Efficacy of combination of chlorhexidine and protamine sulphate against device-associated pathogens

• Published in: Journal of antimicrobial chemotherapy 2008-03, Vol.61 (3), p.651-657
• Main Authors: Darouiche, Rabih O., Mansouri, Mohammad D., Gawande, Purushottam V., Madhyastha, Srinivasa
• Format: Article
• Language: English
• Subjects: Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; antimicrobial activity; Biological and medical sciences; Catheters; Chlorhexidine - administration & dosage; device-related infections; Disinfection & disinfectants; Drug Combinations; Drug therapy; E coli; Equipment Contamination; Escherichia coli; Escherichia coli - drug effects; Escherichia coli - growth & development; Female; Medical sciences; Pharmacology. Drug treatments; Protamines - administration & dosage; Pseudomonas aeruginosa; Rabbits; Staphylococcus epidermidis; Urinary Catheterization - adverse effects
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkn006

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.