Chlorine Dioxide for the Prevention of Biomaterial-Associated Infections

Abstract

Biomaterial-associated infections remain a significant complication of medical implants. Of the different strains of bacteria associated with nosocomial infections, 70% are resistant to at least one of the drugs used for treatment (Bren 2002). In 2000 the Center for Disease Control ranked microbial agents as the 4th leading actual cause of death in the United States of America (Mokdad et al. 2004).In an effort to improve the prevention and treatment of infections, this research has three objectives: the development of an alternative sterilization method for medical devices; assessing a new antimicrobial material for the prevention of infections in situ; and assessing mechanisms of acquired microbial resistance. The biocide being investigated in this body of work is chlorine dioxide gas.While multiple sterilization methods are available, there are limitations to all of these technologies. For example, chemical sterilization can leave residues on the surface of the material. These residuals can be toxic, causing sensitization reactions when the materials are implanted in the body (Dolovich et al. 1984; Marshall et al. 1985; Chapman et al. 1986; Dolovich et al. 1987). Research has shown that materials sterilized with increasing concentrations of the chemical sterilizing agent have increasing quantities of residuals (Lyarskii et al. 1984). The studies presented here will ascertain the environmental parameters required for sterilization of biomaterials with low concentrations of chlorine dioxide gas and assess polymers sterilized using these conditions for the cytotoxicity of possible chemical residuals.Investigations into preventing biomaterial-based infections in situ have focused on changing the biomaterial properties. Materials with altered physicochemical characteristics to prevent bacterial adhesion have been developed, and antibiotics and silver have been incorporated into the biomaterials to inhibit bacterial colonization. Unfortunately, the rapid depletion of incorporated antimicrobial agents, altered bactericidal activity in vivo, and the development of antibiotic resistance, have all limited the effectiveness of current technologies. In these studies a chlorine dioxide generating material was assessed using in vitro and in vivo assays.While assessing the bactericidal efficacy of a selection of chlorine dioxide generating materials, a spontaneous bacterial mutant with a reduced susceptibility to chlorine dioxide was isolated. The final section of this work will investigate a potential mechanism of resistance to chlorine dioxide.