Hospital Acquired Bloodstream Infections in Pediatric Patients Undergoing Hematopoietic stem Cell Transplantation

Purpose The purpose of this thesis was to investigate hospital acquired bloodstream infections, in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT), using a subset of data from an ongoing study. The goal of the larger study was to track changes in central line-associated bloodstream infections (CLABSIs), in children with immune-compromised conditions to guide interventions to reduce infection. Background Children undergoing HSCT are a distinct subset of pediatric hematology and oncology patients who are at significant risk for developing CLABSIs due to their extended use of central venous catheters and prolonged immunosuppression. Understanding characteristics of children who developed CLABSIs after HSCT and the organisms involved in these events can help refine strategies to reduce these infections. Methods CLABSI events involving HSCT patients from a single pediatric hospital between January 2006 to June 2019 were reviewed. CLABSI events and their associated characteristics were compared during 1) a 5-year pre-intervention baseline (2006-2010) and 2) following the introduction of CLABSI-reduction interventions (2011 to June 2019). Interventions included the introduction of Children's Hospital Association's best practice bundles in 2011 as well as the addition of structured hygiene supportive cares in 2013. Because the hospital was unable to separate central line days for HSCT patients from the total number of central line days for the unit to provide a comparison of rates, events were descriptively compared between the two periods. Results During the baseline and intervention periods, the unit averaged 32 transplants per year. Twenty-eight CLABSIs involving 25 patients occurred during 2006-10 (average 5.6 CLABSIs/year), and 26 CLABSIs involving 24 patients occurred from 2011- June 2019 (average 3.1 CLABSIs/year). Even though the annual frequency of CLABSI events decreased during the intervention period (t=2.4; p=.04), characteristics of patients who developed CLABSIs and the predominant organisms were similar across both periods. CLABSIs were most frequent among children with leukemia (n=11; 39% in the baseline and n=9; 35% in the intervention period) and in those 0 to 4 years of age (n=17; 61% in the baseline and n=13; 50% in the intervention period). During both time periods, over half (54%) of the patients who developed CLABSIs were neutropenic. The most frequent causative organisms were also similar across both periods and included coagulasenegative staphylococci (baseline n=9; 32%; intervention period n=8; 31%) and Enterococcus species (baseline n=7; 25%; intervention period n=4; 15%). Implications The introduction of structured interventions including best-practice bundles and intensified hygiene cares were successful at decreasing the frequency of CLABSI events. Children who remain at greatest risk for CLABSIs post-HSCT include those less than five years of age and those with leukemia. These data provide guidance for understanding the characteristics of children undergoing HSCT who are at highest risk for CLABSIs. By continuing a safe environment and promoting a culture of patient safety in nursing cares, CLABSI events can be reduced and decreased rates can be maintained.

HOSPITAL ACQUIRED BLOODSTREAM INFECTIONS IN PEDIATRIC PATIENTS UNDERGOING HEMATOPOIETIC STEM CELL TRANSPLANTATION by Mayra Rodriguez A Senior Honors Thesis Submitted to the Faculty of The University of Utah In Partial Fulfillment of the Requirements for the Honors Degree in Bachelor of Science In Nursing Approved: ______________________________ Lauri A. Linder, PhD, APRN, CPON Thesis Faculty Supervisor _____________________________ Connie Madden, PhD, RN Assistant Dean for the Baccalaureate Program and Student Services College of Nursing _ _________ Sara Simonsen, PhD, CNM, MSPH, BSN Honors Faculty Advisor _____________________________ Sylvia D. Torti, PhD Dean, Honors College March 2020 Copyright © 2020 All Rights Reserved Abstract Purpose The purpose of this thesis was to investigate hospital acquired bloodstream infections, in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT), using a subset of data from an ongoing study. The goal of the larger study was to track changes in central line-associated bloodstream infections (CLABSIs), in children with immune-compromised conditions to guide interventions to reduce infection. Background Children undergoing HSCT are a distinct subset of pediatric hematology and oncology patients who are at significant risk for developing CLABSIs due to their extended use of central venous catheters and prolonged immunosuppression. Understanding characteristics of children who developed CLABSIs after HSCT and the organisms involved in these events can help refine strategies to reduce these infections. Methods CLABSI events involving HSCT patients from a single pediatric hospital between January 2006 to June 2019 were reviewed. CLABSI events and their associated characteristics were compared during 1) a 5-year pre-intervention baseline (2006-2010) and 2) following the introduction of CLABSI-reduction interventions (2011 to June 2019). Interventions included the introduction of Children's Hospital Association's best practice bundles in 2011 as well as the addition of structured hygiene supportive cares in 2013. Because the hospital was unable to separate central line days for HSCT patients from the total number of central line days for the unit to provide a comparison of rates, events were descriptively compared between the two periods. Results During the baseline and intervention periods, the unit averaged 32 transplants per year. Twenty-eight CLABSIs involving 25 patients occurred during 2006-10 (average 5.6 CLABSIs/year), and 26 CLABSIs involving 24 patients occurred from 2011- June 2019 (average 3.1 CLABSIs/year). Even though the annual frequency of CLABSI events decreased during the intervention period (t=2.4; p=.04), characteristics of patients who developed CLABSIs and the predominant organisms were similar across both periods. CLABSIs were most frequent among children with leukemia (n=11; 39% in the baseline and n=9; 35% in the intervention period) and in those 0 to 4 years of age (n=17; 61% in the baseline and n=13; 50% in the intervention period). During both time periods, over half (54%) of