Chapter 50. Infectious Complications of Intravascular Access Devices

• Intravascular access device–associated infections may be either local or bacteremic, and the risk of developing an infection varies with the patient population, the type of device, the microbe, and the patient-microbe-device interaction.
• The status of all indwelling vascular access devices should be reviewed daily by the critical care team, with attention to the duration of placement, appearance of the exit site, and continued clinical indication for the intravascular device.
• Central venous catheters account for over 90% of all intravascular device–related bacteremias.
• Most intravascular device–related bacteremias are caused by endogenous skin flora at the catheter insertion site that migrate along the transcutaneous portion of the catheter with subsequent colonization of the catheter tip.
• Coagulase-negative staphylococci and Staphylococcus aureus account for just over 50% of all intravascular device–related bacteremias, followed in frequency by gram-negative bacilli and yeast.
• Diagnosis of intravascular device–related infection, either local or bacteremic, is best approached using a combination of clinical and laboratory criteria.
• Although treatment of central line infections due to coagulase-negative staphylococci may be successful without catheter removal, infections caused by S. aureus necessitate catheter removal.
• Central intravascular catheter infections are essentially preventable infections. Successful prevention entails attention to a careful needs assessment for the device, careful site selection, maximal barrier precautions and aseptic technique on insertion, insertion by the most skilled operators, rigorous catheter-site care, and interrupting the integrity of the system as little as possible.

The use of intravascular access devices has become an integral part of modern patient care, and nowhere is this more evident than the ICU. Progress over the last two to three decades has provided an increasing array of devices other than the original peripheral and single-lumen central catheters. Included in the list of devices currently in use are multilumen central venous catheters (CVCs); tunneled CVCs such as the Hickman, Broviac, Cook, and Quinton catheters; flow-directed pulmonary artery catheters (PACs), peripherally inserted central and midline catheters, peripheral arterial catheters, and totally implantable devices. These indwelling intravascular devices provide a route for the administration for fluids, blood products, nutritional products, and medications; allow the monitoring of hemodynamic functions; and permit bloodletting and the maintenance of emergency access. However, vascular access devices may be associated with several complications, including local and bacteremic infections related to the device, thrombosis, thrombophlebitis, and septic thrombophlebitis. Infectious complications are the most frequent and among the most serious of these complications. The magnitude of CVC-related infectious complications can be appreciated when one realizes there are an estimated 15 million days of exposure to CVCs in patients in ICUs in the United States each year.1 Bacteremias caused by intravascular devices are associated with increased morbidity, prolonging hospitalization a mean of 7 days, and have a reported attributable mortality of up to 35% in studies that are not controlled for severity of illness.1–4

The risk of developing device-related infection (either local or bacteremic) varies considerably with the patient population, the type of device and its intended use, the microorganisms involved, and the patient-microbe-device interaction. The risk factors for device-associated infection that have been identified for the host, the microbe, the device, and the interaction among them are listed in Table 50-1. In addition, representative incidence-density rates for device-associated bacteremias are shown in Table 50-2.

Of the many intravascular devices available, the peripheral venous catheter is by far the most commonly used. Most peripheral venous catheters currently are made of polyurethane, Teflon, or steel and are associated with a very low risk of bacteremia, with less than 1 episode of bacteremia per 500 devices.5,6 There is little difference currently in the risk of bacteremia regardless of whether polyurethane, Teflon, or steel needles are used if the same level of asepsis is applied at the time of placement.

Peripheral arterial catheters are in widespread use in ICUs for blood pressure monitoring and for obtaining arterial samples for blood gas determination. The incidence of bacteremia related to peripheral arterial devices is about 1%,7–9 and the rate of significant colonization (≥15 colony-forming units [cfu] on semiquantitative culture) is about 5%.7–11 Insertion by cutdown, catheterization lasting 4 days or longer, and inflammation at the catheter exit site are associated with a higher risk of significant catheter colonization.

