title: In vivo biocompatibility and in vitro efficacy of antimicrobial gendine-coated central catheters.
abstract: Antimicrobial peripherally inserted central catheters (PICCs) might reduce the incidence of central line-associated bloodstream infections (CLABSI). We tested the biocompatibility of a novel gendine-coated (combination of chlorhexidine [CHX] and gentian violet [GV]) PICC in a rabbit intravascular model and tested antimicrobial efficacy in comparison with commercially available minocycline/rifampin (M/R)- and CHX-treated PICCs in an in vitro biofilm colonization model. Gendine-coated and uncoated control PICCs were inserted in the jugular veins of rabbits for 4 days. Histopathological analysis was performed at the end of the 4-day period, and circulating levels of CHX and GV in the blood were measured at different time points using liquid chromatography-mass spectrometry. The antimicrobial efficacy of the PICCs was tested following simulated intravascular indwells of 24 h and 1 week against clinical isolates of methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, Enterobacter cloacae, Candida albicans, and Candida glabrata. Rabbits implanted with gendine-coated PICCs exhibited reduced levels of thrombosis and inflammation compared to those of the rabbits with uncoated controls. No GV was detected in blood samples over the entire study period, and trace concentrations of CHX were detected. The gendine-coated PICCs completely prevented the adherence of all pathogens from 24 h to 1 week (P ≤ 0.001), while M/R-treated, CHX-treated, and control PICCs did not. Gendine-coated PICCs were highly effective in preventing biofilm formation of multidrug-resistant pathogenic bacteria and fungi. Gendine-coated PICCs were biocompatible in an intravascular setting. Further, the pharmacokinetic testing established that acute systemic exposures of CHX and GV from the gendine-coated catheters were well within safe levels.
authors.affiliation: Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Jamal
authors.affiliation: Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Ray Y
authors.initials: RY
authors.lastname: Hachem
authors.affiliation: Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Rosenblatt
authors.affiliation: Department of Veterinary Medicine and Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: McArthur
authors.affiliation: Institute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Edd
authors.initials: E
authors.lastname: Felix
authors.affiliation: Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Ramesh C
authors.initials: RC
authors.lastname: Tailor
authors.affiliation: Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA iraad@mdanderson.org.
authors.forename: Issam
authors.initials: I
authors.lastname: Raad
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects; D000818:Animals; D000890:Anti-Infective Agents / Q000009:adverse effects / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects; D041221:Candida glabrata / Q000187:drug effects; D002408:Catheters, Indwelling / Q000382:microbiology*; D016972:Enterobacter cloacae / Q000187:drug effects; D005260:Female; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000009:adverse effects / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D011817:Rabbits; D012293:Rifampin / Q000009:adverse effects / Q000494:pharmacology; D065507:Vancomycin-Resistant Enterococci / Q000187:drug effects
chemical_list: D000890:Anti-Infective Agents; D008911:Minocycline; D012293:Rifampin