DEFINITION

This document intends to review the available evidence and provide a more international spectrum, including specific recommendations to address situations that are particularly concerning in low- and middle-income countries (LMIC). It highlights practical recommendations in a concise format designed to assist acute-care hospitals in implementing and prioritizing their central line-associated bloodstream infection (CLABSI) prevention efforts in LMICs as well as in high-income countries. We acknowledge recommendations from several previous guidelines, such as those of the Infusion Nurses Society, 2021 Infusion Therapy Standards of Practice Update¹, and SHEA/IDSA/APIC, Practice Recommendation Strategies to prevent CLABSIs in acute-care hospitals: 2022 Update². This expert guidance document,  sponsored by the International Society of Infectious Diseases, updates the previous position paper published in 2019³.

KEY ISSUES

• The CLABSI rates reported by the World Health Organization, through a systematic review and meta-analysis of published data, identified that in high-income countries, the CLABSI rate was 3.5 CLABSI per 1,000 CL-days, while in LMICs, it was 12.2⁴.
• CLABSI rates in the USA, as reported by the CDC National Healthcare Safety Network (NHSN), show a median CLABSI rate of 0.8/1,000 central line (CL)-days in medical-surgical intensive care units (ICUs)⁵.
• Over the last two decades, the International Nosocomial Infection Control Consortium (INICC) has been conducting prospective active surveillance of CLABSI rates, obtained primary data, and consistently observed higher CLABSI rates in LMICs compared to high-income countries. However, there were positive changes. The INICC report from 2002 to 2005 indicated a CLABSI rate of  5/1,000 CL-days⁶, gradually reducing to 4.5 in the report covering data from 2015 to 2020⁷.
• Costs associated with CLABSI vary globally, with reported costs in the USA, of $36,000 in 2009⁸. Italy reported $9,034 in 2010⁹ and China, $3,528, in 2018¹⁰.
• Associated length of stay (LOS): Pooling 630 ICUs from 2015 to 2020 of 45 LMICs, from Africa, Asia, Eastern Europe, Latin America, and the Middle East, with data from 204,770 patients, 1,480,620 patient-days, 936,976 CL-days, and 4,270 CLABSIs, LOS was as follows: 6.57 days for patients without healthcare-associated infections (HAIs), 23.17 days for those with CLABSI. Patients with two simultaneous HAIs experienced LOS ranging from 29.13 to 32.01 days, while those with all three types of HAIs (CLABSI + ventilator-associated pneumonia [VAP] + catheter-associated urinary tract infection [CAUTI]) had a LOS of 33.53 days⁷.
• Associated mortality. CLABSIs have a significant impact on healthcare, leading to increased mortality rates,⁷ with CLABSIs associated with a 12% to 25% increase in mortality.¹¹ Pooling 630 ICUs from 2015 to 2020 of 45 LMICs, the mortality rates were as follows: 14.06% for patients without HAI, and 39.81% for those with CLABSI. Patients with two simultaneous HAIs experienced mortality rates ranging from 38.79% to 43.32%, while those with all three types of HAIs (CLABSI + VAP + CAUTI) had a mortality rate of 46.56%⁷.
• Risk factors for mortality: Studies have documented that CLABSI is an independent significant risk factor for mortality. In a multicenter, multinational, multicontinental study involving 786 ICUs across 312 hospitals in 147 cities spanning 37 countries between 1998 and 2022, a total of 300,827 patients were followed for 2,167,397 patient-days, with 21,371 HAIs. Multiple logistic regression identified the following mortality risk factors: CLABSIs (p<0.0001), LOS with a risk increase of 1% per day (p<0.0001), CL-days with a risk increase of 2% per day (p<0.0001), VAP (p<0.0001), CAUTI (p<0.0001), medical hospitalization (p<0.0001), female sex (p<0.0001), age (p<0.0001), and mechanical ventilator (MV)-utilization ratio (p<0.0001)¹².
• Hospital-onset bacteremia and fungemia (HOB):
  • CLABSIs require intensive surveillance and review. All-cause HOB may be a simpler reporting metric, correlates with CLABSI, and is viewed positively by HAI experts. HOB is defined as the growth of a recognized bacterial or fungal pathogen from a blood culture specimen collected on or after the third calendar day of admission¹³.
  • A retrospective observational study was conducted on patients in 41 acute-care hospitals. CLABSI cases were defined according to the criteria reported to the NHSN. The cross-sectional analysis revealed that among 1,977 total HOB cases, 403 (20.38%) were classified as NHSN-reportable CLABSIs, while 1,574 (79.61%) were categorized as non-CLABSI HOB¹⁴.
  • Efforts to reinstate well-established, evidence-based infection prevention practices, particularly for CLABSI, have intensified. Enhancing these efforts will also help prepare hospitals for upcoming broader surveillance and intervention activities aimed at reducing HOB associated with all types of vascular access devices¹⁵.

