title: Development of a new CSF-shunt with sustained release of an antimicrobial broad-spectrum combination.
abstract: 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.
authors.affiliation: Institute of Medical Microbiology and Hygiene, University of Cologne, Germany.
authors.forename: J M
authors.initials: JM
authors.lastname: Schierholz
authors.forename: G
authors.initials: G
authors.lastname: Pulverer
mesh_terms: D001419:Bacteria / Q000187:drug effects / Q000254:growth & development; D001422:Bacterial Adhesion / Q000187:drug effects; D002557:Cerebrospinal Fluid Shunts / Q000009:adverse effects / Q000295:instrumentation*; D003692:Delayed-Action Preparations; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004866:Equipment Contamination / Q000517:prevention & control*; D005672:Fusidic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics; D008826:Microbial Sensitivity Tests; D016712:Mupirocin / Q000008:administration & dosage / Q000493:pharmacokinetics; D012293:Rifampin / Q000008:administration & dosage / Q000493:pharmacokinetics; D012828:Silicones / Q000378:metabolism
chemical_list: D003692:Delayed-Action Preparations; D012828:Silicones; D005672:Fusidic Acid; D016712:Mupirocin; D012293:Rifampin