Objective: To assess the incidence of healthcare-associated infections (HAI) and the prevalence

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Abstract Objective: To assess the incidence of healthcare-associated infections (HAI) and the prevalence of pathogens across all pediatric units within a single hospital, and trends in pediatric HAI over a 5-year time period for both device and non-device-associated HAI. Setting: Four units within an academic acute tertiary care hospital in the United States: pediatric intensive care unit, newborn critical care center, children s intermediate and cardiac care, and pediatric nursing units. Patients: Hospitalized children (<18 years of age). Methods: Review of prospectively obtained, comprehensive hospital-wide surveillance, 2008-2012, from an 806-bed acute care academic hospital. Surveillance data was obtained by trained infection control professionals using CDC/NHSN criteria for HAI. Results: Over the five-year study period, the leading types of HAI were CLASBI (18.55%), tracheobronchitis (18.03%), and UTI (12.16%). The highest overall infection rate per 1,000 patient-days was in the PICU (11.23), followed by the CICC (4.96), the NCCC (3.87), and the inpatient floors (2.83). The overall infection rate decreased in all pediatric units with the greatest decline in the PICU. The incidence of CLASBI, CAUTI, and UTI decreased significantly, while the incidence of VAP, NVAP, and BSI did not change significantly. From the 954 identified HAI cases, 1131 pathogens were isolated including Staphylococcus aureus (n=156, 13.79%), Escherichia coli (n=104, 9.20%), and Enterococcus sp (n=103, 9.11%). Conclusion: Pediatric HAI decreased in incidence. Future research is needed to determine the interventions that have driven this decline and to better understand the lower relative percentages of antimicrobial-resistant pathogens in pediatric versus adult populations.! "!

Introduction Healthcare-associated infections (HAI) (i.e., infections acquired in a healthcare setting), are a major concern for patient safety and health outcomes among hospitalized patients. These infections, which include bloodstream infections (BSI), urinary tract infections (UTI), pneumonia and respiratory infections, surgical site infections (SSI), and others, are associated with morbidity, mortality, increased length of stay, and increased financial costs for patients. 1 The Centers for Disease Control and Prevention (CDC) reported an estimated 721,800 HAI among 648,000 patients in U.S. acute care hospitals in 2011 although comprehensive child-specific data are not publically available. 2 HAI have received increased attention in recent years and are now viewed within the medical community as a largely preventable public health concern; a recent study found that up to 70% of such infections are reasonably preventable using current evidencebased strategies. 3 However, the majority of research, discussion, and preventative practices have focused on adult patients. Differences in susceptibility to infection and response to preventative measures between adults and children are evident in the differing rates of central line-associated BSI (CLABSI), SSI, ventilator-associated pneumonia (VAP), and catheter-associated UTI (CAUTI) in national data. 4,5 Although several important studies have examined pediatric HAI within a hospital setting, these studies typically focused on a single hospital unit, a single type of infection, or an analysis of prevalence at a single point in time. 6-9 Furthermore, the majority of literature focuses solely on device-associated HAI. Therefore, a comprehensive longitudinal review of HAI (including those that are non-device-associated) within all pediatric units is warranted. The overall goal of this study is to add to the evidence base around pediatric HAI in hopes of better understanding risk factors and effective preventative measures and ultimately reducing future infection within the pediatric hospitalized population. Our specific study aims were to determine: (1) differences in HAI incidence across all pediatric units within a single hospital, (2) prevalence of pathogenic sources of HAI within a single hospital, and (3) trends in pediatric HAI incidence over a 5-year time period for both device and non-device-associated HAI.! "!