KNOWN FACTS

Risk factors for CLABSI

• Individuals susceptible to acquiring a CLABSI in acute-care facilities are those with a CL in place. The likelihood of CLABSI is elevated among ICU patients, attributed to the frequent insertion of multiple catheters¹⁶, and the utilization of particular catheter types, which carry significant risks (e.g., pulmonary artery catheters with catheter introducers). Additionally, emergency circumstances often necessitate catheter placement, leading to repeated daily access and prolonged usage¹⁷. Efforts in infection prevention and control should encompass additional vulnerable populations, including individuals undergoing hemodialysis through catheters¹⁸, post-surgical patients¹⁹, and cancer patients²⁰,
• Factors that have been identified as independent risks for CLASBI in high-income countries include: extended LOS before catheterization, prolonged catheterization duration, high microbial colonization at the insertion site, substantial microbial colonization of the catheter hub, multi-lumen catheters, simultaneous use of multiple catheters, neutropenia, Body Mass Index exceeding 40, premature birth, the reduced nurse-to-patient ratio in the ICU, patient cared for by a float nurse, parenteral nutrition, inadequate catheter care, blood product transfusion (in children), femoral site of insertion, and presence of internal jugular site and simultaneous tracheostomy².
• Despite the predominant emphasis on the ICU setting in the past two decades, it is noteworthy that the majority of CLABSIs occur in hospital units beyond the ICU or among outpatient cases²¹. Apart from CLs, there is also an elevated risk of infection associated with short-term peripheral catheters, as demonstrated in 727 ICUs of 42 LMICs²². At risk are also peripherally inserted central venous catheters (PICCs), midline catheters, and peripheral arterial catheters¹⁷.
• From 1998 to 2022, a multinational multicenter prospective cohort study, encompassing 728 ICUs within 286 hospitals situated in 147 cities across 41 African, Asian, Eastern European, Latin American, and Middle Eastern countries, utilizing an online standardized surveillance system and unified forms, identified factors independently associated with CLABSI, including a 3% daily risk increase in CLABSI with prolonged LOS (p<0.0001), a 4% risk increase per CL-day (p<0.0001), surgical hospitalization (p<0.0001), tracheostomy use (p<0.0001), hospitalization at a publicly owned facility (p<0.0001) or at a teaching hospital (p<0.0001), and hospitalization in a middle-income country (p<0.0001); with the highest CLABSI risk observed in adult oncology (p<0.0001), followed by pediatric oncology (p<0.0001), and PICU (p<0.0001), while the highest CLABSI risk was associated with internal-jugular (p<0.0001), followed by femoral (p<0.0001), and the lowest CLABSI risk was found with PICCs (p=0.04)²³.

SUGGESTED PRACTICE

Necessary prerequisites

Establishments and implementation of CLABSI prevention interventions should possess the following components:

• Assets for delivering suitable education and training².
• A sufficiently staffed infection prevention program is responsible for identifying patients who meet the surveillance definition for CLABSI².
• An Infection Prevention program with information technology support is crucial for gathering and computing CL-days as a denominator in CLABSI rate calculations².
• Patient days are essential for determining CL device utilization. It is advisable to validate CL-days obtained from information systems by comparing them to a manual method, with an acceptable margin of error not exceeding ±5%²⁴.
• Effective laboratory support is crucial for the timely processing of specimens and reporting results, adhering to the instructions provided by the supervisor of the surveillance program².

Implementation of CLABSI prevention strategies

• Four Es “Engage, Educate, Execute, and Evaluate”. Preventing CLABSI relies on integrating best practices, and one example involves the Four Es—engage, educate, execute, and evaluate²⁵.
  • This approach emphasizes the incorporation of a culture supporting implementation, addressing both technical and socio-adaptive components of CLABSI prevention, including formal health care professionals (HCP) training on indications, placement, and device maintenance, along with regular competency assessments²⁶.
  • Multidimensional approach. Numerous national, multinational, and multicontinental studies, employing a multidimensional approach, have been conducted, achieving a significant reduction in rates of CLABSI and mortality. All of them include six components: (a) bundle, (b) education, (c) surveillance of CLABSI, (d) monitoring compliance with recommendations to prevent CLABSI, (e) internal reports of CLABSI rates, and (f) performance feedback^27-39.

Bundles:

• Care “bundles” in infection prevention and safety aresimple sets of evidence-based practices that, when implemented collectively, improve the reliability of their delivery and improve patient outcomes.⁴⁰   In 2014, Blot et al. conducted a systematic review and meta-analysis regarding the prevention of CLABSIs through quality improvement interventions. Forty-one before-after studies were identified, revealing a decrease in infection rates (p<0.001). This effect was more pronounced for trials implementing a bundle or checklist approach (p=0.03)⁴¹.
• Berenholtz, S. M., et al. at The Johns Hopkins Hospital conducted a study from 1998 through 2002. The aim was to determine whether a multifaceted systems intervention could eliminate CLABSIs. The bundle included the implementation of five interventions: educating the staff; creating a catheter insertion cart; asking providers daily whether catheters could be removed; implementing a checklist to ensure adherence to evidence-based guidelines for preventing CLABSIs; and empowering nurses to stop the catheter insertion procedure if a violation of the guidelines was observed. Before the intervention, it was found that physicians followed infection control guidelines during 62% of the procedures. The CLABSI rate in the study ICU decreased from 11.3/1,000 CL-days to 0/1,000 CL-days⁴².
• Pronovost, P., et al., published a study in 2006 on a collaborative cohort study in 103 ICUs in Michigan. A bundle with 5 components was implemented (hand hygiene, maximal barriers, skin antisepsis with chlorhexidine, avoiding the femoral vein, and removing the catheter as soon as possible). The median rate of CLABSIs per 1000 CL-days decreased from 2.7 CLABSI/1,000 CL-days at baseline to 0 at 3 months, and the mean rate per 1000 CL-days decreased from 7.7 at baseline to 1.4 at 16 to 18 months of follow-up (p<0.002)⁴³.
• The INICC utilizes a bundle as part of its approach to reduce CLABSI rates and was effective in Africa, Asia, Latin America, Eastern Europe, and the Middle East, resulting in a CLABSI rate reduction from 15.34/1,000 CL-days to 2.23 over a follow-up period of 29 months³⁸.