the patients who developed CLABSIs were neutropenic. The most frequent causative organisms were also similar across both periods and included coagulasenegative staphylococci (baseline n=9; 32%; intervention period n=8; 31%) and Enterococcus species (baseline n=7; 25%; intervention period n=4; 15%). Implications The introduction of structured interventions including best-practice bundles and intensified hygiene cares were successful at decreasing the frequency of CLABSI events. Children who remain at greatest risk for CLABSIs post-HSCT include those less than five years of age and those with leukemia. These data provide guidance for understanding the characteristics of children undergoing HSCT who are at highest risk for CLABSIs. By continuing a safe environment and promoting a culture of patient safety in nursing cares, CLABSI events can be reduced and decreased rates can be maintained. RODRIGUEZ 4 TABLE OF CONTENTS 1. INTRODUCTION 2. BACKGROUND 2.1. BONE MARROW TRANSPLANT INTRO 2.2. HEMATOPOIETIC STEM CELL TRANSPLANTATION PRINCIPLES 2.3. THERAPY BEFORE TRANSPLANTATION & TIMELINE 2.4. TYPES OF HEMATOPOIETIC STEM CELLS TRANSPLANTS 2.4.1. ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANT 2.4.2. UMBILICAL CORD TRANSPLANTATION 2.4.3. ALLOGENEIC PERIPHERAL BLOOD STEM CELL TRANSPLANTATION 2.4.4. AUTOLOGOUS PERIPHERAL BLOOD STEM CELL RESCUE 2.5. LIFE THREATENING COMPLICATIONS AFTER TRANSPLANTATION 2.6. HEALTHCARE-ASSOCIATED INFECTIONS 2.7. CENTRAL VENOUS CATHETER CARE 3. PROJECT PURPOSE 4. METHOD 4.1. DESIGN 4.2. DATA SOURCE 4.3. SETTING 4.4. STUDY SAMPLE 4.5. DATA MANAGEMENT AND ANALYSIS 5. RESULTS 5.1. PARTICIPANT CHARACTERISTICS RODRIGUEZ 5 5.2. ORGANISM CHARACTERISTIC 5.3. DISCUSSION RODRIGUEZ 6 1. INTRODUCTION Hospital acquired bloodstream infections can potentially lead to septicemia, causing a significant increase in mortality and morbidity. Those with a heightened risk for bloodstream infections are immunocompromised patients, such as individuals with a cancer diagnosis or those undergoing hematopoietic stem cell transplant. Because many of these patients will have a central venous catheter as part of their supportive care during treatment they are at heightened risk for central-line associated bloodstream infections (CLABSIs). Data from the CDC confirms that bloodstream infections result in thousands of deaths and billions of dollars spent each year, meaning that something needs to be done to decrease the rate (Scott II, 2009). According to the article, Rapid Reduction of Central Line Infections in Hospitalized Pediatric Oncology Patients Through Simple Quality Improvement Methods, "CLABSIs remain a significant cause of treatment-related morbidity, mortality, and increased healthcare costs in hospitalized patients. Simple interventions such as hand washing, the use of medical practice checklists, and implementing a culture of patient safety can reduce the rate of CLABSIs (Choi et al., 2013). Even though CLABSI rates have decreased, particularly over the past 10 years, they continue to occur in pediatric populations, including those undergoing a hematopoietic stem cell transplant. The purpose of this thesis is to investigate hospital acquired bloodstream infections in pediatric patients who are undergoing hematopoietic stem cell transplantation (HSCT). The data have been collected from an ongoing study led by Lauri A. Linder, PhD, APRN, CPON, starting January of 2006. The goal of the study is to track changes in central line-associated bloodstream infections (CLABSIs), in children and adolescents with immune-compromised conditions. The study uses a descriptive design guided by a practice-based evidence approach that identified the RODRIGUEZ 7 most effective care practices, in normal routine care, with the goal of decreasing the number of bloodstream infections. Data have been collected since 2006 on a 32-bed inpatient unit in a tertiary pediatric hospital, serving children with immunocompromised conditions. The larger purpose guiding the project is to continue to review CLABSIs events and to use these practice-based data to develop new ways to decrease bloodstream infections. Among the strategies that have reduced CLABSI rates in this setting is the addition of formalized supportive cares in addition to the best practice maintenance care bundles (Linder, Gerdy, Abouzelof, & Wilson, 2017). Despite these efforts, however, CLABSIs continue to occur (Linder, Gerdy, Jo, & Wilson, 2018). Among the next steps to refine strategies to reduce CLABSIs is to explore these events among patients with specific medical conditions, with attention to individual patient characteristics, to create targeted interventions that could further prevent or reduce bloodstream infections. Using the data collected by Lauri Linder, investigations took place regarding patterns among bloodstream infections occurring in pediatric patients undergoing HSCT. Characteristics of CLABSI events were explored during two key time periods: 1) pre-intervention baseline (2006-10) and 2) during implementation of best practice bundles plus supportive cares (20112019 Q2). Analysis included description of frequencies regarding CLABSIs during each of these time periods, as well as the clinical characteristics of the patients who developed these events, the organisms involved in the events, and the timing of these events in relation to the patient's HSCT. RODRIGUEZ 8 2. BACKGROUND 2.1 INTRODUCTION TO HEMATOPOIETIC STEM CELL TRANSPLANTION Hematopoietic stem cell transplant (HSCT) is a therapy for patients who have been diagnosed with cancer or other immune-related diseases and whose disease is unlikely to be cured by other treatment options. Because the earliest transplant used cells obtained from the bone marrow and the bone marrow continues to be the primary source of cells for allogeneic transplants, the terms HSCT and bone marrow transplant (BMT) are often used interchangeably. This special treatment involves harvesting hematopoietic stem cells from the bone marrow, peripheral blood, or umbilical cord blood. These cells are then filtered and transfused to the patient from whom they were originally taken (autologous transplant) or donated to another individual (allogeneic transplant). The simple goal of HSCT is to transfuse the healthy bone marrow cells into a patient after their own unhealthy bone marrow has been eradicated and/or to "rescue" the patient by providing a new functioning immune following high doses of chemotherapy and/or radiation to irradiate disease. This myeloid tissue contains erythroid (red blood cells) and leukocyte (white blood cells) precursors, as well as megakaryocytes, cells that shed fragments called platelets (Youngson, 2005). HSCT is used to treat selected malignant and non-malignant hematological disorders. It also has a growing role in the treatment of non-hematological malignancies. HSCT can be used to replace diseased, nonfunctioning, bone marrow with healthy, functioning marrow in conditions such as leukemia, sickle cell anemia, and aplastic anemia. In addition, bone marrow will be replaced to restore normal function after high doses of chemotherapy or radiation are given to treat cancer. HSCT is also capable of preventing further damage from non-malignant RODRIGUEZ 9 genetic diseases processes such as Hurler's syndrome and adrenoleukodystrophy disorder (Shenoy & Boelens, 2015). 