title: In vitro exposure of bacteria to antimicrobial impregnated-central venous catheters does not directly lead to the emergence of antimicrobial resistance.
abstract: OBJECTIVE
  Use of central venous catheters (CVCs) impregnated with minocycline and rifampin reduces the density of bacterial growth on catheters and decreases the incidence of catheter-related bloodstream infections. Questions have been raised over the possibility that the use of these catheters will lead to the emergence of antibiotic-resistant organisms. In this study, we sought to determine if in vitro exposure of four test organisms to catheter segments impregnated with minocycline and rifampin would lead to the development of antibiotic resistance.
  
  
  METHODS
  Catheter segments (1.0 cm) were placed on the surface of agar plates previously inoculated with bacterial suspensions, such that a subconfluent lawn of colony growth would be apparent after 24 h incubation at 35 degrees C in air. Test organisms included American Type Culture Collection strains of Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Escherichia coli, and Pseudomonas aeruginosa. Zones of inhibition of colony growth surrounding catheters were measured at 24-h intervals up to 7 days (two catheter segments per test). Colonies on agar surfaces located at varying distances from catheter segments were examined for minocycline and rifampin resistance following various periods of exposure (six catheter segments per test). In addition, selected colonies were subsequently exposed to minocycline and rifampin in broth and examined for selection of minocycline and rifampin resistance (> 28 colonies per selection test).
  
  
  RESULTS
  Inhibitory zones of 14 to 47 mm were observed with S aureus, S epidermidis, E faecalis, and E coli. Growth of P aeruginosa was not inhibited by CVC segments. Testing of colonies of the first four organisms at various distances from CVC segments after varying periods of exposure revealed only a single instance of the emergence of resistance (eg, S aureus vs rifampin). Recovery of resistant clones was enhanced with minocycline and rifampin broth selection; however, a direct link between CVC exposure and the emergence of resistance was not established.
  
  
  CONCLUSIONS
  Our in vitro data suggest that the exposure of Gram-positive cocci to either rifampin or minocycline can lead to the development of resistance. However, exposure of bacteria to these antibiotics in combination does not directly lead to resistance. Clinical investigations will be required to determine the true risk and implications of the development of resistance.
authors.affiliation: Department of Anesthesiology, University of Massachusetts Medical School, 55 Lake Ave North, Worcester, MA 01655, USA.
authors.forename: Erik L
authors.initials: EL
authors.lastname: Munson
authors.forename: Stephen O
authors.initials: SO
authors.lastname: Heard
authors.forename: Gary V
authors.initials: GV
authors.lastname: Doern
mesh_terms: D001419:Bacteria / Q000187:drug effects* / Q000302:isolation & purification*; D002405:Catheterization, Central Venous; D004352:Drug Resistance, Microbial; D004866:Equipment Contamination; D008911:Minocycline / Q000494:pharmacology*; D012293:Rifampin / Q000494:pharmacology*
chemical_list: D008911:Minocycline; D012293:Rifampin