Improve CRBSI Prevention: Target Intraluminal Risks

By Marcia Ryder PhD RN

Hospitals are experiencing the economic repercussions of healthcare-acquired infections. Among these, catheter related bloodstream infections (CRBSI) are a major focus for risk reduction due to high cost and attributable mortality, especially in the ICU. The estimated annual cost burden of these infections exceeds $ 1.4 billion dollars. Since both the number of devices as well as their associated infection rate is more than double outside the ICUs, the need for improvement in all areas is compelling and urgent [1,2].

Within the last five years, healthcare systems investigated strict process measures and effective technology for innovative, evidence based solutions. A “bundle” and “checklist” approach to prevention was quickly adopted [3]. The most notable the Institute for Healthcare Improvement’s Campaign to save lives from CRBSI by bundling evidence-based prevention measures including hand hygiene, maximum sterile barrier, chlorhexidine skin antisepsis, optimal catheter site selection, and prompt catheter removal [4]. This strategy has been somewhat effective in ICUs but has not reduced the central line infection rate to zero [5,6].

The current prevention bundles focus primarily on the prevention of extraluminal colonization. This may explain their success in the ICUs where catheters are used over a short four-day mean length of stay. None of the bundle interventions address the intraluminal source of infection, the origin of most CRBSIs in longer dwelling catheters required in neonatal, pediatric, TPN, antibiotic, hemodialysis, oncology and hematology, and non-ICU adult patient populations.

In order to develop a comprehensive approach to both extra and intraluminal CRBSI prevention, it is imperative to scrutinize the causative factors of intraluminal contamination as rigorously as has been done with extraluminal risks. But to do this effectively, it is necessary to understand how the internal lumen becomes colonized and how this can lead to CRBSI.
The pathogenesis of all vascular access-related bloodstream infections originates with biofilm formation (i.e. colonization) on either the external and/or the internal surfaces of a venous or arterial catheter [7]. The primary source of bacteria colonizing the external surface of the catheter is the skin. The initial colonization occurs with attachment of bacteria to the tip and external catheter surface with passage through the skin during insertion. The adherent bacteria form a biofilm on the catheter surface or within the skin tract. Microbial biofilms on the intraluminal surface originate from microorganisms transported through contaminated injection ports, needleless connectors, stopcocks and catheter hubs. When the number of bacteria released from the biofilm overwhelms the immune system, bloodstream and focal infection can occur.

Catheter-related bloodstream infection originating from extralumnial biofilm usually occurs within one week of insertion while the internal lumen is the primary source after six to seven days. However, Safdar and Maki found that after changing protocols in short term ICU catheters to chlorhexidine skin antisepsis and/or a chlorhexidine foam disc dressing, the primary source of infection shifted from extraluminal  to the internal lumen as few as 3.8 days (mean) [8].

The external and internal surface of the female luer, i.e. the hub of the catheter or stopcock, is the immediate portal of entry to the intraluminal surface of the catheter. Biofilm forming within the catheter hub migrates within the lumen and disperses cells that are flushed into the bloodstream [9]. The hub becomes contaminated by the healthcare worker or caregiver’s hands during catheter manipulation e.g. tubing or connector changes, bolus injections, or blood sampling. The risk of colonization increases with poor hand hygiene, as well as in the presence of residual blood, lipid emulsion, or nutrient solutions within the hub.

This is important because colonization of the intraluminal surface of the catheter hub has been identified as a significant risk for CRBSI. Hub colonization due to frequent opening and manipulation of intravenous systems is the cause of 29-38% of catheter infections and 60% of CRBSI in the ICUs [10]. Mahieu et. al. studied CRBSI risk factors in neonatal intensive care unit patients and found that hub colonization demonstrated the highest risk for infection (OR=44.4, CI=4.8 to 42.6), much higher than exit site colonization (OR=5.13) and other factors [11].