Methods This study was conducted at University of North Carolina (UNC) Hospitals, an 806-bed tertiary care facility. During the period analyzed, 2008 through 2012, infection control surveillance was conducted by 5 infection control professionals supervised by 3 full time faculty (DJW, WAR, EES- B). Comprehensive hospital-wide surveillance included all CDC-defined sites and was performed in accordance with CDC/NHSN (National Health Care Safety Network) criteria. This research was approved by the institutional review board of UNC Chapel Hill. The study population was comprised of all patients under 18 years of age hospitalized between 2008 and 2012. There were four pediatric units included in this study: the 20-bed pediatric intensive care unit (PICU), 58-bed newborn critical care center (NCCC), 8-bed children s intermediate and cardiac care (CICC), and 64-bed pediatric nursing unit(s). BSI included both primary infections (i.e., those not related to a secondary site) and secondary infections (i.e., bacteremia associated with infection at another site). In accordance with CDC criteria, primary bloodstream infections were considered central catheter associated if the patient had a catheter in place for more than 48 hours prior to infection and a secondary site of infection was not identified. Respiratory infections included pneumonia, empyema, and other infections of the respiratory tract; tracheobronchitis was reported separately. Pneumonia was categorized as ventilator-associated if the patient had been intubated and received ventilation for more than 48 hours prior to the development of pneumonia; otherwise, it was considered hospital acquired (i.e. non-ventilator associated) pneumonia (NVAP). Sources for identification of HAI included laboratory reports of positive culture results, results of serological testing or molecular tests (e.g., polymerase chain reaction), morbidity and mortality conferences, autopsies, and reports of infections from clinics and physicians (such as SSI). Infections with an onset 48 or more hours after admission were considered to be healthcareassociated. For patients who moved from one hospital location to another, infections that! "!

developed within 48 hours after admission to a new unit were categorized as occurring in the previous unit. Cases were entered into a computerized database after having been reviewed by a nurse supervisor and a physician who specialized in infectious diseases and critical care medicine. Data available from this prospectively maintained database include the patient s name, age, sex, admission date, date of infection onset, hospital location, site of infection, presence of indwelling device(s), and infecting pathogen(s). The antimicrobial susceptibilities of the infecting pathogens were recorded on patient case forms but were not entered into the computerized database, with the exception of methicillin-resistant S. aureus (MRSA), vancomycin resistant Enterococcus (VRE) species, and multi-drug resistant Pseudomonas aeruginosa (MDRPA). Only pathogens associated with nosocomial infections that met CDC criteria were included in our database (i.e., patients who were colonized but not infected were not included in this study). The infection rate was defined as the number of nosocomial infections per 1,000 patient days. Device associated infection rates were calculated as the number of device associated infections for a specified body site per 1,000 device-days. The device utilization ratio was calculated as the number of device-days per number of patient-days. Preliminary analyses were conducted in Excel, and SAS software was used for subsequent analyses of trend-lines and statistical significance. The study did not assess specific infections by unit and year due to the instability of the data due to small numerators. Results This study utilized data from the children s units at UNC Hospitals. During the five-year period of the study, there were 6,179 total reported HAI at UNC Hospitals. Of these, 15.44% (954) were in pediatric patients.! "!

Infection Rates across Units Over the full five-year study period, the leading types of HAI were CLASBI (18.55%), tracheobronchitis (18.03%), and UTI (12.16%). VAP (8.81%) and CAUTI (7.02%) also comprised a sizeable percentage of total infections. One-sixth of infections (16.67%) were an assortment of other less-common infections including gastroenteritis, conjunctivitis, and meningitis. (Table 1) Over the study period, the highest overall infection rate per 1,000 patient-days was in the PICU (11.23), followed by the CICC (4.96), the NCCC (3.87), and the nursing units (2.83). The highest rates of both CLASBI (3.35 per 1,000 central line-days) and BSI (0.33 per 1,000 patient-days) were in the CICC. The highest rates of both CAUTI (4.01 per 1,000 catheter days) and UTI (0.94 per 1,000 patient days) were in the PICU. The highest rate of VAP (4.19 per 1,000 ventilator days) was in the NCCC while the highest non-device pneumonia rate (0.45 per 1,000 patient days) was in the PICU. The rate of tracheobronchitis was higher in the PICU (3.66 per 1,000 patient days) than the other units included in this study. The PICU and the nursing units saw the highest rates of SSI (0.64 and 0.45 per 1,000 patient days, respectively). (Table 2). Pathogenic Source of Infection From the 954 HAI cases identified over the study period, 1131 pathogens were isolated and reported, averaging 1.19 pathogens per infection. The most predominant pathogenic sources of infection were Staphylococcus aureus (n=156, 13.79%), Escherichia coli (n=104, 9.20%), Enterococcus sp (n=103, 9.11%), coagulase negative staphyloccocus (n=101, 8.93%), and Pseudomonas aeruginosa (n=96, 8.49%). Figure 1 shows the top ten pathogens responsible for HAI at the study site over the five-year period. Antimicrobial-resistant pathogens accounted for 7.69% of all identified pathogens in this study. Overall, 48.72% (n=76) of Staphylococcus aureus infections were oxacillin-resistant pathogens. Nearly one-tenth (9.71%, n=10) of Enterococcus species were resistant to vancomycin. Of 96 identified Pseudomonas aeruginosa pathogens, 1.05% (n=1) was multi-drug resistant.! "!

