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A Review of Risk Factors for Catheter-Related Bloodstream Infection Caused by Percutaneously Inserted, Noncuffed Central Venous Catheters

Implications for Preventive Strategies

SAFDAR, NASIA M.D.; KLUGER, DANIEL M. M.D.; MAKI, DENNIS G. M.D.

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Strategies for preventing central venous catheter (CVC)-related bloodstream infection are most likely to be effective if guided by an understanding of the risk factors associated with these infections. In this critical review of published studies of risk factors for CVC-related bloodstream infection that were prospective and used multivariable techniques of data analysis or that were randomized trials of a preventive measure, a significantly increased risk of catheter-related bloodstream infection was associated with inexperience of the operator and nurse-to-patient ratio in the intensive care unit, catheter insertion with less than maximal sterile barriers, placement of a CVC in the internal jugular or femoral vein rather than subclavian vein, placement in an old site by guidewire exchange, heavy colonization of the insertion site or contamination of a catheter hub, and duration of CVC placement > 7 days. Prospective studies or randomized trials of control measures focusing on these risk factors have been shown to reduce risk significantly: formal training in CVC insertion and care, use of maximal sterile barriers at insertion, use of chlorhexidine rather than povidone-iodine for cutaneous antisepsis, applying a topical anti-infective cream or ointment or a chlorhexidine-impregnated dressing to the insertion site, and the use of novel catheters with an anti-infective surface or a contaminationresistant hub.

Better prospective studies of sufficient size to address all potential risk factors, including insertion site and hub colonization, insertion technique, and details of follow-up care, would enhance our understanding of the pathogenesis of CVC-related bloodstream infection and guide efforts to develop more effective strategies for prevention.

From the Section of Infectious Diseases, Department of Medicine, University of Wisconsin Medical School, and the Infection Control Department, University of Wisconsin Hospital and Clinics, University of Wisconsin-Madison, Madison, Wisconsin.

Presented in part at the Fourth Decennial Conference on Nosocomial Infections, Atlanta, GA, March 4, 2000, and published in abstract form (reference 72a).

Address reprint requests to: Dennis G. Maki, MD, H4/574 University of Wisconsin Hospital and Clinics, Madison, WI 53792. Fax: 608-263-4464; e-mail: dgmaki@facstaff.wisc.edu.

Accessible online at “http://www.md-journal.com.” To search for Medicine articles in PubMed, use the journal name “Medicine Baltimore.”

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Introduction

Stable and safe vascular access has become essential to modern medical practice. Noncuffed percutaneously inserted central venous catheters (CVCs) are widely used, with over 7 million sold each year in the United States alone (88), and are used for administration of intravenous fluids, blood products, medications, hemodynamic monitoring, parenteral nutrition, and access for blood specimens. The most common life-threatening complication of central venous access is bloodstream infection, caused by colonization of the implanted catheter or contamination of the catheter hub or infusate administered through the device (88,91). CVCs are now the most frequent source of nosocomial bloodstream infection (13,87,88,94,141), and it has been estimated that 250,000– 500,000 episodes occur in the United States annually (13,59,87,94,110,141), with an estimated 10% mortality (88,135,168) and marginal cost to the health care system of $25,000 per episode (9,59,110,135,168).

Measures to prevent CVC-related bloodstream infection are most likely to be effective if they are guided by a full understanding of the pathogenesis and epidemiology of these infections. We report a critical analysis of reported risk factors for the development of CVC-related bloodstream infection deriving from percutaneously inserted, noncuffed CVCs.

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Methods

English-language prospective studies in adults were identified by a MEDLINE (National Library of Medicine, Bethesda, MD) search (keywords:risk factors, intravascular devices, central venous catheter and infection) and by reviewing the citations of published reviews of intravascular device-related infection (1,31,40,41,47,54,77,88,94,110–112,116,131,141,142,144). The following criteria were required for a study to be included in this analysis: 1) the exact type of device was described; 2) all devices were prospectively evaluated for risk of device-related bloodstream infection by removal and culture of the device for evidence of colonization by the same organism (genus and species) isolated from blood cultures, with no extravascular source of bloodstream infection identified; and 3) the relative risk of device-related bloodstream infection was evaluated by a multivariable regression model or a potential control measure was assessed in a prospective randomized trial.

