Methods for Preventing Central Line Associated Bloodstream Infection in Pediatric Hematology-Oncology Patients: a Systematic Literature Review, 2010-2020

THESIS

CALIFORNIA STATE UNIVERSITY SAN MARCOS

THESIS SIGNATURE PAGE

PROJECT SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE

MASTER OF PUBLIC HEALTH

TITLE: Methods for preventing central line associated bloodstream infection in pediatric hematology-oncology patients: A systematic literature review, 2010-2020

AUTHOR(S): Kimberly Balkan

DATE OF SUCCESSFUL DEFENSE: 11/16/2020

THETHE THESISPROJECT HAS HAS BEEN BEEN ACCEPTED ACCEPTED BY BY THE THE THESIS PROJECT COMMITTEE COMMITTEE IN IN

PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF

MASTER OF PUBLIC HEALTH PUBLIC HEALTH

Deborah Morton Nov 17, 2020 COMMITTEE CHAIR SIGNATURE DATE

Christina Holub Nov 17, 2020 COMMITTEE MEMBER SIGNATURE DATE

COMMITTEE MEMBER SIGNATURE DATE

COMMITTEE MEMBER SIGNATURE DATE 1

Methods for preventing central line associated bloodstream infection in pediatric

hematology-oncology patients: A systematic literature review, 2010 - 2020

Kim Balkan

Department of Public Health, California State University, San Marcos

PH 698: Thesis

Dr. Deborah Morton

November 30, 2020

Abstract

Central line associated bloodstream infections (CLABSIs) are a significant source of

patient morbidity and mortality with high financial costs. CLABSI is the most common complication of having a central line (Castro et al., 2020). Central lines are used for a variety of purposes, including the transportation of life-saving fluids and medicine in emergent situations, nutrition and cancer therapies (Castro et al., 2020). Potential sources of CLABSI infection include skin colonization, intraluminal contamination of central lines, hematogenous seeding, and infusate contamination (Marschall et al., 2014; O’Grady et al., 2011).

A systematic literature review was conducted to identify methods of preventing the first occurrence of CLABSI in pediatric cancer patients. Pediatric patients age 18 and younger have unique microbiology and epidemiology of infection, pharmacology, and physiological development (McNeil et al., 2019). Pediatric patients undergoing cancer treatment are disproportionately affected by CLABSI (Duffy et al., 2015). Susceptibility to infection, caused by prolonged periods of immunosuppression from cancer or cancer therapy, can result in

CLABSI rates up to 17.95% (McMullen et al., 2013). Cancer patients may receive treatment in an inpatient or outpatient setting. In recent years, central lines have become more common for outpatients. Patients must take proper care of the catheter outside of the healthcare environment to prevent infection.

The preventative methods to reduce the risk of CLABSI focus on staff education, patient hygiene, and insertion and maintenance of central lines (McNeil et al., 2019). Based on the articles included in this systematic literature review, care bundles, catheter flushing, and catheter lock therapy should be part of infection control best practices for preventing CLABSI in pediatric cancer patients. 3

Acknowledgements

I have much appreciation for California State University, San Marcos and the Master of

Public Health program and staff for keeping my cohort on track to graduate as scheduled during the COVID-19 pandemic. I wish to thank Dr. Deborah Morton for serving as my thesis chair and

Dr. Christina Holub for serving as my second committee member. A special thanks to Dr.

Rodney Beaulieu for taking the time to read my thesis drafts and provide helpful feedback. I have sincere gratitude for everyone else who supported my participation in this graduate program and for being accommodating and flexible throughout my studies, especially Kathleen Korn,

Ekaette Mbong and Pam Balkan.

