Bloodstream infections

Bloodstream infections

  • Vascular Catheter Related BSIs

  • Mechanical Circulating Support-Related BSIs

Vascular catheters are placed for intravascular medication, treatment or monitoring. Risk of bloodstream infection is higher when these vascular access devices (VADs) are placed as central lines. There are a number of VADs listed in Table I.

Mechanical Circulatory Support Devices (MCSDs) are placed in large veins or arteries to augment or maintain cardiac function in patients with severe heart failure. One of the major determinants of patient survival is device-related infection. The most recent generation of MCSDs use axial flow rotary pumps with contact bearings with and smaller percutaneous leads. Because of engineering improvements, this newer generation of devices is expected to have lower rate of device-related infectious complications. Data from clinical trials demonstrate a lower incidence of pocket infection. However, only one of these studies showed that the lower BSI was linked to second-generation devices. Long-term results from the large multicenter studies, the Interagency Registry for Mechanical Circulatory Support (INTERMACS) will be available in the near future.

Definitions of CLABSI for NHSN surveillance

Central line: Central line is an intravascular catheter that terminates at or close to the heart or in one of the great vessels which is used for infusion, withdrawal of blood, or hemodynamic monitoring. Neither the insertion site nor the type of device may be used to determine if a line qualified as a central line.

Primary bloodstream infection: Primary BSIs are laboratory-confirmed (cultured blood grows organisms) bloodstream infections (LCBSI) that do not result from an infection at another body site.

Central line-associated bloodstream infection: The Centers of Disease Control and Prevention (CDC) develops definitions that are used for surveillance. surveillance system called the National Healthcare Surveillance Network (NHSN) the primary system. Of note the NHSN definitions for CLABSIs are being updated currently.

A bloodstream infection (culture blood growing organisms) is defined when a central catheter was in place at the time of, or within 48 hours before the infection onset. There is no minimum period of time that the central line must be in place in order to be considered as central line associated bloodstream infection (CLABSI).

Laboratory-confirmed bloodstream infections (LCBSI): To be considered the event must meet one of the following criteria in a patient:

  • has a “recognized pathogen” from cultured blood and the organism cultured is not related to an infection at another site. Organisms considered common skin contaminants are not included in the definition of a recognized pathogen.

  • has at least one of the following signs or symptoms:

    fever (>38°C), chills, or hypotension if the patient is > 1 year of age OR

    fever (>38°C core) hypothermia (<36°C core), apnea, or bradycardia if the patient is 1 year of age AND

    microbiology results (blood cultures growing organisms) that not related to an infection at another site OR

    a common skin contaminant (i.e., diphtheroids [Corynebacterium spp.], Bacillus [not B. anthracis] spp., Propionibacterium spp., coagulase-negative staphylococci [including S. epidermidis], viridans group streptococci, Aerococcus spp., Micrococcus spp.) is cultured from two or more blood cultures drawn on separate occasions.

Attribution of BSI: The BSI is attributed to the location where the patient was housed on the date of the BSI event (first clinical evidence of BSI appeared or the date the specimen used to meet the BSI criteria was collected). If a CLABSI develops within 48 hours of transfer from one inpatient location to another in the same facility, the infection is attributed to the location that transferred the patient.

Measurement of CLABSI for NHSN Surveillance

Data collected by infection prevention programs is frequently reported to the NHSN and includes patient demographic information, the type of central line associated with the CLABSI, the patient location, the specific criteria to classify the event as a CLABSI, the patient outcome, the organism(s) isolated from cultured blood and the organisms’ antimicrobial susceptibilities.

Numerator data: Patients meeting criteria of CLABSIs will be used to calculate line-specific infection rate.

Denominator data: Two measures are used, patient days and device days. Patient days, while easier to obtain, may underestimate the CLABSI rate as not all patients have central lines. Most experts and regulatory bodies prefer the use of device days that can be used to calculate a risk adjustment rate. Ideally, the denominator data should be validated.

Device-days: Collection of “device days” data is done in a variety of ways. Generally, staff identifies all patients with a VAD in a specified patient care location during for a day. The data should be collected daily at the same time every day i.e. 12 midnight. If a patient has three catheters this is still considered one device day. The number of catheters is summed each day to provide a number of devices and then at the end of the month the total number of catheters for all the days in the month are summed. If electronic databases are available, this information may be used as long as the electronic counts are not substantially different (e.g. +/- 5%) from the manually counts.

Data analysis:

The CLABSI rate is calculated by dividing the number of CLABSIs identified in a month or quarter by the number of central line days identified for the same period of time. The resulting number is multiplied by 1,000. Rates can be calculated by unit and for an entire unit. The most commonly used formula to calculate CLABSI rates is listed in Table II.

Rates can be calculated monthly or quarterly depending on the number of catheter days.

The Central line Utilization Ratio provides an estimate of how many patients days also have devices utilized. This ratio is calculated by dividing the number of central line days by the number of patient days. These calculations are performed separately for different types of intensive care units (ICUs), specialty care areas, and other locations in the institution. Separate rates and ratios are be calculated for different types of catheters in specialty care areas and neonatal intensive care units (NICUs), and stratified by birth weight categories for in NICUs, as appropriate. CLABSI rate and the utilization ratio are calculated and reported to promote performance improvement.

Clinical Definitions of Vascular Access Device-related Infections

These definitions are used to categorize different types of VAD-related infections and are useful if surveillance efforts need to be broadened.

Catheter colonization is most commonly defined as growth of > 15 colony-forming units (CFU) from a 5-cm segment of a catheter tip or subcutaneous catheter segment by semi-quantitative (roll-plate) culture or growth of > 102 CFU of on species of microorganism from a catheter by quantitative (sonication) broth technique.

Phlebitis is an inflammation along the tract of a catheter or recently catheterized vein. Signs and symptoms include induration, erythema, warmth, and pain or tenderness.

An exit site infection has two common used definitions. For a microbiological diagnosis, the culture exudate at catheter exit site must grow a microorganism. A concomitant bloodstream infection may or may not be present. The clinical diagnosis requires erythema, induration, and/or tenderness along 2 cm of the catheter exit site and may be associated with signs and symptoms of infection.

A tunnel infection is an infection along the subcutaneous tract that houses the catheter. It manifests with tenderness, erythema, and/or induration at least 2 cm from the catheter exit sit. Cultured blood may or may not grow organisms.

A pocket infection is diagnosed when infected fluid develops in the subcutaneous pocket of a totally implanted intravascular device such as a pacemaker. These infections are often associated with tenderness, erythema, and/or induration over the pocket and occasionally spontaneous rupture and drainage. Concomitant bloodstream infections can occur.

Primary bloodstream infections are bloodstream infections that are not secondary to other sources such as the urine or a surgical wound. These infections are generally associated with infusates, or related to the catheter. These definitions tend to be used clinically and in clinical trials but not for routine infection control surveillance.

An infusate-related bloodstream infection is diagnosed when an identical microorganism grows from both the infusate and cultured blood with no other identifiable source of infection.

A catheter-related bloodstream infection is bacteremia or fungemia that develops in a patient with an intravascular device and at least one culture of the blood growing an organism. Clinical signs and symptoms of infection include fever, chills, and/or hypotension. Again, no other source for the bloodstream infection (except the catheter) should be identified. One of the following should be present:

  • a semi-quantitative (>15 CFU per catheter segment) or quantitative (>102 CFU per catheter segment) result from catheter cultures, and the same organism (species) is isolated from a catheter segment and a peripheral blood culture;

  • simultaneous quantitative cultures of blood with a ratio of >3:1 CFU/mL of blood (catheter versus peripheral blood);

  • differential time to positivity (growth in a culture of blood obtained through catheter hub is detected at least 2 hours earlier than a culture of simultaneously drawn peripheral blood of equal volume).

What are the key guidelines and principles of preventing bloodstream infections?

Several federal public health authorities and professional organizations have developed guidelines and recommendations that have been published. The majority of these recommendations are based on studies conducted in the Intensive Care Units (ICUs) setting. Some recommendations are directed at high-risk patients in non-ICU setting such as hematological patients, or patients who need cardiac catheterization. The Society for Healthcare Epidemiology of America and the Infectious Disease Society of America (SHEA/IDSA) Compendium has synthesized basic practices for prevention and monitoring of CLABSI prevention efforts. In addition, several recent studies provide strong evidence for several additional measures to prevent CLABSI and are included below.

1. Before insertion:

a. Educate healthcare personnel who insert, care for, and maintain CVCs about risk factors for developing CLABSIs, prevention strategies, indication for CVC use, evidence based insertion and maintenance practices, and general infection prevention strategies.

b. Verify that personnel involved the insertion and care of CVCs has been educated as defined above.

c. Assess the knowledge of personnel periodically and develop programs to measure compliance with best practices.

2. While inserting the catheter:

a. Provide all supplies in one place such as in an all-inclusive catheter tray or in a line cart.

b. Avoid placing the catheter in the femoral vein (adults).

c. Use a checklist to promote evidence-based infection prevention practices.

d. Perform hand hygiene before beginning the procedure or manipulating the catheter.

e. Use maximal sterile barrier precautions during CVC insertion—both the inserter and assistant.

f. Use a chlorhexidine and alcohol-based antiseptic to cleanse the skin in patients more than 2 months of age.

3. After the catheter is inserted and while it is maintained:

a. Remove any catheter that is not needed.

b. Clean catheter hubs, connectors, and injection ports with a disinfectant before they are accessed.

c. Change transparent dressing and clean the site with a chlorhexidine-based antiseptic every 5-7 days. When the dressing is damp, bloody, or loose, additional cleaning and dressing changes are needed. When gauze dressings are used, they should be changed at least every 2 days if damp, bloodied, or loose.

d. Replace all administration sets that are used for blood, blood products, or lipids at least every 96 hours.

e. Do not use topical antimicrobial ointments except for hemodialysis lines.

f. Consider using chlorhexidine impregnated patches or implement daily bathing of all ICU patients with CVCs.

4. Accountability:

a. Assure senior leadership and hospital’s management team is accountable for providing support and visibility for the infection prevention program and campaign to reduce CLABSI.

b. Support an infection prevention program(s) with the needed clinical informatics, trained personnel and other resources to prevent CLABSIs. Such a program should identify and feedback CLABSIs data regularly to clinical care teams and leadership.

c. Assure that healthcare providers follow appropriate infection prevention and control practices are used at all times and that they are accountable for their actions.

d. Ensure that appropriate training and educational programs to prevent CLABSIs are developed and provided to healthcare personnel, patients and families.

5. The prevention bundle:

1. Clean hands prior to insertion

2. Use a chlorhexidine based product to clean the patient skin

3. Use maximal barrier precautions while inserting the catheter

4. Avoid the femoral site and use subclavian preferentially

5. Remove the catheter when no longer needed

6. Clean the hub or injection ports prior to accessing them

What are the conclusions of clinical trials and meta-analyses regarding bloodstream infections?

