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Managing and preventing vascular catheter infections: A position paper of the international society for infectious diseases

Open AccessPublished:April 18, 2019DOI:https://doi.org/10.1016/j.ijid.2019.04.014

      Highlights

      • Central lines are essential vascular access devices that can be associated with bloodstream infections.
      • This position paper overviews the techniques relevent to the insertion of these devices and procedures to maintain the catheter.
      • The paper also underscores the differences in management problems between high and middle to low income countries and between adults and children.
      • This paper also overviews the diagnosis and choice of antimicrobials in the treatment of central line-associated bloodstream infections.

      Abstract

      A panel of experts was convened by the International Society for Infectious Diseases (ISID) to overview recommendations on managing and preventing vascular catheter infections, specifically for the prevention and management of central line-associated bloodstream infections. These recommendations are intended to provide insight for healthcare professionals regarding the prevention of infection in the placement and maintenance of the catheter and diagnosis as well as treatment of catheter infection. Aspects of this area in pediatrics and in limited-resource situations and a discussion regarding the selection of empiric or targeted antimicrobial therapy are particular strengths of this position paper.

      Keywords

      Introduction

      Central lines are essential vascular access devices used in critically-ill patients in many medical settings. Central line-associated bloodstream infections (CLABSIs) are common complications encountered with their use, with up to 60% of all hospital-acquired bacteremias/fungemias occurring with a vascular access device (
      • Crnich C.J.
      • Maki D.G.
      The role of intravascular devices in sepsis.
      ). CLABSIs substantially increase morbidity, mortality, length of hospital stay, and increased hospital costs, both in developed and resource-limited countries (
      • Al-Abdely H.M.
      • Alshehri A.D.
      • Rosenthal V.D.
      • Mohammed Y.K.
      • Banjar W.
      • Orellano P.W.
      • et al.
      Prospective multicentre study in intensive care units in five cities from the Kingdom of Saudi Arabia: Impact of the International Nosocomial Infection Control consortium (INICC) multidimensional approach on rates of central line-associated bloodstream infection.
      ,
      • Devrim I.
      • Yasar N.
      • Isguder R.
      • Ceylan G.
      • Bayram N.
      • Ozdamar N.
      • et al.
      Clinical impact and cost-effectiveness of a central line bundle including split-septum and single-use prefilled flushing devices on central line-associated bloodstream infection rates in a pediatric intensive care unit.
      ,
      • Ziegler M.J.
      • Pellegrini D.C.
      • Safdar N.
      Attributable mortality of central line associated bloodstream infection: systematic review and meta-analysis.
      ,
      • Tarricone R.
      • Torbica A.
      • Franzetti F.
      • Rosenthal V.D.
      Hospital costs of central line-associated bloodstream infections and cost-effectiveness of closed vs. open infusion containers. The case of Intensive Care Units in Italy.
      ,
      • Higuera F.
      • Rangel-Frausto M.S.
      • Rosenthal V.D.
      • Soto J.M.
      • Castanon J.
      • Franco G.
      • et al.
      Attributable cost and length of stay for patients with central venous catheter-associated bloodstream infection in Mexico City intensive care units: a prospective, matched analysis.
      ,
      • Rosenthal V.D.
      • Guzman S.
      • Migone O.
      • Crnich C.J.
      The attributable cost, length of hospital stay, and mortality of central line-associated bloodstream infection in intensive care departments in Argentina: a prospective, matched analysis.
      ). The CLABSI rates in resource-limited countries are 3–5 times higher than that encountered in high-income settings (
      • Al-Abdely H.M.
      • Alshehri A.D.
      • Rosenthal V.D.
      • Mohammed Y.K.
      • Banjar W.
      • Orellano P.W.
      • et al.
      Prospective multicentre study in intensive care units in five cities from the Kingdom of Saudi Arabia: Impact of the International Nosocomial Infection Control consortium (INICC) multidimensional approach on rates of central line-associated bloodstream infection.
      ) and 75% of the world’s population live in low-to-middle income countries (LMICs) (
      • Alp E.
      • Rello J.
      Implementation of infection control bundles in intensive care units: which parameters are applicable in low-to-middle income countries?.
      ). Established in 1998, the International Nosocomial Infection Control Consortium (INICC) is one group which has used surveillance and applied research to promote appropriate practices to decrease this rate (
      • Rosenthal V.D.
      International Nosocomial Infection Control consortium (INICC) resources: INICC multidimensional approach and INICC surveillance online system.
      ). This paper summarizes the key recommendations for CLABSI control and prevention by the International Society for Infectious Diseases.

      Known facts - prevention

      Many guidelines for decreasing CLABSI rates recommend use of “care bundles” (
      • Marwick C.
      • Davey P.
      Care bundles: the holy grail of infectious risk management in hospital?.
      ,
      • Agency for Healthcare Research and Quality
      Toolkit for Reducing Central Line-Associated Blood Stream Infections. Content last reviewed March 2018.
      ), to simplify and enable the reliable application of 4–6 evidence-based best practices simultaneously, to achieve better outcomes than when implemented individually. Care bundles for device-associated infections e.g. CLABSI bundles, are widely-adopted and effective infection prevention strategies in high-income countries and some low-resource settings.
      Compliance with bundle elements should be easily and objectively measureable (e.g. ‘yes/no’ or ‘completed/not completed’), allowing for tracking of bundle compliance rates. Infection rate trends can be followed using run-charts. CLABSI bundles have been created for both the insertion and maintenance of central lines. Many CLABSI events are attributed to breaches in catheter maintenance, rather than insertion which, because it remains longer in situ than a peripheral line, accounts for most of the cases of intravascular catheter bacteremia. These bundles are summarized here (
      • Ling M.L.
      • Apisarnthanarak A.
      • Jaggi N.
      • Harrington G.
      • Morikane K.
      • Thu L.T.A.
      • et al.
      APSIC guide for prevention of central line associated bloodstream infections (CLABSI).
      ,
      • Bell T.
      • O’Grady N.P.
      Prevention of central line-associated bloodstream infections.
      ,
      • Han Z.
      • Liang S.
      • Marschall J.
      Current strategies for the prevention and management of central line-associated blood stream infections.
      ):