For respiratory infections, the most predominant pathogens were Staphylococcus aureus (17.69%, n=72), Pseudomonas aeruginosa (12.53%, n=51), and Enterobacter cloacae (8.11%, n=33). A notable difference between device and non-device infections was seen in Escherichia coli, which was responsible for nearly four times as many infections in non-device respiratory infections (5.96%) compared to device infections (1.64%). For bloodstream infections, the most predominant pathogens were coagulase negative staphylococcus (21.24%, n=55), Enterococcus species (14.67%, n=38), and Staphylococcus aureus (11.20%, n=29). Coagulase negative staphylococcus was the leading cause of bloodstream infection for both CLASBI and BSI. For urinary tract infections, the most predominant pathogens were Escherichia coli (23.30%, n=48), Enterococcus species (20.39%, n=42), and Candida species (10.68%, n=22). The pathogenic trends for device and non-device urinary tract infections were largely similar, although Candida was responsible for three times as many CAUTI compared to non-device UTI. For SSI, Staphylococcus aureus (19.79%, n=19), Escherichia coli (16.67%, n=16), and coagulase negative staphylococcus (12.50%, n=12) were the leading causing of infection. (Table 3) Longitudinal Trends and Devices The overall patient infection rate decreased over the five-year study period in all pediatric units. The greatest decrease was seen in the PICU, where incidence declined 42.00% from 2008 to 2012 (p<0.01). This was followed by the NCCC, nursing units and CICC. As seen in Figure 2, over the five-year study period, the incidence of CLASBI and CAUTI decreased significantly. The incidence rate difference was -1.83 per 1,000 central-line days (p=0.02) and -1.69 per 1,000-catheter days (p=0.02). The incidence of UTI also decreased by -0.45 infections per 1,000 patient days (p=0.05). The incidence of VAP (-3.11 per 1000 ventilator days, p=0.11), NVAP (-0.11 infections per 1,000 patient days, p=0.12), and BSI (+0.10 infections per 1,000 patient days, p=0.24) did not change significantly over the same period. Over the fiveyear period, the percentage of total bloodstream infections that were non-device related grew! "!

from 10.45% in 2008 to 40.00% in 2012 and the percentage of total pneumonia infections that were non-device rated grew from 26.32% to 38.89%. Discussion This study is the largest and most comprehensive assessment of pediatric HAI in the published literature. The study aimed to determine (1) differences in HAI incidence across all pediatric units within a single hospital, (2) prevalence of pathogenic sources of HAI within a single hospital, and (3) trends in pediatric HAI incidence over a 5-year time period for both device and non-deviceassociated HAI. In analyzing five years of data from an academic hospital, we found that pediatric HAI trends have largely aligned with trends seen in the adult population, with several notable exceptions (detailed below). As expected, given the different patient populations and disease burdens, we found that HAI incidence varied substantially among the four pediatric hospital units. Considering all infections together, the highest incidence per 1,000 patient days was seen in the PICU, followed by the CICC, the NCCC, and the inpatients floors. This study supports previous research that found high HAI rates within pediatric intensive care units. 9,10 The PICU rate was nearly four-times higher than the rate among the nursing units, and this is likely due to greater severity of disease and immune deficiencies, and more frequent and lengthy device usage in the PICU. Per the data in Table 3, compared to all other pediatric units, the PICU had the highest device utilization ratio (ratio of device days to total patient days) for Foley-days, central line-days, and ventilator-days. Although device-associated infections are decreasing, devices still carry a substantial risk for HAI; high PICU infection rates are therefore unsurprising and attention to reducing these rates is needed. The study further demonstrated that the top ten pathogenic sources of infection make up more than three-fourths of all identified pathogens. Of the top four pathogens, three were Gram-positive cocci (Staphylococcus aureus, Enterococcus sp, Staphylococcus coagulase negative) and one was Gram-negative (E. coli). Of the remaining six pathogens, three were nonenteric pathogens! "!