2.2 HEMATOPOIETIC STEM CELL TRANSPLANTATION PRINCIPLES The pluripotent stem cell is capable of replicating itself, proliferating, and differentiating into both myeloid and lymphoid cell lines. These stem cells are the main progenitor cells responsible for maintaining hematopoiesis and the immune system through lymphopoiesis. The stem cells used for transplantation are found within the mononuclear fraction of the collected sample. About 35% of patients receive their transplant from a genotypically human lymphocyte antigen (HLA) identical sibling donor and others are being transplanted with marrow grafts obtained from unrelated donors (Norville & Staton, 2014). With the advances in medical sciences, it's now possible to find a compatible donor who is unrelated amongst the registered volunteers. Appropriate cell populations are identified by staining cell surface molecules with a monoclonal antibody (MoAb), which are linked to fluorescent dyes. The CD antigens and the MoAbs that attach to them are assigned CD numbers. Thus, the antibody assay that associates with the identification of these stem cells, which are necessary for engraftment, is the CD34 assay. Transplantation of these stem cells is possible because these cells can be removed from one person through a process known as "harvesting," and infused into the recipient. The stem cells can be harvested from the bone marrow, the peripheral blood, and the umbilical vein of the placenta. If the hematopoietic stem cells are obtained from a related or unrelated donor it is assigned as the allogeneic, and if it's obtained from the patient itself, it is autologous. In special cases the twin is providing the donor stem cell source, and this would be referred to as syngeneic (Nuss, Barnes, Fisher, Olson, & Skeens, 2011). RODRIGUEZ 10 The HLA typing can be accomplished through either a blood test or a buccal swab. Because all the HLA genes are located in close proximity to one another in a single chromosome, they're usually inherited as a package. This means that an individual receives one chromosome carrying the HLA gene from their mother and one from their father. This creates a ¼ chance that two children in a family will receive the same two chromosomes from their parents. When this happens, the children will be HLA identical and will express the same HLA antigens on their cells (Horowitz, 2015). 2.3 THERAPY BEFORE TRANSPLANTATION & TIMELINE It is common practice that children who are undergoing stem cell transplantation receive myeloablative therapy before their infusion, which is also known as conditioning regimen. This is a very intensive, very high-dose combination of chemotherapy. It is designed to destroy any unwanted cell population and suppress the body's immune system (Norville & Staton, 2014). In order for the patient to receive the allogeneic stem cell transplant, effective suppression of the immune system needs to happen to prevent rejection of the donor cells. The actual day of the HSCT is termed "Day Zero." When the patient is admitted to the hospital before transplantation, the days that lead up to and prepare the patient for the procedure are considered negative numbers. After the transplantation occurs and the patient moves forward into recovery, the numbers change to positive, and the counting up begins. The following is a general, basic flow of events related to the HSCT process: - The child is diagnosed with malignant cancer or blood disease - Day -100 to -28: The pediatric patient is identified as requiring a stem cell transplant. The type of transplant (i.e. autologous or allogeneic) necessary to treat the child's disease is also identified. Children receiving autologous transplants will have their own stem cells RODRIGUEZ 11 harvested. Children receiving allogeneic transplant must have their tissue type identified and matched with a suitable donor. Typically, siblings are the donor source. - Day -10 to -1: For children receiving allogeneic transplants, the stem cells are gathered from the selected donor through the use of an intravenous line, special catheter, or from the bone marrow. - Day -10 to -6: admission to the hospital - Day -6 to -1: ablative therapy is done to eradicate the disease to eliminate the immune system so that it will not fight the new stem cells when they are given to the patient. - Day Zero: Day of transplantation occurs. The patient will receive the new stem cells as an intravenous infusion, much like a red blood cell transfusion. The stem cells will migrate to the bone marrow where they engraft, and begin producing new and healthy blood cells. - Day +1 to +30: the goal during these first 30 days is to prevent any lethal infections from developing. Strict protective isolation precautions must be followed. These include being confined to the hospital room, the floor, having limited visitors, and limited to no items brought in from outside. - Day +30: The return of white blood cell count. This begins to allow the child to regain the ability to fight off infections. - Day +30 to +100: Still vulnerable, isolation precautions at home, but several visits to the hospital are required to monitor progress and measure blood count. - Day +100: Seen as graduation, a milestone for recovering stem cell patients, when their immune system begins to fully return. (Norville & Staton, 2014) RODRIGUEZ 12 The long road to Day Zero and then to Day +100 is a difficult journey. The process involving the stem cell process involves molecules of the infused hematopoietic cells that have preferential binding sites on the bone marrow stromal cells. Once in contact with the stromal tissue, the hematopoietic cells engraft and begin replication and differentiation; full engraftment usually occurs 10 to 21 days after the infusion of the stem cell product (Norville & Staton, 2014). The steps are not always this clear and complications arise from the suppressed immune system. 