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Infected implantable devices represent a clinical challenge, because the customary option is to surgically remove the device, and that is associated with substantial cost and morbidity to the patient, along with patient dissatisfaction with the physician. Although prophylactic systemic antibiotics and sterile technique are the mainstay of prevention of surgical site infection (SSI) after implant, the incidence of SSI remains relatively high. Although some surgeons add local antibiotic at implant site during surgery, there is no scientific research to demonstrate if there is a benefit.Rats and mice were randomly assigned to 4 treatment groups: systemic vancomycin alone, local vancomycin alone, combined systemic and local vancomycin, and untreated. After systemic vancomycin or saline preinjection, a surgical incision was performed for placement of a metal disc, and local vancomycin or saline was injected in the superficial tissue pocket created. The metal disc (implant) was placed in that space, followed by local injection of Staphylococcus aureus bacteria and wound closure. After 1 and 6 days, samples of the tissue surrounding the disc implant, the disc itself, and the spleen (systemic infection marker) were processed, and bacterial levels assayed.In both mice and rats, local vancomycin was more potent in reducing tissue SSI, implant infection, and spleen infection than systemic vancomycin at 1 day after induction of bacteria to a surgical wound. At 6 days, in both mice and rats, local vancomycin was again more potent in reducing tissue SSI than systemic vancomycin.This study suggests that local vancomycin should be added to systemic vancomycin to reduce SSI with cardiac pacemaker, defibrillator, implantable pulse generator of neurostimulator, or intrathecal pump implants.