Autor: |
Smilnak GJ; Department of Neurosurgery, Duke University Medical Center, Durham, North Carolina., Charalambous LT; Department of Neurosurgery, Duke University Medical Center, Durham, North Carolina., Cutshaw D; Department of Neurosurgery, Duke University Medical Center, Durham, North Carolina., Premji AM; Department of Neurosurgery, Duke University Medical Center, Durham, North Carolina., Giamberardino CD; Department of Medicine, Division of Infectious Diseases, Duke University Medical Center, Durham, North Carolina., Ballard CG; Department of Neurosurgery, Duke University Medical Center, Durham, North Carolina., Bartuska AP; Department of Neurosurgery, Duke University Medical Center, Durham, North Carolina., Ejikeme TU; Department of Neurosurgery, Duke University Medical Center, Durham, North Carolina., Sheng H; Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina., Verbick LZ; Minnetronix, Inc, Saint Paul, Minnesota., Hedstrom BA; Minnetronix, Inc, Saint Paul, Minnesota., Pagadala PC; Department of Neurosurgery, Duke University Medical Center, Durham, North Carolina., McCabe AR; Minnetronix, Inc, Saint Paul, Minnesota., Perfect JR; Department of Medicine, Division of Infectious Diseases, Duke University Medical Center, Durham, North Carolina., Lad SP; Department of Neurosurgery, Duke University Medical Center, Durham, North Carolina. |
Abstrakt: |
Cryptococcal meningitis (CM) has emerged as the most common life-threatening fungal meningitis worldwide. Current management involves a sequential, longitudinal regimen of antifungals; despite a significant improvement in survival compared with uniform mortality without treatment, this drug paradigm has not led to a consistent cure. Neurapheresis therapy, extracorporeal filtration of yeasts from cerebrospinal fluid (CSF) in infected hosts, is presented here as a novel, one-time therapy for CM. In vitro filtration of CSF through this platform yielded a 5-log reduction in concentration of the yeast and a 1-log reduction in its polysaccharide antigen over 24 hours. Additionally, an analogous closed-loop system achieved 97% clearance of yeasts from the subarachnoid space in a rabbit model over 4-6 hours. This is the first publication demonstrating the direct ability to rapidly clear, both in vitro and in vivo, the otherwise slowly removed fungal pathogen that directly contributes to the morbidity and mortality seen in CM. |