List of Tables

Table 1. Characteristics of included literature

Table 2. Analysis of included literature

Table 3. Research findings

Table 4. Research conclusions

List of Figures

Figure 1. Flowchart of literature screening and assessment 6

Table of Contents Methods for preventing central line associated bloodstream infection in pediatric hematology-oncology patients: A systematic literature review, 2010 - 2020 ...... 1 Abstract ...... 2 Acknowledgements ...... 3 List of Tables ...... 4 List of Figures ...... 5 Methods for preventing central line associated bloodstream infection in pediatric hematology- oncology patients: A systematic literature review, 2010 - 2020 ...... 7 Healthcare-associated infections ...... 7 Infection prevention ...... 7 Surveillance ...... 10 CLABSI ...... 11 Statement of the Problem ...... 13 Morbidity, Mortality and Financial Cost ...... 13 Pediatric Population ...... 13 Hematology-Oncology ...... 14 Methods of CLABSI Prevention ...... 14 Research Goal ...... 16 Literature Themes ...... 16 Hypotheses ...... 17 Methods ...... 17 Search Strategy ...... 18 Characteristics of Literature ...... 19 Results ...... 19 Methods for preventing CLABSI ...... 19 Research Themes and Conclusions ...... 21 Discussion ...... 22 Strengths ...... 23 Limitations ...... 23 Public Health Implications ...... 24 Future Direction ...... 25 References ...... 26 Table 1 ...... 36 Table 2 ...... 1 Table 3 ...... 1 Table 4 ...... 2 Figure 1 ...... 3 7

Methods for preventing central line associated bloodstream infection in pediatric

hematology-oncology patients: A systematic literature review, 2010 - 2020

Healthcare-associated infections

Patients seeking care at hospitals and outpatient clinics are at risk for healthcare- associated infections (HAI) (California Department of Public Health [CDPH], 2019). Lifesaving procedures and medicines, including antibiotics, chemotherapeutic agents, medical devices and advanced surgical techniques come with the unintended risk of HAI (McNeil et al., 2019). In the

United States, one in 25 hospital patients is diagnosed with at least one HAI and additional infections occur in other healthcare settings (Centers for Disease Control & Prevention [CDC],

2017). Every year two million patients are diagnosed with HAI and nearly 90,000 will die as a result (Stone, 2009). The financial cost of HAIs to hospitals range from $28 billion to $45 billion annually (Stone, 2009).

Infection prevention

The CDC publishes guidelines of best practices for HAI prevention. These guidelines are specific to certain healthcare settings or type of infections, such as Guidelines for Prevention of

Intravascular Catheter-Related Infections and CDC Vital Signs: Making Healthcare Safer

Reducing Bloodstream Infections (CDC, 2011). The CDC recognizes the shift of healthcare delivery from inpatient hospital settings to outpatient clinics over the past several decades and the risk for preventable infection (CDC, 2016). Data describing HAI risk in the outpatient setting is lacking, but numerous reports of bacteria, mycobacteria, viruses and parasite outbreaks have been reported in association with breakdowns in infection prevention practices. In response, the

CDC issued a Guide to Infection Prevention for Outpatient Settings: Minimum Expectations for

Safe Care (2016). The guide includes recommendations for administration, healthcare personnel 8

training, HAI surveillance, hand hygiene and use of personal protective equipment, safe injection practices, environmental cleaning, disinfection or sterilization; and respiratory hygiene and cough etiquette. Facilities are encouraged to use the CDC Infection Prevention Checklist for

Outpatient Settings to assess compliance.

Administrative Recommendations

Key administrative recommendations by the CDC include: the development and maintenance of infection prevention and occupational health programs; the availability of sufficient and appropriate supplies for hand hygiene products, personal protective equipment and injection equipment; an employed and regularly available infection prevention specialist; and written infection prevention policies and procedures appropriate for the services provided at the facility (2016).

Healthcare personnel training

Healthcare personnel include all paid and unpaid staff with the potential for exposure to patients or to infectious materials, contaminated medical supplies and devices, surfaces or air

(CDC, 2016). Healthcare personnel training recommendations by the CDC include job or task- specific infection prevention education and training; training should focus on healthcare personnel and patient safety; training should be provided upon hire, repeated annually, and when policies change; and competencies should be documented after training is completed.

Hand hygiene

Hand hygiene recommendations by the CDC include the use of an alcohol-based hand rub as the preferred method of hand hygiene and washing hands with soap and water when hands are visibly soiled or after caring for patients with known or suspected Clostridium difficile or

norovirus (2016). Hand hygiene should be performed before contact with a patient; before 9

performing an aseptic task, such as the insertion of an intravenous line or preparing an injection; after contact with a patient or objects in the immediate vicinity of the patient; after contact with blood, bodily fluids, or contaminated surfaces; when hands will be moving from a contaminated- body site to a clean body side during patient care; and after removal of personal protective equipment (PPE).