Some of the following measures have been combined into a “prevention bundle” that focuses on catheter insertion. We review some of the strategies used to prevent central line associated bloodstream infections from well-designed clinical trials and meta-analyses.

a. At insertion

Hand hygiene and aseptic technique are the key elements of prevention efforts for CLABSIs. Other measures may confer additional and incremental benefits.

Site of catheter insertion:

CLABSIs rates vary depending on the site of catheter insertion. Several studies found that rate of CLABSIs is highest with femoral, then jugular, and finally subclavian venous access. Emergency insertion increases the risk of catheter contamination, but not clinical infection. A meta-analysis further demonstrated that femoral venous access had higher rates of gram-positive and gram-negative organisms compared with subclavian access. However, one clinical study found that femoral and jugular venous access CLABSI rates did not differ except among adults with a high body mass index over 28.4.

Maximal sterile barrier (MSB):

The use of maximal sterile barrier protection includes head caps, facemasks, sterile body gowns, sterile gloves in the catheter inserter and others directly involved in the procedure, and full-size sterile drapes for the patient has been shown to reduce the rate of CLABSIs. One large randomized clinical trial found that MSB decreased the rate of CLABSIs by about 65% in oncology patients. Another prospective study found that the use of MSB was independent risk factor that lowered the risk of acquiring CLABSIs. The use of MSB has not been shown to prevent infections associated with arterial access.

Antiseptic use:

Several studies have compared chlorhexidine-based to povidone-iodine based solutions in lowering the incidence of catheter colonization and/or infections. The povidone-iodine based solutions used in these evaluation includes 10% povidone-iodine in aqueous solution or 5% povidone-iodine in 70% alcohol. Chlorhexidine-based solutions have been used in form of 0.25% chlorhexidine gluconate, 0.025% benzakonium chloride, and 4% benzylic alcohol, so called Biseptine, 0.5% chlorhexidine in 70% alcohol, or 1% chlorhexidine in 75% alcohol.

Because of the variety of solutions studied and the small sample sizes in these studies a meta-analysis of studies was performed and demonstrated that chlorhexidine-based solutions as skin antisepsis insertion decrease the incidence of CLABSIs by 50%. Although chlorhexidine-based solutions are more expensive than previously used solutions, cost-benefit analyses using data from randomized, controlled, clinical trials support the use of these products.

Currently, the United States Food and Drug Administration (FDA) does not recommend using chlorhexidine antisepsis in infants less than 2 months of age, because safety data in this particular patient group is lacking. However, limited data from clinical trials or meta-analyses support the use of these compounds in children. One prospective clinical study in the NICU patients demonstrated a significant reduction in rate of catheter colonization and catheter-related bacteremia. Importantly, recent large well-designed clinical studies do not report serious adverse events associated with chlorhexidine use in neonates.

b. After insertion (maintenance)

Dressing change:

Standard guidelines for non-tunneled catheter recommend changing transparent dressings site care with a chlorhexidine-based antiseptic. Soiled, loose or damp dressings should be changed more frequently. These recommendations are based on a clinical study that compared outcome in adult patients with dressing changes two and five days. However, in adults, the colonization and CLABSI rate increased if the interval between changes increased. A clinical study in pediatric patients found no difference in CLABSI rate between dressing changes every 4 or 15-days.

Replace administration set:

Intravenous fluid administration sets, not used for blood, blood products or lipids should be replaced every 96 hours. Clinical studies and a meta-analysis demonstrate that replacing administration sets more frequently than every 96 hours does not decrease catheter colonization and catheter-related infection rates.

Antibiotic ointment for hemodialysis patients:

Topical antibiotic ointments or creams should not be used to decrease the risk of CLABSIs. However, among patients on hemodialysis, topical antibiotic ointments do reduce the risk of CLABSIs, however, their use does not impact patient mortality. Among these patients, the use of topical antibiotics can decrease rate of catheter removal due to infection and episodes of hospitalization. In addition, a recent meta-analysis showed that topical ointment containing honey as the main ingredient are more effective than topical antibiotic ointments and significantly decrease the rate of catheter-related bloodstream infection/100,000 catheter-days. Topical antibiotic ointments that have been studied include mupirocin, povidone-iodine, and polysporin. High-level mupirocin resistance has been reported with its long-term local use, but polysporin resistance has not been reported even when used long-term.


Coagulation factors can promote bacterial adherence and increase risk of CLABSIs in both in-vitro studies and animal models. Many clinical studies demonstrate a relationship between developing a central vein-related thrombosis and catheter-related bacteremia or sepsis. Based on these findings, low-dose unfractionated continuous infusion or heparin coated non-tunneled central venous catheter are used to prevent catheter-related colonization and bloodstream infection and have not increased heparin-induced thrombocytopenia. Other anticoagulants and thrombolytics, including very low dose of warfarin and urokinase, have been used without inducing hemorrhagic complications. One meta-analysis showed that a urokinase lock or flush solution might reduce risk of CLABSIs.

c. Special approaches for CLABSI prevention

After implementing all the elements of the CLABSIs prevention bundle previously mentioned, other strategies can be implemented if the CLABSIs rates remain unacceptably high. The other strategies that can be used are listed below.

Chlorhexidine bathing:

The daily use of 2% chlorhexidine gluconate solution or impregnated to bath patients in medical and surgical ICUs, reduce CLABSIs rates when compared to soap-and-water bathing. These have also been shown to reduce transmission of resistant organisms especially in MRSA. Similar data is forthcoming in pediatric intensive care unit patients. One study found that bathing twice weekly was sufficient but these findings have not been confirmed. Again, the FDA does not approve the use of chlorhexidine products among children younger than 2 month-old.

Chlorhexidine impregnated sponges or dressings for CVC insertion sites:

Using chlorhexidine-containing sponge dressings for CVCs in patients older than 2 months of age reduces the rate of catheter colonization. A recent randomized controlled trial found that these dressing can decrease risk of catheter-related infections in critically ill adults, but not in patients undergoing hemodialysis using nontunneled catheters. It is not known if there is an incremental benefit to the use of these dressings/sponges in the setting of chlorhexidine bathing or if bathing is superior to sponges or vice versa.

Antiseptic- or antimicrobial-impregnated coated catheters:

Coating of short-term catheters with either antiseptics or antimicrobials has been of interest of the years. Early generation catheters were coated extraluminally and more recently companies has introduced coating on the intra and extraluminal catheter surfaces or even materials that are impregnated. Both antiseptic- and antimicrobial-impregnated catheters have been shown to decrease rates of CLABSIs compared with standard catheters. Antiseptic-coated CVCs in the forms of silver-coated and chlorhexidine-silver sulfadiaxine (CH/SS) – coated catheters have been studied. Other agents used include 5-fluorourecil and benzalconium-chloride.

Both clinical studies and meta-analyses demonstrate that minocycline/rifampicin-coated (MR) CVCs were associated with lower catheter-related infectious complications than first generation antiseptic-coated catheters, defined as catheters coated with CH-SS on the external surface. Second generation catheters, or those catheters CH/SS-coated on internal and external surfaces, reduce CLABSIs more than standard catheters and first generation CH-SS coated catheters. However, no head-to-head comparison between the CH-SS catheters and antimicrobial-impregnated catheters has been published. An uncontrolled observational study demonstrated that using MR-impregnated CVCs reduces overall nosocomial bloodstream infections in the ICUs. For long-term catheters, there are very limited clinical trials and their results are varied.

At this point, the FDA has not approved the use of these catheters in children. While, clinical studies demonstrate that coated catheters decrease the rate of central venous catheter colonization and delay CLABSIs, one randomized clinical trial noted unexpected consequences in very low birth weight infants.

Although antimicrobial- and antiseptic-impregnated catheters are both efficacious and cost-effective, they are not routinely recommended. Current guidelines promote their use only in 1) hospital units or patient populations have a CLABSI rate higher than the institutional goal, in the settings of good compliance with other prevention strategies and bundled practices, 2) patients who have limited venous access with a history of recurrent CLABSIs or 3) patients who are at heightened risk for severe sequelae from a CLABSI.

Antimicrobial/anti-infective lock solutions:

To decrease the rate of catheter-related bloodstream infections in patients with long-term central intravenous devices some experts promote the use of antimicrobial lock solutions. Compounds that have been used include heparin, alcohol and antibiotics. Four meta-analyses confirmed that antibiotic containing locks are superior to heparin containing locks in reducing CLABSIs; one focused on vancomycin-containing lock only. Tested antimicrobials include gentamicin, minocycline, ciprofloxacin, vancomycin and fusidic acid, mainly aimed at preventing gram-positive bacterial infections. Limited data are available for alcohol lock solutions but small clinical trials show promising results. A newer agent, that is not an antimcirobial, taurolidine has antimicrobial activities and resistance has not been observed in vitro. Only two clinical trials evaluated short-term catheters.

Despite their advantages, antimicrobial locks are not routinely recommended because of concerns about emergence of antimicrobial resistance and systemic adverse events in case of leakage into blood circulation. Current guidelines suggested that this strategy be used in the same setting as antiseptic- and antimicrobial-impregnated catheters.

The ethanol lock technique sterilizes the intra-catheter lumen and has been studied in persons with long-term catheters. Clinical studies about this method reported tolerable adverse events and trend of benefit. Because these studies contained many variables such as ethanol concentrations, luminal dwell times, catheter type, their results are not easily comparable and requires a large outcome study or meta-analysis.

Closed infusion systems:

One source of CLABSIs is from contaminated infusates. This source of infection is more common in developing countries where resources to mix intravenous medications are more limited. Four large time-sequence clinical trials carried out in four countries demonstrated that a close infusion system, when compared with an open system, reduces CLABSI rates significantly. A recent meta-analysis confirmed this finding, and the meta-analysis also found that a closed infusion system can decrease overall ICU mortality. Because guidelines commonly are developed in regions of the world with access to more sophisticated and expensive technologies, this important technical finding is not included in any guidelines.

d. Approaches that should NOT be used routinely to prevent CLABSIs.

Systemic antimicrobial prophylaxis:

Administration of systemic antimicrobial administration to prevent CLABSIs especially coagulase-negative staphylococci, does not decrease the risk of CLABSIs significantly. Cochrane reviews concluded that there is no role for using systemic antimicrobials routinely to prevent CLABSIs in adults and neonates. While flushing the central venous catheter with a combination of an antibiotic and heparin has been used in very high-risk adult patients, including those patients with hematological malignancies receiving induction chemotherapy, who are neutropenic at the time of CVC insertion and whom are undergoing a bone-marrow transplant, none of the CLABSIs prevention guidelines recommend using systemic antimicrobial prophylaxis.

Routinely CVC change:

Scheduled and routine replacement of CVCs is not recommended. Clinical trials have not demonstrated a benefit. Furthermore, exchanging over a guide-wire increases risk of bloodstream infections, and replacement by insertion at new sites increases risk of mechanical complications. Prevention efforts should focus on catheter removal as soon as medically indicated.

What are the consequences of ignoring bloodstream infections?

