In vitro and in vivo efficacy of a rifampin-loaded silicone catheter for the prevention of CSF shunt infections.

Infection of cerebrospinal fluid (CSF) shunts is one of the major complications associated with their use and is usually managed by shunt removal, temporary insertion of an external drainage and implantation of a new shunt system. We have evaluated the efficacy of a rifampin-loaded silicone ventricular catheter to prevent bacterial colonization and infection in vitro and in an animal model. On the basis of an incorporation process a rifampin-loaded catheter was developed which is capable of releasing rifampin in bacteriocidal concentrations for 60 days and more. In a stationary bacterial adherence assay using S. epidermidis as test strain, the colonization resistance of the device was demonstrated. To assess the capability of the catheter to prevent CSF shunt infections, a rabbit model was developed which allowed the establishment of a reliable and reproducible CSF infection by implantation of silicone catheters into the ventricle and inoculating S. epidermidis (minimal dose 10(6) cfu) or S. aureus (minimal dose 10(3) cfu). Rifampin-loaded catheters (12 animals inoculated with S. epidermidis, 8 animals inoculated with S. aureus) were compared with non-loaded (14 animals inoculated with S. epidermidis, 19 animals inoculated with S. aureus) control catheters, and infection was documented by clinical, microbiological and histological methods. In contrast to the control group, none of the animals with rifampin-loaded catheters showed clinical signs of infection. Furthermore, in none of the materials obtained after sacrifice of the animals (catheter, brain tissue, CSF, blood) could the infecting bacteria be cultured, whereas in materials from animals with the unloaded catheter the infecting strains could always be cultured from the catheter and from surrounding brain tissue. The histological examination of catheter-adjacent tissue supported these findings. We conclude that a rifampin-loaded silicone ventricular catheter is capable of completely preventing bacterial colonization and infection by staphylococci as the main causative organisms in CSF shunt infections and should be further evaluated in clinical trials.