Personal protective equipment

The CDC recommends facilities have sufficient and appropriate PPE available to healthcare personnel (2016). Healthcare personnel should be educated on proper PPE selection and use. Gloves should be worn in situations with potential blood contact, body fluids, mucous membranes and non-intact skin or contaminated equipment. A gown should be worn to protect skin and clothing during procedures or activities where body fluid or blood is anticipated. Mouth, nose and eye protection are recommended during procedures that generate splashes or sprays of body fluids.

Injection safety

Key recommendations for injection safety by the CDC include use of aseptic technique when preparing and administering medications; cleanse access diaphragms of medication vials with alcohol before inserting a device into the vial; never administering medications from the same syringe to multiple patients; not reusing a syringe; dedicate multidose vials to a single patient whenever possible; dispose of used sharps at the point of use in a puncture-resistant, leak- proof sharps container; and wear a facemask when placing a catheter or injecting material into the epidural or subdural space (2016).

Cleaning and disinfection

The CDC recommends establishing policies and procedures for routine cleaning and disinfection of any facility surfaces and property cleaning and decontamination of blood and potentially infectious material (2016). EPA-registered disinfectants or detergents with designated healthcare-use labels should be used based on manufacturer’s instructions. Reusable medical devices, such as blood glucose meters, point-of-care devices and surgical instruments should be cleaned prior to use on another patient and maintained according to the manufacturer’s instructions. Healthcare personnel should be assigned responsibilities for cleaning and reprocessing of medical devices and wear appropriate PPE when handling contaminated medical devices.

Respiratory Hygiene/Cough Etiquette recommendations

Patients and individuals who have signs and symptoms of respiratory infections and secretions should practice the following CDC recommendations; inform healthcare personnel of respiratory symptoms, cover mouth and nose when coughing or sneezing; use and dispose of tissues, perform hand hygiene after contacting respiratory secretions, masks should be offered to coughing and symptomatic patients, separate symptomatic patients from others when possible, or provide space to sit as far away from others as possible (2016).

Surveillance

The CDC publishes the annual HAI Progress Report of national and state healthcare- associated infections most commonly reported to CDC’s National Healthcare Safety Network

(NHSN) (CDC, 2018). The state of California requires acute care hospitals to track and report five types of HAI quarterly through Health and Safety Code sections 1288.5 and 1288.55

(California Legislative Information, 2020). Surveilled HAI include Methicillin-resistant 11

Staphylococcus aureus bloodstream infection (MRSA BSI), clostridium difficile infection (CDI),

Vancomycin-resistant enterococcal bloodstream infection (VRE BSI), surgical site infection

(SSI), and central line associated bloodstream infection (CLABSI) (California Legislative

Information, 2020). CDPH publishes HAI data annually to inform the public and identify hospitals and communities needing outreach and intervention.

The U.S. Department of Health and Human Services (HHS) published an HAI action plan in 2009. The National Action Plan to Prevent Health Care-Associated Infections: Road

Map to Elimination set five-year goals for HAI prevention (CDC, 2018). The CDPH HAI

Advisory Committee identified necessary reduction levels for each surveilled HAI to meet national goals (2019). From 2015 to 2020, California hospitals need a 50% reduction in MRSA

BSI and CLABSI. The most recent available data from 2018 shows 401 California general acute care hospitals reported 2,428 fewer HAI than were reported in 2017. CLABSI incidence in

California hospitals in 2018 was better than the national baseline; however, only inpatients were included. Neither CDPH nor the CDC require CLABSI reporting for outpatients.

Pediatric hospitals can take advantage of the quality improvement network Children’s

Hospitals’ Solutions for Patient Safety (SPS). SPS allows hospitals to work together to develop

HAI interventions that work best for children (McNeil et al., 2019). Hospitals share data and benchmark HAI rates against other participating facilities for quality control purposes.