      Insertion bundle

      • 1.
        Site/Catheter Selection
      Optimal site selection will depend on catheter types and expected duration of use with avoidance of placement in the femoral vein, except for hemodialysis and in some pediatric patients. The type of device and placement site selection are influenced by the training and experience levels of the clinician inserting the device. Ultrasound guidance should be used when available. The hub number on the catheter should be kept to the minimum essential for management, as every additional hub increases the risk for CLABSI development. All components of the system should be compatible to minimize leakages. For needleless systems, a split septum valve may be preferable to a mechanical valve.
      Peripherally inserted central catheters (PICC lines) seem more vulnerable to thrombosis and dislodgement than central venous catheters placed in the internal jugular or subclavian veins. Importantly, in patients with renal injury who may require hemodialysis, preservation of upper extremity veins for future dialysis access is advisable so use of PICC lines needs to be prudent in these patients.
      The use of a midline catheter (placed in proximal veins such as the brachial or cephalic with the tip in the axillary vein) is associated with a lower complication risk of pneumothorax and thrombosis and lower CLABSI rates in some reports.
      • 1.
        Hand Hygiene
      Hand hygiene is vital before and after palpating the insertion site and before and after all interactions in the placement and maintenance sequences. Hand hygiene can be performed with an alcohol-based hand rub or antiseptic soap with water. Optimal asepsis dictates the use of sterile gloves with placement. The wearing of gloves does not obviate the need for hand hygiene.
      • 1.
        Skin Preparation
      Skin prep is generally done with the use of a 0.5–2% chlorhexidine/70% isopropyl alcohol solution, with alternatives such as iodophors (povidone-iodine) or alcohol alone in patients with known hypersensitivity to chlorhexidine gluconate. The antiseptic should be allowed to dry before catheter insertion.
      • 1.
        Barrier Precautions
      Barrier precautions include the use of sterile gowns and gloves, a surgical mask and cap/hair net as well as a full body sterile drape over the patient (akin to drapes utilized in an operating theater).
      All aspects of the insertion bundle are likely essential in preventing CLABSIs. Insertion in the femoral area, not using a full body drape, not using all components of the maximal sterile barrier precautions and not performing all components of the bundle, have been identified as factors associated with an increased risk of CLABSI (
      • Lee K.H.
      • Cho N.H.
      • Jeong S.J.
      • Kim M.N.
      • Han S.H.
      • Song Y.G.
      Effect of central line bundle compliance on central line-associated blood stream infections.
      ).

      Catheter maintenance bundle

      • 1.
        Review of Need and Replacement
      The need for the line should be reviewed daily since risk of CLABSI development increases over time. If the catheter was placed as an emergency intervention, it should be replaced as soon as possible. Fever alone is not an indication for catheter removal and replacement. However, if CLABSI is clinically suspected in a non-tunneled device, the device should not simply be replaced over a guidewire, but removed, with a new catheter inserted at a different site.
      • 1.
        Hand Hygiene
      This should be performed before and after accessing, repairing or dressing the catheter to maintain aseptic technique at all times. This includes wearing sterile or at least clean gloves when changing dressings.
      • 1.
        Hub/Access Device Disinfection
      Catheter hubs, connectors, and injection ports should be disinfected with alcoholic chlorhexidine, 70% alcohol solution or an iodophor while applying mechanical friction before access. All needleless parts of the system should be changed when the administration set is changed or based on manufacturers’ recommendations. There is no benefit in changing more often than 72 h. Access ports should be treated with an antiseptic prior to any access (
      • Marschall J.
      • Mermel L.A.
      • Fakih M.
      • Hadaway L.
      • Kallen A.
      • O’Grady N.P.
      • et al.
      Strategies to prevent central line-associated bloodstream infections in acute care hospitals: 2014 update.
      ). Disinfectant cap protectors may also have a role but require further study (
      • Jimenez A.
      • Barrera A.
      • Madhivanan P.
      Systematic review on impact of disinfectant caps protectors for intravenous access ports on central line-associated bloodstream infections (CLABSI).
      ).
      • 1.
        Dressing Changes
      A sterile transparent and semipermeable dressing is preferred over sterile gauze. Sterile gauze can be used if the patient is diaphoretic or the site is actively bleeding or oozing. The dressing should be replaced if it becomes damp, loosened or visibly soiled or every 7 days for non-tunneled catheters (
      • Marschall J.
      • Mermel L.A.
      • Fakih M.
      • Hadaway L.
      • Kallen A.
      • O’Grady N.P.
      • et al.
      Strategies to prevent central line-associated bloodstream infections in acute care hospitals: 2014 update.
      ). The use of a chlorhexidine-impregnated dressing, if available, may decrease the risk of infection as compared to non-impregnated dressings, through reduction of bacterial colonization of the skin at the point of catheter insertion. In settings with high CLABSI rates, chlorhexidine-impregnated sponge dressings may be used as an additional intervention.
      Topical antimicrobial ointments or creams are generally not used except for hemo-dialysis catheters where they may have a role in minimization of fungal infections and antimicrobial resistant infections.
      Patients should be encouraged to report any changes to the catheter insertion site or any discomfort as soon as possible.
      Additional Measures (mainly in case of sustained high CLABSI rates or during an outbreak):
      • 1.
        Daily chlorhexidine bathing has been demonstrated to reduce CLABSI rates among adult and children in intensive care units (
        • Frost S.A.
        • Alogso M.C.
        • Metcalfe L.
        • Lynch J.M.
        • Hunt L.
        • Sanghavi R.
        • et al.
        Chlorhexidine bathing and health care-associated infections among adult intensive care patients: a systematic review and meta-analysis.
        ,
        • Dicks K.V.
        • Lofgren E.
        • Lewis S.S.
        • Moehring R.W.
        • Sexton D.J.
        • Anderson D.J.
        A multicentre pragmatic interrupted time series analysis of chlorhexidine gluconate bathing in community hospital intensive care units.
        ).
        • Huang S.S.
        • Septimus E.
        • Kleinman K.
        • Moody J.
        • Hickok J.
        • Heim L.
        • et al.
        Chlorhexidine versus routine bathing to prevent multi-drug-resistant organisms and all-cause bloodstream infections in general medical and surigcal units (ABATE Infection trial): a cluster-randomised trial.
        , despite a lack of overall protective effect in non-ICU patients, found reductions in MRSA and VRE infections in patients with medical devices.
      • 2.
        Antibacterial impregnated catheters (minocycline/rifampin or chlorhexidine/silver sulfadiazine) can be used as an additional intervention in units with high CLABSI rates or in patients where a prolonged catheter dwell time is anticipated.
      • 3.
        A prophylactic antimicrobial (e.g. vancomycin) or antiseptic lock solution (e.g. ethanol or taurolidine-citrate) can be considered in patients with long-term catheters (such as hemodialysis) or in patients with a history of recurrent CLABSI.
      Variability in application of CLABSI prevention bundles, compliance assessment and degree of stakeholder involvement, all likely result in suboptimal clinical outcomes. Such variability may explain issues related to suboptimal clinical impact of the guidelines and their implementation (
      • Blanco-Mavillard
      • Rodriguez-Calero M.A.
      • Castro-Sanchez E.
      • Bennasar-Veny M.
      • De Pedro-Gomez J.
      Appraising the quality standard underpinning international clinical practice for the selection and care of vascular access devices: a systematic review of reviews.
      ).

