Chapter 14
Central Venous Access Catheter Infections: An Overview
Long-term central venous access devices represent a major advance in medical care, allowing continuous access to the circulatory system for ongoing intravenous infusional therapy and therapeutic interventions such as plasmapheresis and hemodialysis. As with any invasive therapy, complications occur. The goal of this chapter is to provide an overview of infectious complications of these devices. Although much of what is published in the medical literature on this subject involves studies of nontunneled, acute-use devices, most of the principles regarding the pathogenesis, treatment, and prevention of catheter-related infection apply to long-term devices as well and are worth reviewing in this context.
The placement of any venous access device involves disruption of the normally protective integument, allowing the potential access of microorganisms into the body. Catheter-related infection results in a spectrum of difficulties, ranging from minor inconvenience, to device removal, to lifethreatening sepsis.
Device removal as a result of infection can be a particularly serious outcome in vein-depleted patients, who then must suffer the placement of additional temporary or long-term devices to complete therapy. Indeed, the prevention of catheter infection becomes one of the primary goals of both the providers and recipients of central venous access devices.
DEFINITIONS OF INFECTION
One of the difficulties in comparing results in the medical literature regarding infectious complications is that there is an inconsistency in the definitions used for the various forms of catheter-related infections. For the purpose of this chapter, the following definitions will be used:
Colonization refers to the presence of pathogens in quantities in excess of generally accepted thresholds by either quantitative or semiquantitative culture techniques. Contamination refers to the presence of pathogens in quantities below these thresholds. Device-related infection requires the presence of clinical symptoms of infection in addition to device contamination. Exitsite infection refers to evidence of infection confined to the skin wound or the catheter tunnel within 2 cm of the skin wound. Tunnel infection refers to evidence of infection anywhere in the path of the subcutaneous catheter tract greater than 2 cm from the skin wound to the venous entry site. Pocket infection refers to evidence of infection confined to the subcutaneous pocket of an implanted venous access port. Catheter-related bacteremia is defined as the presence of the same organism colonizing the device that is present in the bloodstream. Catheter-elated sepsis is present when clinical sepsis occurs in the presence of a proven catheter-related bacteremia.
MECHANISMS OF INFECTION
Several theories exist regarding the mechanism of venous access device infection. A clinically evident infection begins with colonization by pathogens of the device or its surrounding tissue. Most investigators believe that the primary source of infecting flora is commensal organisms living on the skin at the device entry site.1 This is practically substantiated by the observation that most catheter-related infections are caused by staphylococcal species such as S. epidermidis, which is a prolific human skin commensal. One pathway of bacterial contamination may begin with the migration of organisms through the wound at the catheter entry site. The extent of the resulting invasion depends on multiple factors, including the health of the host and the vigor of the host’s immune response, the virulence of the organism, and the integrity of the soft tissues at the access site. Colonization may be confined to the area of the entry site, or organisms may ascend along the catheter surface to cause a more widespread contamination of the subcutaneous tunnel or the reservoir pocket of an implanted port. Ultimately, this may result in the spread of organisms to the vessel and the onset of bacteremia.
Another well-investigated source of device colonization is contamination of the device hub.2,3 The pathway of infection in this case is colonization of the lumen of the catheter by organisms introduced to the hub during catheter manipulation. This infection may progress to bacteremia as a result of ascending colonization of the catheter lumen. Similarly, the reservoir of an implanted venous access device may harbor thrombus as a result of insufficient flushing following aspiration of blood or transfusion of blood products. This may become colonized and thus become a source of ascending endoluminal bacterial contamination. A parallel concern with the endoluminal route of catheter infection is the resulting colonization of the fibrin sheath that ubiquitously forms around the catheter inside the vessel. In theory, colonization of this entity can lead to ongoing bacteremia and risk for sepsis.
Contamination of the infusate is another possible cause of catheter-related infection. Several instances of epidemic sepsis as a result of contaminated intravenous solutions were widely reported in the United States in the 1970s. These infections are usually caused by gram-negative organisms that grow well in nutrient infusates such as lipid emulsions used for total parenteral nutrition. Fortunately, this is a rare cause of infection today, but clusters of infections caused by unusual organisms, especially in patients with low-risk factors for catheter-related infection, should be regarded with suspicion for infusate contamination.
Last, catheter infection may result from an internal source of organisms contaminating the device by hematogenous spread. In this case, the fibrin sheath or thrombus at the catheter becomes colonized by bacteremia resulting from the breakdown of mucosal surfaces from a variety of causes, such as mucositis resulting from chemotherapy, tumor invasion of the bowel or bronchus, or the denuded skin surface of burn patients.