Education:

HCPs, patients, and caregivers participating in the care of a CL should receive training and demonstrate competence, commensurate with their roles, in understanding the suitable indications for insertion, recommendations to prevent CLABSI, and conducting daily assessments to determine the ongoing necessity of the device⁴⁴.

Surveillance of CLABSI:

• CLABSI. Employ uniform surveillance methods and definitions to facilitate the comparison of data with benchmark standards as published by the CDC/NHSN⁴⁵.
• Calculate the CLABSI rate using CDC/NHSN definitions by dividing the number of CLABSIs in each unit by the total number of CL-days, then multiply the result by 1,000 to express the measure as the number of CLABSIs/1,000 CL-days⁴⁵.
• Risk adjustment: Stratify CLABSI rates based on the type of patient-care unit and provide comparisons using both historical data, CDC/NHSN data⁵, and INICC data⁷.
• Device utilization ratio (DUR): DUR can be monitored longitudinally to identify any variations, allowing for comparisons at both hospital and unit levels, and serving as a surrogate for assessing patient exposure risk⁴⁶. The DUR, a CDC/NHSN⁵, and INICC measure⁷, considers facility- and location-level factors influencing device use, calculated as the observed device days divided by observed patient days.
• Surveillance of other types of catheters⁴⁷. Most surveillance systems typically exclude peripheral arterial catheters, short-term peripheral venous catheters, and midline catheters, despite their association with infection risk. Future surveillance systems should encompass these catheter types and may contemplate extending their surveillance programs to cover all catheter types to accurately assess the scope of the issue. Several studies from LMICs demonstrated that short-term peripheral venous catheter-associated bloodstream infections are a significant challenge ²².

Internal reporting of CLABSI rates:

• These measures are crafted to enhance internal hospital quality improvement initiatives, and it is important to convey these measures to senior hospital leadership, nursing leadership, and clinicians engaged in the care of patients at risk for CLABSI⁴⁸.
• When providing internal reporting as a benchmark, compare the CLABSI rates of the given hospital against data from the CDC/NHSN⁵, and the INICC⁷.

Monitoring Compliance with Recommendations to Prevent CLABSI:

• Assess compliance with CL insertion and maintenance guidelines by employing a documented insertion paper or online checklist across all hospital settings, assigning knowledgeable HCP to this task³⁸.
• This checklist could be a paper form or an online form. Documenting compliance using the checklist ensures adherence to proper procedural steps, identifies and addresses any gaps, with the Institute for Health Improvement (IHI) offering a CL checklist as an example⁴⁹.
• Document CL insertion procedures, encompassing all relevant measures.
• Calculate compliance by dividing the compliance of each recommendation by the total number of CL insertions, then multiply by 100 for a percentage expression. As one example, evaluate compliance with the documentation of daily assessments for the necessity of continuing CL access by measuring the percentage of patients with a CL where daily assessment documentation is present.

Performance feedback:

• For the performance feedback, IPPs present charts, showcasing data related to attending HCPs' monthly degree of compliance with infection prevention practices³⁸.
• The infection control tool plays a crucial role, enabling attending HCPs to identify areas for improvement in cases of low degree of compliance with infection prevention practices. Leveraging the "observer effects" on HCPs' behavior, this method's strength lies in influencing their practices to enhance efficiency⁵⁰.
• This approach aimed to shape behaviors for more effective implementation⁵¹.

Main approaches

Before insertion

• Mandated education and competency assessments for HCPs engaged in the insertion, care, and maintenance of CL with a focus on CLABSI prevention. (Quality of Evidence: MODERATE)⁵².
  • Incorporate information on indications for catheter use, proper insertion and maintenance practices, the risk of CLABSI, and general infection prevention strategies into the education and competency assessments for HCPs involved in CL procedures².
  • Guarantee that all HCPs engaged in catheter insertion and maintenance undergo an educational program covering crucial practices to prevent CLABSI before undertaking these responsibilities⁵³.
  • Conduct periodic assessments of HCP's knowledge and adherence to preventive measures².
  • Mandate that all HCPs involved in CL insertion undergo a credentialing process, as determined by the healthcare institution, to verify their competence. This process should ensure their ability to independently insert a CL and maintain an aseptic technique throughout the procedure and subsequent access and maintenance of the CL².
  • Provide additional education when an institution modifies components of the infusion system, necessitating a corresponding change in practice. For instance, if a shift to a new needleless connector occurs, re-education should be conducted to align with the updated nursing practices².
  • If accessible, incorporate simulation training for accurate catheter insertion and maintenance procedures⁵⁴.

