Lauren M. DiBiase

BRCA1 deficient embryonic stem cells display a decreased homologous recombination frequency and an increased frequency of non-homologous recombination that is corrected by expression of a Brca1 transgene

BRCA1 is a nuclear phosphoprotein that has been classified as a tumor suppressor based on the fact that women carrying a mutated copy of the BRCA1 gene are at increased risk of developing breast and ovarian cancer. The association of BRCA1 with RAD51 has led to the hypothesis that BRCA1 is involved in DNA repair. We describe here the generation and analysis of murine embryonic stem (ES) cell lines in which both copies of the murine homologue of the human BRCA1 gene have been disrupted by gene targeting. We show that exogenous DNA introduced into these BRCA1 deficient cells by electroporation is randomly integrated into the genome at a significantly higher rate than in wild type ES cells. In contrast, integration of exogenous DNA by homologous recombination occurs in BRCA1 deficient cells at a significantly lower rate than in wild type controls. When BRCA1 expression is re-established at 5 – 10% of normal levels by introduction of a Brca1 transgene into BRCA1 deficient ES cells, the frequency of random integration is reduced to wild type levels, although the frequency of homologous recombination is not significantly improved. These results suggest that BRCA1 plays a role in determining the response of cells to double stranded DNA breaks.

Reduction of Healthcare-Associated Infections by Exceeding High Compliance with Hand Hygiene Practices

Improving hand hygiene from high to very high compliance has not been documented to decrease healthcare-associated infections. We conducted longitudinal analyses during 2013–2015 in an 853-bed hospital and observed a significantly increased hand hygiene compliance rate (p<0.001) and a significantly decreased healthcare-associated infection rate (p = 0.0066).

Integration of Syndromic Surveillance Data into Public Health Practice at State and Local Levels in North Carolina

Objectives. We sought to describe the integration of syndromic surveillance data into daily surveillance practice at local health departments (LHDs) and make recommendations for the effective integration of syndromic and reportable disease data for public health use. Methods. Structured interviews were conducted with local health directors and communicable disease nursing staff from a stratified random sample of LHDs from May through September 2009. Interviews captured information on direct access to the North Carolina syndromic surveillance system and on the use of syndromic surveillance information for outbreak management, program management, and the creation of reports. We analyzed syndromic surveillance system data to assess the number of signals resulting in a public health response. Results. Syndromic surveillance data were used for outbreak investigation (19% of respondents) and program management and report writing (43% of respondents); a minority reported use of both syndromic and reportable disease data for these purposes (15% and 23%, respectively). Receiving data from frequent system users was associated with using data for these purposes (p=0.016 and p=0.033, respectively, for syndromic and reportable disease data). A small proportion of signals (<25%) resulted in a public health response. Conclusions. Use of syndromic surveillance data by North Carolina local public health authorities resulted in meaningful public health action, including both case investigation and program management. While useful, the syndromic surveillance data system was oriented toward sensitivity rather than efficiency. Successful incorporation of new surveillance data is likely to require systems that are oriented toward efficiency.

Reducing health care-associated infections by implementing a novel all hands on deck approach for hand hygiene compliance.

Hand hygiene is a key intervention for preventing health care-associated infections; however, maintaining high compliance is a challenge, and accurate measurement of compliance can be difficult. A novel program that engaged all health care personnel to measure compliance and provide real-time interventions overcame many barriers for compliance measurement and proved effective for sustaining high compliance and reducing health care-associated infections.

Healthcare-Associated Infections among Patients in a Large Burn Intensive Care Unit: Incidence and Pathogens, 2008–2012

Burn injuries are a common source of morbidity and mortality in the United States, with an estimated 450,000 burn injuries requiring medical treatment, 40,000 requiring hospitalization, and 3,400 deaths from burns annually in the United States. Patients with severe burns are at high risk for local and systemic infections. Furthermore, burn patients are immunosuppressed, as thermal injury results in less phagocytic activity and lymphokine production by macrophages. In recent years, multidrug-resistant (MDR) pathogens have become major contributors to morbidity and mortality in burn patients. Since only limited data are available on the incidence of both device- and nondevice-associated healthcare-associated infections (HAIs) in burn patients, we undertook this retrospective cohort analysis of patients admitted to our burn intensive care unit (ICU) from 2008 to 2012.