CLABSIs are associated with high mortality, prolonged hospitalization, and higher healthcare costs. CLABSI prevention bundle has been demonstrated that it can significantly decrease CLABSI rate and down to zero; as a result, CLABSIs are defined as one of preventable conditions.


The Department of Health and Human Services (HHS) targeting CLABSI as part of their response to the 2005 Deficit Reduction Act. Because CLABSIs are associated with (1) high costs and high volume, (2) result in cases being assigned to a diagnosis-related group that receives a higher payment when presented as a secondary diagnosis, and (3) can reasonably have been prevented through the use of evidence-based guidelines, the Centers for Medicare and Medicaid Services (CMS) and some health maintenance organizations, promulgated regulations that will limit or no longer reimburse costs related to CLABSIs. Beginning on January 2011, CMS is requiring that hospitals use the CDC’s National Healthcare Safety Network, or NHSN, to report their incidences of CLABSIs, in order to receive a full Medicare payment update for 2013.


CLABSIs are included in patient safety indicators in many settings. To be accredited and/or certificated by accreditation organization, such as The Joint Commission (TJC), hospitals have to use evidence-based strategies to prevent CLABSIs. Furthermore, evidence that checklists or strategies to enforce basic principles must be available and analyzed within an institution.

Legal issues:

Interest in healthcare-associated infections is increasing among the public. Because these infections are preventable and prevention strategies are well developed and agreed upon, there is an increasing focus on associated poor outcomes from the legal community. Failure to adhere infection prevention and control protocols, CLABSIs prevention bundle in particular, may be interpreted as medical negligence. Although legal systems in different countries have their own perspective, adequate infection control practices and procedures can ensure patient safety and protect healthcare providers and hospitals from lawsuits.

What other information supports the studies about bloodstream infections, e.g., case-control studies and case series?

Based on clinical studies other than randomized clinical trials and meta-analyses, we review some of the strategies used to prevent central line associated bloodstream infections from well-designed case control, cohort and observational studies.

a. Before insertion:

The impact of educational interventions to prevent catheter-associated bloodstream infection has been established in two elegant studies. Education may take the form of study modules including self-study, infection control short courses, lectures, bedside teaching, interactive educational videotape, and hands on training such as in simulation centers but they should have pre- and post-test evaluation. To magnify the impact of education, performance feedback should be performed. Healthcare personnel who take care of critically ill patients must be included in a mandatory education program. Clinical studies showed significant decrease in rate of central line associated bloodstream infection if frontline staff, including ICU nurses, intensivists, physicians-in-training complete education in some form. One study showed impact by training patients receiving long-term home parenteral nutrition. Most studies did not provide effect of education alone; nevertheless, education is a critical part of implementing the CLABSI prevention bundle.

b. At insertion:


Although benefit of checklist alone is not clearly known, checklists are tools that ensure micro- and macro-strategies are implemented. They facilitate “best practices” and improve culture within units and ultimately support CLABSI elimination programs. Compliance with processes as captured by checklists should be provided at multiple levels including hospital board, executive/senior leader and infection preventionists.

Line cart:

Using all-inclusive catheter cart facilitates standard of care for central line insertion by making available needed equipment. They can improve healthcare providers compliance with the central line prevention bundle.

c. After insertion

Remove nonessential vascular catheters:

Daily the need for any central venous catheters should be considered. Unnecessary central lines should be removed.

Disinfectant before using catheter hub or needleless connector:

A potential portion of entry of microorganisms into bloodstream is from contaminated vascular-catheter hubs or needleless connectors. In vitro data reveal that both 70% and 95% alcohol significantly decreased microbial contamination of catheter hubs and was superior to 1% chlorhexidine. Another clinical study found that 70% alcohol, 0.5% chlorhexidine or 10% povidone-iodine was equivalent.

Perform surveillance:

Healthcare associated infections surveillance and data feedback, together with appropriate infection prevention and control strategies, have been demonstrated to reduce infection rates, and can be sustained. The incidence of CLABSIs should be reported regularly to unit-level to healthcare providers including physicians and nurses, and the data should be compared with institutional historical data and national rates. Data that includes units other than ICUs is still required.

d. Approaches that do not need to be considered

Routine use of needleless connectors:

While clinical trials demonstrate that needleless hub devices decrease the rate of device and skin contamination, but they do not significantly decrease clinical infections. In fact, several studies suggest that the use of devices with positive pressure increase CLABSI rates. More recently, an in-vitro study demonstrated that if the membranous septum of a needleless luer-cap connector is heavily contaminated, an antiseptic barrier cap provided was superior to 70% alcohol for decontamination. A randomized, controlled trial showed that using disinfectable needle-free connectors can decrease rate of catheter colonization and bloodstream infections. Given the controversies, the routine use of positive-pressure needleless connectors with mechanical valves is not recommended without a thorough assessment of risks, benefits, and education regarding their proper use.

Summary of current controversies

Nurse-to-patient ratio:

Patient density and understaffing, mainly examining registered nurses are associated with increased CLABSI rates. A case-control study suggested that nurse-to-patient ratio should be at least 2:1. However, these studies cannot control all nurse related factors that may be play role in CLABSI infection such as the composition of the nursing skill mix, nurse overtime and other assigned duties. Results of clinical trials are still required to establish a strong recommendation.

Phlebotomy and intravenous team:

Phlebotomy and intravenous therapy teams commonly insert and maintain vascular catheters (peripheral lines primarily) and reduce vascular catheter-related infectious complications including bloodstream infections. Two observational studies have shown a reduction of the CLABSI rate after implementation of an intravenous therapy team. The data from clinical studies do not support a recommendation for CLABSIs prevention at this point.

Surveillance systems and surveillance that includes other types of catheters:

As CMS and other agencies implement strategies to enhance performance in healthcare settings, strategies to identify events of interest will be increasingly important. In addition, institutions will be interested in a level playing field to assure that events are identified in a similar way. Most of current surveillance systems do not include all types of catheters that play role in CLABSIs (e.g., arterial catheters) or catheter related infections. Future surveillance systems including all kinds of high-risk VADs are needed.

Surveillance of non-ICU setting:

Very limited surveillance data and information about prevention strategies exist in non-ICU settings. Because of the number of beds in non-ICU settings, high-risk settings like dialysis, the CLABSI rate is significant. It is difficult to perform surveillance for infections and implement current CLABSI prevention bundle in these settings.

Estimating catheter-days:

Current gold standard to evaluate the CLABSI rate is by using central line-day as the denominator. This risk-adjusted measurement is, however, burdensome especially in resource-limited settings. While one report found that this method has more impact than the less-sophisticated method (the patient-day rate), another study found that a sample-based method to estimate CLABSI rate can provide acceptable surveillance data.

The appropriate denominator has been a source of controversy and a recent study demonstrated the variation in rates depending on whether the traditional method of counting catheters was used or a novel method that counted the total number of catheters in a patient.

What is the impact of bloodstream infections, and how can they be controlled relative to infections at other sites or from other specific pathogens?

Central line-associated bloodstream infections (CLABSI) are healthcare-associated infections (HAIs) that contribute to morbidity and mortality despite often being preventable. CLABSI-induced mortality varies. The International Nosocomial Infection Control Consortium (INICC) reported crude mortality of the patients was 38.1% compared with 14.4% in patients who did not have HAIs. In the United States the mortality is estimated to be 12.3% and accounts for almost 31,000 deaths. These are the second most common cause of HAI associated death. CLABSIs increase length of stay and hospital cost. The cost of one CLABSI has been estimated to be as high as $45,000 (mean cost was $23,242). Cost estimates per episode of other HAIS were $25,072 per VAP, $10,443 per SSI, and $758 per CA-UTI.

CLABSI rates vary also and depend on the country, type of unit and surveillance strategy. The pooled rate of CLABSI in developing countries is higher than in the United States and Europe. INICC ICUs report a pooled rate of 7.6 per 1,000 CVC-day while in US ICUs the CDC NHSN (National Healthcare Safety Network) pooled mean rate was 2.0 per 1,000 CVC-day.

Prevention of CLABSIs and strategies used overlap with those for other healthcare associated infections. Many of the basic tenets impact other types of infections or transmission of epidemiologically significant organisms. Improved hand hygiene compliance decreases the overall HAIs rate that includes CLABSIs, VAP, UTIs and SSIs. Moreover, feedback of data also impacts rates for all HAIs. However, implementation of CLABSIs prevention bundle does not impact VAP or UTI rates. Staphylococcus aureus decolonization with chlorhexidine bathing reduces CLABSI, MRSA colonization and MRSA VAP. The use of rifampicin/minocycline-impregnated CVCs can reduce nosocomial BSIs, including VRE bacteremia.

Recommended prevention strategies for all acute care hospitals

The recommended prevention strategies for all acute care hospitals are listed in Table III, Table IV, and Table V.

a. Before insertion.

See Table III for Educational program.

b. At insertion

See Table IV Avoid using the femoral vein for central venous access in adult patients

See Table V Use maximal sterile barrier precautions during CVC insertion.

Table VI describes the use of a chlorhexidine-based antiseptic for skin preparations in patients older than 2 months.

c. After insertion

See Table VII, Table VIII, Table IX, and Table X for information about after insertion strategies.

II. Special approaches for CLABSIs prevention

See Table XI for special approaches for bloodstream infection prevention.

See Table XII, Table XIII, Table XIV, Table XV, Table XVI, and Table XVII for information about the use of antiseptic- or antimicrobial-impregnated CVCs for adults.

III. Prevention strategies not recommended:

These are described in Table XVIII and Table XIX.

Controversies in detail.

1. Routine use of antimicrobial/antiseptic-impregnated catheters

CDC/HICPAC (2002) and IDSA/SHEA (2009) guidelines do not recommend antimicrobial/antiseptic-impregnated catheters routinely. Some organizations recommended their use.

Pros: As we discussed above, both of antiseptic-coated, silver and chlorhexidine-silver sulfadiazine (CH-SS), and antimicrobial-coated catheters, minocycline-rifampicin, prevent CLABSIs. Cost-effectiveness studies confirm the benefit of these catheters in preventing patient harm. While the emergence of antimicrobial resistance and toxicity should be considered, no large longitudinal study reports antimicrobial resistance when these catheters have been used. In vitro studies demonstrated significance increase of the MICs of minocycline and rifampicin in S. epidermidis both in antiseptic-, and antimicrobial-impregnated catheters after being in place for 7 days.

Cons: The use of CLABSI bundles has resulted in dramatic reductions of CLABSIs in many settings. The incremental role of coated catheters has not been studied and may not be cost beneficial in the setting where best practices have been implemented and complied with. Emergence of antimicrobial and chlorhexidine, resistant organisms argues for caution. There are several reports of rifampicin- and minocycline-resistance among S. aureus and S. epidermidis isolates. Chlorhexidine-resistant organisms from both intra- and extraluminal sources are reported so the efficacy of CH-SS-coated catheters may be limited.