PATHOGENESIS
The remarkable feature of catheter infection is that rather ordinary organisms are most frequently responsible for catheter-related infection. The most common organisms are those usually found on the normal skin surface, the skin commensals such as coagulase-negative and coagulase-positive staphylococcal species, diphtheroids, and certain streptococcal species. Most yeast infections appear to result from hematogenous spread from another site.1 Bacteremia caused by gram-negative organisms should implicate the gut or viscera as sources because contamination of a venous access device by these organisms by the usual routes of colonization is unusual in the absence of infusate contamination.
Interactions between pathogens, blood proteins, and the surface of the catheter are thought to play a role in bacterial colonization of venous access devices. Following placement, the intravascular portion of the device becomes rapidly coated with certain proteinaceous components of blood, including fibronectin, fibrin, and other associated substances.4 These elements form a continuous surface over the catheter, referred to as the fibrin sheath. Besides being implicated in catheter malfunction, the constituents of the fibrin sheath can act as a “scaffolding” that allows bacterial attachment. It also may cause changes in the local immunologic milieu that protect attached pathogens from antibiotic eradication.5 Individual organisms have their own qualities that promote affinity to the catheter surface. S. epidermidis produces glycoproteins that create a “slime” that aid in its adherence to the catheter surface.6 Both S. epidermidis and S. aureus attachment appears to benefit from interaction with proteins adherent to the catheter surface, including constituents of thrombus.7 This fact has been implicated in the difficulty of in situ treatment of S. aureus catheter infections.5
DIAGNOSIS
Signs and Symptoms
The contamination of a venous access device may merely result in colonization with no clinical evidence of infection. There are clinical mimics of infection that should be recognized. Mild erythema at the entry site of a catheter is a frequent occurrence and may not be the result of infection. Irritation from cleansing agents, tape, or other types of catheter dressings can cause redness and discomfort. Superficial phlebitis also can result in a syndrome of erythema, warmth, and pain that may involve the catheter entry site and the catheter tunnel and can be mistaken for infection. Extravasation of infusate from access needles incorrectly placed in the reservoir can result in a spectrum of clinical findings that could be mistaken for infection, ranging from local swelling to skin exfoliation.
In general, as infection progresses, a discharge of some type can be expressed from the entry site. This is a more sensitive indicator of infection compared with other causes of the clinical syndrome of pain, warmth, and redness. The discharge may be frankly purulent, but it can also be serous in quality. The presence of any type of discharge should raise the level of suspicion for catheter-related infection. Tunnel and pocket infections may demonstrate fluctuance and tenderness indicating drainage, and device removal may be necessary. Fever is not an uncommon symptom of catheter-related infection, but usually it is more often associated with bacteremia or sepsis. Fever associated with localized infection is a clear indicator of severity. Fever alone as a presenting symptom of local infection would be unusual without other associated clinical signs.
Bacteremic patients are also more likely to exhibit leukocytosis than patients with localized extravascular infections. Others symptoms of catheter-related sepsis are typical and include malaise, anorexia, chills and night sweats, and, in advanced cases, hypotension and cardiovascular collapse. Immunocompromised patients are of particular concern because they more often present with symptoms of florid sepsis than do patients with intact immune systems capable of more subtle responses to bacteremia.
A rare, but dreaded, presentation of catheter-related infection is suppurative thrombophlebitis, which can occur in both superficial and deep veins. In this syndrome, a catheter-related thrombus becomes colonized and the patient exhibits signs typical of occlusive deep venous thrombosis, such as arm swelling, but also exhibits other manifestations of infection. Since the advent of long-term central venous catheterization for venosclerosing infusates, superficial suppurative thrombophlebitis is rare.
Laboratory
The precise role of cultures in the management of suspected catheter-related infection has been the subject of numerous clinical and laboratory investigations. A sick patient with a venous access device who becomes febrile presents a management dilemma because catheter-related sepsis has no distinguishing clinical features from sepsis resulting from another focus of infection. Prompt catheter removal is an effective way of proving or disproving suspected catheter-related sepsis, but it necessitates removal of the venous access device and placement of another catheter to provide antibiotic therapy and for ongoing treatment of the patient’s underlying condition. On the other hand, making a decision about catheter removal by simply verifying growth of the same organism in both catheter and peripheral blood aspirates is a nonspecific practice of little clinical value. Quantitative bacterial and fungal cultures have been advocated to pinpoint the role of a venous access device in a particular case of sepsis.