CLABSI

CLABSI is caused by contamination of a central venous catheter (CVC), also known as a central line, inserted into a large vein to carry medication or fluids to a patient (CDPH, 2019). A central line allows for rapid administration of high-volume fluids and medication that would damage most peripheral veins (Castro et al., 2020). Central lines are used for a variety of 12

purposes, including the transportation of life-saving fluids and medicine in emergent situations, nutrition and cancer therapies (Castro et al., 2020). CLABSI is the most common complication of having a central line (Castro et al., 2020). Potential sources of CLABSI infection include skin colonization, intraluminal contamination of central lines, hematogenous seeding, and infusate contamination (Marschall et al., 2014; O’Grady et al., 2011).

CLABSI is the surveillance term used by the Centers for Disease Control and

Prevention’s (CDC) National Healthcare Safety Network (NHSN). CLABSI refers to a primary

BSI developed within the 48-hour period after a central line was placed and is unrelated to any other infection occurring at another site on or within the patient’s body (CDC, 2015). The most common symptoms of CLABSI are fever and chills (Haddadin et al., 2020). Examination of the catheter site for inflammation, pain, redness, swelling or discharge is important. Blood culture is necessary to confirm CLABSI and determine severity. Some BSIs are secondary to sources other than the central line, but are not easily identifiable (CDC, 2015). Healthcare facilities with the ability to run more robust laboratory tests can determine the catheter is the true source of infection. The clinical term catheter related bloodstream infection (CRBSI) is used when diagnosing and treating these patients. Not all healthcare facilities have the ability to test for

CRBSI due to a limited availability of microbiologic methods. Many labs do not use quantitative

blood cultures or differential time to positivity, which is required for CRBSI confirmation. In

addition, it is problematic to precisely establish if a BSI is a CRBSI when the catheter cannot be

removed due to clinical needs of the patient. CLABSI may overestimate the true incidence of

CRBSI, but the numbers are officially recognized as the surveillance measure of BSI related to

central lines.

Statement of the Problem

Morbidity, Mortality and Financial Cost

CLABSIs are a significant source of patient morbidity and mortality with high financial

costs. Intensive care (ICU) CLABSIs contribute to 28,000 deaths each year and cost over two

billion dollars (Haddadin et al., 2020). The mean cost and length of hospital stay attributable to pediatric CLABSI from 2008 through 2011 was $55,646 and 19 days (Goudie et al., 2014). Cost increases to nearly $70,000 in cancer patients undergoing hematology-oncology (hem-onc) treatment with a mean length of stay of 21 days (Wilson et al., 2014).

Pediatric Population

Pediatric patients, surveilled as age 18 and younger, have unique microbiology and epidemiology of infection, pharmacology, and physiological development compared to adults

(McNeil et al., 2019). Children have thinner skin, less fluid in their bodies and breathe in more air per pound of bodyweight than adults (CDC, 2020b). Organs and tissues grow during

childhood so more cells are dividing rapidly, and children have a longer lifespan ahead of them

compared to adults, giving cancers more time to develop (CDC, 2020b).

Children may have underlying risk factors for CLABSI, including the presence of genetic

and congenital abnormalities, extracorporeal membrane oxygenation, prematurity, gastrointestinal disease, neutropenia, immune deficiency, and oncologic conditions (Marschall et

al., 2014). CLABSI risk has been found to be 2.7 times higher in pediatric patients with

gastrointestinal disease and 2.6 times higher in pediatric patients with oncologic disease (Niedner

et al., 2011).

Hematology-Oncology

In the United States, 15,000 children are diagnosed with cancer annually (CDC, 2020a).

Cancer is the leading cause of death from disease for children under age 15. The most common types of cancer for children are leukemia, lymphoma, brain and other nervous system cancers.

Cancer is a complex disease with many possible causes, including exposure to harmful environmental factors and over time. The CDC recommends the following preventative measures to reduce cancer risk in children: mothers should avoid alcohol and tobacco use during pregnancy; keep children away from secondhand smoke; reduce childhood exposure to traffic- related air pollution and cancer-causing chemicals; limit the amount of radiation during medical tests; and prevent adverse childhood experiences, such as violence victimization, substance misuse at home and witnessing intimate partner violence (CDC, 2020c).