2.4 TYPES OF HEMATOPOIETIC STEM CELLS TRANSPLANTS 2.4.1 ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION Allogeneic hematopoietic stem cell transplant (HSCT) corrects congenital or acquired defects in marrow production, immune function, or both. In other patients it is used to restore hematopoiesis after high dose, myeloablative, cytotoxic therapy (Horowitz, 2015). Allogeneic HSCT differs from solid organ transplant in that organ grafts contain only limited number of cells with immunologic function, and the main concern is preventing rejection by the recipient's immune system. In allogeneic HSCT, the patient receives stem cells from a related or unrelated donor. The transplanted stem cells contain larger numbers of precursors and mature cellular elements that can replace those of the patient's immune system (Norville & Staton, 2014). This means that the immune system in the patient is being restored by the donor's graft. This does bring up a complication of donor cells causing immune-mediated injury in the patient. Graft versus Host Disease (GVHD) is a serious complication of allogeneic stem cell transplantation. GVHD occurs when the donor's T-cells, also known as the graft, view the patient's healthy cells as foreign and attack them until they are damaged or destroyed. Acute GVHD (aGVHD), if it occurs, typically develops within the first 100 days after transplantation. It mainly starts by affecting the skin, the gastrointestinal tract and the liver. RODRIGUEZ 13 Symptoms include rash, burning of the skin, blistering of the skin, nausea, vomiting, abdominal cramping, loss of appetite, diarrhea, and jaundice. Treatment for acute GVHD typically includes corticosteroids. A second type of GVHD is chronic (cGVHD). cGVHD can involves a single organ or multiple organs. Again, main symptoms are abdominal swelling, jaundice, abnormal liver function tests, shortness of breath, chronic cough, nausea, vomiting, diarrhea, loss of hair, rash, change in color of skin, damaged sweat glands, gum disease, tooth decay, muscle weakness, joint stiffness. In order to manage chronic GVHD, the patient must receive a systemic treatment. Both aGVHD and cGVHD are associated with increased morbidity and mortality posttransplant. The severity ranges and as you focus on specific body system, GVHD is classified into grades I-IV. For example, in Grade III Gastrointestinal GVHD, loss of crypt epithelial cells with some ulceration of the gastrointestinal tract occurs. In Grade IV Gastrointestinal GVHD, there is mucosal denudation, which is widespread ulceration with loss of the surface epithelium and crypts (Horowitz, 2015). Unrelated/mismatched allogeneic HSCTs involve transplantation of cells from HLAphenotypically identical unrelated donors for patients who lack a family donor. Unrelated HSCT is possible due to the expansion of registries of HLA-Typed individuals who are willing become donors. Selection is currently based on matching HLA-A, HLA-B, and HLA-DRBI (Nuss et al., 2011). 2.4.2 UMBILICAL CORD TRANSPLANTATION Umbilical cord blood, collected right at birth, contains a larger concentration of stem cells and is another source of cells for allogeneic transplants. The fetus normally generates generous amounts of CD34+ cells in their liver and bone marrow during development. These RODRIGUEZ 14 cells are present in the circulation and therefore, in the umbilical cord. Since cord blood is richer in stem cells compared with peripheral blood or bone marrow, less volume is needed to reconstitute hematopoiesis. Fortunately, the umbilical cord blood also has reduced immunoreactivity, so there is a lower risk that a patient will develop GVHD. The possible explanation to this is a muted immune system that not been educated to attack specific antigens (Nuss et al., 2011). These cord stem cells have a greater capacity for retroviral transduction, making their use "more advantageous than bone marrow" (Norville & Staton, 2014). Another advantage of stem cells in umbilical cord is the absences of diseases such as cytomegalovirus or Epstein-Barr virus, which can be life threatening in the stem cell transplant population. Even though umbilical cord stem cells have several advantageous there are also risks that follow the use of this transplant method. Umbilical cord blood has limited number of nucleated cells which are the precursors of platelets and neutrophils. Therefore, the smaller the total count of nucleated cells in an umbilical cord collection, the more compromised the neutrophil and platelet recovery will be. Overall, recipients of cord blood transplants have delayed neutrophil and platelet recovery, increasing their risk of bleeding and infection (Norville & Staton, 2014). 2.4.3 ALLOGENEIC PERIPHERAL BLOOD STEM CELL TRANSPLANTATION Allogeneic peripheral blood stem cell transplantation (PBSCT) has been considered as an alternative to allogeneic bone marrow. Using PBSCT makes it easier to collect larger numbers of stem cells per harvest. This is usually necessary in the newer immunoablative and adoptive immunotherapy approaches to transplantation. This technique is limited in children because of the donor's requirement to be extremely healthy (Nuss et al., 2011). 2.4.4 AUTOLOGOUS PERIPHERAL BLOOD STEM CELL RESCUE RODRIGUEZ 15 Pediatric patients often use autologous peripheral blood stem cell rescue (PBSCR) for metastatic and recurrent pediatric solid tumors. To be eligible for autologous PBSCR the pediatric patient's tumor must show evidence of chemosensitivity, have a poor prognosis with standard therapy, and convey a steep dose response with traditional chemotherapeutic agents. Stem cells are collected by leukapheresis weeks to months before admissions to PBSCR (Finlay et al., 2008). After high-dose therapy is given, the newly infused stem cells give rise to both a new hematopoietic and immune system. Engraftment typically is faster than with bone marrow transplant and occurs about 7 to 10 days earlier (Nuss et al., 2011). 