Chapter 4 B IOFOULING AND A NTI - FOULING OF M EDICAL D EVICES
نویسندگان
چکیده
Biofouling of medical devices involves the formation of a biofilm by bacteria. The infecting bacteria produce extensive exopolysaccharides to form a confluent biofilm. Bacteria within a biofilm can be 1,000 times more resistant to antimicrobials than their planktonic counterparts and less susceptible to host immune systems. According to an estimate by the NIH (USA), about 80% of all human bacterial infections involve biofilms. Over 45% of all hospital-acquired infections in the U.S. (>2 million/year) are device-related. Therefore, development of anti-infective products possessing both antibiofilm and antimicrobial activity is of utmost importance for the effective control of biofouling in clinical settings. We have developed the following unique synergistic antimicrobial compositions with antibiofilm activity for coating indwelling medical devices and disinfecting dental unit waterlines: (i) A combination of protamine sulfate (PS) and chlorhexidine (CHX) has shown a significant synergistic antimicrobial and antibiofilm activity against nosocomial infection associated Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis, Staphylococcus aureus, Enterococcus faecalis, Klebsiella pneumoniae, Enterococcus faecium, Proteus mirabilis and Candida albicans. Protamine sulfate enhances the activity of CHX by increasing the permeability of cell membrane and inhibits as well as moderately disperses biofilms; (ii) N-acetyl-D-glucosamine-1-phosphate acetyltransferase (GlmU) is involved in the biosynthesis of lipopolysaccharides in both gram-positive and gram-negative bacteria. An antimicrobial composition comprising GlmU inhibitor (GUI) and PS is effective against catheter-associated uropathogens, including E. coli and P. ∗ Kane Biotech Inc. 5-1250 Waverley Street, Winnipeg, Manitoba, Canada, R3T 6C6, ph: 204-478-5600, fax: 204453-1314 email*: [email protected]. Karen LoVetri, Purushottam V. Gawande, Nandadeva Yakandawala et al. 2 aeruginosa. The GUI interferes with cell wall formation and exhibits antimicrobial activity. PS enhances GUI activity; (iii) The composition comprising ovotransferrin (OT), PS and EDTA is effective against the growth and biofilm formation of both gram-positive and gram-negative bacteria associated with medical devices. While chelating agents OT and EDTA sequester iron and magnesium, calcium plus iron, respectively and thus making them unavailable for bacterial growth, the PS increases membrane permeability; (iv) The synergistic combination of a broad-spectrum antimicrobial triclosan (TCSN) and DispersinB® (DspB), an antibiofilm enzyme, has antimicrobial and antibiofilm activity against vascular catheter associated bacteria. DspB inhibits as well as disperses biofilms and thus makes the CVC-associated bacteria more susceptible to TCSN killing; (v) The combination of sodium bicarbonate (SB), sodium metaperiodate (SMP) and SDS is effective in reducing the growth as well as biofilm formation in dental unit waterline (DUWL)-associated microorganisms such as Legionella pneumophila, P. aeruginosa, S. aureus, K. pneumoniae, C. albicans, Mycobacterium avium and Mycobacterium chelonae. The biofilm dispersal activity of SMP makes biofilmembedded bacteria and yeasts more susceptible to the antimicrobial action of SDS and SB.
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