Pediatric patients undergoing cancer treatment are disproportionately affected by

CLABSI (Duffy et al., 2015). Susceptibility to infection, caused by prolonged periods of immunosuppression from cancer or cancer therapy, can result in CLABSI rates up to 17.95%

(McMullen et al., 2013). Hem-onc patients may receive treatment in an inpatient or outpatient setting. Outpatient care occurs at facilities where patients do not stay overnight. In recent years, central lines have become more common for outpatients. Patients have a central line placed in order to receive chemotherapy, medications, blood products and fluids in the clinic. The central line catheter is not removed between therapy sessions. Patients must take proper care of the catheter outside of the healthcare environment to prevent infection.

Methods of CLABSI Prevention

Most CLABSI are preventable and low CLABSI rates indicate adherence to infection

control best practices (CDPH, 2019). CLABSI can occur when infection control measures are 15

not appropriately applied during central line insertion or use (CDPH, 2019). The preventative methods to reduce the risk of CLABSI focus on staff education, patient hygiene, and insertion and maintenance of central lines (McNeil et al., 2019). Data supporting these methods of prevention are predominantly from studies of adult patients in inpatient and ICU settings

(McNeil et al., 2019). The CDC published a Basic Infection Control and Prevention Plan for

Outpatient Oncology Settings in 2011. The plan contains policies and procedures specifically for outpatient oncology facilities to meet the CDC’s minimal expectations for patient protection in outpatient settings. The recommended infection prevention precautions for outpatients are similar to the recommendations in the Guide to Infection Prevention for Outpatient Settings: hand hygiene, use of PPE, respiratory hygiene and cough etiquette, safe injection practices and safe handling of potentially contaminated equipment or surfaces (CDC, 2011). The Basic

Infection Control and Prevention Plan for Outpatient Oncology Settings highlights the importance of consulting with oncology pharmacy specialists, the Oncology Nursing Society and the Infusion Nursing Society for proper chemotherapy medication storage and handling and CVC care (CDC, 2011).

The CDC encourages facilities to customize the Basic Infection Control and Prevention

Plan for Outpatient Oncology Settings by adding the facility name, relevant locations, rooms, personnel, and instructions to the document so it is directly applicable to the facility (2011). The plan does not address aspects of patient care related to occupational health requirements, appropriate preparation and handling of sterile medications, clinical recommendations on guidance on antimicrobial prescribing practices and infection prevention issues unique to bone marrow transplant or stem cell transplant centers. The plan also does not include policies or 16

procedures specific to pediatric patients. CLABSI is also not discussed or defined for the outpatient setting.

The National Association of Children’s Hospitals and Related Institutions (NACHRI) led

a national quality transformation initiative in 2006 to reduce CLABSI among critically ill pediatric patients (Duffy et al., 2015). The result was a reduction from 6.3 infections per 1000 catheter days to 4.3 infections per 1000 catheter days (Jeffries et al., 2009; Duffy et al., 2015).

The initiative demonstrated the effectiveness of nurses using a CVC daily maintenance care bundle. A care bundle is a holistic approach to preventing CLABSI using specific infection control best practices within specific timeframes. In the past decade, additional studies have analyzed the effectiveness of care bundles and other methods for preventing CLABSI in pediatric hem-onc patients.

Research Goal

The goal of this study was to conduct a systematic literature review to answer the research question: What are the methods for preventing CLABSI in pediatric hem-onc patients?

The existing literature was evaluated and synthesized to address the complexity of CLABSI prevention due to patient age, patient setting, catheter placement and infectious organisms.

Literature themes was identified and associated hypotheses were tested. The result is a summary of evidence for effective CLABSI prevention in pediatric hem-onc patients.

Literature Themes

Clinical methods for preventing CLABSI were evaluated to determine themes in the following areas:

1. pediatric patients compared to adult patients,

2. inpatients and outpatients, 17

3. catheter location, and

4. characteristics of the organism.

Hypotheses

Hypotheses were tested. Null (H0 ) and alternative (H1) hypotheses were identified for each theme:

1. H0: Methods for preventing CLABSI in pediatric hem-onc patients are the same

as methods used in adult hem-onc patients,

H1: Methods for preventing CLABSI in pediatric hem-onc patients are different

from methods used in adult hem-onc patients;

2. H0: Methods for preventing CLABSI are the same for pediatric hem-onc

inpatients and outpatients,

H1: Methods for preventing CLABSI are different for pediatric hem-onc

inpatients and outpatients;

3. H0: Methods for preventing CLABSI are the same for all catheter locations,

H1: Methods for preventing CLABSI differ based on catheter location; and

4. H0: Methods for preventing CLABSI are the same for all CLABSI-causing

organisms,

H1: Methods for preventing CLABSI differ for CLABSI-causing organisms.