      Open vs closed intravenous infusion systems

      The impact of the infusion system on CLABSI rates has been studied by comparing open and closed intravenous systems. It has been widely accepted that open systems may increase the risk of contamination and administration-related CLABSI, because of microbial entry into the system through air entry (
      • Maki D.G.
      • Rosenthal V.D.
      • Salomao R.
      • Franzetti F.
      • Rangel-Frausto M.S.
      Impact of switching from an open to a closed infusion system on rates of central line-associated bloodstream infection: a meta-analysis of time-sequence cohort studies in 4 countries.
      ). As reported in a recent systematic review (
      • Perin D.C.
      • Erdmann A.L.
      • Higashi G.D.
      • Sasso G.T.
      Evidence-based measures to prevent central line-associated bloodstream infections: a systematic review.
      ), by way of illustration, the rate of CLABSI was 35.3% greater among patients who received compounded parenteral nutrition (PN) through an open system in comparison to those who received PN through a closed system.
      In a randomized clinical trial comparing rates of CLABSI between patients using an open system (three-way stopcocks) and standard flushing, and patients using a closed system (pre-pierced septa) and single-use prefilled flushing devices, it was shown that closed systems had significantly lower rates of CLABSI (2.21 per 1000 CL-days vs. 6.40 per 1000 CL-days, 95% CI 0.16-0.76, p = 0.006) and was cost-effective (
      • Rosenthal V.D.
      • Udwadia F.E.
      • Kumar S.
      • Kavathekar M.
      • Sakle A.
      • Munshi N.
      • et al.
      Clinical impact and cost-effectiveness of split-septum and single-use prefilled flushing device vs 3-way stopcock on central line-associated bloodstream infection rates in India: a randomized clinical trial conducted by the International Nosocomial Infection Control Consortium (INICC).
      ). However, open infusion containers and systems, such as three-way stopcocks, continue to be widely used in limited-resource settings.

      Management of the CLABSI (suggested practice)

      In a patient with a suspected CLABSI, the healthcare professional is usually presented with a febrile individual without focal signs or symptoms suggesting systemic or device-associated infection. In the case of Staphylococcus aureus (S. aureus) infection (either methicillin sensitive or resistant), secondary metastatic infection can be found in any organ. Fever without a focus is a clue that should prompt investigation for CLABSI. Blood cultures should be obtained in parallel from the central line and from a peripheral site. A shorter time to positivity (or a higher bacterial load on quantitative blood cultures) from the central source can be a hint that the line is the primary source but it is not particularly sensitive (
      • Bouzidi H.
      • Emirian A.
      • Marty A.
      • Chachaty E.
      • Laplanche A.
      • Gachot B.
      • et al.
      Differential time to positivity of central and peripheral blood cultures is inaccurate for the diagnosis of Staphylococcus aureus long-term catheter-related sepsis.
      ).
      The most common organisms causing CLABSI are biofilm-producing Gram positive cocci including S. aureus and coagulase negative staphylococci (CNS). Most CNS-associated CLABSI events present with a milder or more indolent course, however S. lugdunensis infections manifest with more prominent symptomatology, behaving clinically similar to S. aureus-associated CLABSI.
      While cultures are pending, vancomycin is an appropriate antimicrobial to use empirically until identification and antimicrobial sensitivities are available. In countries without high rates of MRSA, an anti-staphylococcal beta-lactam antimicrobial could be the first option. However, in severe illness, neutropenic or otherwise immunocompromised patients and those with a femoral catheter, additional empiric coverage for Gram-negative bacilli is reasonable. Agents such as an extended spectrum penicillin (such as piperacillin/tazobactam), a cephalosporin (such as cefepime) or a carbapenem (such as meropenem) may be appropriate, based on prevailing institutional antimicrobial resistance patterns. Other organisms associated with CLABSIs include fungi (yeasts), especially Candida species including the more resistant C. auris, and some of the more indolent Gram-positive organisms such as “diphtheroids”, primarily Corynebacterium species and Cutibacterium (formerly Propionibacterium) acnes.
      The decision to begin antimicrobials before cultures are positive should be based on clinical judgement and illness severity. Fever in a patient with a central vascular catheter does not necessarily mean that the etiology of the pyrexia is a CLABSI. Numerous other diagnoses, infectious or non-infectious, may be the source of the fever. Absence of fever does not rule out CLABSI, or any other infection for that matter, as especially in debilitated, elderly or with renal injury, a febrile response may not occur. When blood cultures are positive without another identified source for a likely organism, CLABSI is likely the diagnosis. Catheters are often not removed prior to laboratory-confirmation of CLABSI, unless the catheter is no longer required.
      Once the blood cultures are positive, especially in the absence of an identified focus, all peripheral venous or arterial catheters, midline catheters and short term nontunneled central venous catheter should ideally be removed (
      • Han Z.
      • Liang S.
      • Marschall J.
      Current strategies for the prevention and management of central line-associated blood stream infections.
      ). In the case of long-term catheters such as PICC lines, tunneled central lines and implantable devices, explantation is done in most instances. The approach to removal of a central catheter in a patient with bacteremia and a clear alternative focus should be individualized based on the organism and clinical circumstances. Antimicrobial locks as a catheter salvage strategy are unlikely to be effective but may be considered under certain conditions for salvage (
      • Mermel L.A.
      • Allon M.
      • Bouza E.
      • Craven D.E.
      • Flynn P.
      • O’Grady N.P.
      • et al.
      Clinical practice guidelines for the diagnosis and management of intravascular catheter-relation infection: 2009 update by the Infectious Diseases Society of America.
      ). Certainly, any persistent bacteremia despite appropriate antimicrobials should be managed with antimicrobials and prompt catheter removal.
      The length of antimicrobial therapy after catheter removal is often 7–14 days but varies with the pathogen (longer for Gram-negative and fungal infections) and the degree of illness. Some microbes are more likely to cause secondary metastatic infections, especially S. aureus, and the clinician should be aware of this possibility. Certainly, if a cardiac valve infection (endocarditis) or a bone infection (osteomyelitis) develops as a secondary manifestation of the CLABSI, more prolonged antimicrobial therapy (4–6 weeks) is required. Classically, endocarditis and osteomyelitis have been treated with parenterally administered antimicrobials but recent data suggests that oral treatment can substitute for some of the course (
      • Iversen K.
      • Ihlemann N.
      • Gill S.U.
      • Madsen T.
      • Elming H.
      • Jensen K.T.
      • et al.
      Partial oral versus intravenous antibiotic treatment of endocarditis.
      ,
      • Li H.-K.
      • Rombach I.
      • Zambellas R.
      • Walker A.S.
      • McNally M.A.
      • Atkins B.L.
      • et al.
      Oral versus intravenous antibiotics for bone and joint infection.
      ) in defined patient groups. This approach, as it becomes more validated (
      • Boucher H.W.
      Partial oral therapy for osteomyelitis and endocarditis — Is it time?.
      ) will, like effective antimicrobial stewardship programs that facilitate intravenous to oral therapy switches, decrease the time that the central line is present and therefore will decrease the risk of CLABSI.