Where there is suspicion of systemic or vascular infection, peripheral blood cultures are very important when bacteremia is present. The fate of the venous access device depends on several considerations. If determination of the source of infection is unclear, the results of semiquantitative cultures of the catheter tip must be evaluated. Maki and associates compared 388 peripheral and central catheter tip cultures with peripheral blood cultures. They found that the presence of 15 or more colonies on the tip culture plate was associated with a 16% incidence of bacteremia in patients with mostly peripheral catheters; however, all cases of clinical sepsis and asymptomatic bacteremia were associated with colony counts above this threshold. No cases of bacteremia were associated with growth of less than 15 colonies.8 The test is useful in that a low colony count “exonerates” the catheter as the source and focuses the search for the source of infection elsewhere. Unfortunately, the technique requires catheter removal. Several studies describe the value of obtaining and comparing simultaneous quantitative blood cultures from a peripheral vein and the venous access device in cases of suspected catheter-related sepsis.9–12 This test evaluates for an increase in the number of organisms in the catheter aspirate versus the peripheral aspirate. Step-ups in counts from the catheter blood culture of five to ten times the counts from the peripheral culture were found to correlate well with the diagnosis of catheter-related infection as evidenced by patient improvement following catheter removal and antibiotic therapy.9,10,13 This method has the advantage of in situ evaluation for catheter-related infection. Unfortunately, these tests are complicated and expensive; however, quantitative cultures are useful in certain situations, such as when the cost or difficulty of line replacement is unacceptably high or for the evaluation of implanted venous access devices.
Another technique that does not require catheter removal was described in a study that compared semiquantitative cultures of catheter tips with semiquantitative cultures of the skin at the insertion site and the interior of the catheter hub with peripheral blood cultures in patients suspected of having catheter-related sepsis.14 The positive predictive value of positive superficial cultures was 66%, but the negative predictive value of negative cultures was 96.7%, making this method of detection potentially useful in the triage of patients with venous access devices and unexplained fever.
MANAGEMENT
The most important factor in decision making for suspected catheter-related infection is the condition of the patient and the severity of the signs and symptoms of infection. Few would hesitate to remove a device in a patient with clear signs of sepsis and serial positive blood cultures for a typical organism, despite appropriate antibiotic therapy. These patients generally require hospitalization, intravenous antibiotics, and close observation. Likewise, purulent tunnel or pocket infections or pocket infections that present with wound dehiscence have little hope of eradication and device preservation with antibiotic therapy alone. Antibiotic therapy, device removal, and wound packing or surgical drainage is the best option in these situations.
On the other hand, tunnel or pocket infections presenting with mild signs of infection and serous or minimal purulent exudate often respond well to a short course of intravenous antibiotics, followed by 2 weeks of oral antibiotics based on the results of the culture. In these situations, salvage of the device becomes a priority, especially in patients who have limited accesses as a result of previous cannulations. There are no precise guidelines for which strategy to pursue, however, and the decision to remove a catheter should made on a case-by-case basis.
Treatment of bacteremia in immunocompetent patients with intravenous antibiotics and close observation, rather than catheter removal, may be considered in certain cases,10,12,15,16 including infections caused by coagulase-negative staphylococcal species, streptococcal species, and other skin diphtheroids, because negative outcomes of sepsis from these organisms are uncommon. Treatment is followed by serial peripheral blood cultures, and catheter removal may be necessary for persistent bacteremia. Special caution is needed when dealing with infections by S. aureus, Candida and other fungal species, and Pseudomonas species. Serious complications from incompletely treated infections and hematogenous seeding of distant organs may occur. S. aureus is a particularly tenacious organism because of its tendency to become adherent to proteins of the fibrin sheath, which decreases the effectiveness of antibiotic therapy. Infection secondary to resistant staphylococcal species is an indication for catheter removal. Pseudomonas infections in patients with colonized venous access devices are rarely, if ever, eradicated by antibiotic therapy alone, and fear of Pseudomonas sepsis dictates device removal.