• Administer a daily chlorhexidine preparation bath to ICU patients aged over two months. (Quality of Evidence: HIGH)⁵⁵
  • In long-term acute-care hospitals, contemplating daily chlorhexidine bathing is an option to be considered for preventive measures⁵⁶.
  • The effectiveness of chlorhexidine bathing in non-ICU patients is still uncertain⁵⁷. In a cluster-randomized study, a notable decrease in device-associated bacteremia was observed with chlorhexidine bathing in this patient population. However, it is important to note that some of these patients also underwent methicillin-resistant Staphylococcus aureus (MRSA) decolonization, complicating the ability to definitively attribute the observed effects solely to chlorhexidine bathing⁵⁷. Multiple studies have indicated potential benefits for adult hematology-oncology patients; nevertheless, a comparable reduction was not observed in pediatric patients with similar conditions⁵⁸. Thus, it is crucial to carefully weigh the potential benefits and risks, including concerns about resistance and cost implications.
  • The safety and effectiveness of routinely employing chlorhexidine bathing in infants under two months of age after birth are not established⁵⁹. While life-threatening skin injuries resulting from chlorhexidine have been reported in very young or extremely preterm infants, such incidents typically occur in infants with a birth weight below 1,000 grams who are less than 7 days postnatal age. Such occurrences appear to be rare in older infants⁶⁰.
  • The extensive use of chlorhexidine may lead to a decrease in its effectiveness as an antiseptic, although the clinical significance of this observation is not clearly defined⁶¹.

At insertion

• In both ICU and non-ICU settings, it is recommended for facilities to implement a process, such as a checklist, to ensure strict adherence to infection prevention practices during the insertion of CL. (Quality of Evidence: MODERATE)⁶².
  • Guarantee and document the adherence to aseptic technique².
  • Utilizing checklists to ensure optimal insertion practices is recommended. In such cases, documentation should be completed by an individual other than the inserter².
  • Observation of CL insertion should be conducted by a nurse, physician, or another HCP who has undergone suitable education (as mentioned above) to ensure the maintenance of aseptic technique².
  • HCPs should be authorized to halt the procedure if any lapses in aseptic technique are identified².
• Use an all-inclusive catheter cart or kit (Quality of Evidence: MODERATE)⁴².
  • Ensure that all units where CLs are inserted have readily accessible catheter carts or kits containing all essential components for aseptic catheter insertion².
• Perform hand hygiene before catheter insertion or manipulation (Quality of Evidence: MODERATE)⁶³.
  • Utilize either an alcohol-based waterless product or soap and water².
  • Wearing gloves does not eliminate the need for hand hygiene².
• Adopt maximum sterile barrier precautions during CL insertion. (Quality of Evidence: MODERATE)⁶⁴
  • Employ maximum sterile barrier precautions by ensuring that all HCP involved in the catheter insertion procedure wear a mask, cap, sterile gown, and sterile gloves. Additionally, cover the patient with a large ("full-body") sterile drape during catheter insertion, and adhere to these measures as well as when exchanging a catheter over a guidewire⁶⁴.
  • Despite a prospective, randomized study in surgical patients showing no additional benefit for maximum sterile barrier precautions, the majority of available evidence suggests a risk reduction with this intervention⁶⁵.
• Utilize an alcoholic chlorhexidine antiseptic for skin preparation. (Quality of Evidence: HIGH)⁶⁶
  • Before catheter insertion, apply an alcoholic chlorhexidine solution containing a minimum of 2% chlorhexidine to the insertion site, allowing the antiseptic solution to dry before making the skin puncture. Consider the use of alcoholic chlorhexidine for skin antisepsis to prevent CLABSI in Neonatal Intensive Care Unit (NICU) patients based on a risk-benefit assessment, ensuring that the benefits outweigh potential risks².
• In the ICU setting, avoid using the femoral site to minimize infectious complications when placing the catheter. (Quality of Evidence: HIGH)⁶⁷
  • According to several studies, the femoral site of insertion increases the risk of CLABSI⁶⁸.
  • In an ICU setting, according to three recent large, prospective multicenter, multinational, and multicontinental research studies that utilized multiple logistic regression analyses, PICCs demonstrate a lower risk of CLABSI compared to other types of central lines. This suggests that employing a PICC could be a strategy to decrease the risk of CLABSI⁶⁹. Previous studies showed a similar risk of CLABSI compared PICC with other types of CLs⁷⁰.
  • In non-ICU settings, the risk of infection among different catheter insertion sites is not definitively established. Particularly in emergent situations, the priority may be to secure life-saving vascular access as quickly as possible, which could influence the choice of access site.²
  • For children and infants, femoral vein catheterization may be contemplated if upper body sites are contraindicated⁷¹. The use of tunneled femoral vein catheters, positioned with an exit site outside the diaper area on the mid-thigh, could be safer and offer an additional level of risk reduction⁷².
  • The evaluation of risk and benefit for different insertion sites must be conducted on an individual basis, taking into account both infectious and noninfectious complications.⁷³ This consideration is particularly relevant for patients currently undergoing or anticipated to require hemodialysis, where the subclavian site is avoided due to the associated risk of stenosis.
  • Midline catheters are increasingly chosen as an alternative to CLs for short-term vascular access. Certain observational studies indicate a potential decrease in CLABSI risk with midline catheters compared to PICCs⁷⁴, and versus CLs⁷⁵, respectively. There is a need for randomized controlled trials to compare the risk of CLABSIs and other complications associated with these devices.
• Incorporate ultrasound guidance for catheter insertion. (Quality of Evidence: HIGH)⁷⁶
  • Utilizing ultrasound guidance for internal jugular and femoral vein catheterization has been shown to reduce the risk of noninfectious complications associated with CL placement⁷⁶, However, it is crucial to acknowledge that the use of ultrasound may introduce challenges in maintaining aseptic technique.
  • The impact of ultrasound-guided subclavian vein insertion on the reduction of infectious complications is not established⁷⁷.

