Abstract
BackgroundCerebrospinal fluid (CSF) shunt placement is frequently complicated by bacterial infection. Shunt infection diagnosis relies on bacterial culture of CSF which can often produce false-negative results. Negative cultures present a conundrum for physicians as they are left to rely on other CSF indices, which can be unremarkable. New methods are needed to swiftly and accurately diagnose shunt infections. CSF chemokines and cytokines may prove useful as diagnostic biomarkers. The objective of this study was to evaluate the potential of systemic and CSF biomarkers for identification of CSF shunt infection.MethodsWe conducted a retrospective chart review of children with culture-confirmed CSF shunt infection at Children’s Hospital and Medical Center from July 2013 to December 2015. CSF cytokine analysis was performed for those patients with CSF in frozen storage from the same sample that was used for diagnostic culture.ResultsA total of 12 infections were included in this study. Patients with shunt infection had a median C-reactive protein (CRP) of 18.25 mg/dL. Median peripheral white blood cell count was 15.53 × 103 cells/mL. Those with shunt infection had a median CSF WBC of 332 cells/mL, median CSF protein level of 406 mg/dL, and median CSF glucose of 35.5 mg/dL. An interesting trend was observed with gram-positive infections having higher levels of the anti-inflammatory cytokine interleukin (IL)-10 as well as IL-17A and vascular endothelial growth factor (VEGF) compared to gram-negative infections, although these differences did not reach statistical significance. Conversely, gram-negative infections displayed higher levels of the pro-inflammatory cytokines IL-1β, fractalkine (CX3CL1), chemokine ligand 2 (CCL2), and chemokine ligand 3 (CCL3), although again these were not significantly different. CSF from gram-positive and gram-negative shunt infections had similar levels of interferon gamma (INF-γ), tumor necrosis factor alpha (TNF-α), IL-6, and IL-8.ConclusionsThis pilot study is the first to characterize the CSF cytokine profile in patients with CSF shunt infection and supports the distinction of chemokine and cytokine profiles between gram-negative and gram-positive infections. Additionally, it demonstrates the potential of CSF chemokines and cytokines as biomarkers for the diagnosis of shunt infection.
Highlights
Cerebrospinal fluid (CSF) shunt placement is frequently complicated by bacterial infection
Organisms identified from culture included the following: methicillin-resistant Staphylococcus aureus (1), viridans group streptococci (1), coagulase-negative staphylococci (2), Enterococcus faecalis (1), Gemella haemolysans (1), Serratia marcescens (1), Pseudomonas aeruginosa (2), Escherichia coli (1), Enterobacter cloacae (1), and Stenotrophomonas maltophilia (1)
While there is an interesting trend in the CSF cytokines that could greatly improve diagnosis of CSF shunt infection, there are several limitations with this pilot study
Summary
Cerebrospinal fluid (CSF) shunt placement is frequently complicated by bacterial infection. Cerebrospinal fluid (CSF) shunts are the most common treatment of hydrocephalus in the USA; they are frequently complicated by bacterial infection [1]. The inflammatory response to biofilm infection is distinct from planktonic infection, such as bacterial meningitis or intracranial abscess [9,10,11,12]. Due to their biofilm nature, shunt infection treatment requires both removal of the infected shunt and days or weeks of intravenous antibiotics [13]. With the extensive nature of treatment, it is essential that shunt infections are diagnosed accurately and rapidly
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