128 Vascular Catheter–Related Infections

Catheter-related bloodstream infection (CRBSI) is the third leading device-related infection among U.S. hospitals and ambulatory surgical centers in the United States participating in the National Healthcare Safety Network (NHSN) that report to the Centers for Disease Control and Prevention (CDC).¹ In the 2009 report, 14,332 primary bloodstream infections over 7.4 million catheter days (1.93 infections per 1000 catheter days) were identified. This infection rate ranks third in magnitude behind catheter-associated urinary tract infections and ventilator-associated pneumonias.¹ CRBSI ranks second worldwide only to ventilator-associated pneumonia.² The estimates in both of these reports are limited to only central venous catheter (CVC) infections. However, peripheral venous catheters, more permanent cuffed and tunneled catheters, arterial catheters, and peripherally inserted central catheters (PICC) also have associated bloodstream infection rates.³^–⁴

The cost of CRBSI in terms of morbidity is significant to both the patient and the healthcare provider. The impact on resource utilization was summarized by Dimick et al., who conducted a prospective cohort study among surgical ICU patients at a large tertiary care center. A single CRBSI increased hospital costs by $56,167 and hospital length of stay by 22 days.⁵ The increased mortality of CRBSI was estimated in a meta-analysis by Siempos et al. He analyzed eight different studies that included 2540 ICU patients and determined the relative risk of mortality to be 1.57.⁶ In a mixed cohort of 2201 medical and surgical patients hospitalized in 15 French ICUs, CRBSI was associated with an estimated excess mortality of 11.5% to 20%.⁷

Because of the burden of mortality to patient populations and the increased costs to payers, CRBSI was included in the list of eight hospital-acquired conditions, the so-called “never events.” By inclusion as a “never event,” the Centers for Medicare and Medicaid Services (CMS) are prohibited by Congress from reimbursing hospitals for charges associated with these conditions after October 1, 2008.⁸ Thus, prevention of CRBSI has attracted substantial attention from multiple stakeholders in the healthcare industry.

This chapter will clarify some commonly used terms associated with CRBSI, discuss various pathogenic theories, analyze patient- and hospital-related risk factors, discuss available diagnostic techniques, and review the existing data on infections associated with the most commonly employed types of vascular catheters.

Definitions

Clinicians and researchers historically have used different definitions for vascular catheter–related infections. Infections can be linked to peripheral, central, venous, and arterial catheters. These catheters can further be designated as permanent, short-term, or long-term. The clinical presentation of a catheter-related infection can be designated as either local (site inflammation, purulent drainage, tenderness) or systemic (bacteremia with or without systemic sepsis). Although it is certain that inanimate objects do not become “infected,” there is strong evidence to suggest that bacteria may be able to live and multiply on catheter surfaces, possibly deriving nutrients from catheter polymers, the deposited glycocalyx of certain bacterial species, and other nonviable bacteria.^9,¹⁰ Earlier clinical investigations used erroneous descriptions and definitions for catheter contamination, colonization, and infection. These different definitions have led to confusion and incorrect interpretations by previous investigators.¹¹ This is further complicated by confusion regarding subtle differences between surveillance definitions by the NHSN¹ and clinical definitions. The commonly accepted clinical definitions have been previously published^11,¹²:

Localized catheter colonization: significant growth of a microorganism in a semiquantitative or quantitative culture of the catheter tip, subcutaneous segment of the catheter, or the catheter hub (see Diagnostic Techniques), without evidence of systemic infection.

Microbiological exit site infection: exudate at the catheter exit site yields bacterial or fungal growth on a standard qualitative culture with or without concomitant bloodstream infection.

Clinical exit site infection: tenderness, erythema or site induration greater than 2 cm from the catheter exit site, with or without other signs or symptoms of infection.

Tunnel infection: tenderness, erythema, and/or induration greater than 2 cm from the catheter exit site, along the subcutaneous tract of a tunneled catheter.

Pocket infection: purulent fluid in the subcutaneous pocket of a totally implanted intravascular device that might or might not be associated with spontaneous rupture and drainage or necrosis of the overlying skin, in the absence of concomitant bacteremia.

It is important to understand that both microbiological and clinical exit site infections, tunnel infections, and pocket infections, when accompanied by a positive blood culture, will be classified as a CRBSI for hospital surveillance purposes.^1,^11,¹²

Culture of drainage around a catheter insertion site may in some situations be helpful in that a positive bacterial culture result assists in confirming the presence of an exit site infection. It is important to also understand that values of 15 CFUs or less for semiquantitative and 10³ CFUs or less for quantitative cultures may be regarded as a negative culture, a contaminant, or an insignificant infection that does not require treatment in the absence of a confirmatory blood culture. Insertion site manifestations of inflammation are neither sensitive nor specific for diagnosing CRBSI or catheter colonization. Immunosuppressed patients may manifest local signs of inflammation, and other patient groups may develop intense local insertion site inflammation without associated CRBSI.¹⁴

Pathogenesis

Microbial colonization and biofilm formation on intravascular catheters are universal, occurring soon after catheter insertion.^9,^10,¹⁵ The final determinate of whether colonization progresses to clinical infection is multifactorial. A variety of host factors, catheter composition, and the interaction between microorganisms and the catheter surface may all contribute to the ultimate development of CRBSI.