2. ‘Zero tolerance’ target of CLABSIs

CLABSI are significant healthcare-associated infections and their rate should be minimized. It is one of hospital-acquired conditions that Medicare has targeted to encourage hospitals to improve performance by reducing reimbursement.

Pros: A pound of cure is penny wise. Successful CLABSI prevention bundle implementation reduces CLABSI rates significantly and dramatically down to zero, so it is reasonable for healthcare institutions to put more effort to assure compliance with bundled interventions. Implementation of these strategies not only reduces patient harm but is cost effective for institutions.

Cons: Risk of healthcare-associated conditions depends on many factors (e.g., host factors, severity of illness) and most of them are not preventable. While we can implement care bundles based on evidence-based practices, we cannot change or alter the patient’s impaired immunity or underlying disease. Hence, there will always be some nosocomial infections that cannot be prevented. Moreover, the push to zero and the zero tolerance is creating a climate of fear and healthcare workers are fearful of the reprisals associated with infectious complications of healthcare. This has lead to providers not obtaining blood cultures and other diagnostic tests that are in the patient’s best interest. Furthermore, some institutions because of financial pressures or worries about their reputations are gaming the system and not reporting infections. This leads to a ‘questionable zero’ because surveillance data does not reflect the reality of the situation.

What national and international guidelines exist related to bloodstream infections?

We included international and national guidelines to prevent CLABSIs. Level of recommendation is listed in Table XX.

What other consensus group statements exist, and what do key leaders advise?

Table XXI describes the consensus group statements.


Scales K. Intravenous therapy: a guide to good practice. Br J Nurs 2008;17:S4-S12.

Scales K. Central venous access devices. Part 1: devices for acute care. Br J Nurs 2010;19:88-92.

Maki DG, Kluger DM, Crnich CJ. The risk of bloodstream infection in adults with different intravascular devices: a systematic review of 200 published prospective studies. Mayo Clin Proc 2006;81:1159-71.

Gallieni M, Pittiruti M, Biffi R. Vascular access in oncology patients. CA Cancer J Clin 2008;58:323-46.

Tokars JI, Cookson ST, McArthur MA, Boyer CL, McGeer AJ, Jarvis WR. Prospective evaluation of risk factors for bloodstream infection in patients receiving home infusion therapy. Ann Intern Med 1999;131:340-7.

Geffers C, Baerwolff S, Schwab F, Gastmeier P. Incidence of healthcare-associated infections in high-risk neonates: results from the German surveillance system for very-low-birthweight infants. J Hosp Infect 2008;68:214-21.

Geffers C, Gastmeier A, Schwab F, Groneberg K, Ruden H, Gastmeier P. Use of central venous catheter and peripheral venous catheter as risk factors for nosocomial bloodstream infection in very-low-birth-weight infants. Infect Control Hosp Epidemiol 2010;31:395-401.

Pujol M, Hornero A, Saballs M, et al. Clinical epidemiology and outcomes of peripheral venous catheter-related bloodstream infections at a university-affiliated hospital. J Hosp Infect 2007;67:22-9.

Hammarskjold F, Berg S, Hanberger H, Malmvall BE. Low incidence of arterial catheter infections in a Swedish intensive care unit: risk factors for colonisation and infection. J Hosp Infect 2010;76:130-4.

Koh DB, Gowardman JR, Rickard CM, Robertson IK, Brown A. Prospective study of peripheral arterial catheter infection and comparison with concurrently sited central venous catheters. Crit Care Med 2008;36:397-402.

Gowardman JR, Lipman J, Rickard CM. Assessment of peripheral arterial catheters as a source of sepsis in the critically ill: a narrative review. J Hosp Infect 2010;75:12-8.

Mermel LA, Parenteau S, Tow SM. The risk of midline catheterization in hospitalized patients. A prospective study. Ann Intern Med 1995;123:841-4.

Fearonce G, Faraklas I, Saffle JR, Cochran A. Peripherally inserted central venous catheters and central venous catheters in burn patients: a comparative review. J Burn Care Res 2010;31:31-5.

Garland JS, Alex CP, Sevallius JM, et al. Cohort study of the pathogenesis and molecular epidemiology of catheter-related bloodstream infection in neonates with peripherally inserted central venous catheters. Infect Control Hosp Epidemiol 2008;29:243-9.

Parellada JA, Moise AA, Hegemier S, Gest AL. Percutaneous central catheters and peripheral intravenous catheters have similar infection rates in very low birth weight infants. J Perinatol 1999;19:251-4.

Sengupta A, Lehmann C, Diener-West M, Perl TM, Milstone AM. Catheter duration and risk of CLA-BSI in neonates with PICCs. Pediatrics 2010;125:648-53.

Nagata E, Brito AS, Matsuo T. Nosocomial infections in a neonatal intensive care unit: incidence and risk factors. Am J Infect Control 2002;30:26-31.

Butler-O’Hara M, Buzzard CJ, Reubens L, McDermott MP, DiGrazio W, D’Angio CT. A randomized trial comparing long-term and short-term use of umbilical venous catheters in premature infants with birth weights of less than 1251 grams. Pediatrics 2006;118:e25-35.

Balkhy HH, Alsaif S, El-Saed A, Khawajah M, Dichinee R, Memish ZA. Neonatal rates and risk factors of device-associated bloodstream infection in a tertiary care center in Saudi Arabia. Am J Infect Control 2010;38:159-61.

O’Grady NP, Alexander M, Dellinger EP, et al. Guidelines for the prevention of intravascular catheter-related infections. Infect Control Hosp Epidemiol 2002;23:759-69.

Mermel LA, Farr BM, Sherertz RJ, et al. Guidelines for the management of intravascular catheter-related infections. Clin Infect Dis 2001;32:1249-72.

Fitzpatrick Iii JR, Woo YJ. Mechanical circulatory assistance. Circ J 2010;75:38-46.

El-Hamamsy I, Jacques F, Perrault LP, et al. Results following implantation of mechanical circulatory support systems: the Montreal Heart Institute experience. Can J Cardiol 2009;25:107-10.

Kirklin JK, Naftel DC. Mechanical circulatory support: registering a therapy in evolution. Circ Heart Fail 2008;1:200-5.

Holman WL, Pamboukian SV, McGiffin DC, Tallaj JA, Cadeiras M, Kirklin JK. Device related infections: are we making progress? J Card Surg 2010;25:478-83.

Schulman AR, Martens TP, Christos PJ, et al. Comparisons of infection complications between continuous flow and pulsatile flow left ventricular assist devices. J Thorac Cardiovasc Surg 2007;133:841-2.

Siegenthaler MP, Martin J, Pernice K, et al. The Jarvik 2000 is associated with less infections than the HeartMate left ventricular assist device. Eur J Cardiothorac Surg 2003;23:748-54; discussion 54-5.

McKee C, Berkowitz I, Cosgrove SE, et al. Reduction of catheter-associated bloodstream infections in pediatric patients: experimentation and reality. Pediatr Crit Care Med 2008;9:40-6.

Boersma RS, Schouten HC. Clinical practices concerning central venous catheters in haematological patients. Eur J Oncol Nurs 2010;14:200-4.

Chambers CE, Eisenhauer MD, McNicol LB, et al. Infection control guidelines for the cardiac catheterization laboratory: society guidelines revisited. Catheter Cardiovasc Interv 2006;67:78-86.

Kallen AJ, Patel PR, O’Grady NP. Preventing catheter-related bloodstream infections outside the intensive care unit: expanding prevention to new settings. Clin Infect Dis 2010;51:335-41.

Yokoe DS, Mermel LA, Anderson DJ, et al. A compendium of strategies to prevent healthcare-associated infections in acute care hospitals. Infect Control Hosp Epidemiol 2008;29 Suppl 1:S12-21.

Timsit JF, Schwebel C, Bouadma L, et al. Chlorhexidine-impregnated sponges and less frequent dressing changes for prevention of catheter-related infections in critically ill adults: a randomized controlled trial. JAMA 2009;301:1231-41.

Popovich KJ, Hota B, Hayes R, Weinstein RA, Hayden MK. Effectiveness of routine patient cleansing with chlorhexidine gluconate for infection prevention in the medical intensive care unit. Infect Control Hosp Epidemiol 2009;30:959-63.

Warren DK, Cosgrove SE, Diekema DJ, et al. A multicenter intervention to prevent catheter-associated bloodstream infections. Infect Control Hosp Epidemiol 2006;27:662-9.

Lubelchek RJ, Weinstein RA. Strategies for preventing catheter-related bloodstream infections: the role of new technologies. Crit Care Med 2006;34:905-7.

Climo MW, Sepkowitz KA, Zuccotti G, et al. The effect of daily bathing with chlorhexidine on the acquisition of methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, and healthcare-associated bloodstream infections: results of a quasi-experimental multicenter trial. Crit Care Med 2009;37:1858-65.

Boyce JM, Pittet D. Guideline for Hand Hygiene in Health-Care Settings: recommendations of the Healthcare Infection Control Practices Advisory Committee and the HICPAC/SHEA/APIC/IDSA Hand Hygiene Task Force. Infect Control Hosp Epidemiol 2002;23:S3-40.

Yilmaz G, Koksal I, Aydin K, Caylan R, Sucu N, Aksoy F. Risk factors of catheter-related bloodstream infections in parenteral nutrition catheterization. JPEN J Parenter Enteral Nutr 2007;31:284-7.

Zingg W, Imhof A, Maggiorini M, Stocker R, Keller E, Ruef C. Impact of a prevention strategy targeting hand hygiene and catheter care on the incidence of catheter-related bloodstream infections. Crit Care Med 2009;37:2167-73; quiz 80.

Marra AR, D’Arco C, Bravim Bde A, et al. Controlled trial measuring the effect of a feedback intervention on hand hygiene compliance in a step-down unit. Infect Control Hosp Epidemiol 2008;29:730-5.

Rosenthal VD, Guzman S, Safdar N. Reduction in nosocomial infection with improved hand hygiene in intensive care units of a tertiary care hospital in Argentina. Am J Infect Control 2005;33:392-7.

Lorente L, Henry C, Martin MM, Jimenez A, Mora ML. Central venous catheter-related infection in a prospective and observational study of 2,595 catheters. Crit Care 2005;9:R631-5.

Merrer J, De Jonghe B, Golliot F, et al. Complications of femoral and subclavian venous catheterization in critically ill patients: a randomized controlled trial. JAMA 2001;286:700-7.

Luft D, Schmoor C, Wilson C, et al. Central venous catheter-associated bloodstream infection and colonisation of insertion site and catheter tip. What are the rates and risk factors in haematology patients? Ann Hematol 2010;89:1265-75.

Goetz AM, Wagener MM, Miller JM, Muder RR. Risk of infection due to central venous catheters: effect of site of placement and catheter type. Infect Control Hosp Epidemiol 1998;19:842-5.

Hamilton HC, Foxcroft DR. Central venous access sites for the prevention of venous thrombosis, stenosis and infection in patients requiring long-term intravenous therapy. Cochrane Database Syst Rev 2007:CD004084.