In addition to the catheter hub, intraluminal contamination can also result from the misuse of the numerous components of the vascular access system. Components most often cited as infection risks include access sites such as needleless connectors, injection ports and stopcocks. The CDC has recommended the practice of cleaning injection ports since 1982 but compliance has been poor.

Appropriately, access site and hub disinfection (AS/HD) is now recognized as a key prevention strategy. The 2009 Joint Commission’s National Patient Safety Goals require both access site and hub disinfection in all patient care settings including hospitals, critical access hospitals, long- term care facilities, home care, and ambulatory care [12]. There are currently seven U.S. and international documents with recommendations for AS/HD protocols. The SHEA/IDSA recommendations not only include AS/HD procedures but also recommend monitoring for compliance. [13]

Disinfection of access sites and hubs seems like a relatively simple low-tech procedure but in reality the ability to accomplish complete eradication of organisms on the various shaped connectors and catheter hubs is quite complex. Complete disinfection is dependent on a combination of variables 1) the microbial burden, 2) the antiseptic agent, 3) concentration of the agent, 4) contact time of the agent and 5) the method of application.

Passage of bacteria through needleless connectors appears to be associated with the level of microbial burden on the external septum. Yebenes et al. contaminated the septums of three different connectors with 100, 500, and 1000 CFU/ml of S. epidermidis [14]. The connectors were flushed with or without prior disinfection with 70% isopropyl alcohol (IPA) and the CFU then counted in the effluent. No bacteria were found in the effluent of one connector after disinfection at any inoculum level but pass through did occur with 1,000 CFU when not disinfected. Bacteria were present in the effluent of the other two connectors at 500 CFU with no disinfection and at 1,000 CFU after disinfection. These differences demonstrate that the level of microbial burden on the septum is a risk factor but transfer through to the catheter is dependent on the design of the device and septum disinfection.

In the clinical setting, the microbial burden on needleless connectors was found to be greater than 1,000 CFU on 64% of patient connectors studied in a bone marrow transplant unit [15]. Casey et al. found that 18% of stopcock entry ports with a positive displacement connector attached were contaminated after only 72h in situ [16]. Ryder et al. collected needleless connectors from patients in a medical ICU and found extensive multi-organism biofilms on both the external septums and within the connector flow path [17].

Biofilm

Biofilm Inner Flow Connector

Investigators measuring hub colonization as an infection risk culture the internal surface of the catheter hub or stopcock. Casey et al. found a range of 1-810 cfu within the hub after disinfection of the external surface of the stopcock with a needleless connector in place [16]. Horvath et al. cultured the external threads of 51 catheter hubs in pediatric cancer patients and found that 57% of the hubs were culture positive with up to five different organisms [18]. Horvath then implemented an education program to include cleaning of the catheter hub that resulted in a reduction of culture positive external hubs from 57% to 36%, some of which still had as many as five different organisms detected. The presence of multiple organisms is consistent with the findings of Ryder where multiple species biofilms were identified on and within needleless connectors [17].

Therefore, identifying the optimum agent and method of application to eliminate the microbial burden of both access sites and internal and external surfaces of catheter hubs is essential. The effectiveness of all chemicals used for this purpose is dependent on the concentration, contact time, and the method of application of the agent.

Choice of disinfectants has come under intense scrutiny. The most common agent used for AS/HD is 70% IPA. Chlorhexidine has been found to be the most effective antiseptic agent in the prevention of CRBSI and has been recommended for use for AS/HD in several guidelines [13,19,20]. The combination of chlorhexidine and 70% IPA is superior to the single use of each agent. The benefit of chlorhexidine is the residual activity, and effectiveness in the presence of serum; the addition of alcohol increases the kill rate and drying time [21].

