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Intravascular catheter-related infections
Introduction
Intravascular catheters are essential in the care of critically ill patients in order to allow safe intravenous administration of medications, help in the monitoring of hemodynamic parameters, and aid in the intravenous administration of fluid resuscitation. In European intensive care units (ICUs), the central venous catheter (CVC) utilization rate was, on average, 71 CVC days per 100 patient days. Moreover, bloodstream infections (BSIs) were catheter-related in 42.6% of cases, and rates of catheter-related BSIs (CR-BSI) ranged to levels as high as 1–6.2 per 1000 catheter days. In the United States, 15 million CVC days are estimated to occur each year in ICU patients, in addition to about 40,000 CVC-related BSIs, leading to a rate of more than 2 per 1000 CVC days. However, peripherally inserted central venous catheters (PICCs) are less frequently placed for central access in critically ill patients, and their use in the ICU setting remains debated.
CR-BSIs are associated with a significantly increased mortality. However, recent studies describe a nonincreased risk of mortality in a cohort of patients where catheters were systematically removed. The excess of ICU length of stay is estimated at 9–12 days. , Early adequate antimicrobial therapy and catheter removal are key components of therapy in the case of CR-BSI with severe sepsis or shock. Data on duration of antimicrobial therapy are scarce and will be discussed.
In contrast to other hospital-acquired infections, the majority of the risk factors for intravascular catheter infection are linked to the device itself and can be prevented efficiently. , Healthcare worker education and training and continuous unit–based improvement programs are therefore instrumental. , We will discuss the potential interests of new technical developments and put them into perspective according to the available recommendations. Our focus will be mostly on short-term CVC use in critically ill patients, though other catheters are also mentioned.
PICCs, arterial, and short-term dialysis catheters will be discussed separately in the electronic supplemental material.
Pathophysiology and microbiology
The colonization of the catheter can occur by two main pathways: the extraluminal route or the intraluminal route. Colonization of the catheter from its dermal surface is the predominant route of colonization for short-term CVCs (<15–30 days), whereas colonization via the intraluminal route resulting from hub contamination predominates for long-term CVCs. These main differences should be kept in mind when choosing between different diagnostic options and preventive strategies.
The occurrence of bacteremia caused by common skin organisms (e.g., coagulase-negative staphylococci [CoNS] or Staphylococcus aureus ) is a major criterion for the diagnosis of CR-BSI, although Enterobacteriaceae and Pseudomonas aeruginosa are increasingly observed these last years, especially in case of femoral site of insertion. ,
Definitions
Definitions that are currently accepted are displayed in Table 111.1 and apply to all types of vascular catheters. Having them in mind is important to better interpret clinical evidence. Two major definitions are used to define BSIs caused by vascular catheters: central line associated–BSI (CLA-BSI) and catheter-related BSI (CR-BSI). The CLA-BSI definition requires a single positive blood culture for a typical pathogen (or two positive blood cultures for a skin commensal) without positive tip culture or positive peripheral blood cultures. Although this definition is accepted for surveillance, it overestimates the true incidence of catheter infections and remains subjective in assigning the source of infection. , A recent meta-analysis illustrated that the consistency between CLA-BSI and CR-BSI definitions was rather poor. Indeed, the CR-BSI definition is a more specific clinical definition that requires specialized microbiologic data (e.g., differential time to positivity [DTP], catheter tip culture) and positive peripheral blood cultures.
Diagnosis of catheter infections
Clinical diagnosis
An old study showed that inflammation signs (e.g., erythema or redness) at the exit site are nonspecific and are rarely present in case of CR-BSI. However, an analysis including four randomized controlled trials (RCTs) with more recent data illustrated that local signs at removal were significantly associated with CR-BSI and were highly predictive for catheter infection, especially in the first 7 catheter days. Usually, when CR-BSI is suspected, the common practice in the ICU is to remove the CVC and replace it at a new site. However, only about 15%–25% of CVCs so removed indeed proved infected upon quantitative tip culture.