(Pseudomonas aeruginosa, Candida sp, Clostridium difficile) and three were enteric pathogens (Enterobacter cloacae, Klebsiella pneumoniae, Serratia marcescens). The study found that HAI declined among the study population in all four units over the five-year period. That CLASBI and CAUTI declined significantly is a promising finding, since critically ill pediatric patients frequently require device intervention, and it suggests that such devices may not increase the risk of infection as greatly as in the past. However, the lack of significant decline in VAP (which comprised nearly 9% of infections within the study population) indicates that a focus on infection prevention in the PICU and NCCC (the two units in which ventilators are utilized) is needed. Although UTI rates declined significantly over the five-year period, incidence rates of non-device pneumonia and BSI have remained stagnant. Compared to overall patient data from the CDC s National Healthcare Safety Network (NHSN), which tracks device-associated HAI nationally, pathogenic sources of HAI among this pediatric population are quite similar. 11 Although the rank order differs slightly, the top eight pathogens among both patient populations are identical. However, patterns of antimicrobial-resistance differed. 11 Compared with NHSN, the pediatric population at UNC had lower relative percentages of overall drug-resistant pathogenic isolates (20% vs. 7.69%, respectively), oxacillin resistance among Staphylococcus aureus (56.2% vs. 48.7%, respectively), vancomycin resistance among Enterococcus species (33.3% vs. 9.7%, respectively), and multi-drug resistance among Pseudomonas aeruginosa (>6.0% vs. 1.1%, respectively). 11 Small numbers did not allow for statistical analysis of multi-drug resistance by individual unit, but previous research has found minimal differences in resistance trends among hospital units. 11 The five-year pediatric infection trends differ from previously published trends found among the general patient population over the same time period within the same hospital. 12 In both populations, HAI rates saw rapid declines from 2008-2012, driven by declines in deviceassociated HAI. 12 However, the general population saw significant declines in all device-! "!

associated HAI, including VAP, while this infection did not decline significantly among pediatric patients. Further research is needed to understand why the decline in VAP among adult patients has not carried over to children. Additionally, the general population saw no significant changes in infection rates for any non-device HAI, while the pediatric population saw a significant decline in UTI. An exploration of interventions enacted among pediatric units during this timeframe may help determine UTI-reduction strategies that can be applied to an adult patient population. For both populations, device-associated infection incidence remains notably higher than incidence of nondevice infections, but this gap is narrowing as device-associated infections decline more rapidly. 12 The study was strengthened by its large patient population, inclusion of data from all pediatric units within a single hospital over five years, and use of surveillance data from trained infection prevention specialists. The inclusion of nursing unit data here is notable because most literature does not include a focus on these units, despite the presence of infection. Furthermore, the inclusion of five years of data from a single location allows for a temporal analysis that cannot be conducted from the CDC s NHSN data alone. The inclusion of pathogenic data and breakout by device and non-device HAI adds to the existing literature base around pediatric HAI. Study results are limited in that they come from a single academic site and longitudinal data is over only five years, resulting in some small sample sizes. Larger samples sizes would have allowed us to assess specific infections by unit and year, and compare infection-specific longitudinal trends among units. As healthcare-associated infections persist and a focus on hospital epidemiology continues to build, the need for pediatric-specific data and prevention plans will be of greater importance. The CDC s NHSN is the nation s most widely used healthcare-associated infection tracking system with data from more than 12,000 medical facilities, but pediatric reporting is very limited. 13,14 Greater surveillance and reporting for pediatric patients, including specific breakout of drugresistant pathogenic isolates in children, would increase the sample size for analyses and allow for better understanding of the disease burden of pediatric HAI. There is also a need for! "!