Methods

A systematic literature review was conducted to identify methods of preventing the first occurrence of CLABSI in pediatric cancer patients. A systematic literature review is a comprehensive search for relevant literature. A quality assessment was performed to determine

inclusion and exclusion criteria. The research did not focus on the risk factors for CLABSI, 18

methods for treating CLABSI, or the methods for preventing recurring CLABSI. The selected literature was appraised and synthesized to provide a summary of CLABSI prevention methods,

what is effective and what requires additional research.

Search Strategy

The Cochrane Library, PubMed and CSUSM Library OneSearch databases were

searched to identify relevant peer-reviewed articles. A total of 1,654 articles were found on

CLABSI and CRBSI. Articles were screened for criteria to determine eligibility; 1,031 articles

published before 2010 were excluded and 537 articles not focused on pediatric hem-onc patients

were also excluded. Twenty-three articles were accepted for final inclusion with a focus on

methods for preventing CLABSI or CRBSI in pediatric hem-onc patients. See Figure 1,

Flowchart of literature screening and assessment.

Inclusion Criteria

Articles included were published in English in high impact journals, peer-reviewed and

limited to the last ten years. Articles were filtered using terms found in the title or abstract. The terms central line associated bloodstream infection (CLABSI) and catheter related bloodstream infection (CRBSI) were searched, since CLABSI is the surveillance term and CRBSI is the clinical term.

Exclusion Criteria

Articles not published in English and all articles prior to 2010 were excluded. Literature on methods for treating and preventing a recurrence of CLABSI were also excluded, since patients with a previous catheter-related infection are at a higher risk for BSI (Chin et al., 2010)

Characteristics of Literature

The distribution of the following study characteristics are shown in Table 1: country,

patient population, publication year and research design. Half of the articles were published outside of the United States or were systematic literature reviews that incorporated data from studies that took place outside of the United States. Only two articles focused on outpatients.

Studies slightly increased over the past ten years. Eight articles were case studies of individual hospitals or collaboratives, five were systematic literature reviews and the remainder were retrospective or prospective randomized studies.

Results

The included literature was analyzed for research quality. Analysis is shown in Table 2, identifying the article, objective, methods, analysis, results and conclusion.

Methods for preventing CLABSI

Table 3 summarizes information from the literature to answer the research question: What

are the methods for preventing CLABSI in pediatric hem-onc patients? The prevention method is identified alongside the objective of the method, the area the method targets, and whether the method was found to be effective in the pediatric hem-onc population. Care bundles and

caregiver skills and education target multiple areas that include the catheter site, catheter dressing, catheter flushing and caretaker hygiene. Three methods were found to be effective in preventing CLABSI in the pediatric hem-onc population: care bundles, catheter flushing, and catheter lock therapy.

Care Bundles

A care bundle is a holistic approach to preventing CLABSI using seven best practices

within specific timeframes that affect patient hygiene, catheter dressing changes, catheter access 20

and IV line care (Duffy et al., 2015). All steps must be completed at the specified time or the

patient will be predisposed to CLABSI. The CDC CLABSI prevention guidelines provide

instructions for both a CVC insertion bundle and a CVC daily maintenance care bundle. The

bundles include items and procedures that promote consistent application of evidence-based

infection control practices, such as: daily review of central line necessity, medical record

documentation, hand hygiene before handling the central line, sanitization of catheter injection

ports, and scheduled catheter dressing changes. A 2019 study found oral care as part of a hygiene

bundle was also effective (Kemp et al.). The oral care bundle included items and procedures for

proper oral hygiene: a toothbrush, fluoride toothpaste, twice-daily brushing, sodium bicarbonate rinses, lip balm and oral moisturizer.