      CLABSIs in pediatrics

      CLABSI rates in children and neonates are a challenge and have been reported to be higher than in the adults (
      • The Joint Commission
      CLABSI Toolkit — preventing central-line associated bloodstream infections: useful tools, an international perspective.
      ,
      • Leighton P.
      • Cortina-Borja M.
      • Millar M.
      • Kempley S.
      • Gilbert R.
      A toolkit for monitoring hospital-acquired bloodstream infection in neonatal intensive care.
      ). In a review, neonatal intensive care unit (NICU) CLABSI rates ranged from 2.6 to 60 cases per 1000 central line days in limited-resource countries in comparison with 2.9 cases per 1000 central line days in the USA (
      • Rosenthal V.D.
      Central line-associated bloodstream infections in limited-resource countries: a review of the literature.
      ). As a host, the newborn infant, and especially premature newborn, is more susceptible to bloodstream infections (BSIs) because of poor skin integrity and an immature immune system. Their care usually involves A long hospital stay with repeated invasive procedures, exposure to many caregivers, and being in an environment prone to microbial colonization. Neonatal outcomes have been affected by health care-associated infections including CLABSIs. Indeed, the risk of neurodevelopmental impairment especially in very low birthweight infants significantly increases with one or more episodes of infection (
      • Stoll B.J.
      • Hansen N.I.
      • Adams-Chapman I.
      • Fanaroff A.A.
      • Hintz S.R.
      • Vohr B.
      • et al.
      Neurodevelopmental and growth impairment among extremely low-birth-weight infants with neonatal infection.
      ). The mortality related to bloodstream infections has been reported to be 21%. In neonates, they lead to increase in length of stay by 23 days and substantial excess costs (
      • Helder O.
      • van den Hoogen A.
      • de Boer C.
      • van Goudoever J.
      • Verbon-Maciolek M.
      • Kornelisse R.
      Effectiveness of non-pharmacological interventions for the prevention of bloodstream infections in infants admitted to a neonatal intensive care unit: a systematic review.
      ,
      • Verstraete E.
      • Boelens J.
      • De Coen K.
      • Claeys G.
      • Vogelaers D.
      • Vanhaesebrouck P.
      • et al.
      Healthcare-associated bloodstream infections in a neonatal intensive care unit over a 20-year period (1992-2011): trends in incidence, pathogens, and mortality.
      ,
      • Payne V.
      • Hall M.
      • Prieto J.
      • Johnson M.
      Care bundles to reduce central line-associated bloodstream infections in the neonatal unit: a systematic review and meta-analysis.
      ).
      Unlike in the adult ICU, implementations of care bundles in pediatric and neonatal intensive care units have had inconsistent outcomes in reducing CLABSIs (
      • Wirtschafter D.D.
      • Pettit J.
      • Kurtin P.
      • Dalsey M.
      • Chance K.
      • Morrow H.W.
      • et al.
      A statewide quality improvement collaborative to reduce neonatal central line-associated blood stream infections.
      ). Additionally, studies in neonates have failed to demonstrate a significant difference in CLABSI risk between catheter types used mostly in the NICU (peripherally inserted, umbilical and femoral) (
      • Dubbink-Verheij G.H.
      • Bekker V.
      • Pelsma I.C.M.
      • van Zwet E.W.
      • Smits-Wintjens V.E.H.J.
      • Steggerda S.J.
      • et al.
      Bloodstream infection incidence of different central venous catheters in neonates: a descriptive cohort study.
      ). Studies have also shown that it is possible to reduce neonatal CLABSI rates with hospital-based interventions (
      • Bizzarro M.J.
      • Sabo B.
      • Noonan M.
      • Bonfiglio M.P.
      • Northrup V.
      • Diefenbach K.
      • et al.
      A quality improvement initiative to reduce central line–associated bloodstream infections in a neonatal intensive care unit.
      ,
      • Pronovost P.
      Interventions to decrease catheter-related bloodstream infections in the ICU: the Keystone Intensive Care Unit Project.
      ). A recent meta-analysis which included observational and case control studies from different settings but no randomized control trails has revealed a statistically significant reduction in CLABSIs rate (by 60%) following the introduction of care bundles (rate ratio = 0.40 (CI 0.31 to 0.51), p < 0.00001) although it is not clear which bundle elements are effective in specific settings (
      • Wirtschafter D.D.
      • Pettit J.
      • Kurtin P.
      • Dalsey M.
      • Chance K.
      • Morrow H.W.
      • et al.
      A statewide quality improvement collaborative to reduce neonatal central line-associated blood stream infections.
      ). Some of the evidence-based interventions to reduce CLABSIs in pediatric and neonatal units are summarized in Table 1.
      Table 1Neonatal CLABSI Recommended Preventive Measures.
      CategorySuggested intervention
      Administrative
      • Providing hand hygiene facilities in the unit and monitor complains
      • Provide CVL insertion and maintenance kits
      • Increase staff/patient ratio
      • Dedicated central line team
      • Training and monitoring staff competency in infection control practices and line insertion and maintenance skills.
      • Continuous monitoring of CLABSIs as quality indicator with periodic feedback
      • Case root analysis for CLABSI events
      Policies and Guidelines
      • CVL necessity, insertion, removal and daily line care checklists
      • Guidelines for the enteral and parental feeding of VLBW infants (support breast feeding, duration of TPN and intravenous fluid and medication)
      • Antimicrobial stewardship
      Risk Assessment based intervention
      • Assess for prematurity, intraabdominal pathology, mucosal barrier injury, invasive procedures
      • Colonization and/or infection with multidrug resistant pathogen
      Implement Standard Infection Prevention Techniques
      • Perform hand hygiene with an approved alcohol-based product or antiseptic-containing soap before and after accessing a catheter or changing the dressing
      • Maintain aseptic technique during catheter insertion, changing intravenous tubing and when entering the catheter including ‘scrub the hub’
      • Non-sterile gloves for routine handling of babies <1000 g
      Skin prep for neonates
      • Age less than 2 months : use povidone –iodine with 2 minutes dry time
      • Age more than 2 months: use 2% chlorhexidine gluconate/70% isopropyl alcohol scrub
      Site selection
      • For catheter insertion in children the upper or lower extremities (or the scalp in neonates or young infants) can be used
      Dwell time
      • No cut-off duration beyond which PICC should be removed electively.
      • Early UVC removal and replacement by PICC before day 4 might be considered
      Other risk reduction measures
      • Antimicrobial PICCs may reduce CLABSI, especially in high-risk subgroups
      • Heparin in TPN (0.5 Units/mL)
      • Fluconazole prophylaxis for babies <1000 g
      • Minimize the use of H2 receptor blocker and proton pump inhibitor
      • Minimize the use of broad-spectrum antimicrobials
      (UVC)Umbilical venous catheter, (PICC) Peripherally inserted central catheter, (VLBW) very low birth weight, (CVL) Central Venous line.
      (
      • Bizzarro M.J.
      • Sabo B.
      • Noonan M.
      • Bonfiglio M.P.
      • Northrup V.
      • Diefenbach K.
      • et al.
      A quality improvement initiative to reduce central line–associated bloodstream infections in a neonatal intensive care unit.
      ,
      • Pronovost P.
      Interventions to decrease catheter-related bloodstream infections in the ICU: the Keystone Intensive Care Unit Project.
      ,
      • Mimoz O.
      • Villeminey S.
      • Ragot S.
      • Dahyot-Fizelier C.
      • Laksiri L.
      • Petitpas F.
      • et al.
      Chlorhexidine-based antiseptic solution vs alcohol-based povidone-iodine for central venous catheter care.
      ,
      • Garland J.S.
      • Alex C.P.
      • Sevallius J.M.
      • Murphy D.M.
      • Good M.J.
      • Volberding A.M.
      • et al.
      Cohort study of the pathogenesis and molecular epidemiology of catheter-related bloodstream infection in neonates with peripherally inserted central venous catheters.
      ,
      • Birch P.
      • Ogden S.
      • Hewson M.
      A randomised, controlled trial of heparin in total parenteral nutrition to prevent sepsis associated with neonatal long lines: the Heparin in Long Line Total Parenteral Nutrition (HILLTOP) trial.
      ,
      • Cleminson J.
      • Austin N.
      • McGuire W.
      Prophylactic systemic antifungal agents to prevent mortality and morbidity in very low birth weight infants.
      ,
      • Puopolo K.P.
      • Escobar G.E.
      Neonatal sepsis.
      ,
      • Sanderson E.
      • Yeo K.T.
      • Wang A.Y.
      • Callander I.
      • Bajuk B.
      • Bolisetty S.
      • et al.
      Dwell time and risk of central-line-associated bloodstream infection in neonates.
      ,
      • Kramer R.D.
      • Rogers M.A.
      • Conte M.
      • Mann J.
      • Saint S.
      • Chopra V.
      • et al.
      Are antimicrobial peripherally inserted central catheters associated with reduction in central line-associated bloodstream infection? A systematic review and meta-analysis.
      ,
      • Rosenthal V.D.
      • Maki D.G.
      • Rodriguez C.
      • Alvarez-Moreno C.
      • Leblebicioglu H.
      • Sobreyra-Oropeza M.
      • et al.
      Impact of International Infection Control Consortium (INICC) strategy on central line-associated infection rates in the intensive care units of 15 developing countries.
      .