Parienti JJ, Thirion M, Megarbane B, et al. Femoral vs jugular venous catheterization and risk of nosocomial events in adults requiring acute renal replacement therapy: a randomized controlled trial. JAMA 2008;299:2413-22.

Raad, II, Hohn DC, Gilbreath BJ, et al. Prevention of central venous catheter-related infections by using maximal sterile barrier precautions during insertion. Infect Control Hosp Epidemiol 1994;15:231-8.

Lee DH, Jung KY, Choi YH. Use of maximal sterile barrier precautions and/or antimicrobial-coated catheters to reduce the risk of central venous catheter-related bloodstream infection. Infect Control Hosp Epidemiol 2008;29:947-50.

Rijnders BJ, Van Wijngaerden E, Wilmer A, Peetermans WE. Use of full sterile barrier precautions during insertion of arterial catheters: a randomized trial. Clin Infect Dis 2003;36:743-8.

Balamongkhon B, Thamlikitkul V. Implementation of chlorhexidine gluconate for central venous catheter site care at Siriraj Hospital, Bangkok, Thailand. Am J Infect Control 2007;35:585-8.

Humar A, Ostromecki A, Direnfeld J, et al. Prospective randomized trial of 10% povidone-iodine versus 0.5% tincture of chlorhexidine as cutaneous antisepsis for prevention of central venous catheter infection. Clin Infect Dis 2000;31:1001-7.

Mimoz O, Villeminey S, Ragot S, et al. Chlorhexidine-based antiseptic solution vs alcohol-based povidone-iodine for central venous catheter care. Arch Intern Med 2007;167:2066-72.

Maki DG, Ringer M, Alvarado CJ. Prospective randomised trial of povidone-iodine, alcohol, and chlorhexidine for prevention of infection associated with central venous and arterial catheters. Lancet 1991;338:339-43.

Chaiyakunapruk N, Veenstra DL, Lipsky BA, Saint S. Chlorhexidine compared with povidone-iodine solution for vascular catheter-site care: a meta-analysis. Ann Intern Med 2002;136:792-801.

Crawford AG, Fuhr JP, Jr., Rao B. Cost-benefit analysis of chlorhexidine gluconate dressing in the prevention of catheter-related bloodstream infections. Infect Control Hosp Epidemiol 2004;25:668-74.

Marschall J, Mermel LA, Classen D, et al. Strategies to prevent central line-associated bloodstream infections in acute care hospitals. Infect Control Hosp Epidemiol 2008;29 Suppl 1:S22-30.

Garland JS, Buck RK, Maloney P, et al. Comparison of 10% povidone-iodine and 0.5% chlorhexidine gluconate for the prevention of peripheral intravenous catheter colonization in neonates: a prospective trial. Pediatr Infect Dis J 1995;14:510-6.

Mullany LC, Darmstadt GL, Khatry SK, et al. Topical applications of chlorhexidine to the umbilical cord for prevention of omphalitis and neonatal mortality in southern Nepal: a community-based, cluster-randomised trial. Lancet 2006;367:910-8.

Tielsch JM, Darmstadt GL, Mullany LC, et al. Impact of newborn skin-cleansing with chlorhexidine on neonatal mortality in southern Nepal: a community-based, cluster-randomized trial. Pediatrics 2007;119:e330-40.

Tamma PD, Aucott SW, Milstone AM. Chlorhexidine use in the neonatal intensive care unit: results from a national survey. Infect Control Hosp Epidemiol 2010;31:846-9.

Maki DG, Stolz SS, Wheeler S, Mermel LA. A prospective, randomized trial of gauze and two polyurethane dressings for site care of pulmonary artery catheters: implications for catheter management. Crit Care Med 1994;22:1729-37.

Curchoe RM, Powers J, El-Daher N. Weekly transparent dressing changes linked to increased bacteremia rates. Infect Control Hosp Epidemiol 2002;23:730-2.

Carrer S, Bocchi A, Bortolotti M, et al. Effect of different sterile barrier precautions and central venous catheter dressing on the skin colonization around the insertion site. Minerva Anestesiol 2005;71:197-206.

Laura R, Degl’Innocenti M, Mocali M, et al. Comparison of two different time interval protocols for central venous catheter dressing in bone marrow transplant patients: results of a randomized, multicenter study. The Italian Nurse Bone Marrow Transplant Group (GITMO). Haematologica 2000;85:275-9.

Raad I, Hanna HA, Awad A, et al. Optimal frequency of changing intravenous administration sets: is it safe to prolong use beyond 72 hours? Infect Control Hosp Epidemiol 2001;22:136-9.

Gorbea HF, Snydman DR, Delaney A, Stockman J, Martin WJ. Intravenous tubing with burettes can be safely changed at 48-hour intervals. JAMA 1984;251:2112-5.

Snydman DR, Donnelly-Reidy M, Perry LK, Martin WJ. Intravenous tubing containing burettes can be safely changed at 72 hour intervals. Infect Control 1987;8:113-6.

Jakobsen CJ, Grabe N, Nielsen E, et al. Contamination of intravenous infusion systems–the effect of changing administration sets. J Hosp Infect 1986;8:217-23.

Rickard CM, Lipman J, Courtney M, Siversen R, Daley P. Routine changing of intravenous administration sets does not reduce colonization or infection in central venous catheters. Infect Control Hosp Epidemiol 2004;25:650-5.

Gillies D, O’Riordan L, Wallen M, Morrison A, Rankin K, Nagy S. Optimal timing for intravenous administration set replacement. Cochrane Database Syst Rev 2005:CD003588.

McCann M, Moore ZE. Interventions for preventing infectious complications in haemodialysis patients with central venous catheters. Cochrane Database Syst Rev 2010:CD006894.

Battistella M, Bhola C, Lok CE. Long-term Follow-up of the Hemodialysis Infection Prevention With Polysporin Ointment (HIPPO) Study: A Quality Improvement Report. Am J Kidney Dis 2011.

Lok CE, Stanley KE, Hux JE, Richardson R, Tobe SW, Conly J. Hemodialysis infection prevention with polysporin ointment. J Am Soc Nephrol 2003;14:169-79.

Levin A, Mason AJ, Jindal KK, Fong IW, Goldstein MB. Prevention of hemodialysis subclavian vein catheter infections by topical povidone-iodine. Kidney Int 1991;40:934-8.

Jassal SV, Lok CE, Group MPS. A randomized controlled trial comparing mupirocin versus Polysporin Triple for the prevention of catheter-related infections in peritoneal dialysis patients (the MP3 study). Perit Dial Int 2008;28:67-72.

Zakrzewska-Bode A, Muytjens HL, Liem KD, Hoogkamp-Korstanje JA. Mupirocin resistance in coagulase-negative staphylococci, after topical prophylaxis for the reduction of colonization of central venous catheters. J Hosp Infect 1995;31:189-93.

Perez-Fontan M, Rosales M, Rodriguez-Carmona A, Falcon TG, Valdes F. Mupirocin resistance after long-term use for Staphylococcus aureus colonization in patients undergoing chronic peritoneal dialysis. Am J Kidney Dis 2002;39:337-41.

Annigeri R, Conly J, Vas S, et al. Emergence of mupirocin-resistant Staphylococcus aureus in chronic peritoneal dialysis patients using mupirocin prophylaxis to prevent exit-site infection. Perit Dial Int 2001;21:554-9.

Lobbedez T, Gardam M, Dedier H, et al. Routine use of mupirocin at the peritoneal catheter exit site and mupirocin resistance: still low after 7 years. Nephrol Dial Transplant 2004;19:3140-3.

Mehall JR, Saltzman DA, Jackson RJ, Smith SD. Fibrin sheath enhances central venous catheter infection. Crit Care Med 2002;30:908-12.

Vaudaux P, Pittet D, Haeberli A, et al. Host factors selectively increase staphylococcal adherence on inserted catheters: a role for fibronectin and fibrinogen or fibrin. J Infect Dis 1989;160:865-75.

Herrmann M, Vaudaux PE, Pittet D, et al. Fibronectin, fibrinogen, and laminin act as mediators of adherence of clinical staphylococcal isolates to foreign material. J Infect Dis 1988;158:693-701.

Darouiche RO. Device-associated infections: a macroproblem that starts with microadherence. Clin Infect Dis 2001;33:1567-72.

Timsit JF, Farkas JC, Boyer JM, et al. Central vein catheter-related thrombosis in intensive care patients: incidence, risks factors, and relationship with catheter-related sepsis. Chest 1998;114:207-13.

Raad, II, Luna M, Khalil SA, Costerton JW, Lam C, Bodey GP. The relationship between the thrombotic and infectious complications of central venous catheters. JAMA 1994;271:1014-6.

Musher D, Goldsmith E, Dunbar S, et al. Association of hypercoagulable states and increased platelet adhesion and aggregation with bacterial colonization of intravenous catheters. J Infect Dis 2002;186:769-73.

Abdelkefi A, Torjman L, Ladeb S, et al. Randomized trial of prevention of catheter-related bloodstream infection by continuous infusion of low-dose unfractionated heparin in patients with hematologic and oncologic disease. J Clin Oncol 2005;23:7864-70.

Abdelkefi A, Achour W, Ben Othman T, et al. Use of heparin-coated central venous lines to prevent catheter-related bloodstream infection. J Support Oncol 2007;5:273-8.

Pierce CM, Wade A, Mok Q. Heparin-bonded central venous lines reduce thrombotic and infective complications in critically ill children. Intensive Care Med 2000;26:967-72.

Bern MM, Lokich JJ, Wallach SR, et al. Very low doses of warfarin can prevent thrombosis in central venous catheters. A randomized prospective trial. Ann Intern Med 1990;112:423-8.

Boraks P, Seale J, Price J, et al. Prevention of central venous catheter associated thrombosis using minidose warfarin in patients with haematological malignancies. Br J Haematol 1998;101:483-6.

van Rooden CJ, Schippers EF, Guiot HF, et al. Prevention of coagulase-negative staphylococcal central venous catheter-related infection using urokinase rinses: a randomized double-blind controlled trial in patients with hematologic malignancies. J Clin Oncol 2008;26:428-33.

Kethireddy S, Safdar N. Urokinase lock or flush solution for prevention of bloodstream infections associated with central venous catheters for chemotherapy: a meta-analysis of prospective randomized trials. J Vasc Access 2008;9:51-7.

Munoz-Price LS, Hota B, Stemer A, Weinstein RA. Prevention of bloodstream infections by use of daily chlorhexidine baths for patients at a long-term acute care hospital. Infect Control Hosp Epidemiol 2009;30:1031-5.

Bleasdale SC, Trick WE, Gonzalez IM, Lyles RD, Hayden MK, Weinstein RA. Effectiveness of chlorhexidine bathing to reduce catheter-associated bloodstream infections in medical intensive care unit patients. Arch Intern Med 2007;167:2073-9.

