Anti-infective external coating of central venous catheters: A randomized, noninferiority trial comparing 5-fluorouracil with chlorhexidine/silver sulfadiazine in preventing catheter colonization*

Abstract

The antimetabolite drug, 5-fluorouracil, inhibits microbial growth. Coating of central venous catheters with 5-fluorouracil may reduce the risk of catheter infection. Our objective was to compare the safety and efficacy of central venous catheters externally coated with 5-fluorouracil with those coated with chlorhexidine and silver sulfadiazine. Prospective, single-blind, randomized, active-controlled, multicentered, noninferiority trial. Twenty-five US medical center intensive care units. A total of 960 adult patients requiring central venous catheterization for up to 28 days. Patients were randomized to receive a central venous catheter externally coated with either 5-fluorouracil (n = 480) or chlorhexidine and silver sulfadiazine (n = 480). The primary antimicrobial outcome was a dichotomous measure (<15 colony-forming units or ≥ 15 colony-forming units) for catheter colonization determined by the roll plate method. Secondary antimicrobial outcomes included local site infection and catheter-related bloodstream infection. Central venous catheters coated with 5-fluorouracil were noninferior to chlorhexidine and silver sulfadiazine coated central venous catheters with respect to the incidence of catheter colonization (2.9% vs. 5.3%, respectively). Local site infection occurred in 1.4% of the 5-fluorouracil group and 0.9% of the chlorhexidine and silver sulfadiazine group. No episode of catheter-related bloodstream infection occurred in the 5-fluorouracil group, whereas two episodes were noted in the chlorhexidine and silver sulfadiazine group. Only Gram-positive organisms were cultured from 5-fluorouracil catheters, whereas Gram-positive bacteria, Gram-negative bacteria, and Candida were cultured from the chlorhexidine and silver sulfadiazine central venous catheters. Adverse events were comparable between the two central venous catheter coatings. Our results suggest that central venous catheters externally coated with 5-fluorouracil are a safe and effective alternative to catheters externally coated with chlorhexidine and silver sulfadiazine when used in critically ill patients.