      Limited-Resource settings

      A 2016 report of responses from 95 both high and middle incomes countries showed a poor adherence to CLABSI prevention guidelines is a universal observation (
      • Valencia C.
      • Hammami N.
      • Agodi A.
      • Lepape A.
      • Herrejon E.P.
      • Blot S.
      • et al.
      Poor adherence to guidelines for preventing central line-associated bloodstream infections (CLABSI): results of a worldwide survey.
      ). In resource-rich countries, risk reduction bundles are more readily accepted and implemented, with proven efficacy in CLABSI rate reduction. In resource limited settings, however, the CLABSI bundle uptake, implementation, and program sustainability are major barriers to wider adoption of this best practice intervention (Table 2). Indeed, in a 2019 report, 5 of 16 sites (27%) in middle-income countries reported no CLABSI prevention bundle use (
      • Alp E.
      • Cookson B.
      • Erdem H.
      • Rello J.
      • Survey Group
      Infection control bundles in intensive care: an international cross-sectional survey in low- and middle-income countries.
      ).
      Table 2Barriers, Challenges and Considerations for CLABSI Risk Reduction in Low and Middle Income Countries.
      Measures to reduce CLABSI riskBarriers/ChallengesConsiderations/ Solutions
      Establishing Surveillance system to reduction targets and identify areas of priority
      • Complex case definitions
      • Limited laboratory capacities
      • Training of lab staff
      • Introduction of lab quality systems
      Staff shortages/

      Inadequate number of skilled personnel for data management
      • Use of cheap technology (Smart phone-based tools/preprogramed data analysis systems)
      • Online resources for data management (e.g. ISOS)
      Implementing interventions to enhance preventive measuresStaff shortages/