Diagnosis of CR-BSI after catheter removal
Cultures at catheter removal should only be performed if an intravascular catheter infection is suspected (see Table 111.1 ). Although the qualitative broth tip culture has a high sensitivity, its specificity is very low, and contamination cannot be discriminated from infection; it should therefore be abandoned. Quantitative culture techniques have been developed and explore either the extraluminal part of the catheter (semiquantitative Maki technique) or the extraluminal and intraluminal parts via vortex wash or sonication. The semiquantitative culture techniques appear to be as accurate as the quantitative methods for diagnosis of catheter-related infections. Of note, the sensitivity of the catheter culture may be decreased in case of prior use of antimicrobials. , This point should be kept in mind when interpreting negative or borderline culture results. Therefore the need to perform diagnostic tests (blood and catheter cultures) before starting any new antimicrobials should be always emphasized.
TABLE 111.1
Proposed Definitions
Adapted from Timsit JF, Rupp M, Bouza E, et al. A state of the art review on optimal practices to prevent, recognize, and manage complications associated with intravascular devices in the critically ill. Intensive Care Med . 2018;44(6):742–759; and Buetti N, Timsit JF. Management and prevention of central venous catheter-related infections in the ICU. Semin Respir Crit Care Med. 2019;40(4):508–523.
| Definition | Comments | |
|---|---|---|
| Catheter tip colonization | Positive culture of the catheter tip that grew to ≥15 cfu/mL (semiquantitative), 10 2 cfu/mL (quantitative sonication), or 10 3 cfu/mL (quantitative vortexing). | Qualitative culture should no longer be used. |
| Exit site infection | Tenderness, erythema, or induration > 0.5 cm at the exit site. It may be associated with other signs and symptoms (e.g., fever or purulent drainage). | Positive culture of exudate confirms the exit site infection microbiologically. |
| Catheter-related bloodstream infection (CR-BSI) | One positive blood culture obtained from peripheral vein and clinical manifestation of infection and (1) a catheter tip colonization or (2) a differential time to positivity of more than 120 min and no obvious source of bacteremia except the catheter or (3) simultaneous quantitative cultures of blood with a ratio of >3:1 cfu/mL of blood (catheter vs. peripheral blood). | Simultaneous quantitative culture from a peripheral vein and the catheter of 3–5: 1 ratio is rarely used. |
| Central line associated–bloodstream infection (CLA-BSI) | One positive blood culture and clinical manifestation of infection in a patient with a catheter in place with no other source of bacteremia except the catheter. | Easy to use for surveillance purposes. However, this definition can lead to an overestimation of the BSI incidence caused by catheter infection, especially in ICU and in onco-hematologic patients. |
| Catheter-related clinical sepsis | Clinical manifestation of infection that disappears within 48 hours of catheter removal and a positive catheter tip culture and no other obvious treated source of infection. | Represent 30%–50% of catheter-related infections with general manifestation. Not easy to collect routinely, but may need antimicrobial treatment. |
| Suspected intravascular catheter infection | The presence of one of the following signs: elevation of inflammatory signs (fever or organ dysfunction) after catheter placement without other infectious or noninfectious explanations; exit site infection signs (purulent discharge, redness, or cellulitis >0.5 cm diameter, abscess); positive blood culture without identification of infectious focus. | This definition is based on expert opinion. The exclusion of other sources of infection can lead to important variability in the final classification in ICU patients. The purulence of the exit site of the catheter is a strong argument to impute the catheter as the source of infection. |
| Clinical/laboratory signs or risk factors for complicated catheter infection |
|
This definition is based on exclusion criteria used in a study investigating a watchful waiting strategy versus immediate catheter removal in ICU patients with suspected catheter-related infection. |
| Noncomplicated intravascular catheter infection |
|
In contrast, a persistent CR-BSI is defined as the presence of positive blood cultures after 72 hours of adequate antimicrobial therapy. |
| Catheter-related thrombophlebitis | Clinical definition: induration or erythema, warmth, and pain or tenderness along the tract of a catheterized or recently catheterized vein. Alternatively, imaging evidence of vascular thrombosis and clinical manifestations concordant with location of a catheterized or recently catheterized vein. |
BSI , Bloodstream infection; cfu , colony-forming unit; CoNS , coagulase-negative staphylococci; ICU , intensive care unit.