Evans HL, Dellit TH, Chan J, Nathens AB, Maier RV, Cuschieri J. Effect of chlorhexidine whole-body bathing on hospital-acquired infections among trauma patients. Arch Surg 2010;145:240-6.

Fraser TG, Fatica C, Scarpelli M, et al. Decrease in Staphylococcus aureus colonization and hospital-acquired infection in a medical intensive care unit after institution of an active surveillance and decolonization program. Infect Control Hosp Epidemiol 2010;31:779-83.

Rumbak M, Cancio M. Prevention of infection caused by gram-positive bacteria in the bloodstream and lungs. Infect Control Hosp Epidemiol 2010;31:879-80; author reply 80.

Levy I, Katz J, Solter E, et al. Chlorhexidine-impregnated dressing for prevention of colonization of central venous catheters in infants and children: a randomized controlled study. Pediatr Infect Dis J 2005;24:676-9.

Ho KM, Litton E. Use of chlorhexidine-impregnated dressing to prevent vascular and epidural catheter colonization and infection: a meta-analysis. J Antimicrob Chemother 2006;58:281-7.

Garland JS, Alex CP, Mueller CD, et al. A randomized trial comparing povidone-iodine to a chlorhexidine gluconate-impregnated dressing for prevention of central venous catheter infections in neonates. Pediatrics 2001;107:1431-6.

Camins BC, Richmond AM, Dyer KL, et al. A crossover intervention trial evaluating the efficacy of a chlorhexidine-impregnated sponge in reducing catheter-related bloodstream infections among patients undergoing hemodialysis. Infect Control Hosp Epidemiol 2010;31:1118-23.

Ramritu P, Halton K, Collignon P, et al. A systematic review comparing the relative effectiveness of antimicrobial-coated catheters in intensive care units. Am J Infect Control 2008;36:104-17.

Veenstra DL, Saint S, Saha S, Lumley T, Sullivan SD. Efficacy of antiseptic-impregnated central venous catheters in preventing catheter-related bloodstream infection: a meta-analysis. JAMA 1999;281:261-7.

Boswald M, Lugauer S, Regenfus A, et al. Reduced rates of catheter-associated infection by use of a new silver-impregnated central venous catheter. Infection 1999;27 Suppl 1:S56-60.

Kalfon P, de Vaumas C, Samba D, et al. Comparison of silver-impregnated with standard multi-lumen central venous catheters in critically ill patients. Crit Care Med 2007;35:1032-9.

Camargo LF, Marra AR, Buchele GL, et al. Double-lumen central venous catheters impregnated with chlorhexidine and silver sulfadiazine to prevent catheter colonisation in the intensive care unit setting: a prospective randomised study. J Hosp Infect 2009;72:227-33.

Schuerer DJ, Zack JE, Thomas J, et al. Effect of chlorhexidine/silver sulfadiazine-impregnated central venous catheters in an intensive care unit with a low blood stream infection rate after implementation of an educational program: a before-after trial. Surg Infect (Larchmt) 2007;8:445-54.

Maki DG, Stolz SM, Wheeler S, Mermel LA. Prevention of central venous catheter-related bloodstream infection by use of an antiseptic-impregnated catheter. A randomized, controlled trial. Ann Intern Med 1997;127:257-66.

Chatzinikolaou I, Finkel K, Hanna H, et al. Antibiotic-coated hemodialysis catheters for the prevention of vascular catheter-related infections: a prospective, randomized study. Am J Med 2003;115:352-7.

Walz JM, Avelar RL, Longtine KJ, et al. Anti-infective external coating of central venous catheters: a randomized, noninferiority trial comparing 5-fluorouracil with chlorhexidine/silver sulfadiazine in preventing catheter colonization. Crit Care Med 2010;38:2095-102.

Jaeger K, Osthaus A, Heine J, et al. Efficacy of a benzalkonium chloride-impregnated central venous catheter to prevent catheter-associated infection in cancer patients. Chemotherapy 2001;47:50-5.

Darouiche RO, Raad, II, Heard SO, et al. A comparison of two antimicrobial-impregnated central venous catheters. Catheter Study Group. N Engl J Med 1999;340:1-8.

Casey AL, Mermel LA, Nightingale P, Elliott TS. Antimicrobial central venous catheters in adults: a systematic review and meta-analysis. Lancet Infect Dis 2008;8:763-76.

Fraenkel D, Rickard C, Thomas P, Faoagali J, George N, Ware R. A prospective, randomized trial of rifampicin-minocycline-coated and silver-platinum-carbon-impregnated central venous catheters. Crit Care Med 2006;34:668-75.

Rupp ME, Lisco SJ, Lipsett PA, et al. Effect of a second-generation venous catheter impregnated with chlorhexidine and silver sulfadiazine on central catheter-related infections: a randomized, controlled trial. Ann Intern Med 2005;143:570-80.

Hanna HA, Raad, II, Hackett B, et al. Antibiotic-impregnated catheters associated with significant decrease in nosocomial and multidrug-resistant bacteremias in critically ill patients. Chest 2003;124:1030-8.

Darouiche RO, Berger DH, Khardori N, et al. Comparison of antimicrobial impregnation with tunneling of long-term central venous catheters: a randomized controlled trial. Ann Surg 2005;242:193-200.

Hanna H, Benjamin R, Chatzinikolaou I, et al. Long-term silicone central venous catheters impregnated with minocycline and rifampin decrease rates of catheter-related bloodstream infection in cancer patients: a prospective randomized clinical trial. J Clin Oncol 2004;22:3163-71.

Dahlberg PJ, Agger WA, Singer JR, et al. Subclavian hemodialysis catheter infections: a prospective, randomized trial of an attachable silver-impregnated cuff for prevention of catheter-related infections. Infect Control Hosp Epidemiol 1995;16:506-11.

Collin GR. Decreasing catheter colonization through the use of an antiseptic-impregnated catheter: a continuous quality improvement project. Chest 1999;115:1632-40.

Chelliah A, Heydon KH, Zaoutis TE, et al. Observational trial of antibiotic-coated central venous catheters in critically ill pediatric patients. Pediatr Infect Dis J 2007;26:816-20.

Khattak AZ, Ross R, Ngo T, Shoemaker CT. A randomized controlled evaluation of absorption of silver with the use of silver alginate (Algidex) patches in very low birth weight (VLBW) infants with central lines. J Perinatol 2010;30:337-42.

Veenstra DL, Saint S, Sullivan SD. Cost-effectiveness of antiseptic-impregnated central venous catheters for the prevention of catheter-related bloodstream infection. JAMA 1999;282:554-60.

Yahav D, Rozen-Zvi B, Gafter-Gvili A, Leibovici L, Gafter U, Paul M. Antimicrobial lock solutions for the prevention of infections associated with intravascular catheters in patients undergoing hemodialysis: systematic review and meta-analysis of randomized, controlled trials. Clin Infect Dis 2008;47:83-93.

Labriola L, Crott R, Jadoul M. Preventing haemodialysis catheter-related bacteraemia with an antimicrobial lock solution: a meta-analysis of prospective randomized trials. Nephrol Dial Transplant 2008;23:1666-72.

Jaffer Y, Selby NM, Taal MW, Fluck RJ, McIntyre CW. A meta-analysis of hemodialysis catheter locking solutions in the prevention of catheter-related infection. Am J Kidney Dis 2008;51:233-41.

Safdar N, Maki DG. Use of vancomycin-containing lock or flush solutions for prevention of bloodstream infection associated with central venous access devices: a meta-analysis of prospective, randomized trials. Clin Infect Dis 2006;43:474-84.

Slobbe L, Doorduijn JK, Lugtenburg PJ, et al. Prevention of catheter-related bacteremia with a daily ethanol lock in patients with tunnelled catheters: a randomized, placebo-controlled trial. PLoS One 2010;5:e10840.

Broom JK, O’Shea S, Govindarajulu S, et al. Rationale and design of the HEALTHY-CATH trial: a randomised controlled trial of Heparin versus EthAnol Lock THerapY for the prevention of Catheter Associated infecTion in Haemodialysis patients. BMC Nephrol 2009;10:23.

Maiefski M, Rupp ME, Hermsen ED. Ethanol lock technique: review of the literature. Infect Control Hosp Epidemiol 2009;30:1096-108.

Sanders J, Pithie A, Ganly P, et al. A prospective double-blind randomized trial comparing intraluminal ethanol with heparinized saline for the prevention of catheter-associated bloodstream infection in immunosuppressed haematology patients. J Antimicrob Chemother 2008;62:809-15.

Mouw E, Chessman K, Lesher A, Tagge E. Use of an ethanol lock to prevent catheter-related infections in children with short bowel syndrome. J Pediatr Surg 2008;43:1025-9.

Bradshaw JH, Puntis JW. Taurolidine and catheter-related bloodstream infection: a systematic review of the literature. J Pediatr Gastroenterol Nutr 2008;47:179-86.

Bisseling TM, Willems MC, Versleijen MW, Hendriks JC, Vissers RK, Wanten GJ. Taurolidine lock is highly effective in preventing catheter-related bloodstream infections in patients on home parenteral nutrition: a heparin-controlled prospective trial. Clin Nutr 2010;29:464-8.

Carratala J, Niubo J, Fernandez-Sevilla A, et al. Randomized, double-blind trial of an antibiotic-lock technique for prevention of gram-positive central venous catheter-related infection in neutropenic patients with cancer. Antimicrob Agents Chemother 1999;43:2200-4.

Garland JS, Alex CP, Henrickson KJ, McAuliffe TL, Maki DG. A vancomycin-heparin lock solution for prevention of nosocomial bloodstream infection in critically ill neonates with peripherally inserted central venous catheters: a prospective, randomized trial. Pediatrics 2005;116:e198-205.

Saxena AK, Panhotra BR, Naguib M. Sudden irreversible sensory-neural hearing loss in a patient with diabetes receiving amikacin as an antibiotic-heparin lock. Pharmacotherapy 2002;22:105-8.

Opilla MT, Kirby DF, Edmond MB. Use of ethanol lock therapy to reduce the incidence of catheter-related bloodstream infections in home parenteral nutrition patients. JPEN J Parenter Enteral Nutr 2007;31:302-5.

McKee R, Dunsmuir R, Whitby M, Garden OJ. Does antibiotic prophylaxis at the time of catheter insertion reduce the incidence of catheter-related sepsis in intravenous nutrition? J Hosp Infect 1985;6:419-25.

Ranson MR, Oppenheim BA, Jackson A, Kamthan AG, Scarffe JH. Double-blind placebo controlled study of vancomycin prophylaxis for central venous catheter insertion in cancer patients. J Hosp Infect 1990;15:95-102.

Wong GK, Ip M, Poon WS, Mak CW, Ng RY. Antibiotics-impregnated ventricular catheter versus systemic antibiotics for prevention of nosocomial CSF and non-CSF infections: a prospective randomised clinical trial. J Neurol Neurosurg Psychiatry 2010;81:1064-7.