      Inadequate number of skilled personnel
      • Support from management
      • Unit-based quality nurse to follow up
      • Assigning multispecialty intervention team
      • Ongoing in-service training for all staff involved
      High patient turnover/ Overcrowding
      • Tailored interventions
      Limited resources

      (infrastructure, technology, medical supplies
      • Checklists
      • Audit and feedback
      Poor adherence to guidelines/Lack of written guidelines
      • Relentless focus on education, process and outcomes feedback
      • Local training resources (e.g. peer tutoring)
      • Online training resources
      (
      • Geldenhuys C.
      • Dramowski A.
      • Jenkins A.
      • Bekker A.
      Central-line-associated bloodstream infection in a resource-limited South African neonatal intensive care unit.
      ,
      • Assis D.B.
      • Madalosso G.
      • Padoveze M.C.
      • Lobo R.D.
      • Oliveira M.S.
      • Boszczowski I.
      • et al.
      Implementation of tailored interventions in a statewide programme to reduce central line-associated bloodstream infections.
      ,
      • Ider B.E.
      • Adams J.
      • Morton A.
      • Whitby M.
      • Muugolog T.
      • Lundeg G.
      • et al.
      Using a checklist to identify barriers to compliance with evidence-based guidelines for central line management: a mixed methods study in Mongolia.
      ,
      • The Joint Commission
      Preventing central line-associated bloodstream infection: a global challenge, a global perspective. Oak Brook, Il; Joint commission Resources.
      ).
      The challenges to reduce CLABSI in LMICs start with the surveillance, which is required to measure the baseline rates, identify priority hospital areas to direct the limited resources, and evaluate the effect of the intervention over time. Challenges include complex case definitions that depend on laboratory criteria for case confirmation, where many of these settings lack laboratory microbiological capacities for standard pathogen identification, in addition to the common clinical practices to obtain single drawing of blood for culture (i.e. solitary blood culture) to save resources, which minimize the amount of drawn blood leading to lower chances to yield the BSI pathogen (
      • Lamy B.
      • Dargere S.
      • Arendrup M.C.
      • Parienti J.J.
      • Tattevin P.
      How to optimize the use of blood cultures for the diagnosis of bloodstream infection? A State-of-the-Art.
      ) and also do not allow for estimation of differential time to positivity of blood cultures. As a result, inaccurate rates of BSIs are usually reported. Training of laboratory staff and enforcing lab quality systems in addition to inclusion of clinically based definitions (e.g. the clinical sepsis) have been shown to improve the surveillance sensitivity, and support establishing surveillance programs (
      • See I.
      • Lessa F.C.
      • ElAta O.A.
      • Hafez S.
      • Samy K.
      • El-Kholy A.
      • et al.
      Incidence and pathogen distribution of healthcare-associated infections in pilot hospitals in Egypt.
      ,
      • Talaat M.
      • El-Shokry M.
      • El-Kholy J.
      • Ismail G.
      • Kotb S.
      • Hafez S.
      • et al.
      National surveillance of health care-associated infections in Egypt: Developing a sustainable program in a resource-limited country.
      ).
      Another challenge is the availability of skilled staff and resources for data collection and analysis for baseline numbers in assessing infection prevention. For that, cheap technology such as smart phones-based data collection tools, and preprogrammed analysis and reporting tools can be developed to generate automated standard infection reports (
      • Talaat M.
      • El-Shokry M.
      • El-Kholy J.
      • Ismail G.
      • Kotb S.
      • Hafez S.
      • et al.
      National surveillance of health care-associated infections in Egypt: Developing a sustainable program in a resource-limited country.
      ). Other settings may use online platforms for facilitated standardized data collection, entry, and analysis, as the INICC Surveillance Online System (ISOS) (
      • Rosenthal V.D.
      International Nosocomial Infection Control consortium (INICC) resources: INICC multidimensional approach and INICC surveillance online system.
      ). Additionally, surveillance approaches can be selected to match the limited human resources, as settings may choose to implement short-time, hospital-wide surveillance approach (e.g. repeated point prevalence surveys) to stratify the burden of BSI among hospital departments (
      • Ben Ayed H.
      • Yaich S.
      • Trigui M.
      • Jemaa M.B.
      • Hmida M.B.
      • Karray R.
      • et al.
      Prevalence and risk factors of health care-associated infections in a limited resources country: a cross-sectional study.
      ), whereas other settings utilize their limited resources for surveillance in high risk areas as the ICUs (
      • Rosenthal V.D.
      • Al-Abdely H.M.
      • El-Kholy A.A.
      • Alkhawaja S.A.A.
      • Leblebiciglu H.
      • Mehta Y.
      • et al.
      International Nosocomial Infection Control Consortium report, data summary of 50 countries for 2010-2015: Device-associated module.
      ) (Table 3).
      Table 3Intervention Results Using INICC Multidimensional Approach.
      CountryPre-Intervention

      Rate/1000 central line days
      Post-Intervention

      Rate/1000 central line days
      % DecreaseReference
      Argentina46.6311.1076%
      • Rosenthal V.D.
      • Guzman S.
      • Migone O.
      • Crnich C.J.
      The attributable cost, length of hospital stay, and mortality of central line-associated bloodstream infection in intensive care departments in Argentina: a prospective, matched analysis.
      Colombia12.93.973%
      • Alvarez-Moreno C.A.
      • Valderrama-Beltran S.L.
      • Rosenthal V.D.
      • Mojica-Carreno B.E.
      • Valderrama-Marquez I.A.
      • Matte-Cortes L.
      • et al.
      Multicenter study in Colombia: Impact of a multidimensional International Nosocomial Infection Control Consortium (INICC) approach on central line-associated bloodstream infection rates.
      Mexico46.319.558%
      • Higuera F.
      • Rosenthal V.D.
      • Duarte P.
      • Ruiz J.
      • Franco G.
      • Safdar N.
      The effect of process control on the incidence of central venous catheter-associated bloodstream infections and mortality in intensive care units in Mexico.
      Turkey22.712.047%
      • Leblebicioglu H.
      • Ozturk R.
      • Rosenthal V.D.
      • Akan O.A.
      • Sirmatel F.
      • Ozdemir D.
      • et al.
      Impact of a multidimensional infection control approach on central line-associated bloodstream infections rates in adult intensive care units of 8 cities of Turkey: findings of the International Nosocomial Infection Control Consortium (INICC).
      India6.43.939%
      • Jaggi N.
      • Rodrigues C.
      • Rosenthal V.D.
      • Todi S.K.
      • Shah S.
      • Saini N.
      • et al.
      Impact of an international nosocomial infection control consortium multidimensional approach on central line-associated bloodstream infection rates in adult intensive care units in eight cities in India.
      Saudi Arabia6.93.155%
      • Al-Abdely H.M.
      • Alshehri A.D.
      • Rosenthal V.D.
      • Mohammed Y.K.
      • Banjar W.
      • Orellano P.W.
      • et al.
      Prospective multicentre study in intensive care units in five cities from the Kingdom of Saudi Arabia: Impact of the International Nosocomial Infection Control consortium (INICC) multidimensional approach on rates of central line-associated bloodstream infection.
      15 countries14.79.734%
      • Rosenthal V.D.
      • Maki D.G.
      • Rodriguez C.
      • Alvarez-Moreno C.
      • Leblebicioglu H.
      • Sobreyra-Oropeza M.
      • et al.
      Impact of International Infection Control Consortium (INICC) strategy on central line-associated infection rates in the intensive care units of 15 developing countries.
      5 countries (Pediatric ICU)10.75.251%
      • Rosenthal V.D.
      • Ramachandran B.
      • Villamil-Gomez W.
      • Armas-Ruiz A.
      • Navoa-Ng J.A.
      • Matta-Cortes L.
      • et al.
      Impact of a multidimensional infection control strategy on central line-associated bloodstream infection rates in pediatric intensive care units of five developing countries: findings of the International Nosocomial Infection Control Consortium (INICC).
      4 countries