After insertion

• Maintain an appropriate nurse-to-patient ratio and restrict the use of float nurses in ICUs. (Quality of Evidence: HIGH)^2,78
  • Observational studies indicate the importance of maintaining an adequate nurse-to-patient ratio in ICUs, especially when nurses are handling patients with CLs. Additionally, these studies suggest that the presence of float nurses in the ICU environment should be minimized².
• Apply dressings containing chlorhexidine for CLs in patients over two months of age. (Quality of Evidence: HIGH)⁷⁹
  • The impact of using a chlorhexidine dressing on the reduction of infectious complications is unclear for long-term catheters, such as hemodialysis catheters, in well-healed access sites⁸⁰.
  • The use of chlorhexidine dressings for children under two months of age, especially in very preterm or low birth weight infants, is not clearly defined⁸¹.
  • A matched-pair analysis published in 2023 evaluated the effectiveness of chlorhexidine gluconate (CHG)-coated gel pad dressings in preventing CLABSIs in patients with hematologic malignancies. A total of 2070 CLs were assessed, and there was no statistically significant difference in the incidence of CRBSI (2.0 vs. 3.2/1000 CL-days) between patients with and without CHG gel dressings. The use of CHG gel dressings did not result in a reduction in CRBSI rates among patients with hematologic malignancies⁸².
• For non-tunneled CLs in both adults and children, it is recommended to replace transparent dressings and conduct site care using a chlorhexidine-based antiseptic at least every 7 days. If the dressing becomes soiled, loose, or damp, immediate replacement is advised. Gauze dressings should be changed every 2 days or earlier if they become soiled, loose, or damp. (Quality of Evidence: MODERATE)⁸³
  • For NICU patients or those at a high risk of serious complications from catheter dislodgement, less frequent dressing changes, based on clinical indications, may be considered⁸⁴.
  • If there is considerable bleeding or drainage from the catheter exit site, choose gauze dressings instead of transparent dressings until the drainage resolves².

• Before accessing the catheter, disinfect the catheter hubs, needleless connectors, and injection ports. (Quality of Evidence: MODERATE)⁸⁵
  • Before accessing catheter hubs, needleless connectors (NCs), or injection ports, thoroughly apply mechanical friction using an alcoholic chlorhexidine preparation or 70% alcohol. Alcoholic chlorhexidine is preferred as it may offer additional residual activity compared to alcohol for this purpose⁸⁶.
  • Ensure mechanical friction is applied for at least 5 seconds to effectively reduce contamination⁸⁷. The applicability of this disinfection duration to NCs that were not assessed in these studies remains uncertain.
  • Regularly monitor compliance with hub-connector-port disinfection protocols, as approximately half of such catheter components may become colonized under standard practice conditions⁸⁸.
• Remove catheters that are not essential. (Quality of Evidence: MODERATE)⁶³
  • Evaluate the necessity for ongoing intravascular access daily during multidisciplinary rounds. Remove catheters that are not essential for patient care. Reducing CL utilization contributes to a decrease in the risk of CLABSIs⁶³.
  • Conducting audits to assess whether CLs are consistently removed after their intended use can be beneficial⁸⁹. Both simple and multifaceted interventions have proven effective in reducing the unnecessary use of CLs⁹⁰.
• It is acceptable to routinely replace administration sets not used for blood, blood products, or lipid formulations at intervals of up to 7 days. (Quality of Evidence: HIGH)⁹¹
  • The most effective schedule for replacing intermittently used administration sets is still undetermined.
• Conduct surveillance for CLABSI in both ICU and non-ICU settings. (Quality of Evidence: HIGH)⁹²
  • Quantify the unit-specific incidence of CLABSI, such as CLABSI per 1,000 CL-days, and regularly communicate this data to the respective units, physician and nursing leadership, as well as hospital administrators overseeing the units².
  • Compare the occurrence of CLABSI with historical data specific to individual units and with national, CDC/NHSN⁵, and INICC rates⁷.
  • Conduct periodic audits of surveillance as needed to reduce variation in interobserver reliability⁹³.

Supplementary interventions

These additional measures are recommended for implementation in hospital areas or among populations experiencing unacceptably high CLABSI rates, even after applying essential CLABSI prevention strategies outlined earlier, or individuals who possess restricted venous entry and a background of recurring CLABSI.