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Results

Overall, several thousand studies were ultimately reviewed. Unfortunately, many were very small and had limited statistical power, addressed only a limited number of potential risk factors, or did not quantify the magnitude of risk for individual risk factors. However, 96 studies were identified that provided usable data (167,170–176,183): prospective cohort studies of risk factors that used multivariable techniques of statistical risk factor analysis (170–172,183) and prospective randomized trials of a control measure aimed at reducing the risk of catheterrelated bloodstream infection (4,5,10,16,19,24–27,32,35,44–46,48,49,51,58,61,67,69,71,72,76,79,81,83,89,90,92,93,96,97,99–102,104,107,115,117,120,125,132,137–140,143,151,159–161,163,167,169,173–176,178,179,184).

Tables 1, 2, and 3 summarize the findings of this review. Numerous risk factors were found to be associated with a significantly increased risk of CVCrelated bloodstream infection in at least 1 study; a small number were found to be consistently associated with increased risk in the majority of studies that examined the factor: insertion with less than maximal sterile barriers (120), placement of a CVC in the internal jugular or femoral vein rather than subclavian vein (53,58,113,115,134,152), placement in an old site by guidewire exchange (11,26,45,72,117,129,133,137,157,169,172), heavy cutaneous colonization of the insertion site (8,27,49,85,121), contamination of the catheter hub (159), and duration of CVC placement greater than 7 days (43,121,152).

TABLE 1

TABLE 1

TABLE 2

TABLE 2

TABLE 3

TABLE 3

The largest and best-controlled randomized trials of control measures addressed the use of maximal sterile barriers at the time of CVC insertion (140), the use of chlorhexidine rather than povidone-iodine for cutaneous site disinfection (99,120,163), the utility of topical anti-infective creams or ointments on the insertion site (63,76), the impact of transparent polyurethane film dressings as contrasted with standard sterile gauze (4,27,44,83,125,138,139,184), the use of multi-lumen rather than single-lumen CVCs (25,46,52,75,107,137), and the efficacy of novel technology, such as antiseptic-impregnated site dressings (51,97), attachable silver-impregnated cuffs (48,90,126), or especially, anti-infective coatings (24,35,58,71,79,100,132,143,173). The vast majority of studies was restricted to percutaneously inserted noncuffed single- or more commonly multi-lumen catheters (81 studies) (3–5,7,8,10,12,16,19,21,24–27,33–35,39,43–46,48–53,57,58,61,64–67,69,71,72,75,79–81,84,85,89,90,92,93,95–97,99–107,115,117,119–121,124–126,132,134,137–140,143,151,152,157,159,163,166,167,169–175,178,179,183,184). Far fewer studies addressed risk factors for catheter-related bloodstream infection with noncuffed CVCs used for hemodialysis (2,32,105,129,161,176) or noncuffed pulmonary artery Swan-Ganz catheters (18,33,76,101,113,123,150,160).

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Discussion

This review identified a number of important risk factors associated with a significantly increased risk of catheter-related bloodstream infection with noncuffed percutaneously inserted CVCs, all of which are potentially amenable to control by preventive strategies (Table 4).

TABLE 4

TABLE 4

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Training and experience of the inserter

CVCs are associated with significant potential for life-threatening iatrogenic complications besides catheter-related bloodstream infection, including pneumothorax, vascular injury, arrhythmias and thromboembolism (136). Armstrong et al (7) identified inserter experience as an important risk factor for CVC-related bloodstream infection in a prospective study of 169 catheters. Moreover, a recent survey of United States academic medical centers has shown that up to one-half of clinicians who use pulmonary artery catheters have major gaps in their understanding of when to use the catheter and how to interpret the data derived from it (68). Only in recent years are United States institutions requiring formal training of house officers in the techniques of vascular access (6). Studies (38,130) have shown that intensified training and educational programs can greatly reduce the baseline risk of CVC-related bloodstream infection in a center.

