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 associated with infectious complications, because bacteria tend to colonize plastic material. The use of plastic materials with antibacterial activity may reduce catheter related bacterial colonization. A novel CSF-shunt impregnated with a broad-spectrum antimicrobial combination was designed in order to meet two requirements; lack of toxicity and persistence of antimicrobial efficacy. Incorporation of three antibiotics up to 10% (wt/wt) into the shunt material (polydimethyl-siloxane) was required for sustained release for more than 100 days, measured by HPLC. The combination of antimicrobials showed additive and synergistical effects as measured by the checker-board and time kill technique. These antimicrobial combinations prevented mutations in resistance inducing experiments with several S. epidermidis and S. aureus strains. Using large challenge doses of S. aureus in a catheter colonization model, antimicrobially modified catheters were protected against bacterial colonization 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 unmodified shunt material. These encouraging results indicate that such antibiotic-bonded catheters substantially reduce the incidence and magnitude of catheter-related bacterial colonization and may substantially reduce CSF-shunt infection.