      (Pediatric ICU)
      21.49.755%
      • Rosenthal V.D.
      • Duenas L.
      • Sobreyra-Oropeza M.
      • Anmar K.
      • Navoa-Ng J.A.
      • de Casares A.C.
      • et al.
      Findings of the International Nosocomial Infection Control Consortium (INICC), part III: effectiveness of a multidimensional infection control approach to reduce central line-associated bloodstream infections in the neonatal intensive care units of 4 developing countries.
      Argentina (ICU)9.64.157%
      • Rosenthal V.D.
      • Desse J.
      • Maurizi D.M.
      • Chaparro G.J.
      • Orellano P.W.
      • Chediack V.
      • et al.
      Impact of the International Nosocomial Infection Control Consortium (INICC)’s multidimensional approach on rates of central line-associated bloodstream infection in 14 Intensive Care Units in 11 hospitals of 5 cities in Argentina.
      During implementation of the preventive measures, limitations of human resources affect also the compliance with the prevention guidelines, as shown by a study in Jordan where the nurse to patient ratio of 1:1 was the only predictor of higher compliance with the guidelines (
      • Aloush S.M.
      • Alsaraieh F.A.
      Nurses’ compliance with central line associated bloodstream infection prevention guidelines.
      ). Effective strategies may be used to overcome this challenge during interventions, including assigning a nurse as a unit-based quality nurse (
      • Thom K.A.
      • Li S.
      • Custer M.
      • Preas M.A.
      • Rew C.D.
      • Cafeo C.
      • et al.
      Successful implementation of a unit-based quality nurse to reduce central line-associated bloodstream infections.
      ), or assembly of an intervention team of physician, infection control nurse, and ICU nurse to assess and follow up CLABSI cases (
      • Hussain A.S.S.
      • Ali S.R.
      • Ariff S.
      • Arbah S.
      • Demas S.
      • Zeb J.
      • et al.
      A protocol for quality improvement programme to reduce central line-associated bloodstream infections in NICU of low and middle income country.
      ).
      Prevention efforts should be focused on maximal aseptic insertion of catheters, hand hygiene and adequate dressing changes.
      As highlighted by
      • Rosenthal V.D.
      Central line-associated bloodstream infections in limited-resource countries: a review of the literature.
      , high CLABSI rates suggest that LMICs face significant barriers for CLABSI reduction including resources, appropriate medical supplies and adequate numbers of skilled personnel. Additional examples include inadequate and outdated technologies, lines used without sterile dressings, single dose vials used multiple times covered with contaminated tape, cotton balls impregnated with contaminated antiseptic solutions and semi-rigid plastic containers used for intravenous infusate preparation. Furthermore, general infection prevention gaps and breaches may contribute to high CLABSI rates e.g. lack of supplies such as barrier protections and antiseptics, lack of sinks for hand washing or access to alcohol based handrub, overcrowded surroundings and untrained personnel.
      Implementation of central-line bundles has the potential to reduce the incidence of CLABSIs, as shown in a recent systematic review and meta-analysis (
      • Ista E.
      • van der Hoven B.
      • Kornelisse R.
      • van der Starre C.
      • Vos M.C.
      • Boersma E.
      • et al.
      Effectiveness of insertion and maintenance bundles to prevent central-line-associated bloodstream infections in critically ill patients of all ages: a systematic review and meta-analysis.
      ). It is noteworthy that sustainable compliance with bundles involves the entire infection control team, and a change in their habits may be necessary, as well as continuous institutional support, updated educational interventions, and CLABSI surveillance data to improve patient care practices. In other words, to achieve steady, high levels of compliance with bundle elements, it is not sufficient to implement it as one measure, but rather within a multidimensional infection control approach.
      INICC developed the INICC Multidimensional Approach, which is implemented through a Surveillance Online System (ISOS) software application, which includes: (1) a CLABSI prevention bundle, (2) education, (3) outcome surveillance (4) process surveillance, (5) feedback on CLABSI rates and consequences, and (6) performance feedback of process surveillance. As shown in the literature for developing countries and limited-resource hospital settings, the rate of CLABSI has been successfully reduced through the implementation of such multidimensional programs, which include insertion and maintenance bundles for the prevention of CLABSIs in critically ill patients of all ages, but also other interventions simultaneously (
      • Rosenthal V.D.
      • Maki D.G.
      • Rodriguez C.
      • Alvarez-Moreno C.
      • Leblebicioglu H.
      • Sobreyra-Oropeza M.
      • et al.
      Impact of International Infection Control Consortium (INICC) strategy on central line-associated infection rates in the intensive care units of 15 developing countries.
      ).
      Effective interventions with the INICC multidimensional approach and ISOS were reported in ICUs from Argentina (46.63 vs. 11.10 CLABSIs per 1000 CL-days), showing a 76% reduction, and 57% reduction (incidence density rate: 0.43; 95% confidence interval, 0.34-0.6; P < .001) (
      • Rosenthal V.D.
      • Guzman S.
      • Migone O.
      • Crnich C.J.
      The attributable cost, length of hospital stay, and mortality of central line-associated bloodstream infection in intensive care departments in Argentina: a prospective, matched analysis.
      ); Colombia, showing a 73% CLABSI rate reduction (relative risk, 0.27; 95% confidence interval, 0.14-0.52; P = .002) (
      • Alvarez-Moreno C.A.
      • Valderrama-Beltran S.L.
      • Rosenthal V.D.
      • Mojica-Carreno B.E.