There are four established routes for catheter contamination leading to CRBSI:

1 Microorganisms migrate from the skin at the insertion site into the subcutaneous tract along the external surface of the catheter and ultimately gain access to the distal intravascular catheter segment.¹⁶ This is the most common mechanism for developing infection of short-term non-cuffed non-tunneled central venous catheters.

2 Microorganisms gain access to the catheter through the hubs or ports of the vascular device. The most common sources for contamination are the hands of healthcare workers or the infusion of minimally contaminated fluids (contaminated at the bedside) or attachment of contaminated tubing. This route of infection is more commonly identified in patients with long-term tunneled catheters (Hickman, Broviac, Groshong) or mediports.¹⁶ Bacteria can be introduced via one or more hubs from frequent manipulations. As the biofilm grows, bacteria migrate into the inner luminal surface and gain access to the venous circulation. In low-flow regions, the biofilm attachment is weaker and breaks more easily, allowing entry of bacteria into the venous circulation.¹⁶

3 Remote infections may produce bacteremia and hematogenously seed an intravascular device. Although this scenario is plausible, hematogenous catheter seeding is considered a rare cause of CRBSI.¹⁶

4 Infusate contamination is a rare fourth mechanism for development of CRBSI. Parenteral nutrition solutions, lipid emulsions and heparin flush solutions can support bacterial and fungal growth, but the risk from infusate contamination today is considered very low.^17,¹⁸

Following insertion, the intravascular portion of the catheter is quickly coated with a thrombin layer covering both the external and internal surfaces. Thrombin contains a number of proteins including fibronectin, thrombospondin, and laminin which create an adhesive surface on the catheter that promotes adherence of microbial pathogens. Multiple species of Staphylococcus epidermidis, Staphylococcus aureus, Candida albicans, and various gram-negative organisms are all capable of adhering to catheter surfaces.¹⁹ A mature biofilm can shield organisms from antibiotics at 10 to 1000 times the concentration required to kill planktonic bacteria.²⁰

This helps explain why the commonly reported pathogens for hospital-acquired bloodstream infections remain coagulase-negative staphylococci (Staphylococcus epidermidis), Staphylococcus aureus, enterococci, and Candida species.²⁰ Gram-negative bacilli account for approximately 20% of CRBSIs reported.^20,²¹

Risk Factors

A number of factors potentiate the risk for CRBSI. These are generally similar to the same factors that increase the risk for any hospital-acquired infection. Extremes of age (i.e., pediatric, elderly), immunodeficiency, chronic disease states, remote infection sites, and heavy colonization of the skin with bacteria or fungi may all increase the risk. Alterations in skin integrity (psoriasis, burns) also increase risk. Whereas patient-related factors cannot be significantly modified during an acute illness, they must be considered when developing catheter maintenance protocols. Penel et al. identified age younger than 10 years, difficulties with catheter insertion, and the need for total parenteral nutrition as significant risk factors for intravascular device–related infections.²²

In contradistinction to patient-related risk factors, many hospital-related risk factors can be significantly modified, and prevention protocols are designed to focus on these risks.^22,²³ A number of interventions have been proposed by the CDC to assist in the prevention of CRBSI.^24,²⁵ Implementation of educational programs for hospital personnel regarding proper insertion and maintenance of intravascular catheters and appropriate preventive control measures should reduce infection rates. A number of other interventions and measures are also recommended collectively as the “central line bundle.” These recommended procedures and interventions are: hand washing, using full sterile-barrier precautions during insertion of central venous catheters, preparing the insertion skin site with chlorhexidine, avoiding the femoral site if possible, and removing central venous catheters as soon as possible when no longer needed.²³ In a large multicenter trial involving 108 intensive care units (ICUs), a central line bundle was initiated to determine its effect on reduction of catheter-related bloodstream infections. Implementing these strategies reduced the mean rate of CRBSI from 7.7 to 1.4 per 1000 catheter-days at 16 to 18 months follow-up (P < 0.002).²⁶ This large multicenter study provided evidence that the guidelines recommended by the CDC^24,²⁵ are indeed beneficial in reducing CRBSI rates. Others have suggested that the act of prospective surveillance alone without any specific intervention to reduce CRBSI will also have a beneficial result in decreasing infection rates.²⁷

Although the number of catheter manipulations and the experience of the individual performing the catheter insertion may be risk factors, these often cannot be changed or controlled for the individual patient at risk. The need for total parenteral nutrition, the area within the hospital where the insertion is performed, and the number of catheter lumens have all been associated with increased risk for catheter-related infection.²⁸ Cutdowns should be avoided whenever possible because of the historically high incidence of catheter-related complications.²⁹ The most common risk factors for catheter colonization and CRBSI that can be successfully altered are separately discussed.