Clinicians using CVCs must understand clearly their indications and potential for complications, and should be formally certified in the insertion, maintenance, and use of these catheters. Inexperienced users should be personally supervised and trained by an experienced physician (Table 5) (128).

TABLE 5

TABLE 5

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Sterile barrier precautions

Mermel et al (113) found in a prospective study of 302 pulmonary-artery catheters that failure to use maximal sterile barriers at the time of catheter insertion increased the risk of catheter-related infection more than twofold (relative risk [RR] 2.1; 95% confidence interval [CI] 1.1– 5.2). Whereas the issue has not been studied extensively, in 1 well-controlled randomized trial (140) it was found that the use of maximal sterile barriers when inserting a CVC in a patient with cancer greatly reduced the risk of CVC-related bloodstream infection (RR 0.20; 95% CI 0.02– 1.2). It seems clear that physicians inserting a CVC should wear a long-sleeved sterile surgical gown and sterile gloves and, to be in compliance with universal precautions, a mask and eye cover; the potential insertion site should be draped with a large sterile sheet (see Table 5) (128).

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Site of insertion

At least 6 studies, including 1 randomized clinical trial, have found that percutaneous insertion of a CVC in an internal jugular or femoral vein is associated with a substantially higher risk of catheterrelated bloodstream infection than insertion in a subclavian vein (RR 1–3.3) (53,58,113,115,134,152). Whereas placement in an internal jugular or femoral vein is associated with less risk of pneumothorax and permits control of local hemorrhage by the application of pressure, the risk of mechanical complications with central venous cannulation, such as pneumothorax or hemorrhage, has greatly declined in recent years (118), reflecting better training in the techniques of percutaneous catheter insertion and a much greater experience. It should be possible to place a CVC percutaneously in the subclavian vein with a very low risk of barotrauma, in the range of 1% or less.

These data indicate that training programs should strive to encourage use of the subclavian vein as the preferred site of access for CVCs (other than catheters needed for long-term hemodialysis [17,21]), and should assure that all house officers and fellows are trained in establishing central access in the subclavian vein (see Table 5) (128).

Tunneling a CVC appears to reduce the risk of catheter-related bloodstream infection, both with catheters placed in the internal jugular or femoral veins (148,174,175), and might be considered if circumstances favor cannulation of an internal jugular or femoral vein rather than a subclavian vein (for example, severe coagulopathy or a hemodialysis catheter). Finally, use of a catheter with an anti-infective coating can also reduce the otherwise overall risk of infection in this circumstance (35,100,143).

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Catheter exchange over a guidewire

The Seldinger technique for catheter insertion has been a major advance, permitting the great central veins to be cannulated with considerably less risk of pneumothorax and vascular injury. To avoid iatrogenic mechanical complications associated with percutaneous insertion of another CVC, new catheters are commonly inserted over a guidewire in the site of an old catheter. Numerous studies have examined the impact of this practice on the risk of infection (11,26,45,72,117,129,133,137,157,169,172); however, most did not utilize multivariable techniques. Eight randomized trials addressing this issue have had conflicting results (11,26,45,72,117,137,160,169). The best prospective randomized trial (26), which included pulmonary-artery catheters, found a nearly twofold increased risk of catheter-related bloodstream infection with CVCs replaced on a periodic basis in old sites over a guidewire; 75% of all catheter-related bloodstream infections in the study population occurred within 72 hours of catheter exchange over a guidewire. Authors (28) of a metananalysis of the effect of guidewire exchange and new site replacement strategies for central venous catheters in critically ill patients found a trend toward a higher rate of catheter-related bloodstream infection with guidewire exchange (RR 1.72; 95% CI 0.12–1.91).