increased focus on non-device HAI among both pediatric and general patient populations. Although device-associated HAI continue to comprise the majority of infections, this balance is shifting as device-associated infections decline more rapidly and non-device infections remain relatively stable. 10 Declines in device-associated HAI in adult patients have been largely driven by the introduction of device-focused guidelines, bundles, and new technologies, as well as a focus in traditional surveillance on device-associated infections, but it is unclear whether these are sufficient for infection reduction in children as well. 10,12, 15 Research on prevention of both device and non-device infections should be undertaken in pediatric and adult populations. Finally, there is a need for pediatric-specific HAI definitions and quality control programs. Current definitions from the CDC and NHSN are nearly identical for children and adults, despite known differences in susceptibility and prevention. 9,16 Existing quality control efforts such as the Surgical Care Improvement Project, a national effort from the Joint Commission to reduce post-surgical complications, apply only to patients 18 and older. Comparable programs are needed for pediatric patients. Increased funding and research are key when considering pediatric HAI, because the disease burden is high while the knowledge base remains thin. Pediatric patients are a unique population, and several of the findings in this study highlight differences between this population and a general patient population in regard to longitudinal infection trends and patterns of pathogenic resistance. Further reductions in pediatric HAI are undeniably important and with targeted research, increased knowledge and pediatric-specific guidelines unquestionably possible. Acknowledgments I am grateful for the generous support of Dr. David J. Weber, Dr. Tamar Ringel-Kulka, Dr. William Rutala, Dr. Emily Sickbert-Bennett, and Lauren M. DiBiase, from the Division of Infectious Diseases, the Department of Hospital Epidemiology, and the Department of Maternal and Child Health at the University of North Carolina, Chapel Hill, NC. Their feedback, analyses, and expertise were invaluable throughout the process of writing this paper.! "#!

References 1. Haley RW, Schaberg DR, Crossley KB, Von Allmen SD, McGowan JE. Extra charges and prolongation of stay attributable to nosocomial infections: a prospective interhospital comparison. Am J Med. 1981;70:51-58. 2. Magill SS, Edwards JR, Bamberg W, et al. Multistate point-prevalence survey of health care associated infections. N Engl J Med. 2014;370(13):1198-1208. 3. Umscheid CA, Rajender Agarwal MD M, Kendal Williams MD M, Brennan PJ. Estimating the proportion of healthcare-associated infections that are reasonably preventable and the related mortality and costs. Infect Control Hosp Epidemiol. 2011;32(2):101-114. 4. Foster CB, Sabella C. Health care associated infections in children. JAMA. 2011;305(14):1480-1481. 5. Harris JS. Pediatric Nosocomial Infections: Children Are Not Little Adults. Infect Control Hosp Epidemiol. 1997 Nov;18(11):739-742. 6. Wisplinghoff H, Seifert H, Tallent SM, Bischoff T, Wenzel RP, Edmond MB. Nosocomial bloodstream infections in pediatric patients in United States hospitals: epidemiology, clinical features and susceptibilities. Pediatr Infect Dis J. 2003;22(8):686-691. 7. Richards MJ, Edwards JR, Culver DH, Gaynes RP. Nosocomial infections in pediatric intensive care units in the United States. Pediatrics. 1999;103(4):e39-e39. 8. Sohn AH, et al. Prevalence of nosocomial infections in neonatal intensive care unit patients: results from the first national point-prevalence survey. J Pediatr. 2001 Dec;139(6):821-7. 9. Gravel D, Matlow A, Ofner-Agostini M, Loeb M, et al. A point prevalence survey of health care associated infections in pediatric populations in major Canadian acute care hospitals. Am J Infect Control. 2007 Apr;35(3):157-62. 10. National Nosocomial Infections Surveillance System. National nosocomial infections surveillance (NNIS) system report, data summary from January 1992 through June 2004, issued October 2004. Am J Infect Control. 2004;32(8):470-485! ""!