Diagnosis of CR-BSI with catheter in place
In the case of severe sepsis or shock, the catheter should be promptly removed. , However, most of the suspected catheter infections are not life-threatening, and diagnostic techniques allowing an accurate diagnosis while keeping the catheter in place are an attractive option (see “ Management of Catheter-Related Infections ”).
Quantitative culture of the catheter exit site
A negative culture of the catheter exit site in case of suspicion of infection may rule out the diagnosis of CR-BSI or colonization but their role remains debated in the literature. , Alternatively, the combination of skin and flushed needleless connectors culture (i.e., connectors closing catheter hubs requiring a less invasive microbiologic diagnostic) may be a valuable option for ruling out catheter colonization, thus avoiding any unnecessary catheter replacement.
Differential time to positivity
Simultaneous blood cultures, drawn through the catheter and a peripheral vein without removal or exchange of the catheter, are accurate means for predicting CR-BSI. The time to positivity (TTP) of a blood culture is related to the magnitude of the bacterial inoculum: if a catheter is the source of bacteremia, blood cultures sampled through this catheter will likely have an increased inoculum than peripheral samples and should yield bacterial growth more quickly. Therefore the differential time to positivity (DTP) of hub-drawn blood cultures as compared with peripherally drawn blood cultures has been proposed as a means to diagnose CR-BSI (i.e., the difference in the time to positivity between hub blood and peripheral blood cultures). If a cutoff of 120 minutes is used, sensitivity and specificity are greater than 90% ; moreover, for short-term catheters, a meta-analysis documented a sensitivity of 89% and specificity of 87%. Theoretically, this technique only explores the intraluminal route of infection, but other authors showed that it can be used for both short-term and long-term CR-BSI diagnosis, , thus indirectly suggesting a good yield for the extraluminal route diagnosis. However, aspiration of blood cultures drawn through the catheter lumen is technically impossible in one case out of four. Furthermore, each lumen may represent a source of infection. It has been shown that the sampling of one out of three lumens of triple-lumen catheters misses 37% of the CR-BSI cases. Moreover, the role of DTP for the diagnosis of several specific microorganism CR-BSIs remains debated. For diagnosis of Candida CR-BSI, one retrospective study showed good sensitivity (85%) and specificity (82%), whereas other investigators reported a specificity of only 40%. Similar controversies are observed for the diagnosis of S. aureus, CoNS, or non-AmpC Enterobacteriaceae CR-BSI with DTP.
Paired quantitative blood cultures
A diagnosis of CR-BSI can be made if the microorganism colony count is higher in blood cultures obtained from the CVC versus percutaneously obtained peripheral blood. Although it is an accurate method to diagnose CR-BSI, this technique is limited by the lack of standardized cutoff points. In addition, most laboratories rarely perform quantitative blood cultures. ,
Prevention
The only sure way to prevent CR-BSI, in addition to other catheter-related complications, is to avoid unnecessary intravascular catheters. , An increasing body of studies indicates the safety of peripheral intravenous lines for administration of low-dose vasoactive medication. , Therefore a minimization of catheter use or the use of alternatives are important tools for CR-BSI prevention. The need for CVCs should be assessed daily, and unnecessary CVCs should be removed.
Guidelines on CR-BSI prevention have been recently updated. , , , , , They belong to two categories: studies applying multimodule programs to improve general infection control measures when using catheters, such as surveillance, education, and quality management strategies, and studies that have tested new biomaterials, antiseptic dressings, and catheter locks. Their key points are illustrated in Figs. 111.1 , 111.2 , and 111.3 .
Catheter insertion
Sterile barrier precautions
Full barrier precautions using sterile gloves, long-sleeved sterile gown, procedure mask, cap, and large sterile sheath drape during catheter insertion are essential for the prevention of CR-BSI and should represent the standard during CVC and pulmonary catheter insertion. , Only one prospective randomized study in surgical patients did not show any additional benefit for full sterile barrier precautions. Nevertheless, most available evidence suggests risk reduction with this intervention. A bedside checklist should be used to improve the compliance with appropriate insertion procedures.
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