• Utilize CLs that are impregnated with antiseptic or antimicrobial agents. (Quality of Evidence: HIGH in adult patients⁹⁴, and MODERATE in pediatric patients)⁹⁵
  • The risk of CLABSI is diminished with certain currently available antiseptic-impregnated (e.g., chlorhexidine-silver sulfadiazine) catheters and antimicrobial-impregnated (e.g., minocycline-rifampin) catheters. Some evidence indicates that such interventions may not provide extra advantages in patient care units that have already achieved a low incidence of CLABSI⁹⁶.
  • Clinical evidence supporting the risk reduction linked to the routine use of silver-coated catheter connectors or other antimicrobial catheter connectors is currently limited.
  • Keep a vigilant watch on patients for adverse effects, including the possibility of anaphylaxis⁹⁷.
• Implement antimicrobial lock therapy for long-term CLs. (Quality of Evidence: HIGH)⁹⁸
  • Filling the catheter lumen with a supratherapeutic concentration of an antibacterial or antiseptic solution and maintaining it until catheter hub re-access is known as an anti-infective lock. This method has shown potential in reducing the risk of CLABSI. Ongoing research is focusing on determining the optimal antimicrobial agent or combination, their concentration, and the duration of lock therapy. Due to concerns about potential resistance emergence in exposed organisms, consider employing antimicrobial locks as a preventive strategy for patients with long-term hemodialysis catheters who have a history of recurrent CLABSI⁹⁹. This preventive measure can be considered for patients at an elevated risk of severe consequences from CLABSI, such as those with recently implanted intravascular devices like a prosthetic heart valve or aortic graft.
  • To reduce the risk of systemic toxicity, aspirate the antimicrobial lock solution after the designated dwell time instead of flushing it¹⁰⁰.
  • Before utilizing ethanol locks, it is essential to thoroughly assess the potential for adverse effects¹⁰¹.
  • A meta-analysis published in 2023 investigated ethanol lock therapy (ELT) in pediatric patients with CLs to prevent CLABSI. The post-ELT treatment significantly reduced mean CLABSI rates compared to pre-treatment without ELT (p<0.001). However, the risks of thrombosis and catheter issues increased. ELT proves effective in preventing CLABSIs, but further research is needed to establish optimal protocols and assess adverse events¹⁰².
• Administer recombinant tissue plasminogen activator (rt-PA) once weekly following hemodialysis in patients using a CL for hemodialysis. (Quality of Evidence: HIGH)¹⁰³
• Leverage infusion or vascular access teams to decrease rates of CLABSI. (Quality of Evidence: LOW)^104,105
  • Research indicates that the implementation of an infusion/vascular access team, tasked with the insertion and maintenance of peripheral intravenous catheters, effectively lowers the risk of BSIs¹⁰⁴.
  • Nevertheless, there is a scarcity of studies examining the influence of intravenous therapy teams on rates of CLABSI¹⁰⁵.
• Apply antimicrobial ointments to the insertion sites of hemodialysis catheters. (Quality of Evidence: HIGH)¹⁰⁶
  • Use polysporin "triple" or povidone-iodine ointment for hemodialysis catheter insertion, provided it is compatible with the catheter material. Exercise caution regarding potential interactions between ointment ingredients and the chemical composition of certain catheters. Ensure the selected ointment is compatible with the catheter material before application to the insertion/exit site, considering that ointments containing glycol should not be used on insertion/exit sites of polyurethane catheters. Avoid applying Mupirocin ointment to the catheter insertion site due to the associated risks of fostering mupirocin resistance and potential harm to polyurethane catheters².
• Employ an antiseptic-containing hub/connector cap/port protector to cover connectors. (Quality of Evidence: MODERATE)¹⁰⁷
  • The effectiveness of routinely disinfecting hub connectors and ports while utilizing antiseptic-containing hub/connector cap/port protectors is currently uncertain.

Not Advisable Interventions to Prevent CLABSI

• Avoid employing antimicrobial prophylaxis for short-term or tunneled catheter insertion or while catheters are in place. (Quality of Evidence: HIGH)¹⁰⁸.
• Avoid the routine replacement of CL or arterial catheters. (Quality of Evidence: HIGH)¹⁰⁹.

Interventions Pending Resolution

• The utilization of silver-coated catheter connectors may be linked to decreased intraluminal contamination in ex vivo catheters and a potential reduction in CLABSI¹¹⁰
  • There is limited clinical evidence available regarding the risk reduction associated with the routine use of silver-coated catheter connectors or the use of other antimicrobial catheter connectors.
• The relationship between the use of standard, nonantimicrobial transparent dressings and the risk of CLABSI.
  • An unresolved issue has arisen from a meta-analysis that identified a connection between CLABSI and the usage of transparent dressings¹¹¹.
• The influence of employing chlorhexidine-based products on the development of bacterial resistance to chlorhexidine.
  • Standardized testing for chlorhexidine susceptibility is lacking, and the clinical implications of reduced chlorhexidine susceptibility remain uncertain¹¹².
• Suture-less securement
  • The effectiveness of suture-less securement devices in reducing CLABSI is currently uncertain¹¹³.
• The impact of silver zeolite-impregnated umbilical catheters on preterm infants, especially in areas where approval for pediatric use has been authorized¹¹⁴
  • A randomized study indicates that antimicrobial-impregnated umbilical catheters seem to be both safe and effective in NICU patients¹¹⁴.
• The requirement for mechanically disinfecting a catheter hub, needleless connector, and injection port before catheter access when utilizing antiseptic-containing caps.
  • The efficacy of employing an antiseptic-containing cap in preventing CLABSI, compared to the traditional method of manual disinfection during application and removal, remains uncertain.
  • According to a meta-analysis published in 2022, a total of 391 CLABSIs in 273,993 CL-days occurred in the intervention group versus 620 CLABSIs in 284,912 days in the standard care group, resulting in a risk ratio of 0.65 (p<0.00001). While available evidence suggests that ABCs are effective, safe, easy to use, and cost-effective, however, due to the poor methodological quality of most available studies, more robust data should justify their use at this point¹¹⁵.

