Subcutaneous, catheter-related inflammation in a rabbit model correlates with peripheral vein phlebitis in human volunteers.

In the development of a polyurethane vascular catheter with anti-infective properties, it became desirable to develop a measure of tissue inflammation. This was investigated in a rabbit model by implanting uncoated catheters and catheters coated with heparin (HEP), chlorhexidine (CH), or CH/HEP in the subcutaneous space with or without 10(4) Staphylococcus aureus. At intervals of 2, 4, and 7 days after implantation, animals were sacrificed; tissue blocks containing catheters were removed and preserved with formaldehyde; and sections were stained with hematoxylin and eosin. Using a histologic index, 240 sections (10 for each experimental condition) were evaluated by two investigators blinded to experimental conditions. Uncoated catheters or catheters coated with CH alone had a lower histologic index (less inflammation) than catheters coated with HEP alone or CH/HEP (P < .05). When catheters were inoculated with S. aureus, those coated with CH, with or without HEP, had a lower histologic index than uncoated catheters (P < .05). Next, 30 volunteers had a control catheter inserted in a vein in one forearm and a catheter coated with either CH alone or CH/HEP in a vein in the other forearm. After 96 h of observation there was a greater risk of phlebitis associated with CH/HEP catheters than control catheters (P < .05), and no difference in the risk of phlebitis between CH catheters and control catheters (P = 0.43). Thus, the amount of inflammation around the catheter in the subcutaneous space of rabbit correlated with the risk of peripheral vein phlebitis.

Efficacy of antibiotic-coated catheters in preventing subcutaneous Staphylococcus aureus infection in rabbits.

Vascular catheters coated with antiinfective compounds were evaluated as to their ability to prevent Staphylococcus aureus catheter infection in a rabbit model. Zones of inhibition of agar surface-plated S. aureus demonstrated the following hierarchy: dicloxacillin and clindamycin were each better than fusidic acid or chlorhexidine, which were better than ciprofloxacin, cefotaxime, or cefuroxime. In vivo half-lives of inhibitory activity for clindamycin and dicloxacillin were 5.6 and 17.7 h, respectively, with apparent first-order kinetics. Chlorhexidine disappeared in vivo with apparent two-compartment kinetics: first-compartment t1/2, 16.8 h; second-compartment t1/2, 115.6 h. In a rabbit model, dicloxacillin, clindamycin, fusidic acid, and chlorhexidine decreased the risk of infection compared with uncoated control catheters (P < .05). For dicloxacillin, clindamycin, and chlorhexidine, this was true even if the S. aureus inoculation was delayed 48 or 96 h after catheter implantation. These data suggest that vascular catheters with antiinfective coatings should be investigated further in hospitalized patients.