JAC Advance Access originally published online on February 6, 2008
Journal of Antimicrobial Chemotherapy 2008 61(3):651-657; doi:10.1093/jac/dkn006
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Original research |
Efficacy of combination of chlorhexidine and protamine sulphate against device-associated pathogens
1 Center for Prostheses Infection and Infectious Disease Section, Michael E. Debakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, TX 77030, USA 2 Kane Biotech Inc., 5-1250 Waverley Street, Winnipeg, MB, Canada R3T 6C6
Received 21 August 2007; returned 27 December 2007; revised 20 December 2007; accepted 31 December 2007
* Corresponding author. Tel: +1-713-799-5088; Fax: +1-713-799-5058; E-mail: rdarouiche{at}aol.com
Objectives: The objectives of this study were to examine: (i) the potential in vitro synergy of combining protamine sulphate (PS) with chlorhexidine (CHX); (ii) the in vitro spectrum and durability of antimicrobial activity of CHX + PS-coated catheters; and (iii) the in vivo efficacy of CHX + PS-coated catheters in comparison with silver-hydrogel-coated and uncoated catheters.
Methods: The potential synergistic antimicrobial and antibiofilm activities of CHX and PS were investigated in vitro by the MIC and biofilm assays. The spectrum and durability of antimicrobial activity of CHX + PS-coated catheters were studied in vitro by using a serial plate transfer method. The in vivo efficacy of CHX + PS-coated catheters was assessed in a rabbit model against Escherichia coli.
Results: In vitro studies showed that the combination of CHX + PS has a synergistic inhibitory effect on E. coli and provides a significant synergistic antibiofilm and antimicrobial activity against E. coli, Pseudomonas aeruginosa and Staphylococcus epidermidis. Furthermore, catheters coated with CHX + PS provided a broad-spectrum and enduring in vitro antimicrobial activity over a 10 day period. The in vivo efficacy study demonstrated that subcutaneously implanted CHX + PS-coated catheters in rabbits are significantly less likely to become colonized (2/28 = 7%) than either silver-hydrogel-coated (25/28 = 89%; P < 0.001) or uncoated catheters (18/28 = 64%; P < 0.001) by E. coli.
Conclusions: The synergistic, broad-spectrum and durable in vitro activity of the CHX + PS combination and the robust in vivo efficacy of catheters coated with this unique composition encourage clinical evaluation of this innovative approach.
Keywords: device-related infections , antimicrobial activity , Escherichia coli