      • Valderrama-Marquez I.A.
      • Matte-Cortes L.
      • et al.
      Multicenter study in Colombia: Impact of a multidimensional International Nosocomial Infection Control Consortium (INICC) approach on central line-associated bloodstream infection rates.
      ); Mexico (46.3 vs. 19.5 BSIs per 1000 IVD days) showing a 58% reduction (
      • Higuera F.
      • Rosenthal V.D.
      • Duarte P.
      • Ruiz J.
      • Franco G.
      • Safdar N.
      The effect of process control on the incidence of central venous catheter-associated bloodstream infections and mortality in intensive care units in Mexico.
      ); Turkey (22.7 to 12.0 CLABSIs per 1000 CL-days), showing a 47% reduction (
      • Leblebicioglu H.
      • Ozturk R.
      • Rosenthal V.D.
      • Akan O.A.
      • Sirmatel F.
      • Ozdemir D.
      • et al.
      Impact of a multidimensional infection control approach on central line-associated bloodstream infections rates in adult intensive care units of 8 cities of Turkey: findings of the International Nosocomial Infection Control Consortium (INICC).
      ); India (6.4 CLABSIs to 3.9 CLABSIs per 1000 CL-days), showing a 39% reduction (
      • Jaggi N.
      • Rodrigues C.
      • Rosenthal V.D.
      • Todi S.K.
      • Shah S.
      • Saini N.
      • et al.
      Impact of an international nosocomial infection control consortium multidimensional approach on central line-associated bloodstream infection rates in adult intensive care units in eight cities in India.
      ); and Saudi Arabia (6.9 to 3.1 per 1000 CL-days) (
      • Al-Abdely H.M.
      • Alshehri A.D.
      • Rosenthal V.D.
      • Mohammed Y.K.
      • Banjar W.
      • Orellano P.W.
      • et al.
      Prospective multicentre study in intensive care units in five cities from the Kingdom of Saudi Arabia: Impact of the International Nosocomial Infection Control consortium (INICC) multidimensional approach on rates of central line-associated bloodstream infection.
      ). In multicentric studies conducted in adult ICUs (14.5 vs. 9.7 CLABSIs per 1000 CL-days) from 15 countries (Argentina, Turkey, Colombia, India, Mexico, Philippines, Brazil, Peru, El Salvador, Costa Rica, Cuba, Lebanon, Macedonia, Morocco, and Panama), showed a 33% reduction (
      • Rosenthal V.D.
      • Maki D.G.
      • Rodriguez C.
      • Alvarez-Moreno C.
      • Leblebicioglu H.
      • Sobreyra-Oropeza M.
      • et al.
      Impact of International Infection Control Consortium (INICC) strategy on central line-associated infection rates in the intensive care units of 15 developing countries.
      ); in pediatric ICUs from 5 countries (Colombia, India, Mexico, Philippines, and Turkey)(10.7 vs. 5.2 CLABSIs per 1000 CL-days), showed a 51% reduction (
      • Rosenthal V.D.
      • Ramachandran B.
      • Villamil-Gomez W.
      • Armas-Ruiz A.
      • Navoa-Ng J.A.
      • Matta-Cortes L.
      • et al.
      Impact of a multidimensional infection control strategy on central line-associated bloodstream infection rates in pediatric intensive care units of five developing countries: findings of the International Nosocomial Infection Control Consortium (INICC).
      ), and in NICUs from 4 countries (El Salvador, Mexico, Philippines, and Tunisia) showed a CLABSI rate decrease by 55%, from 21.4 per 1000 CL-days during phase 1 to 9.7 per 1000 CL-days during phase 2 (rate ratio, 0.45 [95% confidence interval, 0.33-0.63]) (
      • Rosenthal V.D.
      • Duenas L.
      • Sobreyra-Oropeza M.
      • Anmar K.
      • Navoa-Ng J.A.
      • de Casares A.C.
      • et al.
      Findings of the International Nosocomial Infection Control Consortium (INICC), part III: effectiveness of a multidimensional infection control approach to reduce central line-associated bloodstream infections in the neonatal intensive care units of 4 developing countries.
      ).
      In addition to the successful model of the INICC, other strategies showed significant impact in increasing staff compliance, and reduction of infection rates. Successful strategies included training and education of the staff through formal sessions of presentations and poster materials (
      • Sahni N.
      • Biswal M.
      • Gandhi K.
      • Kaur K.
      • Saini V.
      • Yaddanapudi L.N.
      Effect of intensive education and training of nurses on ventilator-associated pneumonia and central line-associated bloodstream infection incidence in intensive care unit at a tertiary care care in North India.
      ), peer tutoring where nurses and staff share in preparing and provision of the educative materials (
      • Park S.-W.
      • Ko S.
      • An H.-S.
      • Bang J.H.
      • Chung W.-Y.
      Implementation of central line-associated bloodstream infection prevention bundles in a surgical intensive care unti using peer tutoring.
      ), or online provision of educative materials (
      • Hassan Z.M.
      Improving knowledge and compliance with infection control standard precautions among undergraduate nursing students in Jordan.
      ).
      Finally, as underscored by
      • Alp E.
      • Rello J.
      Implementation of infection control bundles in intensive care units: which parameters are applicable in low-to-middle income countries?.
      , implementation of these prevention techniques can be quite challenging. As presented by
      • Alves J.
      • Pena-Lopez Y.
      • Rojas J.N.
      • Campins M.
      • Rello J.
      Can we achieve zero hospital-acquired pneumonia?.
      , a “4E” approach can be useful:
      Engagement of staff with a multi-disciplinary group with involvement of local champions and using peer networks;
      Education with materials and sessions;
      Execution with standard care processes with redundancy;
      Evaluation with measurement of performance with feedback to staff.

      Conflicts of interest

      None.

      Funding sources

      None.

      Ethical approval

      Done.

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