When a CVC must be replaced because of suspicion of infection (for example, unexplained fever), or the catheter has malfunctioned, it is reasonable to replace a catheter in the same site over a guidewire if the patient has limited sites for new access or would be a high risk for percutaneous central venous cannulation in a new site (for example, coagulopathy or morbid obesity). However, it is imperative that the same meticulous aseptic technique and use of full sterile barriers that are mandatory during the insertion of any new CVC be employed. After vigorously cleansing the site with the antiseptic solution, inserting the guidewire, removing the old catheter, and cleansing the site once more with the antiseptic solution, the operator should reglove and ideally redrape the site, as the original gloves and drapes are likely to have become contaminated from manipulation of the old catheter (110,128).

In general, if the old insertion site is inflamed, especially if it is purulent, or the patient shows signs of sepsis that might be originating from the catheter or the patient has cryptogenic bacteremia or candidemia, it is strongly recommended that a new catheter not be inserted over a guidewire into an old, potentially infected site. When a catheter is inserted in an old site over a guidewire, it is essential to culture the old catheter routinely, and, if the patient is febrile or shows other soft signs of sepsis, to obtain blood cultures. If these cultures demonstrate that the old catheter was infected, the new catheter placed in an old site should be removed immediately to prevent progression of catheter-related bloodstream infection or perpetuation of ongoing bloodstream infection, as a new catheter has been inserted into an infected tract; need for continued access would mandate placement of a new catheter in a new site. If culture of the old catheter shows that it is not colonized, it has been possible to preserve access and exclude it as the cause of fever and sepsis without subjecting the patient to the hazards associated with percutaneous insertion of a new catheter (see Table 5) (128).

The use of novel technologies can further reduce the increased risk of catheter-related bloodstream infection with necessary guidewire catheter exchanges, particularly the use of catheters with an anti-infective coating (35,58,71,79,100,143,173,176). It is noteworthy that the application of silver-impregnated cuffs, which significantly reduced the risk of catheter-related bloodstream infection with first catheters in a site, was not effective for reducing risk with second catheters placed in old sites over a guidewire (90).

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Heavy colonization of the insertion site

Colonization of the insertion site will be greatly influenced by the choice of the site. In a prospective study (86), it was found that the density of the transient cutaneous microflora was highest at the base of the neck, the site of insertion of an internal jugular vein catheter, as contrasted with over the upper chest, the site of insertion of a subclavian vein catheter.

Given the powerful evidence for the importance of cutaneous microorganisms and particularly the density of the microflora at the potential insertion site in the pathogenesis of CVC-related infection, measures to reduce cutaneous colonization of the insertion site are of the highest priority, particularly the choice of the chemical antiseptic used for disinfecting the site. In the United States, iodine-based disinfectants, particularly iodophors such as 10% povidone-iodine, are used most widely. Chlorhexidine, a biguanide with potent and broad-spectrum activity, exhibits prolonged antimicrobial activity on the skin surface after a single application, in contrast with alcohol or iodine-based antiseptics. To date, 7 prospective randomized clinical trials (51,67,92,99,108,120,163) have examined the relative efficacy of 10% povidone-iodine and chlorhexidine antisepsis for vascular access. The largest, a prospective randomized trial (92) with 850 CVCs and arterial catheters used in patients in an intensive care unit, showed that 2% chlorhexidine was superior to 10% povidone-iodine or 70% alcohol for prevention of CVC-related bloodstream infection (RR 0.36; 95% CI 0.14–0.95). In 6 of the 7 trials to date, chlorhexidine was superior to povidone-iodine for preventing catheter colonization, and in 2, CVC-related sepsis was reduced significantly. These studies in aggregate indicate that a 0.5%–2% chlorhexidine-alcohol tincture or a 1%–2% aqueous solution is more effective than iodophors or 70% alcohol for prevention of CVC-related colonization and bloodstream infection.