CVCs are estimated to account for over 90% of all catheter-related bacteremias. Prospective studies of noncuffed, short-term single or multilumen catheters inserted into either internal jugular or subclavian sites have found bacteremia rates of 1% to 5% and rates of significant colonization of the catheters (≥15 cfu on semiquantitative culture) ranging between 5% and 30%12–18 depending on the use and duration of the catheter plus the patient population. Peripherally inserted central catheters (PICCs) have somewhat lower catheter-related bacteremia rates, ranging between 1% to 2%.19 Many of the factors that may influence the risk of catheter colonization and/or catheter-related bacteremia are listed in Table 50-1. The presence of a distant focus of infection, bacteremia, tracheostomy, loss of skin integrity, emergent placement, internal jugular placement, absence of appropriate barrier precautions, transparent dressings, a high frequency of entry into the system, and multilumen catheters increase the risk of significant catheter colonization.1,12–15,20–27

The use of less stringent barrier precautions, the use of 10% povidone-iodine or 70% alcohol alone as compared with 2% chlorhexidine as an antiseptic, the use of transparent dressings (in some but not all randomized studies), duration of catheterization of 4 days or more, and heavy cutaneous insertion-site colonization all have been associated with an increased risk of catheter-related bacteremia for central catheters.12–15,20,28–30 Antibiotic-coated and antiseptic-impregnated31–33 CVCs reduce catheter colonization and bloodstream infection, but a recent meta-analysis suggests that the benefit is only during the first week after insertion.34 Replacement of existing catheters over a guidewire is associated with a significantly lower rate of mechanical complications than replacement by insertion at a new site but more frequently results in infection of the newly placed catheter.35

PACs, which are used frequently in the management of hemodynamically unstable, critically ill patients, carry many of the same risk factors and rates of bacteremia as CVCs. Most PACs consist of a polyurethane catheter that passes through a percutaneous indwelling Teflon introducer sheath. Prospective studies have identified several risk factors associated with significant catheter colonization, including placement with less stringent barrier precautions, internal jugular vein placement, prolonged catheterization (≥4 days), and heavy microbial colonization at the catheter insertion site.20,36,37 Exposure of a PAC to bacteremia from a distant focus of infection, catheterization for 4 days or more, and difficulty with insertion also have been found to increase the risk of bacteremia. The incidence of bacteremia from PACs is about 1%.37

Microorganisms can gain entry (Fig. 50-1) to the intravascular device (usually an intravascular catheter) and the intravenous delivery system in several ways to cause device- or catheter-related bacteremia, including contamination of infusate, contamination of the catheter hub–infusion tubing junction, hematogenous seeding of the catheter tip, and colonization at the cutaneous catheter exit site.

Contamination of infusate may be intrinsic, occurring at the manufacturing level, or extrinsic, occurring via the administration sets, the extension tubing, the use of outdated intravenous solutions, or a break in aseptic technique allowing faulty admixtures. The potential for proliferation of organisms in various infusate fluids after intrinsic contamination has been well documented with strains of Klebsiella, Enterobacter, and Serratia.38,39 Candida species have a propensity to grow in hypertonic glucose solutions used in parenteral solutions, and the commercially available lipid emulsions support the growth of most organisms.40 Nosocomial bacteremias secondary to contaminated infusate usually have occurred in epidemics or clusters but with improvement in manufacturing standards are now exceedingly rare. Extrinsic contamination of infusate causing central catheter–related bacteremia is also a very uncommon problem, with an estimated incidence of less than 1 per 1000 cannula-related septicemias. Most are reported in epidemics occurring as a result of the exposure to a common source of microbial contamination such as multidose vials, administration sets, or contaminated water-bath warmers. The risk of fluid becoming extrinsically contaminated is related to the duration of infusion through the administration set. Most hospitals now have policies that require replacement of the entire delivery system every 72 hours, which represents one of the most important control measures for reducing the complications of contaminated infusates. Similar to intrinsic contamination, hematogenous seeding of the catheter tip with consequent bacteremia is considered to be a rare event.

