DEVELOPMENT OF A NEW CSF-SHUNT WITH SUSTAINED-RELEASE OF AN ANTIMICROBIAL BROAD-SPECTRUM COMBINATION

The use of Cerebro-Spinal-Fluid-shunts (CSF-shunts) is often associate d with infectious complications, because bacteria tend to colonize pla stic material. The use of plastic materials with antibacterial activit y may reduce catheter related bacterial colonization. A novel CSF-shun t impregnated with a broad-spectrum antimicrobial combination was desi gned in order to meet two requirements; lack of toxicity and persistan ce of antimicrobial efficacy Incorporation of three antibiotics up to 10% (wt/wt) into the shunt material (polydimethylsiloxane) was require d for sustained release for more than 100 days, measured by HrLC. The combination of antimicrobials showed additive and synergistical effect s as measured by the checker-board and time kill technique. These anti microbial combinations prevented mutations in resistance inducing expe riments with several S. epidermidis and S. aureus strains. Using large challenge doses of S. aureus in a catheter colonization model, antimi crobially modified catheters were protected against bacterial coloniza tion for more than 14 days. Using a C3a-des-Arg-ELISA-test and a CH50- hemolysis test the modified catheter was as biocompatible as the unmod ified shunt material. These encouraging results indicate that such ant ibiotic-bonded catheters substantially reduce the incidence and magnit ude of catheter-related bacterial colonization and may substantially r educe CSF-shunt infection.