Disinfection of skin should be done with an appropriate antiseptic before catheter insertion and at the time of dressing changes. A 2% chlorhexidine-based preparation is preferred. Alternatively, tincture of iodine, an iodophor, or 79% alcohol could be used. Allow the antiseptic to remain on the insertion site and to dry before inserting the catheter. Allow povidone-iodine to remain on the skin for at least 2 minutes, or longer if it is not yet dry before inserting the catheter (see Table 5) (128).

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“Defatting” the insertion site

Many parenteral nutrition support programs still use acetone to “defat” the skin as part of the regimen for disinfecting the site before insertion of the CVC and in follow-up care of the site, usually every other day. Defatting is widely practiced and included in many published protocols for the care of CVCs but appears to have no scientific rationale. Investigation suggests to the contrary that the natural skin lipids, especially the free fatty acids, contribute substantially to intrinsic antimicrobial properties of normal skin, and application of organic solvents promote and prolong colonization by pathogenic microorganisms (73). In the single prospective randomized clinical trial (93) of this issue, defatting with acetone before CVC insertion and as part of every-other-day site care showed no benefit whatsoever for prevention of catheter colonization or CVC-related bloodstream infection (RR 1.0; 95% CI 0.18–5.5); however, discomfort at the insertion site was twice as frequent with acetone as without (80% versus 35%, p < 0.001). These data suggest that defatting should not be employed routinely as part of the regimen for cutaneous disinfection of insertion sites for CVCs or other percutaneous intravascular devices (see Table 5) (128).

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Topical anti-infective creams or ointments

In theory, application of a topical antimicrobial agent to the catheter insertion site should confer some protection against microbial invasion. Two studies have examined the effectiveness of applying a topical antiseptic (povidone-iodine ointment) daily to CVC insertion sites. The first, a large prospective randomized trial with all types of noncuffed CVCs used in a surgical intensive care unit, showed no benefit whatsoever (104). In contrast, Levin at al (76) found that application of topical 10% povidoneiodine ointment to the insertion site of noncuffed subclavian CVCs used for hemodialysis at the time of insertion and at all subsequent dressing changes, 3 times weekly, was associated with a fourfold reduction in the incidence of staphylococcal catheterrelated bacteremia (RR 0.09; 95% CI 0.01–0.54).

More recently, randomized trials have shown that the periodic application of topical antibacterial creams or ointments, such as mupirocin, can significantly reduce the risk of CVC-related bloodstream infection (63,161). However, studies have also shown that routine use of mupirocin on CVC sites greatly increases mupirocin resistance among staphylococci recovered from infected catheters in the center (185). The ecologic impact of routine use of topical antibacterials on CVC insertion sites bears critical scrutiny because of the high likelihood of promoting resistance (30,145,146,185). Moreover, polyurethane catheters may be damaged by exposure to these agents (149,153).

These data suggest that topical antibiotic ointments or creams should not be applied routinely on CVC insertion sites. Povidone-iodine ointment may be applied at the insertion site of a hemodialysis catheter after catheter insertion and at the end of each dialysis session as long as there is no interaction with the material of the hemodialysis catheter, per manufacturer’s recommendation (see Table 5) (128).

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Site dressings

The importance of the cutaneous microflora in the pathogenesis of CVC-related infection suggests that the dressing applied to the insertion site could have considerable influence on the incidence of catheter-related infection. In recent years, transparent polyurethane film dressings have become available. They secure the device more reliably, permit continuous inspection of the site, and are generally more comfortable than gauze and tape; moreover, they permit patients to bathe and shower without saturating the dressing. Studies of polyurethane dressings on short-term noncuffed CVCs have yielded conflicting results (4,27,44,83,96,102,125,138,139,184); however, a metananalysis (65) of the largest and most rigorously controlled randomized trials has shown that these dressings do not materially increase the risk of CVC-related bloodstream infection (RR 0.99; 95% CI 0.90– 1.09). If the patient is diaphoretic, or if the site is oozing or bleeding, a gauze dressing is preferable to a transparent semipermeable dressing (128).

