Among the factors that affect the risk for infections related to central venous catheters are the site at which the catheter is placed, the type of barrier precautions used during catheter insertion, the skill of the person inserting the catheter, and the use of a guidewire to replace an existing catheter; these factors are usually amenable to preventive measures. The Centers for Disease Control and Prevention and the Hospital Infections Control Practices Advisory Committee recently published a revised guideline for the prevention of intravascular device-related infections [6, 7]. The guideline provides recommendations for many of the difficult catheter-related clinical questions frequently encountered by practicing physicians: How does one appropriately diagnose a central venous catheter-related infection? What type of dressing should be used to cover the catheter site? Should antimicrobial ointments be applied to catheter sites? What is the role of guidewire exchange of central venous catheters? What are the indications for catheter removal in the setting of suspected or documented infection? The recommendations in the guideline are evidence based and are categorized on the basis of the strength of supporting scientific data; applicability; and, when possible, costs.

This issue features two articles on the prevention of infections related to central venous catheters [8, 9]. Both studies evaluated a new technological approach to the control of catheter-associated infection: impregnation with antiseptic or antimicrobial agents. Antimicrobial or antiseptic coating has been shown to reduce bacterial adherence and biofilm formation on vascular catheters [10-12]. Initial studies in humans have shown that such coatings can effectively reduce colonization of catheters but have been less conclusive in showing the benefit of such coatings in reducing clinical outcomes, such as tunnel infections and catheter-related bloodstream infections [13-17].

The two studies reported in this issue provide additional evidence to support the clinical applicability of antiseptic or antimicrobial coating of catheters. The studies evaluated predictors of catheter-related infections (catheter colonization and microbial colonization of the skin at the catheter insertion site) and assessed the overall impact of impregnated catheters in reducing the infectious outcome of primary interest-catheter-related bloodstream infection. In the study by Maki and colleagues [8], use of central venous catheters coated with chlorhexidine-silver sulfadiazine was associated with a 44% reduction in catheter colonization (13.5 colonized catheters per 100 catheters compared with 24.1 colonized catheters per 100 catheters; relative risk, 0.56 [95% CI, 0.36 to 0.89]) and a 79% reduction in the rate of catheter-related bloodstream infections (1.0 infection per 100 catheters compared with 4.6 infections per 100 catheters; relative risk, 0.21 [CI, 0.03 to 0.95]). Use of these catheters was also associated with a significant reduction in the number of organisms colonizing the skin around the catheter insertion site; such organisms are the primary source of catheter-related infections.

In the study by Raad and colleagues [9], use of central venous catheters coated with minocycline and rifampin was also associated with significant reductions in the rates of catheter colonization (adjusted odds ratio, 0.25 [CI, 0.12 to 0.53]) and catheter-related bloodstream infections (0 bloodstream infections per 1000 catheter-days compared with 7.34 bloodstream infections per 1000 catheter days; risk difference, 5.2% [CI, 0.2% to 12.4%]). The beneficial effect of these catheters in reducing catheter-related bloodstream infection seemed greatest in the first 10 days of catheter use. Ideally, a multivariate analysis should have been done to fully evaluate the independent effect of the minocycline-rifampin catheter in preventing catheter-related bloodstream infections, but the small number of catheter-related bloodstream infections observed may have precluded such an analysis. The authors did not report the effect of catheters coated with minocycline and rifampin in reducing microbial colonization of the catheter insertion site.

An important finding of these two studies was that none of the impregnated catheters was associated with adverse events (such as hypersensitivity reaction or toxicity) or infections caused by resistant pathogens. However, additional evaluation seems warranted because catheters were in situ for an average of only 6 days and assessment for rare or uncommon events requires more observations than reported in this study. Emergence of resistant bloodstream pathogens and adverse reactions are two important concerns that still need additional evaluation.