Most cannula-related bacteremias are thought to result from local endogenous microflora colonizing skin at the insertion site and/or the transcutaneous wound29,41,42 that migrate along the subcutaneous tunnel, colonize the subcutaneous portion of the catheter, and then finally colonize the tip of the catheter. Another mechanism is colonization of the internal surface of the catheter hub, with subsequent colonization of the internal surface of the catheter and eventual colonization of the catheter tip.43–45 This could occur as a result of obligate manipulations of the connection during tubing replacements or improper connection. After the hub has been contaminated, the microbes would be carried intraluminally, reach the catheter tip, and colonize the fibrin sheath. The origin of these microorganisms colonizing the hub is often the hands of those manipulating the hub rather than the flora of the patient's skin. This latter mechanism of catheter tip colonization is considered an important contributor to intraluminal colonization of long-term catheters.43–45

Studies of central line infections (short indwelling insertion times) using molecular subtyping techniques to differentiate the different strains of infecting and colonizing organisms have demonstrated that approximately 80% of the microorganisms from distal catheter tips are concordant with organisms present on the skin at the catheter insertion site. The source of the remaining organisms was either contamination of the catheter hub, hematogenous colonization from remote sites, or unknown sources. Of episodes of catheter-related bacteremia, concordance of organisms at the catheter insertion site, the catheter tip, and the blood varied between 86% and 100%.

It also has been shown in several studies15,20,41 that heavy colonization at the catheter insertion site is strongly associated with significant catheter colonization, which in turn is associated with catheter-related bacteremia. Using quantitative insertion-site cultures, the presence of ≥103 cfu/mL per 25 cm2 has been strongly associated with the presence of significant catheter colonization.

Once microorganisms gain access to the catheter tip, they act as a nidus for further colonization because of a loosely formed fibrin sheath that develops around the distal portion of the cannula. This sheath acts as a reservoir within which microorganisms can multiply and be shielded from the body's normal host defense mechanisms. The presence of grossly visible thrombus formation on the catheter tip is also highly correlated with the presence of bacterial colonization.

The species of the microorganism causing a bacteremia is frequently an important clue suggesting the intravascular device as the source of the bacteremia. Coagulase-negative staphylococci (mainly Staphylococcus epidermidis) and Staphylococcus aureus are the most frequently encountered organisms causing cannula-related infections. These two species account for well over 50% of all cannula-related infections. Enteric gram-negative bacilli are the next most frequent group of causative organisms, followed by yeast, especially Candida albicans. Other less commonly identified organisms include Pseudomonas species, Corynebacterium jeikeium, and Malassezia furfur.

Several studies have suggested that coagulase-negative staphylococci may have an intrinsic propensity to adhere to plastic catheters that results in a selective advantage for these organisms in causing device-associated infections.46

Unusual isolates such as Enterobacter species, Burkholderia cepacia, Flavobacterium species, and Stenotrophomonas and Acinetobacter species are uncommonly found as a cause for CVC-associated infection and should suggest the possibility of a contaminated infusion product or a common environmental reservoir.47,48 A summary of the organisms commonly associated with device-associated bacteremia is given in Table 50-3.

There is currently no uniform method for defining local device-related infection or device-related bacteremia. Establishing a firm diagnosis of device-related bacteremia may be very difficult. Basing the diagnosis and subsequent definition of device-related infection on clinical or laboratory criteria alone has its own intrinsic limitations. In addition, the definitions used for clinical purposes may differ from those used for surveillance.49

Several laboratory techniques are available to assist the diagnosis of catheter-related infection. These include qualitative culture of vascular catheters in broth, semiquantitative culture of catheters on solid media, and quantitative culture of catheters in broth, removing organisms by flushing or sonication. Qualitative culture in broth is not specific, is prone to contamination, and probably should not be done. The use of semiquantitative cultures of catheter tips or of the intracutaneous portion of the catheter or central-line sheath using the roll-plate method described by Maki and colleagues50 defines significant colonization as 15 cfu or more. Using this laboratory definition and applying it to diagnosing catheter-related bacteremia, a specificity of 76% to 96% and a positive predictive value of 16% to 31% have been reported. Owing to its simplicity, the roll-plate method has been adopted widely in many hospital microbiology laboratories. The use of quantitative cultures of broth, in which the catheter has been flushed or sonicated, may be more sensitive but is too time-consuming and laborious for routine use.