2.5 LIFE THREATENING COMPLICATIONS AFTER TRANSPLANTATION Most toxicities occur within first 100 days after transplant. Single organ dysfunction can in the post-transplantation period predicts the subsequent development of multiple organ dysfunction. The major complications are usually related to the immunosuppression and associated increased risk of infection. They mainly include GVHD, bacterial infections, fungal infections, CMV infections, idiopathic pneumonitis, and organ dysfunction. Gram negative bacteria, mainly E. coli, Klebsiella, and Pseudomonas species have been the most frequent cause of bacteremia in HSCT patients. Infections can develop as soon as Day 1 and expand to Day 60, and overall up to 1-year post-transplant (Nuss et al., 2011). 2.6 HEALTHCARE-ASSOCIATED INFECTIONS The devices that help treat patients and help them recover are the same ones that contribute to an increased risk of infection. Healthcare-associated infections include central lineassociated bloodstream infections (CLABSI), catheter-associated urinary tract infections, and ventilator-associated pneumonia (Centers for Disease Control and Prevention, 2014). According to the CDC, "CLABSIs results in thousands of deaths each year and billions of dollars added RODRIGUEZ 16 costs to the U.S. healthcare system, yet these infections are preventable" (2014). CLABSIs that occur after a hematopoietic stem cell transplantation are associated with an increased risk of mortality (Dandoy et al., 2016). Central venous catheters, commonly referred to as central lines, are catheters that are placed in large veins to give medications or fluids and to collect blood tests. Since they have access to major veins, which are close to the heart, they are at higher risk of serious infections. A CLABSI develops when pathogens, typically bacteria or fungi, enters the bloodstream through the central line. A CLABSI is defined as primary bloodstream infection occurring in a patient with a central venous catheter and no other attributable cause is identified (CDC, 2019). The most common central venous catheters used in pediatric patients with cancer and those undergoing HSCT are regarded as permanent, meaning they are intended for long term use over a period of at least several months, and are surgically placed. The multi-lumen tunneled CVCs are typically used in patients undergoing HSCT to accommodate the complex supportive care needs associated with the transplant process. Tunneled CVCs are intended only for long term use. They are inserted in the chest wall through a 3-6 in. subcutaneous tunnel, and followed into the jugular or subclavian vein. These lines are typically secured with sutures, which later leads to fibrosis around the catheter, or they can be secured with an IV securing device. Because the catheter is tunneled through the skin before entering the vessel, the risk of infection is less compared with a temporary, percutaneous placed line. Implanted ports are devices made of a radiopaque silicone catheter and a plastic or stainless-steel injection port with silicone septum. The catheter enters the internal jugular vein and is typically tunneled to a completely implanted subcutaneous port in the upper chest. Intended for long-term use, and must be accessed by RODRIGUEZ 17 someone who is specially trained due to the risk of infiltration into the tissue if needle placement is not correct (Bryant, 2018). 2.7 CENTRAL VENOUS CATHETER CARE The CDC has developed guidelines for line placement and guidelines for maintenance care of central venous catheters for healthcare providers to follow. The guidelines also support infection control practices to be followed when changing the dressing or checking the central line following its placement. Among these guidelines to reduce the risk of infection during placement are: performing hand hygiene, apply appropriate skin antiseptic, and ensure the skin prep agent has completely dried before inserting the line. All five maximal sterile barriers need to be used such as sterile gloves, sterile gown, cap, mask, and large sterile drape (Centers for Disease Control & Prevention, 2011). Principles of maintenance care following initial placement include scrubbing the access port if hub with friction immediately prior to each use with an appropriate antiseptic, using only sterile devices to access catheters, and timely replacement of dressings that are wet, soiled, or dislodged. Wash hands with soap and water, and use sterile technique every time a routine dressing change is done. Finally, remove the central line as soon as it is no longer needed (CDC, 2014). Pediatric patients who receive HSCTs face a heightened risk of bloodstream infections. In addition to the potential for pathogens to enter the bloodstream through the central venous catheter, translocation of pathogens across injured mucosal tissue represents an additional mechanism of bloodstream infection. Even though many of these infections are associated with mucosal barrier injury (MBI), they are still reported as hospital-acquired infections (Dandoy & Alonso, 2019). RODRIGUEZ 18 3 PROJECT PURPOSE The purpose of this research project was to investigate CLABSIs in pediatric patients who are undergoing hematopoietic stem cell transplantation (HSCT) and to explore differences in the frequencies and characteristics of CLABSIs following intentional efforts to decrease these infections. The data were collected from an ongoing study led by Lauri A. Linder, PhD, APRN, CPON, starting January of 2006. The goal of the larger study is to characterize CLABSIs occurring in children and adolescents with immunocompromised conditions. The study uses a descriptive design guided by a practice-based evidence approach. A practice-based evidence approach seeks to identify the most effective care practices, in normal routine care (Horn & Gassaway, 2007). The long-term goal of this project is to better identify characteristics of heightened risk for infection to support the development of targeted interventions that could further prevent or reduce bloodstream infections. Characteristics of CLABSI events were explored during two key time periods: 1) preintervention baseline (2006-10) and 2) during the implementation of best practice bundles with supportive cares during the intervention period (2011-2019 Q2). RODRIGUEZ 19 4 METHODS 4.1 DESIGN The study used a descriptive design, guided by a practice-based evidence approach, to compare characteristics of events prior to and following efforts to reduce CLABSI. This study emphasizes the use of data from routine clinical practices to identify trends seen in CLABSIs with an ongoing goal of using the data to guide decision-making for future quality improvement interventions. 