The two studies also have some unique characteristics that bolster the weight of their findings. First, both were large randomized trials; this precluded some of the limitations of previous smaller studies. Second, both studies used standardized definitions for diagnosis of catheter-related infections. Finally, both used molecular typing techniques to confirm the source of infection. Although the two studies share many features and reached similar conclusions, they differ somewhat in design. For example, Raad and colleagues evaluated infection rates and risks associated only with the use of the initial impregnated catheter. Maki and coworkers studied not only initial catheters inserted into a new site but all subsequent catheters, including those placed by a guidewire into an existing site; by doing so they addressed the important risk for infection associated with the sequential use of catheters. Maki and colleagues' findings suggest that impregnated catheters are as beneficial for reducing the rate of infections associated with catheters exchanged by guidewire as they are for infections associated with newly inserted catheters.

Maki and colleagues also addressed a biostatistical issue often raised in studies of catheter-related infections-determination of the proper unit of analysis. Which denominator should be used to determine the risk for infection associated with the use of central venous catheters: the number of patients with catheters or, as is common, measures of catheter use (for example, number of catheters or number of catheter-days)? When the latter measures are used as the denominator, each central venous catheter is assumed to have an independent risk for infection and an individual patient may be represented in the analysis more than once. In addition, the catheter-based analysis assumes that the risks for infection associated with an individual catheter are unique and independent of all previous experiences in that patient, including the number of catheters previously inserted. Calculations that use the number of patients as the denominator eliminate the need for such assumptions. Maki and colleagues provided results by using both catheter-based and patient-based denominators; the results from the two analyses seem consistent.

Despite notable strengths, the two studies have limitations that may make it difficult to generalize their findings to other clinical situations, institutions, and types of catheters. First, both of the study hospitals are large teaching facilities, and one is a cancer hospital. Second, the baseline rates of central venous catheter-related infection at these hospitals (as judged by the rates observed in the control group) were high compared with national figures [18]. Third, the studies were limited to critically ill patients with triple-lumen central venous catheters.

Intuition suggests that impregnated catheters should decrease overall rates of infection and, in turn, reduce costs. Both Maki and Raad and their colleagues conclude that use of impregnated catheters, although more expensive than use of traditional catheters, results in a net cost-savings. However, a more rigorous cost analysis is really required. In addition, because these studies addressed only a subset of central venous catheters-triple-lumen catheters-it remains to be determined whether the economic benefit reported by these authors would persist if the use of impregnated catheters was expanded to include central venous catheters that are more commonly used and have a lower risk for infection (for example, peripherally inserted central venous catheters, single-lumen central venous catheters, or tunneled central venous catheters for long-term use).

National guidelines for the prevention of catheter-related infections have been available since the early 1980s. Moreover, innovative advances in the materials used for the manufacture of catheters have made the catheters more resistant to microbial colonization. Despite these prevention efforts, the rate of central venous catheter-related infections, unlike other device-related infections (such as ventilator-associated pneumonia and catheter-associated urinary tract infections), has not decreased substantially in the past decade and remains an important cause of morbidity and mortality among patients in health care settings [19].

What can practicing physicians do to reduce the risk for catheter-related infection in patients who require central venous catheters? First, health care providers should adhere to existing recommendations, including use of maximal barrier precautions (sterile gloves; large sterile drape; and sterile gown, cap, and mask) for insertion of central venous catheters and use of skilled personnel to insert and maintain these catheters [6, 7]. Adherence to aseptic technique during insertion and maintenance of central venous catheters remains the most important measure for preventing infections related to such catheters. Second, health care providers should be aware of recent data that may influence existing practices [20, 21] and of newer data as they emerge. Despite their success, technologic innovations such as impregnated catheters should be viewed as an adjunct to, rather than a substitute for, good aseptic practices.

In deciding whether to use impregnated central venous catheters in an institution, physicians may be guided by the characteristics of the patient population, the institutional rates of central venous catheter-related infection, and the skill of the personnel at the institution. The studies by Maki and Raad and their colleagues suggest that impregnated catheters, although not a magic bullet, may be an important advance in reducing the rate of central venous catheter-related infections, particularly in critically ill patients with multilumen catheters for the short term and in settings in which rates of central venous catheter-related bloodstream infection remain high despite full adherence to proven infection control measures.

Dr. Abrutyn: Allegheny University of the Health Sciences, MS 487, Suite 6104, Sixth Floor, New College Building, 16th and Vine Streets, Philadelphia, PA 19102.