Quantitative blood cultures have been used as a laboratory method to assist in the diagnosis of catheter-related bacteremia when catheter removal is not possible.51,52 Blood cultures are obtained simultaneously from the central catheter (a retrograde “drawback” culture) and from a peripheral venipuncture. A 10-fold or higher differential count from blood obtained from the central catheter is considered to be indicative of catheter-related bacteremia. The use of quantitative cultures is laborious, and concerns over contamination of drawback cultures have limited the usefulness of this technique. Recent studies have evaluated endoluminal brush sampling and differential blood culture growth rates, which may provide acceptable accuracy without requiring removal of indwelling catheters, but the accuracy of these techniques needs to be confirmed in other studies.53–56

Using clinical criteria alone to make a diagnosis of catheter-related infection also may be difficult. Whereas the presence of culture-positive purulent exudate at the catheter insertion site in the presence of bacteremia with the same organism would define a catheter-related bacteremia, making the diagnosis is much more difficult with bacteremia in the absence of any inflammation at the catheter insertion site. Signs of local inflammation at the catheter insertion site are present in only about 50% of the cases of catheter-related bacteremia. Several clinicoepidemiologic features are helpful in distinguishing catheter-related bacteremia from bacteremia caused by another source. These findings, which may be present alone or in combination, include the following:

1. Absence of an alternative source for bacteremia on clinical examination

2. Patient not considered at high risk for bacteremia

3. Presence of local purulence at the catheter exit site

4. Presence of Candida endophthalmitis in patients who are receiving total parenteral nutrition

5. A septic picture that is refractory to antimicrobial theapy

6. Bloodstream infection caused by staphylococci or Candida species

7. Dramatic improvement of a febrile syndrome following catheter removal

8. Clusters of bacteremia due to Enterobacter species for seemingly unapparent reasons (suggesting common-source contamination of IV fluids)

Many definitions for catheter-related infections have been used, but none is considered standard or uniform. However, any definition used should incorporate both clinical and laboratory criteria in an attempt to increase the utility of the definition. Examples of definitions for local and bacteremic catheter-related infections that may be used are given below. For local infections, definitions include

• Purulent discharge at the exit site, either spontaneous or expressed on palpation of the site, regardless of whether an organism is cultured from the site
• Erythema, tenderness, and/or induration (any two of the three) at the exit site with serous or serosanguineous discharge, either spontaneous or expressed on palpation, in the presence of a positive exit-site culture (moderate to heavy growth of a single or predominant organism)

Definitions for bacteremic infection include those for definite infection:

• A single positive peripheral blood culture from a patient with clinical and microbiologic data disclosing no other source of the bacteremia in the presence of a semiquantitative or quantitative culture of a catheter segment (proximal or distal) from which the same organism (species, antibiogram) was isolated
• Differential quantitative blood cultures with a 10-fold or greater colony-count difference between blood cultures drawn from the catheter and simultaneously from a peripheral venous blood culture
• A single positive peripheral blood culture from a patient with isolation of the same organism (species, antibiogram) from purulent, serous, or serosanguineous discharge from the catheter exit site or along the path of a subcutaneously tunneled catheter or from the subcutaneous pocket containing a reservoir of a totally implantable device

Definitions for probable infection include

• Two or more positive blood cultures for the same organism (species, antibiogram) from any source (peripheral or retrograde intravascular device cultures) from a patient with clinical and microbiologic data disclosing no other source for the bacteremia except the intravascular device
• One positive blood culture for S. aureus or Candida species from any source (peripheral or retrograde intravascular device culture) in a patient with clinical and microbiologic data disclosing no other source for the bacteremia except the intravascular device
• One positive blood culture for any organism commonly associated with intravascular device–related infection (coagulase-negative staphylococci, Bacillus species, Corynebacterium species, and M. furfur) from any source (peripheral or retrograde culture) in an immunocompromised patient or a neutropenic patient (neutrophils <500 cells/μL) with clinical and microbiologic data disclosing no other source for the bacteremia except a centrally placed intravascular device

The management of intravascular device–associated infections depends on several variables, including the type of infection (local or bacteremic), the microorganism(s) involved, the type of device (peripheral or central catheter, totally implanted device), and the severity of illness of the patient. A guideline was published recently that outlines these variables in detail and provides detailed recommendations for the management of intravascular catheter–related infections.57 Local infections at the catheter insertion site may be treated with catheter removal, local care, and topical and/or systemic antimicrobial agents as appropriate. If a spreading cellulitis develops, extending along the course of the catheter, then systemic antimicrobials and catheter removal are indicated. The antimicrobials chosen should be based on microbiologic cultures obtained from the discharge present at the insertion site.