Jardine LA, Inglis GD, Davies MW. Prophylactic systemic antibiotics to reduce morbidity and mortality in neonates with central venous catheters. Cochrane Database Syst Rev 2008:CD006179.

van de Wetering MD, van Woensel JB. Prophylactic antibiotics for preventing early central venous catheter Gram positive infections in oncology patients. Cochrane Database Syst Rev 2003:CD003295.

van de Wetering MD, van Woensel JB, Kremer LC, Caron HN. Prophylactic antibiotics for preventing early Gram-positive central venous catheter infections in oncology patients, a Cochrane systematic review. Cancer Treat Rev 2005;31:186-96.

van de Wetering MD, van Woensel JB. Prophylactic antibiotics for preventing early central venous catheter Gram positive infections in oncology patients. Cochrane Database Syst Rev 2007:CD003295.

Eyer S, Brummitt C, Crossley K, Siegel R, Cerra F. Catheter-related sepsis: prospective, randomized study of three methods of long-term catheter maintenance. Crit Care Med 1990;18:1073-9.

Cobb DK, High KP, Sawyer RG, et al. A controlled trial of scheduled replacement of central venous and pulmonary-artery catheters. N Engl J Med 1992;327:1062-8.

Cook D, Randolph A, Kernerman P, et al. Central venous catheter replacement strategies: a systematic review of the literature. Crit Care Med 1997;25:1417-24.

Siempos, II, Kopterides P, Tsangaris I, Dimopoulou I, Armaganidis AE. Impact of catheter-related bloodstream infections on the mortality of critically ill patients: a meta-analysis. Crit Care Med 2009;37:2283-9.

Rosenthal VD, Maki DG, Rodrigues C, et al. Impact of International Nosocomial Infection Control Consortium (INICC) strategy on central line-associated bloodstream infection rates in the intensive care units of 15 developing countries. Infect Control Hosp Epidemiol 2010;31:1264-72.

Pronovost P, Needham D, Berenholtz S, et al. An intervention to decrease catheter-related bloodstream infections in the ICU. N Engl J Med 2006;355:2725-32.

Stone PW, Glied SA, McNair PD, et al. CMS changes in reimbursement for HAIs: setting a research agenda. Med Care 2010;48:433-9.

Clancy CM. CMS’s hospital-acquired condition lists link hospital payment, patient safety. Am J Med Qual 2009;24:166-8.

McKinney M. The infection connection. Only a few months remain until voluntary participation in CDC’s reporting network begins, and Medicare dollars are on the line. Mod Healthc 2010;40:6-7, 16, 1.

Gardam MA, Lemieux C, Reason P, van Dijk M, Goel V. Healthcare-associated infections as patient safety indicators. Healthc Pap 2009;9:8-24.

Nicklin W, Greco P, Mitchell JI. Healthcare-associated infections: infection prevention and control within the Accreditation Canada Qmentum Program. Healthc Pap 2009;9:26-31; discussion 60-2.

Duffin C. NHS organisations must comply with criteria on healthcare-acquired infections or face prosecution. Nurs Manag (Harrow) 2008;15:5.

Vincent JL, Brun-Buisson C, Niederman M, et al. Ethics roundtable debate: A patient dies from an ICU-acquired infection related to methicillin-resistant Staphylococcus aureus–how do you defend your case and your team? Crit Care 2005;9:5-9.

Warren DK, Cosgrove SE, Diekema DJ, et al. A multicenter intervention to prevent catheter-associated bloodstream infections. Infect Control Hosp Epidemiol 2006;27:662-9.

Rosenthal VD, Guzman S, Pezzotto SM, Crnich CJ. Effect of an infection control program using education and performance feedback on rates of intravascular device-associated bloodstream infections in intensive care units in Argentina. Am J Infect Control 2003;31:405-9.

Warren DK, Zack JE, Mayfield JL, et al. The effect of an education program on the incidence of central venous catheter-associated bloodstream infection in a medical ICU. Chest 2004;126:1612-8.

Coopersmith CM, Rebmann TL, Zack JE, et al. Effect of an education program on decreasing catheter-related bloodstream infections in the surgical intensive care unit. Crit Care Med 2002;30:59-64.

Warren DK, Zack JE, Cox MJ, Cohen MM, Fraser VJ. An educational intervention to prevent catheter-associated bloodstream infections in a nonteaching, community medical center. Crit Care Med 2003;31:1959-63.

Sherertz RJ, Ely EW, Westbrook DM, et al. Education of physicians-in-training can decrease the risk for vascular catheter infection. Ann Intern Med 2000;132:641-8.

Smith CE, Curtas S, Kleinbeck SV, et al. Clinical trial of interactive and videotaped educational interventions reduce infection, reactive depression, and rehospitalizations for sepsis in patients on home parenteral nutrition. JPEN J Parenter Enteral Nutr 2003;27:137-45.

Ramritu P, Halton K, Cook D, Whitby M, Graves N. Catheter-related bloodstream infections in intensive care units: a systematic review with meta-analysis. J Adv Nurs 2008;62:3-21.

Berenholtz SM, Pronovost PJ, Lipsett PA, et al. Eliminating catheter-related bloodstream infections in the intensive care unit. Crit Care Med 2004;32:2014-20.

Tsuchida T, Makimoto K, Toki M, Sakai K, Onaka E, Otani Y. The effectiveness of a nurse-initiated intervention to reduce catheter-associated bloodstream infections in an urban acute hospital: an intervention study with before and after comparison. Int J Nurs Stud 2007;44:1324-33.

Goeschel CA, Holzmueller CG, Pronovost PJ. Hospital Board Checklist to improve culture and reduce central line-associated bloodstream infections. Jt Comm J Qual Patient Saf 2010;36:525-8.

Goeschel CA, Holzmueller CG, Berenholtz SM, et al. Executive/Senior Leader Checklist to improve culture and reduce central line-associated bloodstream infections. Jt Comm J Qual Patient Saf 2010;36:519-24.

Goeschel CA, Holzmueller CG, Cosgrove SE, Ristaino P, Pronovost PJ. Infection preventionist checklist to improve culture and reduce central line-associated bloodstream infections. Jt Comm J Qual Patient Saf 2010;36:571-5.

Lederle FA, Parenti CM, Berskow LC, Ellingson KJ. The idle intravenous catheter. Ann Intern Med 1992;116:737-8.

Parenti CM, Lederle FA, Impola CL, Peterson LR. Reduction of unnecessary intravenous catheter use. Internal medicine house staff participate in a successful quality improvement project. Arch Intern Med 1994;154:1829-32.

Salzman MB IH, Rubin LG. Use of Disinfectants To Reduce Microbial Contamination of Hubs of Vascular Catheters. Journal of clinical microbiology 1993;31:475-9.

Casey AL, Worthington T, Lambert PA, Quinn D, Faroqui MH, Elliott TS. A randomized, prospective clinical trial to assess the potential infection risk associated with the PosiFlow needleless connector. J Hosp Infect 2003;54:288-93.

Haley RW, Culver DH, White JW, et al. The efficacy of infection surveillance and control programs in preventing nosocomial infections in US hospitals. Am J Epidemiol 1985;121:182-205.

Gastmeier P, Geffers C, Brandt C, et al. Effectiveness of a nationwide nosocomial infection surveillance system for reducing nosocomial infections. J Hosp Infect 2006;64:16-22.

Gastmeier P, Schwab F, Sohr D, Behnke M, Geffers C. Reproducibility of the surveillance effect to decrease nosocomial infection rates. Infect Control Hosp Epidemiol 2009;30:993-9.

Edwards JR, Peterson KD, Mu Y, et al. National Healthcare Safety Network (NHSN) report: data summary for 2006 through 2008, issued December 2009. Am J Infect Control 2009;37:783-805.

Edwards JR, Peterson KD, Andrus ML, et al. National Healthcare Safety Network (NHSN) Report, data summary for 2006 through 2007, issued November 2008. Am J Infect Control 2008;36:609-26.

Klevens RM, Edwards JR, Andrus ML, et al. Dialysis Surveillance Report: National Healthcare Safety Network (NHSN)-data summary for 2006. Semin Dial 2008;21:24-8.

Marschall J, Leone C, Jones M, Nihill D, Fraser VJ, Warren DK. Catheter-associated bloodstream infections in general medical patients outside the intensive care unit: a surveillance study. Infect Control Hosp Epidemiol 2007;28:905-9.

Vonberg RP, Behnke M, Geffers C, et al. Device-associated infection rates for non-intensive care unit patients. Infect Control Hosp Epidemiol 2006;27:357-61.

Bouza E, Munoz P, Lopez-Rodriguez J, et al. A needleless closed system device (CLAVE) protects from intravascular catheter tip and hub colonization: a prospective randomized study. J Hosp Infect 2003;54:279-87.

Yoshida J, Ishimaru T, Fujimoto M, Hirata N, Matsubara N, Koyanagi N. Risk factors for central venous catheter-related bloodstream infection: a 1073-patient study. J Infect Chemother 2008;14:399-403.

Maragakis LL, Bradley KL, Song X, et al. Increased catheter-related bloodstream infection rates after the introduction of a new mechanical valve intravenous access port. Infect Control Hosp Epidemiol 2006;27:67-70.

Rupp ME, Sholtz LA, Jourdan DR, et al. Outbreak of bloodstream infection temporally associated with the use of an intravascular needleless valve. Clin Infect Dis 2007;44:1408-14.

Jarvis WR, Murphy C, Hall KK, et al. Health care-associated bloodstream infections associated with negative- or positive-pressure or displacement mechanical valve needleless connectors. Clin Infect Dis 2009;49:1821-7.

Menyhay SZ, Maki DG. Disinfection of needleless catheter connectors and access ports with alcohol may not prevent microbial entry: the promise of a novel antiseptic-barrier cap. Infect Control Hosp Epidemiol 2006;27:23-7.

Yebenes JC, Vidaur L, Serra-Prat M, et al. Prevention of catheter-related bloodstream infection in critically ill patients using a disinfectable, needle-free connector: a randomized controlled trial. Am J Infect Control 2004;32:291-5.

Fridkin SK, Pear SM, Williamson TH, Galgiani JN, Jarvis WR. The role of understaffing in central venous catheter-associated bloodstream infections. Infect Control Hosp Epidemiol 1996;17:150-8.

Stone PW, Mooney-Kane C, Larson EL, et al. Nurse working conditions and patient safety outcomes. Med Care 2007;45:571-8.

Archibald LK, Manning ML, Bell LM, Banerjee S, Jarvis WR. Patient density, nurse-to-patient ratio and nosocomial infection risk in a pediatric cardiac intensive care unit. Pediatr Infect Dis J 1997;16:1045-8.

Cimiotti JP, Haas J, Saiman L, Larson EL. Impact of staffing on bloodstream infections in the neonatal intensive care unit. Arch Pediatr Adolesc Med 2006;160:832-6.

