Characterizing healthcare personnel attitudes toward receipt of a voluntary bivalent COVID-19 booster vaccine during a COVID-19 outbreak at a behavioral health hospital in Connecticut.

COVID-19 vaccine uptake in healthcare personnel (HCP) is poor. A cross-sectional survey study of behavioral health HCP was performed. Commonly identified reasons for vaccination were protecting others and oneself. Reasons against were a lack of perceived protection, dosing intervals, and side effects. Assessing vaccination attitudes can assist in uptake strategy.

Novel Approaches to Multidrug-Resistant Infections in Cystic Fibrosis.

Patients with cystic fibrosis (CF) often develop respiratory tract infections with pathogenic multidrug-resistant organisms (MDROs) such as methicillin-resistant Staphylococcus aureus, and a variety of gram-negative organisms that include Pseudomonas aeruginosa, Burkholderia sp., Stenotrophomonas maltophilia, Achromobacter xylosoxidans, and nontuberculous mycobacteria (NTM). Despite the introduction of new therapies to address underlying cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction, MDRO infections remain a problem and novel antimicrobial interventions are still needed. Therapeutic approaches include improving the efficacy of existing drugs by adjusting the dose based on differences in CF patient pharmacokinetics/pharmacodynamics, the development of inhaled formulations to reduce systemic adverse events, and the use of newer beta-lactam/beta-lactamase combinations. Alternative innovative therapeutic approaches include the use of gallium and bacteriophages to treat MDRO pulmonary infections including those with extreme antibiotic resistance. However, additional clinical trials are required to determine the optimal dosing and efficacy of these different strategies and to identify patients with CF most likely to benefit from these new treatment options.

Reducing MRSA Infection in a New NICU During the COVID-19 Pandemic.

BACKGROUND AND OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) is prevalent in most NICUs, with a high rate of skin colonization and subsequent invasive infections among hospitalized neonates. The effectiveness of interventions designed to reduce MRSA infection in the NICU during the coronavirus disease 2019 (COVID-19) pandemic has not been characterized. METHODS: Using the Institute for Healthcare Improvement's Model for Improvement, we implemented several process-based infection prevention strategies to reduce invasive MRSA infections at our level IV NICU over 24 months. The outcome measure of invasive MRSA infections was tracked monthly utilizing control charts. Process measures focused on environmental disinfection and hospital personnel hygiene were also tracked monthly. The COVID-19 pandemic was an unexpected variable during the implementation of our project. The pandemic led to restricted visitation and heightened staff awareness of the importance of hand hygiene and proper use of personal protective equipment, as well as supply chain shortages, which may have influenced our outcome measure. RESULTS: Invasive MRSA infections were reduced from 0.131 to 0 per 1000 patient days during the initiative. This positive shift was sustained for 30 months, along with a delayed decrease in MRSA colonization rates. Several policy and practice changes regarding personnel hygiene and environmental cleaning likely contributed to this reduction. CONCLUSIONS: Implementation of a multidisciplinary quality improvement initiative aimed at infection prevention strategies led to a significant decrease in invasive MRSA infections in the setting of the COVID-19 pandemic.

A mixed-methods evaluation on the efficacy and perceptions of needleless connector disinfectants.

OBJECTIVE: Optimizing needleless connector hub disinfection practice is a key strategy in central-line-associated bloodstream infection (CLABSI) prevention. In this mixed-methods evaluation, 3 products with varying scrub times were tested for experimental disinfection followed by a qualitative nursing assessment of each. METHODS: Needleless connectors were inoculated with varying concentrations of Staphylococcus epidermidis, Pseudomonas aeruginosa, and Staphylococcus aureus followed by disinfection with a 70% isopropyl alcohol (IPA) wipe (a 15-second scrub time and a 15-second dry time), a 70% IPA cap (a 10-second scrub time and a 5-second dry time), or a 3.15% chlorhexidine gluconate with 70% IPA (CHG/IPA) wipe (a 5-second scrub time and a 5-second dry time). Cultures of needleless connectors were obtained after disinfection to quantify bacterial reduction. This was followed by surveying a convenience sample of nursing staff with intensive care unit assignments at an academic tertiary hospital on use of each product. RESULTS: All products reduced overall bacterial burden when compared to sterile water controls, however the IPA and CHG/IPA wipes were superior to the IPA caps when product efficacy was compared. Nursing staff noted improved compliance with CHG/IPA wipes compared with the IPA wipes and the IPA caps, with many preferring the lesser scrub and dry times required for disinfection. CONCLUSION: Achieving adequate bacterial disinfection of needleless connectors while maximizing healthcare staff compliance with scrub and dry times may be best achieved with a combination CHG/IPA wipe.