SUGGESTED PRACTICE IN UNDER-RESOURCED SETTINGS

The use of outdated technology has been observed, prompting a recommendation to adopt new device designs:

• It was found that the routine use of collapsible closed-system intravenous fluid containers is an effective strategy for preventing CLABSI. (Quality of Evidence: MODERATE)¹¹⁶
  • Open-system semi-rigid or rigid IV fluid containers increase the risk of CLABSI compared with closed-system collapsible IV fluid containers, as demonstrated in prospective studies, and a metanalysis¹¹⁶. 

• It was found that the routine use of needleless connectors is an effective strategy for preventing CLABSI. (Quality of Evidence: MODERATE)^117,118. Three-way stopcocks increase the risk of catheter infections compared with needless connectors (NCs), as demonstrated in randomized clinical trials,¹¹⁸ a systematic review ¹¹⁹, and a meta-analysis¹¹⁷. Multiple devices are currently available, but the optimal design for preventing infections remains unresolved.
  • A study evaluated eight design factors of NC for their impact on bacterial transfer and biofilm formation, based on the following characteristics: the mechanism of access, access portal, flow path, fluid displacement, hydrodynamics, seal length, flow path surface area and volume, and neutral displacement. The NC designs associated with the least bacterial transfer and biofilm formation were: split septum, minimal seal length, internal cannula, low flow path surface area and volume, simple hydrodynamics, and neutral displacement¹²⁰.
  • A secondary analysis of a national US database of CLABSI and manufacturer customer database found that the use of the NC characterized by a split septum, minimal seal length, internal cannula, low flow path surface area and volume, simple hydrodynamics and minimal (neutral) or zero displacement is an effective risk reduction strategy for CLABSI prevention, reduced mortality, and substantial cost savings compared to other types of NCs¹²¹.
  • It is crucial to note that studies published from 2006 to 2009, conducted at the inception of these devices' market launch, revealed an elevated rate of CLABSI, employing a time series before-after analysis methodology rather than randomized clinical trials; it is plausible that the observed rise in CLABSI rates was attributable to the improper utilization of these devices¹²².
• There has been evidence of the need to educate and train HCWs in LMICs.
• Compliance with recommendations to prevent CLABSI in the Middle East: In their 2018 study, Aloush et al. aimed to assess compliance with the CLABSI prevention guidelines. Using a prospective design, observations were conducted over three months in the intensive care units of 58 hospitals across three Middle Eastern countries. Results revealed considerable variability in compliance levels. Lower bed numbers and patient-nurse ratios were associated with higher compliance. Reducing patient-nurse ratios and the number of beds in ICUs could enhance compliance efforts¹²³.
• Compliance with recommendations to prevent CLABSI in Jordan: In their 2022 study, Matlab et al. aimed to evaluate knowledge and compliance regarding the prevention of CLABSIs among registered nurses in Jordan. Using a cross-sectional correlational design, the study selected a sample of 114 registered nurses from three hospitals in Jordan. Significant differences in nurses' compliance with the CVC care bundle were noted across hospitals and nurse-to-patient ratios. Nurse-to-patient ratio was identified as the single significant predictor of nurse compliance with the CVC care bundle. It highlights the importance of programs aimed at enhancing nurses' knowledge about CLABSI prevention and their compliance with CVC care, taking into account factors such as age and workplace circumstances, particularly the nurse-to-patient ratio¹²⁴.
• Bundle Approach: According to published research studies implemented by INICC^27-39, a bundle with the following eleven components was effective in significantly reducing CLABSI rates in LMICs:

1. Strict adherence to hand hygiene before CL insertion or manipulation;
2. Implementation of maximum sterile barrier precautions during CL insertion;
3. Utilization of alcoholic chlorhexidine antiseptic for skin preparation;
4. A preference for avoiding the femoral site;
5. Reduction of CL-days by eliminating nonessential CLs;
6. Maintenance of proper insertion site dressing, changing it when it becomes loose, wet, dirty, or bloody;
7. Minimization of the length of stay by promptly discharging eligible patients;
8. Daily chlorhexidine preparation bathing for ICU patients aged over 2 months;
9. Prioritization of NC connectors over three-way stopcocks;
10. A preference for collapsible closed IV fluid systems over semi-rigid open systems;
11. A focus on single-use flushing over manual admixture.