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Manipulations of the system

Contamination of infusate, stopcocks or catheter hubs, the cause of many CVC-related bloodstream infections, has been the cause of most outbreaks of infusion-related bacteremia or candidemia (36,70,82,98). In general, running infusions should be manipulated as little as possible, and persons handling or entering the sytem should first wash their hands or don clean gloves. Efforts should be made to limit entry into the monitoring circuit for the purpose of drawing blood or other tests (128). The number of stopcocks in the system should also be kept to a minimum. It is unknown whether wiping a stopcock that has been opened with an anti-infective agent is of value.

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New technology for prevention

The development and application of new technology holds the greatest promise for a quantum reduction in the incidence of nosocomial infections in general, and bloodstream infections deriving from devices used for intravascular access in particular (141). Innovations in the design or construction of the device that deny access of microorganisms to the system, or prevent organisms that gain access from proliferating into high concentrations or colonizing the surface of the implanted device, can obviate poor antiseptic technique or heavy cutaneous colonization and undue patient vulnerability.

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Attachable cuffs:

The application of an attachable silver-impregnated detachable cuff to a short-term CVC or Swan-Ganz introducer at the time of insertion in a new site can significantly reduce the risk of CVC-related bloodstream infection (pooled RR 0.90; 95% CI 0.02–0.81) (48,90), but the device does not appear to confer benefit with second catheters placed over a guidewire in an old site (90). Other studies have failed to show a decline in catheter-related bloodstream infection with the cuff (57,126,167); however, the use of the cuff permitted extended placement of the catheter without increasing the incidence of sepsis (126,167). The silver-impregnated cuff has been supplanted by better and more effective technology for reducing risk of CVC-related bloodstream infection, as described below.

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Antiseptic dressings:

The BioPatch (Ethicon, Somerville, NJ) is a novel chlorhexidine-impregnated hydrophilic polyurethane foam dressing that has been shown to reduce cutaneous colonization under the dressing and colonization of percutaneous epidural catheters (162), and to prevent infection of orthopedic traction pin sites (37). The device can be affixed about a newly inserted CVC, pressed firmly onto the skin about the site, and covered with a transparent polyurethane dressing to suppress cutaneous colonization by microorganisms that might invade the tract and cause CVC-related bloodstream infection.

Three randomized trials have evaluated the efficacy of the chlorhexidine sponge dressing for the prevention of CVC-related infection (51,56,97). Hanazaki et al (56) found significantly reduced rates of cutaneous colonization of the catheter insertion site with the use of the chlorhexidine dressing in a randomized trial; however, no attempt was made to identify catheter colonization or CVC-related bloodstream infection. Garland et al (51) examined the efficacy of the chlorhexidine sponge dressing in a multicenter trial in 6 neonatal intensive care units. The study showed that the novel dressing, replaced weekly, gave results comparable to gauze and tape, with periodic cutaneous disinfection with 10% povidone-iodine, for prevention of cutaneous colonization and catheter-related bloodstream infection. However, use of the chlorhexidine dressing in low-birthweight neonates (<1,000 g) was associated with a 15% incidence of dermatotoxicity.

In the third study, a randomized trial (97) of the device in patients in a university hospital intensive care unit scheduled to receive a percutaneously inserted noncuffed CVC, peripherally inserted CVC (PICC), or arterial catheter for hemodynamic monitoring, use of the chlorhexidine dressing was associated with a substantial reduction in the incidence of CVC-related bloodstream infection (3.3 versus 5.7 bloodstream infection per 1,000 intravascular device [IVD]-days, RR 0.41; 95% CI 0.09–0.83). There was no evidence that the routine use of the device led to reduced susceptibility of colonizing organisms to chlorhexidine. These data suggest that this novel and inexpensive technology warrants consideration for use on arterial catheters and PICCs, and, for centers not using anti-infective catheters, on noncuffed CVCs as well (see Table 5) (128).