Recruited monocytes/macrophages drive pulmonary neutrophilic inflammation and irreversible lung tissue remodeling in cystic fibrosis.

Persistent neutrophil-dominated lung inflammation contributes to lung damage in cystic fibrosis (CF). However, the mechanisms that drive persistent lung neutrophilia and tissue deterioration in CF are not well characterized. Starting from the observation that, in patients with CF, c-c motif chemokine receptor 2 (CCR2)+ monocytes/macrophages are abundant in the lungs, we investigate the interplay between monocytes/macrophages and neutrophils in perpetuating lung tissue damage in CF. Here we show that CCR2+ monocytes in murine CF lungs drive pathogenic transforming growth factor ß (TGF-ß) signaling and sustain a pro-inflammatory environment by facilitating neutrophil recruitment. Targeting CCR2 to lower the numbers of monocytes in CF lungs ameliorates neutrophil inflammation and pathogenic TGF-ß signaling and prevents lung tissue damage. This study identifies CCR2+ monocytes as a neglected contributor to the pathogenesis of CF lung disease and as a therapeutic target for patients with CF, for whom lung hyperinflammation and tissue damage remain an issue despite recent advances in CF transmembrane conductance regulator (CFTR)-specific therapeutic agents.

Novel Approaches to Multidrug-Resistant Infections in Cystic Fibrosis.

Patients with cystic fibrosis (CF) often develop respiratory tract infections with pathogenic multidrug-resistant organisms (MDROs) such as methicillin-resistant Staphylococcus aureus, and a variety of gram-negative organisms that include Pseudomonas aeruginosa, Burkholderia sp., Stenotrophomonas maltophilia, Achromobacter xylosoxidans, and nontuberculous mycobacteria (NTM). Despite the introduction of new therapies to address underlying cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction, MDRO infections remain a problem and novel antimicrobial interventions are still needed. Therapeutic approaches include improving the efficacy of existing drugs by adjusting the dose based on differences in CF patient pharmacokinetics/pharmacodynamics, the development of inhaled formulations to reduce systemic adverse events, and the use of newer beta-lactam/beta-lactamase combinations. Alternative innovative therapeutic approaches include the use of gallium and bacteriophages to treat MDRO pulmonary infections including those with extreme antibiotic resistance. However, additional clinical trials are required to determine the optimal dosing and efficacy of these different strategies and to identify patients with CF most likely to benefit from these new treatment options.

Disinfection of Virtual Reality Devices in Health Care Settings: In Vitro Assessment and Survey Study.

BACKGROUND: Virtual reality (VR) devices are increasingly used in health care settings. The use among patients has the potential to unintentionally transmit pathogens between patients and hospital staff. No standard operating procedure for disinfection exists to ensure safe use between patients. OBJECTIVE: This study aims to determine the efficacy of disinfectants on VR devices in order to ensure safe use in health care settings. METHODS: Three types of bacteria were inoculated onto porous and nonporous surfaces of 2 VR devices: the Meta Oculus Quest and Meta Oculus Quest 2. Disinfection was performed using either isopropyl alcohol or alcohol-free quaternary ammonium wipes. A quantitative culture was used to assess the adequacy of disinfection. A survey was separately sent out to VR device technicians at other pediatric health care institutes to compare the methods of disinfection and how they were established. RESULTS: Both products achieved adequate disinfection of the treated surfaces; however, a greater log-kill was achieved on nonporous surfaces than on the porous surfaces. Alcohol performed better than quaternary ammonium on porous surfaces. The survey respondents reported a wide variability in disinfection processes with only 1 person reporting an established standard operating procedure. CONCLUSIONS: Disinfection can be achieved through the use of either isopropyl alcohol or quaternary ammonium products. Porous surfaces showed lesser log-kill rates than the nonporous surfaces, indicating that the use of an added barrier may be of benefit and should be a point of future research. Given the variability in the disinfection process across health care systems, a standard operating procedure is proposed.