The contact time and, to a lesser extent, drying time of the agent are critical steps in the disinfecting process but are not addressed in the various best practice and guidance documents. Access site disinfection has been investigated at intervals ranging from five to 30 seconds [22-25]. In general, the longer the contact time the greater the effect of the agent. Ryder [24] and Menyhany [25] found that the common practice of a 3-5 sec. application of an alcohol prep pad did not eradicate 10⁴ to 10⁵ bacteria on connector surfaces regardless of the connector design. The contact time is also dependent on the concentration of the agent; the higher the concentration, the more rapid the kill time. Complete drying provides additional contact time and prevents passage of the agent into the bloodstream but extends the length of the procedure.

No matter what agent is used, the method of application is crucial. Mechanical friction and chemical kill are the underpinnings of antisepsis and disinfection procedures. In addition to inconsistent time recommendations, the terminology used within the various research reports and guidelines that describe the technique for application with prep pads is undefined verbs such as wipe, scrub, clean, aseptically cleanse, and disinfect. These are subjective measures left to the interpretation of the practitioner that lead to inconsistent and unreliable results.
New technology is needed to accomplish a consistent and reliable method to effectively perform AS/HD. As a result, various novel disinfecting products are being developed and some are now commercially available in the United States. For example a screw-on cap that covers the access surface with an alcohol-saturated foam is available but has demonstrated limited success at complete microbial eradication [26]. Alcohol impregnated caps require contact times of at least five to 15 minutes for complete kill. Dry-out time of the agent while the cap is in place is variable. These devices fit only connectors with a luer and are not applicable for hub or stopcock disinfection.

Screw-on caps with 2%CHG/IPA saturated foam have also been tested. Menyhay and Maki [24] found that connectors inoculated with 10⁵ Enterococcus faecalis were eradicated by 10 minutes but Buchman [2] found that 24 hours was required for a similar cap to achieve complete kill of multiple organisms. Neither of these is commercially available in the U.S.

A novel device, the Site-Scrub™ (PFM Medical, Inc., Oceanside, CA) differs from prep pad and “cap-style” products in that it can be used for both hub and access site disinfection. The device is positioned over the access site or catheter/stopcock hub and twisted for eight 360° turns. The foam is saturated with a 5% CHG/70% IPA solution that, when combined with mechanical friction, reduces the contact and procedure time to 10 seconds. No drying time is required.

Site-Scrub Inj Port

Site-Scrub Cath Hub

When disinfecting a catheter or stopcock hub, the design of the sectioned foam allows the brush(s) to simultaneously scrub both the internal and external surfaces of the catheter hub. It is this feature that differentiates the Site-Scrub from all other disinfection devices.

The Site-Scrub was tested in an in vitro model comparing eight turns of the Site-Scrub to a 5 second timed vigorous back and forth rub with a 70% IPA prep pad on two different brands of connectors [24]. The stopcock was also tested in separate experiments using the same methodology. The connectors were inoculated with a mean of 5x10⁴ Staphylococcus epidermidis on the external septum (access surface) of the connectors and within the hub lumen. After drying, one group received IPA pad disinfection (5 sec) and the other the Site-Scrub (10 sec). The connectors and hubs were immediately flushed. Both surface counts (cfu) and effluent counts were obtained post treatment.

All geometric mean CFU and mean log reduction counts (both surface and flush) of the Site-Scrub were statistically significantly better than the IPA prep pad. The Site-Scrub achieved zero counts on 22 of 24 connector surfaces (< 10¹) and on 23 of 24 of flushes (< 10¹). The difference between the flush counts of the stopcock hubs was significant (p < 0.001) for the Site-Scrub compared to the prep pad. There was no difference between the prep pad and the control where no disinfection was performed.

The demand for prevention of CRBSIs compels healthcare-providers to build on the successes achieved though extraluminal risk reduction bundles to include a similar scientific, evidence- based examination of intraluminal infection risks. The use of antimicrobial products for this purpose is rapidly expanding and clinicians need to not only be aware of this trend, but also critically examine the evidence when considering novel products or technology. The design and initial test results of the Site-Scrub suggest that this new type of product may provide a new and innovative solution for optimum access site and catheter hub disinfection so that connections can be made without infections.

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