4.2 DATA SOURCE Data have been collected since 2006 as part of a project to review CLABSI events and to use these practice-based data to implement and evaluate new strategies to decrease bloodstream infections. Data include the month and year of the CLABSI event, the medical service providing care at the time of the CLABSI, patient demographic and clinical characteristics, and characteristics of the CLABSI event, including the hospital day on which the event occurred and organism(s) involved. Data were organized into two key time periods: a pre-intervention baseline (2006-10) and following the introduction of unit-based efforts to reduce CLABSIs (2011-2019 Q2). Efforts to reduce CLABSIs included implementation of best practice maintenance care bundles recommended by the Children's Hospital Association beginning in 2011. These were followed by the addition of formalized supportive cares in 2013 (Linder et al., 2018). However, despite these efforts, the data acknowledges that CLABSIs continue to occur (Linder et al., 2018). 4.3 SETTING The project setting was a 32-bed inpatient unit in pediatric hospital, in Salt Lake City, Utah, serving children with immunocompromised conditions. The Cancer Transplant Service at RODRIGUEZ 20 Primary Children's Hospital primarily serves children with cancer and those undergoing hematopoietic stem cell transplantation for malignant and non-malignant conditions. The unit also provides care to children who have received liver and kidney transplants. 4.4 STUDY SAMPLE The study sample included all pediatric patients who had been admitted to the Bone Marrow Transplant service and who developed a CLABSI between January 2006 and June 2019. All positive blood culture events were identified and reviewed by Primary Children's Infection Control team. The determination of whether an event met classification as a CLABSI was based on National Health Safety Network criteria that were in place at the time of each event, and all events were reviewed by the hospital's infection prevention team. All CLABSIs, including those designated as MBI events, were included. Because patients undergoing HSCT are only a subset of the larger patient population served by this unit, this project will support exploration of risk factors that may be unique to patients undergoing HSCT relative to other groups of immune compromised patients. 4.5 DATA MANAGEMENT AND ANALYSIS Data from patients meeting inclusion criteria were extracted from the larger data set to support this project. Data were entered in Excel spreadsheets to summarize and compare CLABSI events and their associated characteristics across the study period. Data were then organized to indicate CLABSI occurrence by year and then further grouped into a preintervention baseline period (2006-2010) and an intervention period (2011 through 2019 Q2). RODRIGUEZ 21 5. RESULTS 5.1 PARTICIPANT CHARACTERISTICS Table 1 summarizes demographic and clinical characteristics of pediatric patients admitted to the Bone Marrow Transplant service, who developed CLABSIs during the preintervention baseline period (2006-2010) and the intervention period (2011 to June 2019). Fiftyfour infections among 49 patients met classification of experiencing a CLABSI event according to National Health Safety Network criteria across both time periods. During the pre-intervention baseline period, 25 individual patients developed 28 CLABSIs. During the intervention period 24 patients developed 26 CLABSIs. All of these pediatric patients had double lumen tunneled central venous catheters in place at the time of their CLABSI. The average hospital length of stay at the time of CLABSI was 19 days (median 14; SD=18; range 0-76) during the pre-intervention baseline period and 34 days (median 17; SD=41; range 0-148) during the intervention period. The difference in length of stay at the time of the CLABSI in the pre-intervention baseline vs intervention group was not statistically significant (t= -1.8, p= 0.08) [non- parametric MannWhitney U p= -0.23). RODRIGUEZ 22 TABLE 1: Patient Demographics (Frequencies represent individual patients) Pre - Intervention 2006-2010 n=25 n (%) Intervention 2011-2019 Q2 n=24 n (%) Gender Male 13 (52%) 13 (54%) Female 12 (48%) 11 (46%) 0-4 17 (68%) 13 (54%) 5-9 3 (12%) 5 (22%) 10-14 3 (12%) 2 (8%) 15-19 2 (8%) 2 (8%) 19-24 0 (0%) 2 (8%) Leukemia 11 (44%) 9 (38%) Lymphoma 1 (4%) 1 (4%) Solid Tumor 7 (28%) 5 (21%) Non-Malignant Hematologic Condition 4 (16%) 6 (25%) Other 2 (28%) 3 (12%) No 12 (48%) 9 (38%) Yes 9 (36%) 7 (29%) Not Applicable 4 (16%) 8 (33%) Age (years) Diagnostic Group Relapsed or Refractory Disease RODRIGUEZ 23 Five individuals developed more than one CLABSI, which raises a major concern because developing more than one bloodstream infection increases the risk of mortality for the pediatric HSCT patients (Dandoy et al., 2016). Three patients developed more than one CLABSI during the baseline, pre-intervention (2006-2010) period, and two patients developed more than one CLABSI during the intervention period (2011-2019 Q2). The patients in the pre-intervention period developed infections that consisted of separate causative organisms. Two patients developed the second CLABSI during the same hospital admission, the third patient developed the second CLABSI during separate hospital admissions. Of the two patients who developed more than one CLABSI during the intervention period, the causative organism was the same, suggesting that the infection may not have completely cleared between events. One CLABSI event took place during the same admission the other event took place in a separate hospital admission. Patient characteristics for development of more than one CLABSI are described below (Tables 2 and 3): RODRIGUEZ 24 TABLE 2: Characteristics of patients who developed more than one CLABSI during the preintervention baseline period. Pre - Intervention Baseline (2006 - 2010) Gender Age Diagnosis 1st Infection Male 1 year old Solid Tumor Enterobacter cloacae Female 7 year old Solid Tumor Staphylococcus epidermidis Female <1 year old Benign Pseudomonas hematologic