Recruitment of monocytes primed to express heme oxygenase-1 ameliorates pathological lung inflammation in cystic fibrosis.

Overwhelming neutrophilic inflammation is a leading cause of lung damage in many pulmonary diseases, including cystic fibrosis (CF). The heme oxygenase-1 (HO-1)/carbon monoxide (CO) pathway mediates the resolution of inflammation and is defective in CF-affected macrophages (MΦs). Here, we provide evidence that systemic administration of PP-007, a CO releasing/O2 transfer agent, induces the expression of HO-1 in a myeloid differentiation factor 88 (MyD88) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)-dependent manner. It also rescues the reduced HO-1 levels in CF-affected cells induced in response to lipopolysaccharides (LPS) or Pseudomonas aeruginosa (PA). Treatment of CF and muco-obstructive lung disease mouse models with a single clinically relevant dose of PP-007 leads to effective resolution of lung neutrophilia and to decreased levels of proinflammatory cytokines in response to LPS. Using HO-1 conditional knockout mice, we show that the beneficial effect of PP-007 is due to the priming of circulating monocytes trafficking to the lungs in response to infection to express high levels of HO-1. Finally, we show that PP-007 does not compromise the clearance of PA in the setting of chronic airway infection. Overall, we reveal the mechanism of action of PP-007 responsible for the immunomodulatory function observed in clinical trials for a wide range of diseases and demonstrate the potential use of PP-007 in controlling neutrophilic pulmonary inflammation by promoting the expression of HO-1 in monocytes/macrophages.

Bacterial Surface Detachment during Nebulization with Contaminated Reusable Home Nebulizers.

Patients with chronic respiratory diseases use home nebulizers that are often contaminated with pathogenic microbes to deliver aerosolized medications. The conditions under which these microbes leave the surface as bioaerosols during nebulization are not well characterized. The objectives of this study were to (i) determine whether different pathogens detach and disperse from the nebulizer surface during aerosolization and (ii) measure the effects of relative humidity and drying times on bacterial surface detachment and aerosolization. Bacteria were cultured from bioaerosols after Pari LC Plus albuterol nebulization using two different sources, as follows: (i) previously used nebulizers donated by anonymous patients with cystic fibrosis (CF) and (ii) nebulizers inoculated with bacteria isolated from the lungs of CF patients. Fractionated bioaerosols were collected with a Next-Generation Impactor. For a subset of bacteria, surface adherence during rewetting was measured with fluorescence microscopy. Bacteria dispersed from the surface of used CF patient nebulizers during albuterol nebulization. Eighty percent (16/20) of clinical isolates inoculated on the nebulizer in the laboratory formed bioaerosols. Detachment from the plastic surface into the chamber solution predicted bioaerosol production. Increased relative humidity and decreased drying times after inoculation favored bacterial dispersion on aerosols during nebulized therapy. Pathogenic bacteria contaminating nebulizer surfaces detached from the surface as bioaerosols during nebulized therapies, especially under environmental conditions when contaminated nebulizers were dried or stored at high relative humidity. This finding emphasizes the need for appropriate nebulizer cleaning, disinfection, and complete drying during storage and informs environmental conditions that favor bacterial surface detachment during nebulization. IMPORTANCE Studies from around the world have demonstrated that many patients use contaminated nebulizers to deliver medication into their lungs. While it is known that using contaminated medications in a nebulizer can lead to a lung infection, whether bacteria on the surface of a contaminated nebulizer detach as bioaerosols capable of reaching the lung has not been studied. This work demonstrates that a subset of clinical bacteria enter solution from the surface during nebulization and are aerosolized. Environmental conditions of high relative humidity during storage favor dispersion from the surface. We also provide results of an in vitro assay conducted to monitor bacterial surface detachment during multiple cycles of rewetting that correlate with the results of nebulizer/bacterial surface interactions. These studies demonstrate for the first time that pathogenic bacteria on the nebulizer surface pose a risk of bacterial inhalation to patients who use contaminated nebulizers.

Telehealth Reduces Missed Appointments in Pediatric Patients with Tuberculosis Infection.