Timeline of health care–associated infections and pathogens after burn injuries

BACKGROUND Infections are an important cause of morbidity and mortality after burn injuries. Here, we describe the time line of infections and pathogens after burns. METHODS A retrospective study was performed in a large tertiary care burn center from 2004-2013. Analyses were performed on health care-associated infections (HAIs) meeting Centers for Disease Control and Prevention criteria and on all positive cultures. Incidence rates per 1,000 days were calculated for specific HAI categories and pathogens and across hospitalization time (week 1, weeks 2-3, and week ≥4). RESULTS Among 5,524 patients, the median burn size was 4% of total body surface area (interquartile range, 2%-10%). Of the patients, 7% developed an HAI, of whom 33% had >1 HAI episode. Gram-positive bacteria were isolated earlier, and gram-negative bacteria were isolated later during hospitalization. Of 1,788 bacterial isolates, 44% met criteria for multidrug resistance, and 23% met criteria for extensive drug resistance. Bacteria tended to become increasingly resistant to antibiotics as time from admission increased. CONCLUSIONS We observed differences in infection type, pathogen, and antibiotic-resistant bacterium risk across time of hospitalization. These results may guide infection prevention in various stages of the postburn admission.

Reduction in central line-associated bloodstream infections in patients with burns

2000 Enhanced education of medical staff regarding central lines; addition of 2% chlorhexidine plus 70% isopropyl alcohol for skin preparation to central line kits 2001 Mandatory training for nurses on IV line site care and maintenance 2003 Central line changes over a guidewire every 3 days with use of a new site every 6 days becomes standard practice; use of full body drape for line insertion and changes 2003–2005 Introduction of antibiotic-impregnated central venous catheters for all patients 2004 Enhanced nursing education on central line insertion and maintenance 2005 Customized catheter-insertion kits 2006 Universal glove and gown use for all patient encounters 2007 Implementation of the Institute for Healthcare Improvement bundle to prevent CLABSI 2009 Use of chlorhexidine patch at insertion site

Longitudinal Trends in All Healthcare-Associated Infections through Comprehensive Hospital-wide Surveillance and Infection Control Measures over the Past 12 Years: Substantial Burden of Healthcare-Associated Infections Outside of Intensive Care Units and “Other” Types of Infection

OBJECTIVE Targeted surveillance has focused on device-associated infections and surgical site infections (SSIs) and is often limited to healthcare-associated infections (HAIs) in high-risk areas. Longitudinal trends in all HAIs, including other types of HAIs, and HAIs outside of intensive care units (ICUs) remain unclear. We examined the incidences of all HAIs using comprehensive hospital-wide surveillance over a 12-year period (2001-2012). METHODS This retrospective observational study was conducted at the University of North Carolina (UNC) Hospitals, a tertiary care academic facility. All HAIs, including 5 major infections with 14 specific infection sites as defined using CDC criteria, were ascertained through comprehensive hospital-wide surveillance. Generalized linear models were used to examine the incidence rate difference by infection type over time. RESULTS A total of 16,579 HAIs included 6,397 cases in ICUs and 10,182 cases outside ICUs. The incidence of overall HAIs decreased significantly hospital-wide (-3.4 infections per 1,000 patient days), in ICUs (-8.4 infections per 1,000 patient days), and in non-ICU settings (-1.9 infections per 1,000 patient days). The incidences of bloodstream infection, urinary tract infection, and pneumonia in hospital-wide settings decreased significantly, but the incidences of SSI and lower respiratory tract infection remained unchanged. The incidence of Clostridium difficile infection (CDI) increased remarkably. The outcomes were estimated to include 700 overall HAIs prevented, 40 lives saved, and cost savings in excess of

The Growing Importance of Non-Device-Associated Healthcare-Associated Infections: A Relative Proportion and Incidence Study at an Academic Medical Center, 2008–2012

10 million. CONCLUSIONS We demonstrated success in reducing overall HAIs over a 12-year period. Our data underscore the necessity for surveillance and infection prevention interventions outside of the ICUs, for non-device-associated HAIs, and for CDI.

Evaluation of the implementation of the H1N1 pandemic influenza vaccine in local health departments (LHDs) in North Carolina

Healthcare-associated infections (HAIs) remain a major source of morbidity and mortality in the United States. Overall, 40%–60% of HAIs have been thought to result from device-associated infections with endogenous flora, including central line–associated bloodstream infections (CLA-BSIs), ventilator-associated pneumonia (VAP), and catheter-associated urinary tract infections (CA-UTIs).1 The nosocomial infection surveillance systems managed by the Centers for Disease Control and Prevention (CDC), including the National Nosocomial Infections Surveillance (NNIS) system and, more recently, the National Healthcare Safety Network (NHSN), have long focused on device-associated infections.