INFECTION PREVENTION
Device Choice and Placement
Multiple studies have shown a reduced rate of infections with tunneled catheters and implanted venous access devices compared with nontunneled central venous access devices.17 Peripherally inserted central venous catheters have rates of bacteremia comparable to tunneled, cuffed central venous catheters.18 There is evidence of an increased risk of bacteremia for multiple lumen nontunneled central lines,19 but no similar data are available regarding a similar risk for multiple-lumen tunneled or implanted devices. Silver-impregnated antibiotic cuffs have been studied as a method of reducing infection by reducing the risk of ascending bacterial colonization of the subcutaneous tunnel before complete fibrous attachment of the Dacron catheter cuff. These studies have described decreased rates of local infection and catheter-related sepsis for acute-use, nontunneled catheters.20,21 Other studies, however, have not shown the same benefit for tunneled catheters.22,23
Certain patients may be considered at increased risk for infection from tunneled or implanted devices. These include severely malnourished patients, whose incision for a reservoir pocket may not heal adequately, patients with specific antibody deficiencies, and patients with resistant bacteremia from endocarditis or other difficult-to-eradicate sources of blood-borne infections. In general, an implanted port is not a good choice for a patient receiving a continuous infusion, such as total parenteral nutrition or continuous chemotherapy. The transcutaneous access needle into the device reservoir for more than several days eliminates one of the advantages of an implanted device, namely, the need for frequent flushing and dressing changes, and should be avoided.
There are reports of using novel antiseptic or antibiotic-impregnated catheters to decrease the incidence of infection. A randomized, controlled trial showed that nontunneled devices coated with a combination of Chlorhexidine and silver sulfadiazine were significantly less likely to become colonized and caused a lower rate of sepsis than noncoated devices.24 These results were not duplicated by others.25,26 Minocycline and rifampin in combination also have been studied as a catheter coating in a randomized study of nontunneled catheters in the critical care setting. A statistically significant decrease in both catheter colonization and catheter-related sepsis was reported.27 No reports of randomized trials of these coatings on extended-use devices are available. Indeed, at least one investigator raises the concern of the possibility that these coatings may support the selection of resistant strains of organisms.5
Skin preparation for device placement is a matter of preference. Most operators follow preexisting guidelines for surgical preparation with iodine-based solutions for skin disinfection. There is evidence that chlorhexidine-based cleansers are better than iodine-based solutions or alcohol,28 but their use has not been universally adopted because of the increased cost. Caution must be used when preparing the skin for jugular access not to splash Chlorhexidine agents into the eyes because permanent corneal damage has resulted from prolonged contact with the eye.
Most operators give antibiotics during placement for tunneled or implanted devices. No randomized trials have addressed the use of procedural antibiotics specifically for the placement of venous access devices. There are reports, however, on the use of antibiotics for other vascular procedures that are worth considering when deciding whether to include antibiotic prophylaxis as a part of the implantation procedure. A randomized trial for arterial reconstructive surgery showed a reduction of the infection rate from 6.8% with placebo to 0.9% with cefazolin given intravenously immediately before the procedure.29 Almost identical results were reported recently in another randomized trial evaluating intravenous vancomycin versus placebo in the placement of upper-extremity polyfluoroethylene grafts for hemodialysis.30 A recent metanalysis of randomized studies examining the impact of antibiotics on the risk of pacemaker-related infections showed a statistically significant reduction in the risk of pocket or tunnel infections.31
A typical protocol would be the intravenous administration of a first-generation cephalosporin, such as cephalexin, immediately before device placement, followed by several days of oral antibiotic therapy with an agent such as dicloxacillin. Vancomycin can be a substitute in penicillin-allergic patients, but because of its cost and its special role in the treatment of resistant gram-positive infections, it should not be given as a first-line agent for prophylaxis. Antibiotic choice is directed primarily at gram-positive organisms, and common skin commensals will be sensitive to those antibiotics described.
No antibiotic regimen will substitute for scrupulous adherence to sterile technique during placement, including maintenance of cleanliness of the operative suite. Fluoroscopic suites used for placement of tunneled or implanted venous access devices must be maintained with the cleanliness expected in the operating room.
Device Care
Care of a venous access device after placement is the single greatest determinant of risk for catheter-related infection. Most clinical series on venous access devices have reported low rates of periprocedural infection (i.e., infection occurring within several days of placement). Despite the fact that the Centers for Disease Control defines any infection occurring within 1 year of placement as placement related,32 mismanagement of dressing care and maintenance unfairly involves accountability of the operator who placed the device. Careless technique during infusion can lead to hub or reservoir contamination and colonization with risk of clinical infection. Studies have demonstrated significantly reduced rates of catheter-related infection in centers where dedicated, well-trained practitioners (primarily nurses) are in charge of catheter access and site management.33,34 Unfortunately, the maintenance of these teams is a cost that many hospitals are not willing to bear, even if the cost of treating patients with catheter-related infections exceeds the cost of prevention.
