title: Efficacy of combination of chlorhexidine and protamine sulphate against device-associated pathogens.
abstract: OBJECTIVE
  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.
authors.affiliation: Center for Prostheses Infection and Infectious Disease Section, Michael E. Debakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, TX 77030, USA. rdarouiche@aol.com
authors.forename: Rabih O
authors.initials: RO
authors.lastname: Darouiche
authors.forename: Mohammad D
authors.initials: MD
authors.lastname: Mansouri
authors.forename: Purushottam V
authors.initials: PV
authors.lastname: Gawande
authors.forename: Srinivasa
authors.initials: S
authors.lastname: Madhyastha
mesh_terms: D000818:Animals; D002710:Chlorhexidine / Q000008:administration & dosage*; D004338:Drug Combinations; D004866:Equipment Contamination; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D005260:Female; D011479:Protamines / Q000008:administration & dosage*; D011817:Rabbits; D014546:Urinary Catheterization / Q000009:adverse effects
chemical_list: D004338:Drug Combinations; D011479:Protamines; D002710:Chlorhexidine