11. Hidron AI, Edwards JR, Patel J, et al. NHSN annual update: antimicrobial-resistant pathogens associated with healthcare-associated infections: annual summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2006-2007. Infect Control Hosp Epidemiol. 2013;34(1):1-14. 12. DiBiase LM, Weber DJ, Sickbert-Bennett EE, Anderson DJ, Rutala WA. The growing importance of non-device-associated healthcare-associated infections: a relative proportion and incidence study at an academic medical center, 2008-2012. Infect Control Hosp Epidemiol. 2014 Feb;35(2):200-2. doi: 10.1086/674847. Epub 2014 Jan 8. 13. Centers for Disease Control and Prevention. About NHSN. November 2013. Available at http://www.cdc. gov/nhsn/about.html. Accessed March 28, 2014. 14. Dudeck MA, Weiner LM, Allen-Bridson K, et al. National Healthcare Safety Network (NHSN) report, data summary for 2012, device-associated module. Am J Infect Control. 2013;41 (12): 1148-1166. 15. Miller MR, Griswold M, Harris JM II, et al. Decreasing PICU catheter-associated bloodstream infections: NACHRI's quality transformation efforts. Pediatrics. 2010;125(2):206-213 16. Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health careassociated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control. 2008;36(5):309-332.! "#!

Tables Table 1: Frequency of HAI by Type and Year, % (N), among pediatric inpatients at UNC Hospitals, 2008 2012 2008 2009 2010 2011 2012 Total CLABSI 25.42 (60) 18.81 (38) 21.47 (35) 13.27 (26) 11.46 (18) 18.55 (177) BSI 2.97 (7) 2.48 (5) 4.91 (8) 3.06 (6) 7.64 (12) 3.98 (38) VAP 11.86 (28) 9.41 (19) 5.52 (9) 8.67 (17) 7.01 (11) 8.81 (84) NVAP 4.24 (10) 5.45 (11) 4.29 (7) 2.55 (5) 4.46 (7) 4.19 (40) TRACHEOBRONCHITIS 13.14 (31) 18.32 (37) 22.70 (37) 20.92 (41) 16.56 (26) 18.03 (172) OTHER RESPIRATORY TRACT INFECTION 0.00 (0) 0.99 (2) 1.84 (3) 5.10 (10) 1.27 (2) 1.78 (17) SSI - SUPERFICIAL 2.97 (7) 5.45 (11) 3.68 (6) 2.55 (5) 3.82 (6) 3.67 (35) SSI - DEEP 0.42 (1) 0.99 (2) 1.84 (3) 3.06 (6) 1.91 (3) 1.57 (15) SSI - ORGAN/SPACE 0.85 (2) 5.45 (11) 3.07 (5) 5.10 (10) 3.82 (6) 3.56 (34) CAUTI 8.90 (21) 6.44 (13) 7.98 (13) 5.61 (11) 5.73 (9) 7.02 (67) UTI 15.25 (36) 12.87 (26) 10.43 (17) 11.73 (23) 8.92 (14) 12.16 (116) OTHER 13.98 (33) 13.37 (27) 12.27 (20) 18.37 (36) 27.39 (43) 16.67 (159) Total 100% (236) 100% (202) 100% (163) 100% (196) 100% (157) 100% (954) Key: CLABSI, central line-associated bloodstream infections; BSI, bloodstream infections; VAP, ventilator-associated pneumonia; NVAP, non-ventilator-associated pneumonia, SSI, surgical site infections, CAUTI, catheter-associated urinary tract infection; UTI, urinary tract infections.! "#!

