Evaluation of an in vivo model for ventricular shunt infection: a pilot study using a novel antimicrobial-loaded polymer

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OBJECTIVE

Ventricular shunt infection remains an issue leading to high patient morbidity and cost, warranting further investigation. The authors sought to create an animal model of shunt infection that could be used to evaluate possible catheter modifications and innovations.

METHODS

Three dogs underwent bilateral ventricular catheter implantation and inoculation with methicillin-sensitive Staphylococcus aureus (S. aureus). In 2 experimental animals, the catheters were modified with a polymer containing chemical “pockets” loaded with vancomycin. In 1 control animal, the catheters were polymer coated but without antibiotics. Animals were monitored for 9 to 11 days, after which the shunts were explanted. MRI was performed after shunt implantation and prior to catheter harvest. The catheters were sonicated prior to microbiological culture and also evaluated by electron microscopy. The animals’ brains were evaluated for histopathology.

RESULTS

All animals underwent successful catheter implantation. The animals developed superficial wound infections, but no neurological deficits. Imaging demonstrated ventriculitis and cerebral edema. Harvested catheters from the control animal demonstrated > 104 colony-forming units (CFUs) of S. aureus. In the first experimental animal, one shunt demonstrated > 104 CFUs of S. aureus, but the other demonstrated no growth. In the second experimental animal, one catheter demonstrated no growth, and the other grew trace S. aureus. Brain histopathology revealed acute inflammation and ventriculitis in all animals, which was more severe in the control.

CONCLUSIONS

The authors evaluated an animal model of ventricular shunting and reliably induced features of shunt infection that could be microbiologically quantified. With this model, investigation of pathophysiological and imaging correlates of infection and potentially beneficial shunt catheter modifications is possible.

ABBREVIATIONS AIC = antibiotic-impregnated catheter; CFU = colony-forming unit.

Article Information

Correspondence Mark G. Luciano: Johns Hopkins University School of Medicine, Baltimore, MD. markluciano@jhu.edu.

INCLUDE WHEN CITING Published online August 3, 2018; DOI: 10.3171/2018.1.JNS172523.

Disclosures Dr. Blitz: prior indirect research support from Aesculap. Dr. Zuckerman: employee of Affinity Therapeutics, LLC. Dr. von Recum: ownership in Affinity Therapeutics, LLC. Dr. Luciano: consultant for Codman.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    Immediate postimplantation and postinoculation images obtained in 1 control animal (catheters without antibiotics). A and B: Preoperative coronal T1-weighted postcontrast MR images demonstrating bilateral ventricular catheter placement immediately after catheter implantation and bacterial inoculation. C: Axial T2-weighted FLAIR MR image obtained immediately after catheter insertion and bacterial inoculation demonstrating no associated cerebral edema.

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    Interval postoperative images of shunt infection and ventriculitis. A and B: Nine days following shunt catheter insertion and bacterial inoculation, repeat MR images demonstrate significant catheter-associated contrast enhancement (A) and ventricular lining enhancement (B), indicative of shunt infection and ventriculitis. C: Moderate to severe cerebral edema is also evident on the T2-weighted FLAIR MR image.

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    Shunt catheter electron microscopy. A–C: Electron micrographs (EMs) of a nonimplanted shunt catheter coated with experimental polymer demonstrating association of the polymer with the catheter fenestrations (A and B) and catheter inner surface (C). D–F: EMs of harvested shunt catheters after implantation and bacterial inoculation demonstrated bacterial adherence to the catheter surface in clusters and colonies in both antibiotic-untreated (D and E) and antibiotic-treated (F) catheters that grew significant bacteria after microbiological processing. Debris is seen clogging the catheter fenestration (D). G–I: EMs of harvested shunt catheters after implantation and bacterial inoculation demonstrated no bacterial adherence in antibiotic-treated catheters (G–I) that demonstrated no bacterial growth after microbiological processing.

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    Histopathological evaluation with H & E. A: Light micrograph at 4⋅ magnification demonstrating significant ventriculitis and choroid plexus inflammation in the control animal after antibiotic-untreated catheter implantation, bacterial inoculation, and interval harvest. Note significant periventricular ependymal and subependymal perivascular lymphocytic infiltrates and dense choroid plexus inflammatory infiltration. B and C: Light micrographs obtained in the control animal at 10⋅ magnification, demonstrating perivascular lymphocytic infiltrates (B) and choroid plexus suppurative and lymphocytic infiltration (C). D–F: In an experimental animal with AIC insertion and bacterial inoculation, periventricular (D) and choroid plexus (E) inflammation is still present, but to a lesser degree. Figure is available in color online only.

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