The use of CS1 central venous catheters has been shown to significantly reduce the incidence of catheter-related bloodstream infections when the mean duration of catheterization was between 5 and 11 days (6
). However, no benefit from the use of CS1 catheters could be demonstrated in a large study with a longer duration of catheterization (mean duration, 20 days) (5
). Also, a prospective randomized clinical trial demonstrated that catheters impregnated with minocycline and rifampin were significantly more efficacious in preventing catheter-related bloodstream infections than the currently available CS1 catheters (4
There are at least three reasons that may explain the better efficacy of catheters containing minocycline-rifampin than CS1 catheters. First, catheters containing minocycline-rifampin produce larger zones of inhibition in vitro against various microorganisms (9
), suggesting a more potent antimicrobial activity. Second, they are coated on both the external and the internal surfaces, offering protection against endoluminal infections, which are particularly important in the setting of long-term catheterization (>8 days) (11
). Finally, they have longer half-lives of antimicrobial activity in vitro (9
) and in vivo (2
). The relative importance of these considerations is unknown.
The present study examined whether the higher C content and the extended release of C and S from a CS2 catheter would prolong its antimicrobial activity and improve its efficacy in preventing catheter infections. The zones of inhibition against different microorganisms around CS2 catheters were slightly smaller than the zones of inhibition produced by the CS1 catheters. Yet, these small differences (maximum, 2.1 mm) are probably not clinically relevant (3
), and the in vivo efficacies of the two catheters in the rabbit model were similar when S. aureus
was inoculated immediately after the insertion of the catheter. The smaller zones of inhibition obtained at 24 h with the CS2 catheter, despite the higher C content and the same S content compared with those for the CS1 catheter, may be explained by a slower release of the antiseptics from the CS2 catheter. However, the CS2 catheter had a much longer half-life of antimicrobial activity than the current CS1 catheter both in vitro (≥34 versus 6 days) and in vivo (≥7 versus 2 days), and the more prolonged activity of the CS2 catheter was associated with much greater efficacy than that of the CS1 catheter when S. aureus
inoculation was delayed by 2 days. To our knowledge, this is the first time that extension of the duration of activity of an anti-infective coating has been shown to protect against bacteria whose inoculation was delayed. Interestingly, the protection conferred by the CS2 catheter 2 days after insertion was associated with a zone size of only 9 mm (Fig. ). Previous studies with this animal model with S. aureus
inoculation at the time of catheter insertion have suggested that zones sizes of ≥18 mm are required to confer 100% protection against infection (3
). Conversely, other studies with this model have shown that infections are harder to produce by delayed inoculation and require larger inocula (12
). It therefore seems consistent that a smaller amount of anti-infective activity may be required to prevent such infections than infections caused by inoculation of bacteria at the time of catheter insertion.
Catheter segments inserted into the agar vertically produced slightly smaller, circular zones of inhibition, while horizontally inserted segments produced slightly larger, elliptic zones. This is probably because the different positions of the segments and the different distances of the segments from the bottom of the plate change the dynamics of diffusion of the antiseptics into the agar (1
In conclusion, the present study shows that prolonged anti-infective activity on the external catheter surface provides improved efficacy in preventing infections. The use of a new CS catheter (the CS2 catheter) with a larger amount of C and an extended release of the surface-bound antimicrobials is likely to further reduce the rate of catheter-related infections, especially if it is combined with antimicrobial protection of the catheter lumen and hub. Further studies are necessary to see how the efficacy of the CS2 catheter compares with those of other existing anti-infective catheters.