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 comp lications associated with their use and is usually managed by shunt re moval, temporary insertion of an external drainage acid implantation o f a new shunt system. We have evaluated the efficacy of a rifampin-loa ded silicone ventricular catheter to prevent bacterial colonization an d infection in vitro and in an animal model. On the basis of an incorp oration process a rifampin-loaded catheter was developed which is capa ble of releasing rifampin in bacteriocidal concentrations for 60 days and more. In a stationary bacterial adherence assay using S. epidermid is as test strain, the colonization resistance of the device was demon strated. To assess the capability of the catheter to prevent CSF shunt infections, a rabbit model was developed which allowed the establishm ent of a reliable and reproducible CSF infection by implantation of si licone catheters into the ventricle and inoculating S. epidermidis (mi nimal 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, microbiol ogical and histological methods. In contrast to the control group, non e of the animals with rifampin-loaded catheters showed clinical signs of infection. Furthermore, in none of the materials obtained after sac rifice of the animals (catheter, brain tissue, CSF, blood) could the i nfecting bacteria be cultured, whereas in materials from animals with the unloaded catheter the infecting strains could always be cultured f rom the catheter and From surrounding brain tissue. The histological e xamination of catheter-adjacent tissue supported these findings. We co nclude that a rifampin-loaded silicone ventricular catheter is capable of completely preventing bacterial colonization and infection by stap hylococci as the main causative organisms in CSF shunt infections and should be further evaluated in clinical trials.