Caregiver Skills and Education

Skills and education of hospital staff and home caregivers is important to prevent infection. Leadership line rounds, when clinical leaders visit patients on the unit and observe care, help hold staff accountable for proper infection control hygiene and protocol adherence.

Patient family education for self-care of the catheter is especially important for outpatients who live with the catheter outside of the hospital environment.

Catheter Dressing

The catheter site is covered by a protective dressing on the skin to decrease colonization.

Research addresses the type of dressing and the frequency of dressing changes. In 2017, the

CDC revised recommendations for catheter dressings in adult and pediatric patients.

Chlorhexidine-impregnated dressings were recommended for adult patients to protect the

insertion site of short-term, non-tunneled central venous catheters (CDC, 2015). For pediatric patients, chlorhexidine-impregnated dressings were not recommended due to a risk of serious 21

adverse skin reactions. Data regarding the frequency of dressing changes have been insufficient

to assess if catheter-related infection rates are affected (Arora et al., 2010).

Catheter Flushing

Catheter flushing is a long established practice for cleaning the catheter and preventing occlusion, blood clotting at the catheter site. The flushing method and the flushing solution have been studied. Standardized flushing methods have been compared with aseptic non-touch techniques (Gerceker et al., 2018). Both were found to be effective in reducing CLABSI rates.

Flushing the CVC with urokinase, a drug that dissolves blood clots, may decrease infection rates, but data has been insufficient (Arora et al., 2010).

Catheter Lock Therapy

Catheter Lock Therapy uses a concentrated antibiotic or antiseptic solution to dwell within the catheter for a period of time. The objective is to reduce bacteremia, the presence of bacteria in the blood. Biofilm, a slimy buildup of bacteria, develops quickly once a CVC is inserted into a patient (Handrup et al., 2013). Antibiotics are ineffective against bacteria living in biofilm. Research addresses two issues relating to catheter lock therapy: dwell time and the type of solution used. The anticoagulant Heparin is often used to lock a catheter when not in use; however, Heparin may enhance the growth of biofilm bacteria. Alternatively, the antimicrobial

Taurolidine has shown efficacy in preventing CRBSI when used as a catheter lock without promoting bacterial resistance (Handrup et al., 2013).

Research Themes and Conclusions

Hypotheses related to themes identified in the literature are answered in Table 4. The theme, associated null and alternative hypotheses and conclusion are shown. Methods for preventing CLABSI in pediatric hem-onc patients are different than those for adult patients. 22

Methods also depend on catheter location. Methods used for inpatients are the same for outpatients; however, there is no standard practice for collecting data on home-acquired CLABSI and there is no mechanism for calculating total outpatient catheter days necessary for surveillance (Altounji et al., 2020). Prevention methods are not specific to organism type, though a catheter lock solution that does not promote antibiotic resistance is favored. This literature review focused on preventing the first incidence of CLABSI. No specific organism is targeted by prevention methods. Additional literature would be needed to understand the methods for preventing recurring CLABSI caused by specific organisms.

Discussion

This systematic literature review found care bundles, catheter flushing and catheter lock therapy are effective methods of preventing CLABSI in pediatric hem-onc patients. All four predicted hypotheses were able to be answered. Methods of preventing CLABSI are different for pediatric and adult hem-onc patients and differ based on catheter location. Preventing the first instance of CLABSI relies on general infection control best practices and does not target specific

CLABSI-causing organisms. Unexpectedly, this literature review found methods of preventing

CLABSI are the same for hem-onc inpatients and outpatients despite the differences in patient health, mobility, environment and catheter location. However, this finding is affected by a lack of outpatient CLABSI research and standards for outpatient data collection.

Study design and execution are important factors for weighing the effectiveness of

CLABSI prevention methods. The CDC Community Guide has guidelines and rules to assess the quality of studies in a systematic review. Guidelines include evaluating the study location and setting, the study population, sample size and method of selection, and the measurement of health outcomes and other characteristics of the target population (Zaza et al., 2000). This 23

literature review included 23 studies of various designs. The most common design were case

studies (8), five were systematic literature reviews, four were retrospective and only one was a

randomized controlled trial. The systematic literature reviews each had a sample size of over one

thousand patients. Several studies had less than 100 patients. It is not necessarily possible to compare the effectiveness of CLABSI prevention methods between studies with different designs. This literature review focused on the relative merits of each study. There is limited research on preventing the first instance of CLABSI in pediatric hem-onc patients. More studies of all types with greater numbers of patients are necessary to improve the knowledge and understanding of CLABSI prevention methods in pediatric hem-onc patients.