Pediatric patients with untreated tuberculosis infection (TBI), also called latent TBI, are at risk of progression to active TB disease. The primary aim of this study was to identify factors associated with higher rates of missed appointments and failure to complete therapy for pediatric patients with TBI. A secondary aim was to determine the impact of the COVID-19 pandemic and the rise of telehealth on TBI missed appointment rates. We first performed a retrospective chart review of 129 pediatric patients referred to the free Yale Pediatric Winchester Chest Tuberculosis Clinic from 2016-2019. Associations between demographic/clinical variables and missed appointments/failure to complete therapy were analyzed using univariate and bivariate chi-square tests. Language, lack of primary provider, and distance to clinic were the main contributors to missed appointments and poor treatment adherence. There was an association between the number of missed appointments and failure to complete treatment (p = 0.050). A second cohort of 29 patients was analyzed from January-December 2021 when telehealth was offered for follow-up appointments. Of these follow-up visits, 54% were conducted via telehealth, and the clinic's missed appointment rate dropped significantly from 16.9% to 5.8% during this time frame (p = 0.037). These data demonstrate that telehealth is accepted as an alternative by patients for follow-up TBI visits.

Association of Child Masking With COVID-19-Related Closures in US Childcare Programs.

Importance: It is not known how effective child masking is in childcare settings in preventing the transmission of SARS-CoV-2. This question is critical to inform health policy and safe childcare practices. Objective: To assess the association between masking children 2 years and older and subsequent childcare closure because of COVID-19. Design, Setting, and Participants: A prospective, 1-year, longitudinal electronic survey study of 6654 childcare professionals at home- and center-based childcare programs in all 50 states was conducted at baseline (May 22 to June 8, 2020) and follow-up (May 26 to June 23, 2021). Using a generalized linear model (log-binomial model) with robust SEs, this study evaluated the association between childcare program closure because of a confirmed or suspected COVID-19 case in either children or staff during the study period and child masking in both early adoption (endorsed at baseline) and continued masking (endorsed at baseline and follow-up), while controlling for physical distancing, other risk mitigation strategies, and program and community characteristics. Exposures: Child masking in childcare programs as reported by childcare professionals at baseline and both baseline and follow-up. Main Outcomes and Measures: Childcare program closure because of a suspected or confirmed COVID-19 case in either children or staff as reported in the May 26 to June 23, 2021, end survey. Results: This survey study of 6654 childcare professionals (mean [SD] age, 46.9 [11.3] years; 750 [11.3%] were African American, 57 [0.9%] American Indian/Alaska Native, 158 [2.4%] Asian, 860 [12.9%] Hispanic, 135 [2.0%] multiracial [anyone who selected >1 race on the survey], 18 [0.3%] Native Hawaiian/Pacific Islander, and 5020 [75.4%] White) found that early adoption (baseline) of child masking was associated with a 13% lower risk of childcare program closure because of a COVID-19 case (adjusted relative risk, 0.87; 95% CI, 0.77-0.99), and continued masking for 1 year was associated with a 14% lower risk (adjusted relative risk, 0.86; 95% CI, 0.74-1.00). Conclusions and Relevance: This survey study of childcare professionals suggests that masking young children is associated with fewer childcare program closures, enabling in-person education. This finding has important public health policy implications for families that rely on childcare to sustain employment.

Incidence of Multisystem Inflammatory Syndrome in Children Among US Persons Infected With SARS-CoV-2.