aeruginosa condition Same hospital admission Separate hospital admission Hospital length of stay (days) 0 2nd Infection Hospital length of stay (days) Klebsiella pneumoniae 3 2 Pseudomonas aeruginosa 13 35 Stenotrophomonas maltophilia 46 RODRIGUEZ 25 Table 3: Characteristics of patients who developed more than one CLABSI during the Intervention period (2011- 2019 Q2) Intervention (2011 - 2019 Q2) Gender Age Diagnosis 1st Infection Hospital length of stay (days) 2nd Infection Hospital length of stay (days) Male 22 year old Acute Lymphoblastic Leukemia Pseudomonas aeruginosa 15 Pseudomonas aeruginosa 17 Male <1 year old Immunodeficiency Pantoea spp (MBI 131 organism) Pantoea spp (MBI 148 organism) Same hospital admission Separate hospital admission Next, profound neutropenia was also taken into account with pediatric patients who developed a CLABSI. Neutropenia is characterized by a decrease in the number of white blood cells (WBC). These cells are the body's main defense against infection; indicating that having low amount of WBC's puts the patient at a higher risk of contracting an infection (Linder & McCance, 2019). The established guidelines indicated that anything less than 1,000 neutrophils (a type of WBC) indicated neutropenia. Values less than 500 implied profound neutropenia. Table 4 summarizes presence of neutropenia and profound neutropenia in the pre-intervention baseline period (2006-2010) vs. the intervention period (2011 to June 2019). RODRIGUEZ 26 TABLE 4: Frequencies represent individual infections. There were 54 total infections within the 49 patients. ANC = Absolute Neutrophil Count Pre - Intervention 2006-2010 Intervention 2011-2019 Q2 Number of infections(N)=28 n (%) Number of infections(N)=26 n (%) Neutropenia ANC< 1000 Yes No 15 (54%) 13 (46%) 14 (54%) 12 (46%) 13 14 Profound Neutropenia ANC < 500 Yes Total percentage of neutropenic events in the intervention period was also 54%. From the sample, the percentage of patients who were neutropenic while developing a CLABSI was exactly the same for pre-intervention period and intervention period. 5.2 ORGANISM CHARACTERISTIC Figure 1 summarizes the causative organisms seen in pediatric patients who developed a CLABSI in the pre-intervention vs the intervention period. The numbers convey the individual infections seen during the pre-intervention period (Orange) and intervention (Blue). Although the frequencies decreased, the most common causative organisms across both time periods were coagulase-negative staphylococci and Enterococcus species. Enterobacter species was no longer present during the intervention period. Microorganisms such as E. coli, Lactobacillus, Pantoea, Bacillus cereus, and Leptotrichia became more prevalent during the intervention period, but were not present during pre-intervention. RODRIGUEZ 27 CLABSI Causative Organisms 9 Coagulase-negative staph 8 7 Enterococcus 4 3 Pseudomonas 2 2 Enterobacter 0 2 2 Klebsiella 2 Staph aureus (methicillin sensitive) 1 1 Actinobacillus 0 1 Stenotrophomonas 0 1 1 Viridans group streptococci 0 E. coli 3 0 Lactobacillus 1 0 Pantoea 2 0 Bacillus cereus 1 0 Leptotrichia 1 0 1 2 3 Pre-intervention 4 5 6 7 8 9 Intervention Figure 1: Causative organisms seen in pediatric patients who developed a CLABSI in the preintervention baseline vs the intervention period 10 RODRIGUEZ 28 PRE-INTERVENTION (2006-2010): CAUSATIVE ORGANISMS Viridans group (N=28) Bacillus cereus Lactobacillus 0% 0% Pantoea 0% E. coli Leptotrichia 0% 0% streptococci Stenotrophomonas 3% 4% Actinobacillus 4% Staph aureus (methicillin sensitive) 7% Klebsiella 7% Coagulase-negative staph 32% Enterobacter 7% Pseudomonas 11% Enterococcus 25% Figure 2: Causative organisms responsible for CLABSIs during the pre-intervention baseline period (2006-2010) RODRIGUEZ 29 INTERVENTION (2011- 2019 Q2): CAUSATIVE ORGANISMS (N=26) Leptotrichia 4% Bacillus cereus 4% Pantoea 7% Coagulase-negative staph 31% Lactobacillus 4% E. coli 11% Viridans group streptococci 4% Actinobacillus 0% Stenotrophomonas 0% Enterococcus 15% Pseudomonas Enterobacter 8% 0% Staph aureus (methicillin sensitive) Klebsiella 4% 8% Figure 3: Causative organisms responsible for CLABSIs during the intervention period (20112019 Q2) Figures 4-7 depict both the number of CLABSI infection and those that are also recognized as mucosal barrier injury (MBI) bloodstream infections. In 2013, the CDC added the MBI designation to primary bloodstream infections occurring in patients with neutropenia and/or gastrointestinal GVHD and involve organisms common to the lower gastrointestinal tract, as RODRIGUEZ 30 designated on the CDC's master organism list. While these CLABSI events still remain reportable as hospital acquired infections, the MBI designation indicates that they are most likely attributable to pathophysiologic consequences within the patient rather than actions of the bedside clinician. MBI CAUSATIVE ORGANISMS: PRE- INTERVENTION (N=12) Lactobacillus species Pantoea species 0% Leptotrichia species 0% 0% Enterobacter species 17% E. coli 0% viridans group streptococci 8% Klebsiella species 17% Enterococcus species 58% Figure 4: Causative organisms for MBI bloodstream infections during pre-intervention, baseline period (2006-2010) RODRIGUEZ 31 MBI CAUSATIVE ORGANISMS: INTERVENTION (N=14) viridans group streptococci 7% Pantoea species 14% Leptotrichia species 7% Klebsiella species 14% Lactobacillus species 7% E. coli 22% Enterococcus species 29% Enterobacter species 0% Figure 5: Causative organisms for MBI bloodstream infections during intervention period (2011-2019 Q2) NON-MBI CAUSATIVE ORGANISM: PRE-INTERVENTION (N=16) Actinobacillus 6% Stenotrophomonas maltophilia 6% Staph aureus (methicillin sensitive) 13% Bacillus cereus 0% Coagulase negative staphylococci 56% Pseudomonas species 19% Figure 6: Causative organisms for non-MBI bloodstream infections during pre-intervention, baseline period (2006-2010 RODRIGUEZ 32 NON-MBI CAUSATIVE ORGANISM: INTERVENTION (N=12) Stenotrophomonas maltophilia 0% Actinobacillus 0% Bacillus cereus 8% Staph aureus (methicillin sensitive) 8% Pseudomonas species 17% Coagulase negative staphylococci 67% Figure 7: Causative organisms for non-MBI bloodstream infections during intervention period (2011-2019 Q2) RODRIGUEZ 33 Figure 8 portrays the number of transplants completed per year at Primary Children's Hospital since the inception of its HSCT program. Figure 8: Depicts number of