• Multidimensional Approach: Numerous national, multinational, and multicontinental studies, employing a multidimensional approach, have been conducted in LMICs, achieving a significant reduction in rates of CLABSI and mortality. All of them include six components: (a) bundle, (b) education, (c) surveillance of CLABSI, (d) monitoring compliance with recommendations to prevent CLABSI, (e) internal reports of CLABSI rates, and (f) performance feedback. The following 13 studies were conducted applying this specific intervention:

1. Conducted in Argentina in 2003. Following the intervention, the CLABSI rate was significantly reduced (46.63 vs 11.10 CLABSI/1,000 CL-days [RR= 0.25; 95% CI= 0.17-0.36; p<0.0001])²⁷.
2. Conducted in Mexico in 2005. Following the intervention, the CLABSI rate was significantly reduced (46.3 vs 19.5 CLABSI/1,000 CL-day [RR= 0.42; 95% CI= 0.27-0.66; p=0.0001]). Additionally, crude unadjusted mortality rates significantly decreased from baseline (48.5% vs. 32.8% per 100 discharges [RR= 0.68; 95% CI= 0.50-0.31; p=0.01])²⁸.
3. Applying this strategy, a study was conducted in adult ICUs in 15 LMICs in 2010. Following the intervention, the CLABSI rate was significantly reduced (14.5 vs 7.4 CLABSIs per 1,000 central line days [RR, 0.46, 95% CI, 0.33-0.63; p<0.001]). The number of deaths in CLABSI patients decreased by 58%²⁹.
4. Conducted in pediatric intensive care units across five LMICs in 2012. Following the intervention, the CLABSI rate was significantly reduced (10.7 vs 5.2 CLABSI/1,000 CL-days ([RR 0.48, 95% CI 0.29-0.94, p=0.02])³⁰.
5. Conducted in 16 adult intensive care units (ICUs) across 11 hospitals in India in 2013. Following the intervention, the CLABSI rate was significantly reduced (6.4 vs 3.9 CLABSI/1,000 CL-days [incidence rate ratio 0.47, 95% CI 0.31-0.70; p=0.0001])³¹.
6. Conducted in eight cities in Turkey in 2013. Following the intervention, the CLABSI rate was significantly reduced (22.7 vs 12.0 CLABSI/1,000 CL-days [incidence rate ratio [IRR] 0.613; 95% CI 0.43 - 0.87; p=.007]).³²
7. Conducted in neonatal intensive care units (NICUs) across four LMICs in 2013. Following the intervention, the CLABSI rate was significantly reduced (21.4 vs 9.7 CLABSI/1,000 CL-days [rate ratio, 0.45 [95% CI, 0.33-0.63], p<0.001)³³.
8. Conducted in Colombia in 2016. Following the intervention, the CLABSI rate was significantly reduced (12.9 vs 3.5 CLABSI/1,000 CL-days [RR, 0.27; 95% CI, 0.14-0.52; p=0.002])³⁴.
9. Conducted in five cities in Saudi Arabia in 2017. Following the intervention, the CLABSI rate was significantly reduced (6.9 vs 3.1 CLABSI/1,000 CL-days [incidence-density rate, 0.44; 95% CI, 0.28-0.72; p=0.001])³⁵.
10. Conducted in 14 intensive care units (ICUs) across 11 hospitals in 5 cities in Argentina in 2018. Following the intervention, the CLABSI rate was significantly reduced (9.6 vs 4.1 CLABSI/1,000 CL-days [incidence density rate: 0.43; 95% CI, 0.34-0.6; p<0.001])³⁶.
11. Conducted in Bahrain in 2020. Following the intervention, the CLABSI rate was significantly reduced (10.4 vs 1.2 CLABSI/1,000 CL-days [incidence density rate, 0.11; 95% CI 0.1-0.3; p= 0.001])³⁷.
12. Conducted in 316 ICUs in 30 low- and middle-income countries in 2023. Throughout 283,087 patients, hospitalized during 1,837,750 patient days, 1,218,882 CL-days were utilized. Following the intervention, the CLABSI rate was significantly reduced (15.34 vs 2.23 CLABSI/1,000 CL-days in the 17 to 29 months (RR= 0.15; 95% CI= 0.13-0.17; p<0.001). The in-ICU all-cause mortality rate decreased from 16.17% to 13.68% (p=0.0013) at 17 to 29 months³⁸.
13. Conducted in 122 ICUs in 9 Asian countries in 2024. Throughout 124,946 patients, hospitalized during 717,270 patients days, 238,595CL-days were utilized. Following the intervention, the CLABSI rate was significantly reduced (16.64 vs 2.18 CLABSI/1,000 CL-days in the 17 to 29 months (RR= 0.13; 95% CI= 0.11-0.15; p<0.001). The in-ICU all-cause mortality rate decreased from 13.23% to 10.96% (p=.0001)³⁹.

SUMMARY

The empirical evidence delineated in this review incontrovertibly establishes that CLABSI rates in LMICs persist at a magnitude exceeding fivefold that observed in high-income countries. The review systematically presents scientific insights regarding the efficacy of diverse interventions across all settings, distinguishing between proven effective measures, those demonstrated to be ineffective, and the prescription of supplementary measures specifically advocated for adoption in LMICs.

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