Robert J, Fridkin SK, Blumberg HM, et al. The influence of the composition of the nursing staff on primary bloodstream infection rates in a surgical intensive care unit. Infect Control Hosp Epidemiol 2000;21:12-7.

Soifer NE, Borzak S, Edlin BR, Weinstein RA. Prevention of peripheral venous catheter complications with an intravenous therapy team: a randomized controlled trial. Arch Intern Med 1998;158:473-7.

Miller JM, Goetz AM, Squier C, Muder RR. Reduction in nosocomial intravenous device-related bacteremias after institution of an intravenous therapy team. J Intraven Nurs 1996;19:103-6.

Tomford JW, Hershey CO, McLaren CE, Porter DK, Cohen DI. Intravenous therapy team and peripheral venous catheter-associated complications. A prospective controlled study. Arch Intern Med 1984;144:1191-4.

Volkow P, Sanchez-Mejorada G, de la Vega SL, et al. Experience of an intravenous therapy team at the Instituto Nacional de Cancerologia (Mexico) with a long-lasting, low-cost silastic venous catheter. Clin Infect Dis 1994;18:719-25.

Brunelle D. Impact of a dedicated infusion therapy team on the reduction of catheter-related nosocomial infections. J Infus Nurs 2003;26:362-6.

Rosenthal VD. Device-associated nosocomial infections in limited-resources countries: findings of the International Nosocomial Infection Control Consortium (INICC). Am J Infect Control 2008;36:S171 e7-12.

Tokars JI, Klevens RM, Edwards JR, Horan TC. Measurement of the impact of risk adjustment for central line-days on interpretation of central line-associated bloodstream infection rates. Infect Control Hosp Epidemiol 2007;28:1025-9.

Klevens RM, Tokars JI, Edwards J, Horan T, National Nosocomial Infections Surveillance S. Sampling for collection of central line-day denominators in surveillance of healthcare-associated bloodstream infections. Infect Control Hosp Epidemiol 2006;27:338-42.

Aslakson RA, Romig M, Galvagno SM, et al. Effect of accounting for multiple concurrent catheters on central line-associated bloodstream infection rates: practical data supporting a theoretical concern. Infect Control Hosp Epidemiol 2011;32:121-4.

National Healthcare Safety Network CfDCaP. Device-associated Module CLABSI: Central Line-Associated Bloodstream Infection (CLABSI) Event. In; 2010:4-1-4-3.

Mermel LA, Allon M, Bouza E, et al. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 Update by the Infectious Diseases Society of America. Clin Infect Dis 2009;49:1-45.

National Healthcare Safety Network CfDCaP. Device-associated Module CLABSI: Central Line Insertion Practices (CLIP) Adherence Monitoring. In:5-1-5-3.

Moureau N, Poole S, Murdock MA, Gray SM, Semba CP. Central venous catheters in home infusion care: outcomes analysis in 50,470 patients. J Vasc Interv Radiol 2002;13:1009-16.

Pinon M, Bezzio S, Tovo PA, et al. A prospective 7-year survey on central venous catheter-related complications at a single pediatric hospital. Eur J Pediatr 2009;168:1505-12.

Jarvis WR. Selected aspects of the socioeconomic impact of nosocomial infections: morbidity, mortality, cost, and prevention. Infect Control Hosp Epidemiol 1996;17:552-7.

Rosenthal VD, Maki DG, Jamulitrat S, et al. International Nosocomial Infection Control Consortium (INICC) report, data summary for 2003-2008, issued June 2009. Am J Infect Control 2010;38:95-104 e2.

Klevens RM, Edwards JR, Richards CL, Jr., et al. Estimating health care-associated infections and deaths in U.S. hospitals, 2002. Public Health Rep 2007;122:160-6.

Chittick P, Sherertz RJ. Recognition and prevention of nosocomial vascular device and related bloodstream infections in the intensive care unit. Crit Care Med 2010;38:S363-72.

Anderson DJ, Kirkland KB, Kaye KS, et al. Underresourced hospital infection control and prevention programs: penny wise, pound foolish? Infect Control Hosp Epidemiol 2007;28:767-73.

Eggimann P, Harbarth S, Constantin MN, Touveneau S, Chevrolet JC, Pittet D. Impact of a prevention strategy targeted at vascular-access care on incidence of infections acquired in intensive care. Lancet 2000;355:1864-8.

Mermel LA, McCormick RD, Springman SR, Maki DG. The pathogenesis and epidemiology of catheter-related infection with pulmonary artery Swan-Ganz catheters: a prospective study utilizing molecular subtyping. Am J Med 1991;91:197S-205S.

Sesso R, Barbosa D, Leme IL, et al. Staphylococcus aureus prophylaxis in hemodialysis patients using central venous catheter: effect of mupirocin ointment. J Am Soc Nephrol 1998;9:1085-92.

Johnson DW, MacGinley R, Kay TD, et al. A randomized controlled trial of topical exit site mupirocin application in patients with tunnelled, cuffed haemodialysis catheters. Nephrol Dial Transplant 2002;17:1802-7.

Johnson DW, van Eps C, Mudge DW, et al. Randomized, controlled trial of topical exit-site application of honey (Medihoney) versus mupirocin for the prevention of catheter-associated infections in hemodialysis patients. J Am Soc Nephrol 2005;16:1456-62.

Bach A, Schmidt H, Bottiger B, et al. Retention of antibacterial activity and bacterial colonization of antiseptic-bonded central venous catheters. J Antimicrob Chemother 1996;37:315-22.

Ciresi DL, Albrecht RM, Volkers PA, Scholten DJ. Failure of antiseptic bonding to prevent central venous catheter-related infection and sepsis. Am Surg 1996;62:641-6.

Logghe C, Van Ossel C, D’Hoore W, Ezzedine H, Wauters G, Haxhe JJ. Evaluation of chlorhexidine and silver-sulfadiazine impregnated central venous catheters for the prevention of bloodstream infection in leukaemic patients: a randomized controlled trial. J Hosp Infect 1997;37:145-56.

Tennenberg S, Lieser M, McCurdy B, et al. A prospective randomized trial of an antibiotic- and antiseptic-coated central venous catheter in the prevention of catheter-related infections. Arch Surg 1997;132:1348-51.

Heard SO, Wagle M, Vijayakumar E, et al. Influence of triple-lumen central venous catheters coated with chlorhexidine and silver sulfadiazine on the incidence of catheter-related bacteremia. Arch Intern Med 1998;158:81-7.

Hannan M, Juste RN, Umasanker S, et al. Antiseptic-bonded central venous catheters and bacterial colonisation. Anaesthesia 1999;54:868-72.

Sheng WH, Ko WJ, Wang JT, Chang SC, Hsueh PR, Luh KT. Evaluation of antiseptic-impregnated central venous catheters for prevention of catheter-related infection in intensive care unit patients. Diagn Microbiol Infect Dis 2000;38:1-5.

Jaeger K, Zenz S, Juttner B, et al. Reduction of catheter-related infections in neutropenic patients: a prospective controlled randomized trial using a chlorhexidine and silver sulfadiazine-impregnated central venous catheter. Ann Hematol 2005;84:258-62.

Osma S, Kahveci SF, Kaya FN, et al. Efficacy of antiseptic-impregnated catheters on catheter colonization and catheter-related bloodstream infections in patients in an intensive care unit. J Hosp Infect 2006;62:156-62.

Brun-Buisson C, Doyon F, Sollet JP, Cochard JF, Cohen Y, Nitenberg G. Prevention of intravascular catheter-related infection with newer chlorhexidine-silver sulfadiazine-coated catheters: a randomized controlled trial. Intensive Care Med 2004;30:837-43.

Ostendorf T, Meinhold A, Harter C, et al. Chlorhexidine and silver-sulfadiazine coated central venous catheters in haematological patients–a double-blind, randomised, prospective, controlled trial. Support Care Cancer 2005;13:993-1000.

Raad I, Darouiche R, Dupuis J, et al. Central venous catheters coated with minocycline and rifampin for the prevention of catheter-related colonization and bloodstream infections. A randomized, double-blind trial. The Texas Medical Center Catheter Study Group. Ann Intern Med 1997;127:267-74.

Leon C, Ruiz-Santana S, Rello J, et al. Benefits of minocycline and rifampin-impregnated central venous catheters. A prospective, randomized, double-blind, controlled, multicenter trial. Intensive Care Med 2004;30:1891-9.

Chemaly RF, Sharma PS, Youssef S, et al. The efficacy of catheters coated with minocycline and rifampin in the prevention of catheter-related bacteremia in cancer patients receiving high-dose interleukin-2. Int J Infect Dis 2010;14:e548-52.

Wolf HH, Leithauser M, Maschmeyer G, et al. Central venous catheter-related infections in hematology and oncology : guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO). Ann Hematol 2008;87:863-76.

Pittiruti M, Hamilton H, Biffi R, MacFie J, Pertkiewicz M, Espen. ESPEN Guidelines on Parenteral Nutrition: central venous catheters (access, care, diagnosis and therapy of complications). Clin Nutr 2009;28:365-77.

Sampath LA, Tambe SM, Modak SM. In vitro and in vivo efficacy of catheters impregnated with antiseptics or antibiotics: evaluation of the risk of bacterial resistance to the antimicrobials in the catheters. Infect Control Hosp Epidemiol 2001;22:640-6.

Archer GL, Armstrong BC. Alteration of staphylococcal flora in cardiac surgery patients receiving antibiotic prophylaxis. J Infect Dis 1983;147:642-9.

Teo BW, Low SJ, Ding Y, Koh TH, Hsu LY. High prevalence of mupirocin-resistant staphylococci in a dialysis unit where mupirocin and chlorhexidine are routinely used for prevention of catheter-related infections. J Med Microbiol 2011.

Meyer B, Cookson B. Does microbial resistance or adaptation to biocides create a hazard in infection prevention and control? J Hosp Infect 2010;76:200-5.

Munson EL, Heard SO, Doern GV. In vitro exposure of bacteria to antimicrobial impregnated-central venous catheters does not directly lead to the emergence of antimicrobial resistance. Chest 2004;126:1628-35.

Carlet J, Fabry J, Amalberti R, Degos L. The “zero risk” concept for hospital-acquired infections: a risky business! Clin Infect Dis 2009;49:747-9.

Brown J, Doloresco Iii F, Mylotte JM. “Never events”: not every hospital-acquired infection is preventable. Clin Infect Dis 2009;49:743-6.

O’Grady NP, Alexander M, Dellinger EP, et al. Guidelines for the prevention of intravascular catheter-related infections. Centers for Disease Control and Prevention. MMWR Recomm Rep 2002;51:1-29.

Pratt RJ, Pellowe CM, Wilson JA, et al. epic2: National evidence-based guidelines for preventing healthcare-associated infections in NHS hospitals in England. J Hosp Infect 2007;65 Suppl 1:S1-64.

Miller DL, O’Grady NP. Guidelines for the prevention of intravascular catheter-related infections: recommendations relevant to interventional radiology. J Vasc Interv Radiol 2003;14:S355-8.