Povidone/iodine-containing ointment is effective at reducing the incidence of catheter-related infection with hemodialysis catheters.35 A study comparing a triple-antibiotic ointment with iodophor ointment found no significant difference in the incidence of infection, but patients using the triple-antibiotic ointment had an increased incidence of fungemia, with fungal commensals, specially Candida albicans.36 Multiple studies have evaluated the risk of infection with the use of transparent plastic dressing as opposed to gauze bandages for the protection of the catheter entry site; results have been conflicting37,38 (see Chapter 12).
From a practical standpoint, plastic dressing offers an occlusive barrier that prevents contamination of the exit site during activity and bathing. Plastic dressings also add an element of security against inadvertent catheter removal, especially with peripherally inserted central catheters. Some patients experience irritation that can lead to desquamation and superficial infection as a result of the trauma of tape removal, but these dressings are well tolerated and provide excellent protection for both external devices and during the healing of incisions from implanted device placement.
A large randomized study of gauze dressings versus permeable polyurethane and nonpermeable plastic dressing of nontunneled catheters found an increased incidence of bacterial colonization of the skin under the transparent plastic dressings that had been left in place for 5 days between changes.38 No statistically significant difference in the incidence of device colonization or catheter-related bacteremia or sepsis was noted, however. Randomized studies of the two dressing types for tunneled, cuffed devices in the renal and bone marrow transplant patients failed to demonstrate an increased risk of catheter-related infection, even when the dressings were left in place up to 7 days.30,40
An intriguing scheme to prevent possible bacterial colonization of the catheter tip is the routine use of thrombolytic agents for catheter maintenance. The concept relies on the theory that the biochemistry of the fibrin sheath promotes the adherence of pathogens. By reducing the fibrin sheath, the degree of colonization may be reduced. The thrombolytic agents also have the potential added benefit of reducing catheter malfunction caused by occlusion of the catheter tip by the fibrin sheath. The major drawback is the cost of the thromobolytic agent. In the amounts used for prophylaxis, increased risk of hemorrhage should not be a real clinical concern. The practicality of this approach to prevention of catheter-related bacteremia awaits further clinical study.
PEDIATRIC AND IMMUNOCOMPROMISED PATIENTS
Multiple studies have reported rates of infection for devices in children similar to the rates in adults.11,12,16,41–43 The inability of children, especially very young children, to care for a device means that special attention in the form of training for device care must be given to the child’s parents. Children may be better suited for implanted devices because the absence of external parts that can be damaged by activity and freedom from dressing changes may result in better acceptance of the device.
Patients with acquired immunodeficiency syndrome (AIDS) benefit the same as other chronically ill patients from the placement of long-term venous access devices. There appears to be a trend toward increased incidence of catheter-related infections in AIDS patients. One study that evaluated Hickman catheters and implanted devices in AIDS patients found a statistically significant difference in the incidence of catheter-related infections favoring implanted devices.44 The overall rates of infection were acceptable for both types of devices. S. aureus was the most common organism involved. Therefore, AIDS should not be a contraindication for the placement of a long-term venous access device unless there is preexisting sepsis. In this situation, the bacteremia should be treated before device placement.
FUTURE DIRECTIONS
The ultimate venous access device has yet to be designed. From the standpoint of catheter-related infection, the implanted devices significantly obstruct microorganisms from the common pathways for colonization and infection; however, these devices still fall prey to contamination during placement, by poor antisepsis during access, and colonization of the fibrin sheath by bacteremia from another source in the body. Active areas of research or areas requiring further research are infection rates for catheters impregnated with antibiotic (cefazolin, rifampin, minocycline), silver, Chlorhexidine, benzalkonium, or heparin; use of electric current; and presence of an iodine tincture reservoir in catheter hub.
SUMMARY
Catheter-related infections are well known and many are preventable. Infection prevention requires the commitment of the operator who places the device and of those who will care for the device. Good sterile technique in placement is critical. Operators should accept nothing less than “operating room” standards for patient preparation and in operative technique. Protocols for antibiotic use are quite variable and are based on local practice. Creation of antibiotic resistance is a threat, and there is a need for a randomized study of this problem.
When developing a venous access service, one should consider having a dedicated staff member to teach each patient device care, including instruction on dressing changes and catheter maintenance. Standard written catheter care guidelines to take away also decrease patient confusion and serve as a reference for the patient if problems arise outside the service’s offices. Teaching patients device care is essential.
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