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Anti-infective catheter coatings:

Adherence of microorganisms to the catheter surface is an integral stage in the pathogenesis of CVC-related bloodstream infection (55,180). Thus, binding a nontoxic antiseptic or antimicrobial to the catheter surface or incorporating an anti-infective agent or agents in the catheter material itself might prove to be the most effective technologic innovation for preventing device-related infection (181).

The greatest benefit of new technology has come from coating the catheter surface with a nontoxic anti-infective agent or incorporating such a substance into the catheter material itself. Critical scrutiny of the risk of catheter-related bloodstream infections with pulmonary artery Swan-Ganz catheters suggests that heparin-bonded catheters, which exhibit surface antimicrobial activity because of the benzalkonium chloride used to bind the heparin to the surface, significantly reduce the risk of catheter-related colonization and bloodstream infection (114,122). Beyond the benefit for reduction of surface thrombosis, these data suggest that except for patients with documented intolerance of heparin, such as heparin-related thrombocytopenia, if a pulmonary artery catheter is to be inserted, the use of a heparin-bonded catheter can reduce the risk of catheter-related bloodstream infection (147).

In a randomized clinical trial (71), central venous and arterial catheters coated with cefazolin at the time of insertion were associated with a sevenfold reduction in catheter colonization and a tenfold reduction in catheter-related bloodstream infection. Triple-lumen polyurethane CVCs coated with 2 antiseptics, silver-sulfadiazine and chlorhexidine, appear to reduce the risk of catheter-related bloodstream infection by approximately 50% (181). Careful analysis of all isolates recovered from colonized and infected catheters in 1 study (100) showed no evidence of emerging resistance to the antiseptic agents.

An even more effective strategy aimed at reducing surface colonization by skin organisms is the use of the novel antibiotic combination, minocycline and rifampin, applied both to the external and inner surface of CVCs at the time of manufacture. Randomized trials of these catheters have shown a 90% reduction in CVC-related bloodstream infection (RR 0.08–0.09) (35,143). Limited studies have not shown resistance; however, relatively few isolates were examined.

These studies show that using CVCs with antiinfective coatings clearly reduces risk and should be strongly considered by centers seeking to reduce their rate of CVC-related bloodstream infection, especially in targeted patients at highest risk. However, the long-term impact of using anti-infective-coated CVCs must be closely monitored to ascertain their ecologic impact on skin organisms that are potential bloodstream pathogens. Whenever topical antibacterials have been used on skin or mucosal surfaces in hospitalized patients, significant resistance has been encountered (15,29,42,62,158,185). The challenge for the future will be developing more potent surface agents that are well tolerated and do not promote resistance.

An antimicrobial- or antiseptic-impregnated CVC should be used in adults whose catheter is expected to remain in place >5 days if, after implementing a comprehensive strategy to reduce rates of catheter-related bloodstream infection, the rate remains above the goal set by the institution based on benchmark rates and local factors. The comprehensive strategy should include the following 3 components: education of persons who insert and maintain catheters, use of maximal sterile barrier precautions, and a 2% chlorhexidine preparation for skin antisepsis during CVC insertion (see Table 5) (128).

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Contamination of the catheter hub or lumen

A substantial number of CVC-related bloodstream infections clearly derive from luminal contaminants, particularly organisms that contaminate the hub, where the administration set is attached to the catheter, and which contaminates infusate in the lumen of the catheter. This mechanism of infection is the major cause of catheter-related bloodstream infection with long-term, cuffed Hickman-like CVCs and subcutaneous central ports (23,182), but also becomes important with short-term, noncuffed CVCs that are left in place for prolonged periods, beyond 5–7 days (78,165,166). It is unknown whether routine replacement of the administration set and entire delivery system at periodic intervals, usually 48 hours in the United States, reduces the risk of hub contamination-related bloodstream infections.