Table 2: Frequency (N) and infection rate of HAI by type and unit in pediatric inpatients at UNC Hospitals, 2008 2012 PICU CICC NCCC NU Total CLABSI (N) 41 17 42 77 177 BSI (N) 4 4 23 7 38 VAP (N) 32 0 52 0 84 NVAP (N) 12 2 16 10 40 TRACHEOBRONCHITIS (N) 97 9 45 21 172 OTHER RESPIRATORY TRACT INFECTION (N) 2 4 4 8 18 SSI SUPERFICIAL (N) 5 2 11 17 35 SSI DEEP (N) 1 0 1 13 15 SSI - ORGAN/SPACE (N) 11 1 8 14 34 CAUTI (N) 42 0 4 21 67 UTI (N) 25 5 54 32 116 OTHER (N) 26 16 59 57 158 Total (N) 298 60 319 277 954 Total Patient Days 26525 12107 82354 97915 218901 OVERALL PATIENT DAY INFECTION RATE (PER 1,000 PATIENT DAYS) 11.23 4.96 3.87 2.83 4.36 BSI (PER 1,000 PATIENT DAYS) 0.15 0.33 0.28 0.07 0.17 NVAP (PER 1,000 PATIENT DAYS) 0.45 0.17 0.19 0.10 0.18 UTI PER (1,000 PATIENT DAYS) 0.94 0.41 0.66 0.33 0.53 Total Central Line Days 18037 5076 24455 43557 91125 CLABSI RATE (PER 1000 CENTRAL LINE DAYS) 2.27 3.35 1.72 1.77 1.94 Total Foley Days 10481 * 1180 6002 17663 CAUTI RATE (PER 1000 FOLEY CATHETER DAYS) 4.01 * 3.39 3.50 3.79 Total Ventilator Days 13991 * 12399 * 26390 VAP RATE (PER 1000 VENTILATOR DAYS) 2.29 * 4.19 * 3.18 *Device is not utilized within this unit KEY: PICU, pediatric intensive care unit; CICC, children s intermediate and cardiac care; NCCC, newborn critical care center, NU, nursing units; CLABSI, central line-associated bloodstream infections; BSI, bloodstream infections; VAP, ventilator-associated pneumonia; NVAP, nonventilator-associated pneumonia, SSI, surgical site infections, CAUTI, catheter-associated urinary tract infection; UTI, urinary tract infections! "#!

Table 3: Pathogenic isolates by infection type and device association, % (n), in pediatric inpatients at UNC Hospitals, 2008 2012 Total Rank Staphylococcus aureus* 1 Escherichia coli 2 Enterococcus sp* 3 Staphylococcus coagulase negative 4 Pseudomonas aeruginosa* 5 Enterobacter cloacae 6 Klebsiella pneumoniae 7 Overall BSI UTI Respiratory SSI Other Total % Nondevice Non- (n) Device Total Device device Total Device Non-device Total Total Total 13.79 19.79 18.40 (156) 9.35 (20) 20.00 (9) 11.20 (29) 1.33 (1) 3.82 (5) 2.91 (6) 17.21 (21) 17.89 (51) 17.69 (72) (19) (30) 9.20 16.67 (104) 4.67 (10) 11.11 (5) 5.79 (15) 25.33 (19) 22.14 (29) 23.30 (48) 1.64 (2) 5.96 (17) 4.67 (19) (16) 3.68 (6) 9.11 (103) 16.36 (35) 6.67 (3) 14.67 (38) 13.33 (10) 24.43 (32) 20.39 (42) 1.64 (2) 2.46 (7) 2.21 (9) 7.29 (7) 3.68 (6) 8.93 (101) 20.09 (43) 26.67 (12) 21.24 (55) 4.00 (3) 2.29 (3) 2.91 (6) 3.28 (4) 2.46 (7) 2.70 (11) 12.50 (12) 10.43 (17) 8.49 (96) 6.54 (14) 0.00 (0) 5.41 (14) 6.67 (5) 6.87 (9) 6.80 (14) 12.30 (15) 12.63 (36) 12.53 (51) 7.29 (7) 6.13 (10) 6.19 (70) 7.94 (17) 4.44 (2) 7.34 (19) 2.67 (2) 5.34 (7) 4.37 (9) 13.93 (17) 5.61 (16) 8.11 (33) 5.21 (5) 2.45 (4) 5.92 (67) 7.01 (15) 4.44 (2) 6.56 (17) 8.00 (6) 8.4 (11) 8.25 (17) 5.74 (7) 6.67 (19) 6.39 (26) 6.25 (6) 0.61 (1) 5.39 Candida sp 8 (61) 9.35 (20) 2.22 (1) 8.11 (21) 18.67 (14) 6.11 (8) 10.68 (22) 1.64 (2) 1.75 (5) 1.72 (7) 3.13 (3) 4.91 (8) Clostridium 5.04 34.97 difficile 9 (57) 0.00 (0) 0.00 (0) 0.00 (0) 0.00 (0) 0.00 (0) 0.00 (0) 0.00 (0) 0.00 (0) 0.00 (0) 0.00 (0) (57) Serratia 4.07 marcescens 10 (46) 4.21 (9) 2.22 (1) 3.86 (10) 2. 67 (2) 0.76 (1) 1.46 (3) 7.38 (9) 6.67 (19) 6.88 (28) 3.13 (3) 1.23 (2) 23.87 18.75 13.50 Other** (270) 14.49 (31) 22.22 (10) 15.83 (41) 17.33 (13) 19.85 (26) 18.93 (39) 35.25 (43) 37.89 (108) 37.10 (151) (18) (22) 100% 100% 100% 100% 100% 100% 100% 100% 100% 100% 100% 100% Total (1131) (214) (45) (259) (75) (131) (206) (122) (285) (407) (96) (163) *Includes antimicrobial-resistant pathogens **Rhinovirus/Enterovirus, gram negative rods, Stenotrophomonas maltophilia, Klebsiella oxytoca, RSV, Proteus mirabilis, Enterobacter aerogenes, Beta streptocococcus group b, Citrobacter sp, Haemophilus influenzae, influenza, Acinetobacter, Torulopsis glabrata, Streptococcus viridans group, Streptococcus sp, Bacillus cereus, Parainfluenza, diphtheroids, Moraxella catarrhalis, Klebsiella sp, rotavirus, Streptococcus agalactiae, parvovirus, Asperigillus fumagatus, Lactobacillus sp, Stomatococcus mucilaginosus, yeast, Acrhomobacter sp, Bacteriodes fragilis, Chlamydia trachomatis, Clostridium butyricum, Neisseria sp (saprophytic strain), Staphylococcus epidermis, Streptococcus mitis!! "#!

