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EDITORIALS

Skin: The First Battlefield

Richard C. Prielipp, MD FCCM^*, and Robert J. Sherertz, MD

Departments of *Anesthesiology, Section on Critical Care and Internal Medicine, Section on Infectious Diseases

Address correspondence to Richard C. Prielipp, MD, FACCM, Department of Anesthesiology, Wake Forest University, Winston-Salem, NC 27157. Address e-mail to prielipp{at}wfubmc.edu

Catheter-related bloodstream infections (CRBSI) are a common and costly complication in hospitalized patients, especially the critically ill (1). CRBSI affects over 200,000 patients per year in the United States, and is associated with an increased risk of dying (though whether this association is causal is controversial) (2). The complexity of the pathogenesis of CRBSI is illustrated by the 50-fold range in the risk of bloodstream infection per 1000 catheter days for different types of vascular access devices (Table 1) (1). A central question important to the pathogenesis and prevention of vascular catheter infections is where do the microorganisms on vascular catheters originate? The elegant investigation of Jeske et al. (3) reported in this issue of Anesthesia & Analgesia provides important insight into this question by demonstrating that in intensive care unit (ICU) patients, 71% of bacteria found on the tip of short-term central venous catheters genetically match bacteria found on the insertion device. Thus, these microorganisms probably come from the patient’s own skin.

The findings by Jeske et al. (3) detailed in this issue, and by Elliott et al. (4) and Livesley et al. (5) previously, that the catheter tip can be colonized at the time of catheter insertion have several significant implications. First, it has previously been shown for ICU patients with central venous catheters that the initial site of catheter colonization is divided about evenly 1/3 subcutaneous segment, 1/3 catheter tip, and 1/3 catheter lumen (6). This has been interpreted as indicating that 33% of the time microorganisms originate from the skin and extend down the external catheter surface (subcutaneous segment - 1st week), one third originate from hematogenous seeding (catheter tip - 2nd week), and another third arise from catheter breaks (catheter lumen - 3rd week on). These findings were obtained by culturing the catheter tip segment, catheter lumen segment, and catheter lumens separately. It was then assumed that if both the catheter subcutaneous segment and catheter lumens were culture negative and the catheter tip segment was positive that the only way that this could happen was by hematogenous seeding. That conclusion is clearly incorrect, as more current data suggest that the majority of the early catheter colonization (first 2 weeks) in ICU patients come from skin organisms.

The clinical implication of these findings is that interventions aimed at minimizing the risk of catheter colonization from skin microorganisms should be quite successful at preventing early (first 2 weeks) catheter-related infections in ICU patients. This has clearly been shown to be the case in studies examining what drug to use for skin preparation at the time of catheter insertion (7,8), a study of the use of maximal sterile barriers for catheter insertion (9), studies of educational interventions aimed at improving sterile technique (10–12), and studies of catheters with antiinfective coatings (13–15). In ICU patients, Maki et al. (7) randomized skin preparation solutions for 668 catheters comparing 2% chlorhexidine, 10% povidone-iodine, and 70% alcohol. Chlorhexidine was associated with the lowest incidence of CRBSI (2.3 per 100 catheters, P = 0.02), whereas alcohol and povidone-iodine were associated with 7.1 and 9.3 infections per 100 catheters. A recent meta-analysis analyzed 8 studies with a total of 4,143 catheters (8) which identified a risk reduction for CRBSI = 0.49, 95% confidence interval [0.28–0.88]. Chlorhexidine gluconate decreased CRBSI by 50% compared with povidone-iodine. Despite the greater cost of chlorhexidine compared with that of povidone-iodine, the meta-analysis suggests chlorhexidine is cost-effective and perhaps even cost saving. Most experts and the Centers for Disease Control and Prevention now preferentially recommend use of chlorhexidine gluconate-based preparations in place of either 10% povidone-iodine or 70% alcohol (16). Chlorhexidine-based commercial applicators are now widely available.

The use of maximum sterile barriers (sterile gowns, gloves, and a drape covering the whole patient) has reduced the risk of central venous CRBSI to <1% in comparison to just using sterile gloves and a small sterile drape (9). Education programs focusing on teaching doctors and nurses better sterile technique for the insertion and maintenance of catheters have also been shown to significantly reduce the risk of CRBSI (10–12). In particular, it has been possible to show that such programs can increase compliance with the use of maximum sterile barriers under "battle conditions" (10). Finally, the use of catheters with antiinfective coatings, silver sulfadiazine/chlorhexidine and minocycline/rifampin, have been shown to reduce the risk of catheter-related infections (13–15). Of note, the silver sulfadiazine/chlorhexidine coating was only on the external surface of the catheters in the cited study and therefore mostly reflects the impact of skin microorganisms (13). Furthermore, data from studying the minocycline/rifampin-coated catheter, which was coated on both the inside and outside surfaces and had longer-lasting activity and was more effective in a comparative randomized trial, suggest that our efforts at infection prevention cannot be focused just on the process of catheter insertion and the external surface of the catheter (15).

One must be careful with some of the extrapolations of the findings made by Jeske et al. (3). They imply that prophylactic antibiotics at the time of catheter insertion may be of value. There are a number of randomized trials looking at the efficacy of prophylactic antibiotics to prevent vascular catheter infections (17–21). All of the trials are in cancer patients with long-term catheters and 4 of 5 demonstrate efficacy and raise the possibility that prophylactic antibiotics could be effective in other clinical settings. While it is tempting to extrapolate from these data, further study is required before the recommendation can be made to use prophylactic antibiotics for decreasing the risk of catheter-related infection in ICU patients. Finally, they suggest that it might make sense to culture all insertion apparatus to have data to guide subsequent treatment decisions. Since an average rate of catheter-related bloodstream infection is about 5% in ICU patients and it can be significantly decreased with the use of some of the interventions cited above, even the 60 Euros/culture cited could be quite expensive in the setting of low infection rates. Further cost-effectiveness data are needed before a broad recommendation should be made to perform such cultures.

The future will likely see the development of better catheter materials producing less inflammation, less thrombosis, and surfaces that are intrinsically more resistant to bacterial adherence. The communication molecules produced by bacteria for quorum sensing and biofilm formation may also become important bio-targets. The work of Jeske et al. improves our understanding of the pathogenesis of CRBSI and makes it easier to understand the importance of several evidence-based interventions that should be considered for minimizing the risk of CRBSI in ICU patients.

References

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