot salvage effort. Successful development of such diagnostic tool will critically aid the clinician’s decision to preserve or amputate the infected part of the foot. The host humoral immune response can be assessed by measuring pathogen- specific newly synthesized antibodies (NSA) produced by serum or antibody secreting cells (ASC) that emerge into blood only during active infection. We have developed novel ASC assay for S. aureus infection and have applied this immunoassay to diagnose and monitor the infectivity of S. aureus in foot ulcer. We postulate that the changes of NSA in the blood samples provides useful metrics in monitoring pathogenicity of S. aureus to characterize treatment responses, and early detection of initial treatment failure, which may lead to recurrent infection. These information will enable us to accurately monitor the efficacy of antibiotics treatment and to make timely surgical decision. Therefore, follow up studies are warranted to test the hypotheses that: 1) the ASC assay could serve as a reliable diagnostic tool for S. aureus infection at the initial presentation of infected foot ulcer and 2) the ASC assay provides a measure of treatment response and prognosis of clinical outcome. To test this, we propose two specific aims. In Aim 1, we will measure the sensitivity and specificity of immunoassay to diagnose S. aureus infection in patients with monomicrobial (S. aureus only) and polymicrobial (S. aureus and one or more other bacterial species) infected foot ulcer. Patients with clinical symptoms and signs of foot ulcer infection will be recruited from the PI’s clinical practice and blood samples will be processed for S. aureus specific antibodies. In Aim 2, we will assess the ability of immunoassay to effectively monitor pathogenicity of S. aureus to characterize treatment response and predict clinical outcome. We will obtain blood samples at 4, 8, and 12-weeks to investigate if clinical presentation of healing versus non- healing ulcers correlates with changes of NSA. We will also investigate if elevated NSA level against S. aureus at 8 weeks (2 weeks after completion of 6 weeks course of antibiotics) can predict a persistent or recurrent infection. The novel immunoassay may serve as an important diagnostic and prognostic tools for monitoring S. aureus infection in foot ulcer. The proposed research is needed to formally confirm these initial observations towards novel interventions for infected foot ulcer patients.