Anatomic Insertion Site

An early study by Mermel showed that the use of the internal jugular site, particularly for pulmonary artery catheters, is a significant risk factor for catheter-related infection.³⁰ This may be related to the closer proximity of oropharyngeal secretions, greater catheter motion from neck movement, and greater difficulty in maintaining a sterile occlusive dressing.³⁰ However, it is still recommended that the internal jugular or the femoral vein site be used over the subclavian vein site for short-term hemodialysis catheters to reduce the risk of subsequent subclavian vein stenosis.^24,²⁵

The femoral site is also more likely to become heavily colonized and thus is also at higher risk for CRBSI. Merrer et al. in a randomized controlled clinical trial involving eight different ICUs identified a threefold higher incidence of clinical sepsis (with or without bloodstream infection) and a tenfold increase in thrombotic complications when femoral catheters were compared to subclavian catheters.³¹

Data collected in our own center suggest that colonization rates for femoral sites, even with the use of chlorhexidine and silver sulfadiazine-bonded catheters, are significantly higher than for subclavian or internal jugular catheter sites.³²

Duration of Catheter Use

Bacterial colonization of catheter surfaces begins shortly after insertion and is directly proportional to the length of time a catheter remains in place. The risk of CRBSI increases over time. Nonetheless, the optimal timing of catheter removal remains uncertain. The risk of an individual catheter causing CRBSI is low if inserted under optimal sterile conditions and removed within 4 to 7 days. However, critically ill patients typically require venous access for prolonged periods, and the timing of catheter removal must be weighed against clinical necessity. Central venous catheters and pulmonary artery catheters do not have predetermined lifespans.³³

Recommendations and guidelines for catheter exchange may be used to minimize CRBSI and to prolong site use on the basis of existing published data. However, it is important to realize that CRBSI risk factors are multifactorial and that global recommendations for catheter maintenance or removal may not be applicable to the individual patient. Generally, catheters should be removed (1) when they are no longer needed, or (2) if CRBSI is suspected clinically and appropriate cultures confirm clinical suspicions (see Diagnostic Techniques). Individual hospitals, individual ICUs, and in certain situations individual practitioners should study their catheter infection rates to develop specific guidelines appropriate to their practice patterns and environment. Rates of CRBSI per 1000 catheters-days can be calculated and compared with published standards.^1,^2,^24,²⁵

Diagnostic Techniques

The clinical diagnosis of CRBSI is often inaccurate, leading to premature catheter removal. Assuming that appropriate sterile technique during insertion and appropriate site care have been followed, the presence of entry-site inflammation is neither sensitive nor specific for CRBSI.¹⁴ Qualitative broth cultures collected through the CVC are generally discouraged for determining CRBSI for short-term, non-tunneled catheters. The positive predictive value of blood cultures obtained through the catheter is significantly less than from a peripheral venipuncture,^34,³⁵ and additional cultures are usually necessary to make the definitive diagnosis. However, a negative culture from either a peripheral venipuncture or a CVC has excellent negative predictive value, and cultures obtained through the catheter are frequently performed to rule out CRBSI.³⁵

The unreliability of clinical diagnosis and qualitative blood cultures has led to a variety of microbiological diagnostic techniques. These can be categorized into diagnostic methods that require catheter removal and catheter-sparing diagnostic methods. Because each method has advantages and disadvantages, some investigators have suggested that simply performing peripheral blood cultures and clinical evaluation may be all that is necessary and cost-effective. Clinical diagnosis alone and qualitative blood cultures will both significantly overestimate the rate of CRBSI and should generally be avoided.

Diagnostic Techniques Requiring Removal of the Central Venous Catheter

Quantitative Catheter Cultures

This type of culture involves flushing, sonicating, or vortexing the catheter segment with broth. This is designed to retrieve organisms from both the internal and external catheter surface. This technique is particularly useful for catheters in situ for more than 7 days.¹¹ In this situation, intraluminal spread from the hub is the most likely mechanism for catheter colonization. Therefore, obtaining a culture from both the internal and external surface should be more sensitive and specific. A culture yielding over 10³ CFU is diagnostic for CRBSI if accompanied by the appropriate clinical diagnosis, a positive peripheral blood culture with the same organism, and no other likely source for the infection. A meta-analysis conducted by Safdar in 2005 showed that the pooled sensitivity and specificity for this culture technique was 83% and 87% respectively.³⁶

Semiquantitative Catheter Culture

The semiquantitative (roll-plate) technique developed by Maki and colleagues remains the most common diagnostic technique for determining catheter-related infection.³⁷ A 5-cm segment (either catheter tip or intracutaneous segment) is rolled across a blood-agar plate in a reproducible, defined manner. In the original study, a positive result was defined as more than 15 CFUs per plate, although most of the culture-positive catheters in the original study yielded confluent growth.³⁷ A positive catheter segment culture result (>15 CFUs) resulted in a 16% risk of CRBSI. This technique is probably most accurate for catheters that are removed within the first 7 days.³⁶ It may become less sensitive for more long-term catheters, because this technique does not culture the internal lumen. A recent meta-analysis of 19 studies using the semiquantitative catheter culture technique identified an overall sensitivity of 85% and specificity of 82%.³⁶