transplants per year at Primary Children's Hospital RODRIGUEZ 34 Total number of infections per year 10 9 9 8 7 6 6 6 5 5 4 5 4 3 4 3 3 2 3 2 2 1 1 1 0 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 Total # of infections per year Figure 9: Depicts the number of CLABSIs (MBI included) per year at Primary Children's Hospital involving patients admitted to the BMT service. Comparison of the graphs illustrate that even though number of transplants are increasing, number of CLABSIs are not. During the pre-intervention baseline (2006-2010) period 159 transplants were performed at Primary Children's Hospital (PCH) with 28 CLABSI events. In the intervention period (2011 - 2019 Q2), 255 transplants were performed at PCH with 26 infections. While the average annual number of transplants was similar during the preintervention and intervention periods (t=-0.04; p=0.97; Mann-Whitney U p=0.94), the average number of infections per year decreased during the intervention period (t=2.40; p=0.035; MannWhitney U p= 0.045). RODRIGUEZ 35 5.3 DISCUSSION This thesis summarizes characteristics of CLABSI events occurring in patients undergoing HSCT at Primary Children's Hospital during 2006-2019 (Q2). The number of CLABSIs per year decreased from pre-intervention baseline period (2006-2010) to the intervention period (2011-2019 Q2). The addition of formalized supportive cares plus bestpractice maintenance care bundles during the intervention period has contributed decreases in CLABSI frequencies. However, mucosal barrier infections (MBI) common to the lower gastrointestinal tract did not decrease. CLABSIs occurred most frequently among patients with hematologic malignancies and those 0 to 4 years of age. However, patients in this age group are at higher risk of developing other medical conditions that are treated with HSCT. Brain tumors, immunodeficiency syndromes, leukemias, and neuroblastomas occur more frequently among children age 4 or younger. As a result, these children comprise a greater underlying proportion of those undergoing HSCT. Additionally, more than half of CLABSIs occurred among patients with neutropenia, a well-established risk factor for infection, at the time of the event. CLABSI rates decreased over the 11-year period, however, the predominant organisms remained similar - coagulase negative Staphylococcus species and Enterococcus species. These decreases demonstrate successful implementation of formalized supportive cares plus bestpractice maintenance care bundles on Bone Marrow Transplant Services. Results also demonstrate the clinical importance of these pathogens as causative organisms. 5.3.1 IMPLICATIONS FOR PRACTICE Project outcomes emphasize the importance of instituting a culture of safety on a bone marrow transplant unit, and fundamental principles of nursing practice to reduce the risk of RODRIGUEZ 36 infection. Results of this thesis provide guidance in directing interventions for future efforts to reduce CLABSIs in pediatric hematology/transplant/oncology patients. Best practice bundles have proven effective at reducing CLABSIs on BMT services, and these interventions require continued emphasis. Supporting both the nursing staff, as well as the family, is essential to the project's success. Overall, the use of evidence-based practice emphasizes the need for more controlled and conscientious interventions targeted at patients undergoing hematopoietic stem cell transplantation, in order to help decrease CLABSIs. 5.3.2 LIMITATIONS A limitation for this project is that Primary Children's Hospital is unable to provide the number of central venous catheter days based on admitting service to support comparison of actual CLABSI rates. As a result, comparisons are based on frequencies of CLABSIs. The data set was unable to distinguish between patients admitted for their initial transplant and those who had been readmitted for posttransplant complications. In addition, the data did not include the specific type of transplant (i.e. autologous, allogeneic related donor) which would have supported exploration of additional risk factors. 5.3.3 FUTURE RESEARCH Additional efforts are necessary to evaluate medical practices and strategies to reduce CLABSIs based on specific type of transplant. Frequencies and rates of CLABSIs in both allogeneic and autologous transplantation need to be thoroughly explored, on a pediatric hematology floor. In addition, it is vital to further assess the impact of ambulatory bloodstream infections in pediatric oncology/stem cell transplant because a large portion of their treatment is increasingly occurring in this setting. According to the Wong et al., 2017, "Pediatric oncology and stem cell transplant population with bloodstreams infections in the ambulatory setting result RODRIGUEZ 37 in significant charges and associated length of stay when these result in hospital admission; charges of approximately $37,000 and a 6-day hospital stay." Further CLABSI investigations should be conducted in oncology ambulatory care settings to develop and implement evidencebased practice strategies that will help decrease the number of developing CLABSIs. 5.3.4 CONCLUSION Results of this study emphasize the success in reducing CLABSIs in pediatric patients when adhering to formalized nursing cares and best practice care bundles. There was a decline in CLABSIs from the baseline pre-intervention period (2006 to 2010) to the intervention period (2011 to 2019 Q2). While strategies to date have shown a decrease in CLABSIs, there is still an ongoing challenge to prevent pediatric patients, on Bone Marrow Transplant Services, from developing these infections. There is need for more specific, targeted interventions, that can provide supportive care to pediatric children who require hematopoietic stem cell transplantation. FUNDING ACKNOWLEDGEMENTS This work of this thesis was supported by funding from the Undergraduate Research Opportunities Program at the University of Utah. The retrospective review of CLABSI events from 2006-10 was supported by a grant from the Utah Organization of Nurse Leaders. RODRIGUEZ 38 References Bryant, R (2018). The child with hematologic or immunologic dysfunction. In Wongs nursing care of infants and children (11th ed). Hockenberry, M. J., & Wilson, D. (eds). (pp. 10201070). St. Louis, MO: Elsevier. Centers for Disease Control and Prevention. (2014). 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