The management of bacteremic infections is more complex and depends on the microorganism, the type of device, and the clinical status of the patient. Any peripheral (venous or arterial) or noncuffed central catheters (venous or pulmonary arterial) that are being used in the short term and are suspected of being the source of a bacteremic infection in a patient with no other obvious source should be removed, the administration set changed, and the catheter tip and intracutaneous portion of the insertion sheath sent for culture. The catheter should be removed regardless of whether there is evidence of inflammation at the insertion site because over 50% of the catheter-related bacteremias occur without any evidence of local site inflammation.

An option for the management of CVC-related bacteremia due to coagulase-negative staphylococci, without removal of the catheter, is the use of systemic antimicrobials and the antibiotic-lock technique,57 but the risk of recurrent bacteremic infection is approximately 20%.58 Thus this option must be considered carefully on an individual basis. In general, if the indication for the central catheter remains, a new catheter should be inserted into a new site if the catheter is proved to be or is strongly suspected as the source of the infection. In the absence of inflammation or local purulence at the catheter insertion site, and when the evidence suggesting the line as the source for infection is not compelling, it is reasonable to do a guidewire catheter exchange at the same site, but the catheter that is removed should be cultured, and if it is positive, the newly inserted catheter should be removed and another catheter inserted in a different site.35

Device-related bacteremia that is suspected to arise from cuffed central long-term indwelling catheters (Hickman, Broviac, or Cook catheter) or totally implanted devices does not necessarily require removal of the device.57 If there is obvious local purulence, bacteremia due to S. aureus or Candida species, a spreading tunnel-associated cellulitis, septic thrombophlebitis, tricuspid valve endocarditis, or a persisting bacteremia despite appropriate parenteral antimicrobial therapy, removal of the device is required, often with surgical dissection. Retention of a cuffed long-term central catheter with catheter-related S. aureus bacteremia has been associated with a higher relapse rate of bacteremia and higher sepsis-related mortality.59 In the setting of bacteremia due to other microorganisms and in the absence of complications, a course of parenteral antimicrobial therapy with or without antibiotic-lock therapy without removal of the cuffed central catheter or implantable device may be sufficient in as many as two-thirds of cases.57,60,61 Following treatment, these patients should be monitored carefully for recurrences of bacteremic infection.

Definitive antimicrobial therapy for device-associated bacteremia depends on appropriate identification and susceptibility testing of the infecting microorganism. Empirical therapy prior to the identification and susceptibility results will be influenced by local microbiologic patterns of line-related infection and susceptibilities. However, a combination of an IV antistaphylococcal penicillin (vancomycin if methicillin-resistant S. aureus is prevalent) and an aminoglycoside or a third-generation cephalosporin will provide coverage for most gram-positive and gram-negative microorganisms. Any catheter-related bacteremic infections caused by S. aureus should be treated for 14 days with parenteral therapy to avoid metastatic infectious complications. The optimal duration of therapy for infections caused by organisms other than S. aureus is unknown, but 7 to 14 days has been suggested.57 Catheter-related candidemia may be treated with a short course of amphotericin B (3 to 7 mg/kg total dose) or fluconazole (200 to 400 mg/day for 10 to 14 days). In the susceptible patient population most often found in the ICU, a thorough evaluation for metastatic candidal infection, including careful funduscopic examination, is necessary. The finding of persistently positive blood cultures after catheter removal and initiation of antifungal therapy or the finding of metastatic candidal lesions would necessitate more prolonged therapy.

Attention to detail in all aspects of the placement and care of intravascular devices is necessary to minimize the risks of device-related infection. This attention to detail is particularly important in the ICU, where the use of lines is intensive and patients, by nature of their underlying illnesses, are at high risk of device-related infections. The processes to which preventive strategies may be applied may be divided conveniently into the catheter itself, the catheter insertion, catheter site care, catheter care, and the delivery system (Table 50-4). The details on which attention should be focused, as well as the accompanying rationale for the specific strategy, are presented. Detailed guidelines for the prevention of intravascular device–related infections are available from the Centers for Disease Control and Prevention.49

Although new scientific approaches to establishing improved techniques for catheter care are necessary and new technologic advances such as microbe-resistant materials will help to reduce the incidence of catheter-related infection, there is no substitute for meticulous care and attention to detail in care of the lines.