Strengths

As central lines become more common in outpatient settings, it is important to know the tested methods for CLABSI prevention in the pediatric hem-onc population. This systematic literature review included relevant research on pediatric hem-onc CLABSI prevention methods over the past decade. No similar published review was found during the search of the Cochrane

Library, PubMed and CSUSM Library OneSearch databases. The literature selected for inclusion was able to answer the research question and all four hypotheses. One book by McNeil et al.

(2019), Healthcare-Associated Infections in Children: A Guide to Prevention and Management, was very helpful for understanding infection control best practices and risk factors for CLABSI in children.

Limitations

The definition of CLABSI and CRBSI have important consequences and present a

limitation to this paper. The CDC definition of CLABSI and CRBSI are written for an inpatient

environment (CDC, 2020). There is no standard practice for collecting data on home-acquired 24

CLABSI, likely to affect pediatric hem-onc outpatients (Altounji et al., 2020). There is also no

mechanism for calculating total outpatient catheter days necessary for surveillance. Determining

if a CLABSI was acquired at an outpatient visit or at home can be unknowable. These limitations make it impossible to calculate comparable CLABSI rates for inpatients and outpatients.

Public Health Implications

Most CLABSI are preventable, but CLABSI is still the most common complication of having a central line (Castro et al., 2020). The CDC acknowledges a holistic approach, including

CDC data systems, evidence-based recommendations, public health programs and partnerships have successfully reduced HAI across healthcare settings (CDC, 2017). Based on the articles included in this systematic literature review, care bundles, catheter flushing, and catheter lock therapy should be part of infection control best practices for preventing CLABSI in pediatric hem-onc patients. The CDC’s latest available Basic Infection Control and Prevention Plan for

Outpatient Oncology Settings published in 2011 mentions catheter flushing, but does not mention care bundles or catheter lock therapy. The Joint Commission, the nation's oldest independent accrediting body in health care, created a CLABSI Toolkit and Monograph in 2013.

The toolkit encourages the use of a CVC insertion bundle, but does not mention catheter lock therapy.

The CDC recommends the healthcare industry adopt a new mindset about HAI that

considers all HAI unacceptable and rare (CDC, 2017). Commitment to reducing HAI must come

from traditional and new public health stakeholders at the federal, state and local levels,

including patients. Public and private healthcare providers must embrace more transparency and

accountability. If the FDA approves of Taurolidine for use in catheter locks, physicians and

researchers in the United States will have a new drug for CLABSI prevention and research. 25

Biopharmaceutical companies based in the United States currently have Taurolidine in clinical trials for CLABSI prevention (CorMedix, 2020).

The CDC also recommends patients protect themselves from HAI and CLABSI by

researching the hospital and learning about HAI rates (CDC, 2011). Patients should speak up if healthcare workers are not following infection control best practices and should alert healthcare staff of any symptoms related to an infection. Patients should avoid touching the catheter or tubing and avoid getting the central line insertion site wet. Patients should confirm with healthcare staff that the central line is absolutely necessary and how long it will be in place.

Future Direction

Future research should continue to study methods of preventing CLABSI in pediatric hem-onc patients to build upon the limited existing research. The CDC is collaborating with academic research partners in the Prevention Epicenter Program to identify and test new methods for preventing HAI (CDC, 2017). Additional research is needed to understand best practices for identifying and reporting CLABSI and CRBSI in outpatient hem-onc patients who may acquire a

CVC infection outside of the healthcare environment between treatments. There are two important questions the CDC should answer: how to define and surveil CLABSI infections that occur in outpatients with CVCs, and should the definition of CLABSI be changed so it is not limited to HAI? This is especially important since outpatients who live with a CVC can acquire an infection in non-healthcare environments. The HAI definition allows for surveillance and reporting of CLABSI and CRBSI, while also placing responsibility on the healthcare provider. It may be necessary to define responsibility and liability separately from surveillance and reporting for outpatients. 26

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