Figures Figure 1: Number of identified pathogenic isolates 180 160 140 120 100 80 60 40 20 0 156 STAPHYLOCOCCUS AUREUS Ten pathogenic sources of infection in pediatric inpatients at UNC Hospitals, 2008 2012 104 103 101 96 ESCHERICHIA COLI ENTEROCOCCUS SP STAPHYLOCOCCUS COAGULASE NEGATIVE PSEUDOMONAS AERUGINOSA 70 ENTEROBACTER CLOACAE 67 61 57 KLEBSIELLA PNEUMONIAE CANDIDA SP CLOSTRIDIUM DIFFICILE 46 SERRATIA MARCESCENS Figure 2: Incidence of device-associated and non-device-associated infections in pediatric inpatients with 5-year trend lines at University of North Carolina (UNC) Hospitals, 2008 2012. Infection Rate per 1000 Days at Risk 6.00 5.00 4.00 3.00 2.00 1.00 0.00 Non-device-associated pneumonia and ventilator-associated pneumonia rates per 1,000 days at risk, pediatric inpatients, UNC Hospitals, 2008 2012 p=0.11 2008 2009 2010 2011 2012 NVAP PER 1,000 PATIENT DAYS p=0.12 VAP RATE PER 1,000 VENTILATOR DAYS! "#!

Infection Rate per 1,000 Days at Risk 3.50 3.00 2.50 2.00 1.50 1.00 0.50 0.00 Non-device-associated bloodstream infection and central line associated bloodstream infection rates per 1,000 days at risk, pediatric inpatients, UNC Hospitals, 2008 2012 p=0.02 p=0.24 2008 2009 2010 2011 2012 BSI PER 1,000 PATIENT DAYS CLABSI RATE PER 1,000 CENTRAL LINE DAYS Non-device-associated urinary tract infection and catheterassociated urinary tract infection rates per 1,000 days at risk, pediatric inpatients, UNC Hospitals, 2008 2012 Infection Rate per 1,000 Days at Risk 6.00 5.00 4.00 3.00 2.00 1.00 0.00 p=0.02 p=0.05 2008 2009 2010 2011 2012 UTI PER 1,000 PATIENT DAYS CAUTI RATE PER 1,000 FOLEY CATHETER DAYS! "#!