title: Antibiotic-heparin lock: in vitro antibiotic stability combined with heparin in a central venous catheter.
abstract: Long-term hemodialysis frequently requires vascular access through central venous catheters (CVCs). Infection related to these catheters is a significant complication. The use of an antibiotic-heparin lock could decrease the risks associated with infected permanent catheters. As an initial step in developing an antibiotic-heparin lock, we investigated the in vitro stability of antibiotic-heparin combinations in CVCs. Initially, cefazolin, vancomycin, ceftazidime, ciprofloxacin 10 mg/ml each, and gentamicin 5 mg/ml were incubated separately in glass test tubes in the dark at 37 degrees C for 72 hours. Samples were analyzed spectrophotometrically for stability at 24-hour intervals. The procedure was repeated with the addition of heparin (final concentration 5000 U/ml in glass test tubes), and the combination was also examined in CVCs. High-performance liquid chromatography analysis was conducted on the antibiotic-heparin combinations at 72 hours to confirm the spectrophotometric results. Ciprofloxacin produced an immediate precipitate with the addition of heparin and was not analyzed further. Absorbance values decreased for all antibiotics, with the greatest decreases at 72 hours for cefazolin (27.4%), vancomycin (29.7%), ceftazidime (40.2%), and gentamicin (8%) when combined with heparin. These decreases were postulated to be secondary to adsorption of the antibiotics to the luminal surface of the catheters because submitting the catheters to ultrasound with 1% sodium bicarbonate and analyzing the resulting solution for absorbance revealed that some of the drug was recovered. Although free antibiotic in CVC solution was reduced, the concentration should be sufficient (approximately 5 mg/ml) to decrease the frequency of infections associated with CVCs. We conclude that the concentrations of vancomycin, ceftazidime, cefazolin, or gentamicin used in our study should be sufficient for an antibiotic-heparin lock.
authors.affiliation: Faculties of Pharmacy, University of Manitoba, Winnipeg, Canada.
authors.forename: L M
authors.initials: LM
authors.lastname: Vercaigne
authors.forename: D S
authors.initials: DS
authors.lastname: Sitar
authors.forename: S B
authors.initials: SB
authors.lastname: Penner
authors.forename: K
authors.initials: K
authors.lastname: Bernstein
authors.forename: G Q
authors.initials: GQ
authors.lastname: Wang
authors.forename: F J
authors.initials: FJ
authors.lastname: Burczynski
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000627:therapeutic use*; D016470:Bacteremia / Q000209:etiology / Q000517:prevention & control; D001424:Bacterial Infections / Q000209:etiology / Q000517:prevention & control; D002405:Catheterization, Central Venous / Q000009:adverse effects; D002437:Cefazolin / Q000737:chemistry / Q000627:therapeutic use; D002442:Ceftazidime / Q000737:chemistry / Q000627:therapeutic use; D004355:Drug Stability; D004359:Drug Therapy, Combination; D005839:Gentamicins / Q000737:chemistry / Q000627:therapeutic use; D006493:Heparin / Q000627:therapeutic use*; D006801:Humans; D006435:Renal Dialysis / Q000295:instrumentation; D013997:Time Factors; D014640:Vancomycin / Q000737:chemistry / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins; D014640:Vancomycin; D006493:Heparin; D002442:Ceftazidime; D002437:Cefazolin