Importance: Multisystem inflammatory syndrome in children (MIS-C) is associated with recent or current SARS-CoV-2 infection. Information on MIS-C incidence is limited. Objective: To estimate population-based MIS-C incidence per 1 000 000 person-months and to estimate MIS-C incidence per 1 000 000 SARS-CoV-2 infections in persons younger than 21 years. Design, Setting, and Participants: This cohort study used enhanced surveillance data to identify persons with MIS-C during April to June 2020, in 7 jurisdictions reporting to both the Centers for Disease Control and Prevention national surveillance and to Overcoming COVID-19, a multicenter MIS-C study. Denominators for population-based estimates were derived from census estimates; denominators for incidence per 1 000 000 SARS-CoV-2 infections were estimated by applying published age- and month-specific multipliers accounting for underdetection of reported COVID-19 case counts. Jurisdictions included Connecticut, Georgia, Massachusetts, Michigan, New Jersey, New York (excluding New York City), and Pennsylvania. Data analyses were conducted from August to December 2020. Exposures: Race/ethnicity, sex, and age group (ie, ≤5, 6-10, 11-15, and 16-20 years). Main Outcomes and Measures: Overall and stratum-specific adjusted estimated MIS-C incidence per 1 000 000 person-months and per 1 000 000 SARS-CoV-2 infections. Results: In the 7 jurisdictions examined, 248 persons with MIS-C were reported (median [interquartile range] age, 8 [4-13] years; 133 [53.6%] male; 96 persons [38.7%] were Hispanic or Latino; 75 persons [30.2%] were Black). The incidence of MIS-C per 1 000 000 person-months was 5.1 (95% CI, 4.5-5.8) persons. Compared with White persons, incidence per 1 000 000 person-months was higher among Black persons (adjusted incidence rate ratio [aIRR], 9.26 [95% CI, 6.15-13.93]), Hispanic or Latino persons (aIRR, 8.92 [95% CI, 6.00-13.26]), and Asian or Pacific Islander (aIRR, 2.94 [95% CI, 1.49-5.82]) persons. MIS-C incidence per 1 000 000 SARS-CoV-2 infections was 316 (95% CI, 278-357) persons and was higher among Black (aIRR, 5.62 [95% CI, 3.68-8.60]), Hispanic or Latino (aIRR, 4.26 [95% CI, 2.85-6.38]), and Asian or Pacific Islander persons (aIRR, 2.88 [95% CI, 1.42-5.83]) compared with White persons. For both analyses, incidence was highest among children aged 5 years or younger (4.9 [95% CI, 3.7-6.6] children per 1 000 000 person-months) and children aged 6 to 10 years (6.3 [95% CI, 4.8-8.3] children per 1 000 000 person-months). Conclusions and Relevance: In this cohort study, MIS-C was a rare complication associated with SARS-CoV-2 infection. Estimates for population-based incidence and incidence among persons with infection were higher among Black, Hispanic or Latino, and Asian or Pacific Islander persons. Further study is needed to understand variability by race/ethnicity and age group.

Severe Acute Respiratory Syndrome Coronavirus 2 Testing in Children in a Large Regional US Health System During the Coronavirus Disease 2019 Pandemic.

BACKGROUND: The objective was to evaluate patterns of pediatric coronavirus disease 2019 testing in a large health system throughout the pandemic, before and after school reopening. METHODS: This was a cross-sectional time-series study of clinical virology results from children tested for severe acute respiratory syndrome coronavirus 2 in Southern Connecticut and areas of New York and Rhode Island. Data collected include demographics, hospital admission, changes in percent positive tests over time, detection intervals in persistently positive children and cycle threshold values. The setting was the Yale New Haven Health System has 6 hospitals at 4 Connecticut locations, 1 hospital in Rhode Island and ambulatory locations in Connecticut, Rhode Island and New York. Participants included twenty-three-thousand one-hundred thirty-seven children ≤ 18 years of age, tested for coronavirus disease 2019 at an ambulatory testing site, the emergency department or on an inpatient unit within the Yale New Haven Health System. RESULTS: Among all tests, 3.2% were positive. Older children consistently made up the larger portion of positive pediatric cases, regardless of community prevalence. Increased pediatric cases later in the pandemic when prevalence in adults was relatively low correlates with a higher number of tests performed in children and not with an increased positivity rate. No significant changes in trends of positivity were detected after the reopening of schools. Symptomatic and asymptomatic children had similar cycle threshold values regardless of age, and a subset of children demonstrated persistent viral detection, some for as long as 6 weeks. CONCLUSION: An increase in pediatric cases documented in the late summer was predominately due to increased access to testing for children. The percent positivity in children did not change in the first 3 weeks after school opened. A subset of children has detectable severe acute respiratory syndrome coronavirus 2 RNA in the upper respiratory tract for weeks after the initial infection.

Mass severe acute respiratory coronavirus 2 (SARS-CoV-2) testing of asymptomatic healthcare personnel.

Mass asymptomatic SARS-CoV-2 nucleic acid amplified testing of healthcare personnel (HCP) was performed at a large tertiary health system. A low period-prevalence of positive HCP was observed. Of those who tested positive, half had mild symptoms in retrospect. HCP with even mild symptoms should be isolated and tested.

Targeting the Heme Oxygenase 1/Carbon Monoxide Pathway to Resolve Lung Hyper-Inflammation and Restore a Regulated Immune Response in Cystic Fibrosis.

