Advancing Diagnostics For Pediatric Cerebrospinal Fluid Shunt Infection

Pediatric cerebrospinal fluid (CSF) shunt infection affects thousands of children each year and leads to neurologic morbidity for patients as well as significant medical resource utilization. Identifying these infections swiftly can decrease resource utilization and potentially limit morbidity, however, current diagnostic modalities have many limitations and may only identify two-thirds of infections accurately. There is a critical need to identify new diagnostics that overcome current limitations of microbial testing; therefore, we created a rat model of CSF shunt infection to investigate the utility of CSF biomarkers for the diagnosis of shunt infection. Initial studies demonstrated differentially expressed proteins in CSF could differentiate animals with Staphylococcus epidermidis infected central nervous system (CNS) catheters compared to sterile catheters confirming CSF protein quantification as a potential diagnostic strategy that is independent of pathogen identification. We then expanded our studies to include additional bacterial species, Cutibacterium acnes and Pseudomonas aeruginosa, to determine a unifying host diagnostic biomarker signature across multiple bacterial species that commonly cause pediatric CSF shunt infection. We observed a collection of proteins that identify the presence of shunt infection across these bacterial species compared to sterile shunt placement. Notably, myeloperoxidase (MPO), S100 calcium-binding protein A8 (S100A8), and complement proteins C4 and C6 reliably identified bacterial shunt infection. Collectively, these studies demonstrate the viability of a clinical diagnostic biomarker strategy for CSF proteins and are serving to inform ongoing clinical studies. Additionally, interrogating the proteins in the CSF has the added benefit of providing potential insight and expanded avenues of investigation into the neurologic morbidity associated with CSF shunt infection.