Perhaps the greatest promise here is, again, new technology: a novel catheter hub, engineered to reduce the risk of hub contamination, incorporates an antiseptic solution that is pierced by a blunt needle and was shown in a European randomized trial to substantially reduce the risk of CVC-related bloodstream infection (RR 0.2; 95% CI 0.1–0.7) (159). A subsequent, randomized trial of this new hub device in 130 catheters, however, failed to show a protective effect (81). Further studies are needed to better evaluate the role of this novel, potentially promising hub device for the prevention of catheter-related bloodstream infection. Moreover, the use of luminal lock solutions containing an anticoagulant with intrinsic antibacterial activity, such as oxalate or citrate or an anti-infective such as vancomycin, has been shown to greatly reduce the risk of catheter-related bloodstream infection with hemodialysis and other long-term CVCs or central ports (14,22,60,155).

These studies suggest that these technologies for preventing catheter-related bloodstream infections caused by intraluminal contaminants with long-term CVCs, especially hemodialysis catheters and cuffed and tunneled CVCs, ports, and PICCs, should be considered for routine use in centers with high rates of catheter-related bloodstream infection, or in individual patients who appear to be unusually susceptible to infection.

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Prolonged catheter placement

Exactly how long noncuffed short-term CVCs can be left in place safely, particularly in critically ill patients in an intensive care unit, has not been adequately assessed. In general, however, most studies that have examined duration of placement as a risk factor have shown that prolonged placement significantly increases the cumulative risk of infection, particularly insertions longer than 5–7 days (3,43,45,52,107,152). The need for continued use of an intravascular catheter should be frequently re-assessed, and the device should be removed as soon as the intended use is over (74).

It has not been conclusively established whether routine replacement of a noncuffed CVC to a new site at periodic intervals, such as every 4–5 days, significantly reduces the risk of CVC-related bloodstream infection in patients requiring prolonged central access. While some studies report no decline in the incidence of CVC-related bloodstream infection with routine replacement (16,20,26,45), most have not had sufficient statistical power to answer the question (11,45,177). This question remains unanswered; however, the availability of novel technology may obviate this concern. The studies of anti-infective-coated CVCs show a sufficiently reduced risk of CVC-related bloodstream infection that, in patients requiring prolonged central access, it appears to be safe to leave a CVC in place for 10–20 days, if necessary, perhaps even longer if the device is dedicated to total parenteral nutrition or anti-infective therapy (127). Moreover, the use of chlorhexidine-impregnated dressings or engineered contamination-resistant catheter hubs can further reduce risk and permit virtually indefinite cannulation with a low risk of infection.

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Nurse-to-patient ratio

Recent studies have shown that the intensity of nursing care, measured by a nurse-to-patient ratio, has a significant impact on the risk of nosocomial infections among patients in that unit, especially intensive care units (154). In an era where United States hospitals are struggling to recruit nurses and the temptation to ask nurses to care for increasing numbers of critically ill patients, this finding has much importance. Health care systems must recognize the importance of assuring sufficient numbers of nursing staff to provide basic care, especially in intensive care units (50). We believe that wider use of novel technology, such as chlorhexidineimpregnated site dressings or CVCs with anti-infective coatings, holds the greatest promise to prevent CVC-related bloodstream infections in an era of critical nursing shortages, especially in intensive care units (156).

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Conclusion

In conclusion, the greatest challenge in reducing the risk of CVC-related bloodstream infection is consistently implementing those control measures shown to be most effective. Recent studies have shown that intensive educational efforts in teaching hospitals, which focus essential control measures, can reduce the risk of vascular catheter-related bloodstream infection (38,130,164). But perhaps the greatest promise has been the evolving novel technology designed for prevention (109,156). Many hospitals have been reluctant to adapt these technologies despite an increasing number of studies affirming their benefit and especially their cost-benefit. Hospitals are strongly encouraged to consider adapting these technologies, which can further reduce the risk of serious CVC-related bloodstream infection, especially in those patients at highest risk of infection.

Better prospective studies of sufficient size to address all potential risk factors, including insertion site colonization, hub and luminal contamination, insertion technique, and follow-up care, would enhance our understanding of the pathogenesis of CVC-related bloodstream infection and guide efforts to develop even more effective strategies for prevention.

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