In individuals with cystic fibrosis (CF), lung hyper-inflammation starts early in life and is perpetuated by mucus obstruction and persistent bacterial infections. The continuous tissue damage and scarring caused by non-resolving inflammation leads to bronchiectasis and, ultimately, respiratory failure. Macrophages (MΦs) are key regulators of immune response and host defense. We and others have shown that, in CF, MΦs are hyper-inflammatory and exhibit reduced bactericidal activity. Thus, MΦs contribute to the inability of CF lung tissues to control the inflammatory response or restore tissue homeostasis. The non-resolving hyper-inflammation in CF lungs is attributed to an impairment of several signaling pathways associated with resolution of the inflammatory response, including the heme oxygenase-1/carbon monoxide (HO-1/CO) pathway. HO-1 is an enzyme that degrades heme groups, leading to the production of potent antioxidant, anti-inflammatory, and bactericidal mediators, such as biliverdin, bilirubin, and CO. This pathway is fundamental to re-establishing cellular homeostasis in response to various insults, such as oxidative stress and infection. Monocytes/MΦs rely on abundant induction of the HO-1/CO pathway for a controlled immune response and for potent bactericidal activity. Here, we discuss studies showing that blunted HO-1 activation in CF-affected cells contributes to hyper-inflammation and defective host defense against bacteria. We dissect potential cellular mechanisms that may lead to decreased HO-1 induction in CF cells. We review literature suggesting that induction of HO-1 may be beneficial for the treatment of CF lung disease. Finally, we discuss recent studies highlighting how endogenous HO-1 can be induced by administration of controlled doses of CO to reduce lung hyper-inflammation, oxidative stress, bacterial infection, and dysfunctional ion transport, which are all hallmarks of CF lung disease.

Oxygen nipple and nut (Christmas tree) adaptor contamination rates and decontamination with disinfecting wipes.

OBJECTIVE: Different manufacturers recommend different levels of disinfection for oxygen nipple and nut adaptors, also known as Christmas-tree adaptors (CTAs). We aimed to determine the bacterial contamination rates of CTAs before and after clinical use and whether disinfection wipes effectively eliminate bacteria from CTAs. METHODS: CTAs were swabbed for bacteria directly from the shipment box or after use in a medical intensive care unit to determine levels of contamination. CTAs were also inoculated in the laboratory with a variety of bacteria and disinfected with either 0.5% hydrogen peroxide (Oxivir 1) or 0.25% tetra-ammonium chloride with 44.50% isopropyl alcohol (Super Sani-Cloth), and the effectiveness of each wipe was determined by comparing the bacterial recovery before and after disinfection. RESULTS: CTAs exhibit low levels of bacterial burden before and after clinical use. Both disinfecting wipes were effective at removing bacteria from the CTAs. CONCLUSIONS: Low-level disinfection of CTAs is appropriate prior to redeployment in the clinical setting.

Shifting focus toward healthcare-associated bloodstream infections: The need for neonatal intensive care unit-specific NHSN definitions.

OBJECTIVE: Healthcare-associated bloodstream infections (HABSIs) are a significant cause of mortality and morbidity in the neonatal intensive care unit (NICU) population. Our objectives were to review the epidemiology of HABSIs in our NICU and to examine the applicability of National Healthcare Safety Network (NHSN) definitions to the NICU population. METHODS: We performed a retrospective review of all neonates admitted to the 54-bed, level IV NICU at Yale-New Haven Children's Hospital with a HABSI between January 1, 2013, and December 31, 2018. Clinical definitions per NICU team and NHSN site-specific definitions used for source identification were compared using the McNemar χ2 test. RESULTS: We identified 86 HABSIs with an incidence rate of 0.80 per 1,000 patient days. Only 13% of these were CLABSIs. Both CLABSIs and non-catheter-related bloodstream infections occurred primarily in preterm neonates, but the latter were associated with a significantly higher incidence of comorbidities and the need for respiratory support. The NHSN definitions were less likely to identify a source compared to the clinical definitions agreed upon by our NICU treating team (P < .001). Furthermore, 50% of patients without an identified source of infection by NHSN definitions were bacteremic with a mucosal barrier injury organism, likely from gut translocation. CONCLUSIONS: HABSIs occur primarily in premature infants with comorbidities, and CLABSIs account for a small proportion of these infections. With the increasing focus on HABSI prevention, there is a need for better NHSN site-specific definitions for the NICU population to prevent misclassification and direct prevention efforts.