Outcomes associated with Healthcare-associated Respiratory Syncytial Virus in Children's Hospitals.

To determine if healthcare-associated (HA)-RSV is associated with worse outcomes, this multicenter cohort study studied 26 children with HA-RSV and 78 matched non-HA-RSV patients of whom 58% and 55%, respectively, had >2 comorbidities. Overall, 39% of HA-RSV versus 18% of non-HA-RSV patients required respiratory support escalation (aOR 5.1, CI95 1.4,19.1).

Diagnostic stewardship for blood cultures in the pediatric intensive care unit: lessons in implementation from the BrighT STAR Collaborative.

Objective: BrighT STAR was a diagnostic stewardship collaborative of 14 pediatric intensive care units (PICUs) across the United States designed to standardize and reduce unnecessary blood cultures and study the impact on patient outcomes and broad-spectrum antibiotic use. We now examine the implementation process in detail to understand how sites facilitated this diagnostic stewardship program in their PICUs. Design: A multi-center electronic survey of the 14 BrighT STAR sites, based on qualitative data about the implementation process collected during the primary phase of BrighT STAR. Setting: 14 PICUs enrolled in BrighT STAR. Participants: Site leads at each enrolled site. Methods: An electronic survey guided by implementation science literature and based on data collected during BrighT STAR was administered to all 14 sites after completion of the primary phase of the collaborative. Results: 10 specific tasks appear critical to implementing blood culture diagnostic stewardship, with variability in site-level strategies employed to accomplish those tasks. Sites rated certain tasks and strategies as highly important. Strategies used in top-performing sites were distinct from those used in lower-performing sites. Certain strategies may link to drivers of culture overuse and represent key targets for changing clinician behavior. Conclusions: BrighT STAR offers important insights into the tasks and strategies used to facilitate successful diagnostic stewardship in the PICU. More work is needed to compare specific strategies and optimize stewardship outcomes in this complex environment. Clinical trial registry information: Blood Culture Improvement Guidelines and Diagnostic Stewardship for Antibiotic Reduction in Critically Ill Children (Bright STAR). NCT03441126. https://www.clinicaltrials.gov/study/NCT03441126?term=Bright%20STAR&aggFilters=status:com&checkSpell=false&rank=1.

Evaluation of a Comprehensive Algorithm for PICU Patients With New Fever or Instability: Association of Clinical Decision Support With Testing Practices.

OBJECTIVES: Previously, we implemented a comprehensive decision support tool, a "New Fever Algorithm," to support the evaluation of PICU patients with new fever or instability. This tool was associated with a decline in culture rates without safety concerns. We assessed the impact of the algorithm on testing practices by identifying the proportion of cultures pre- vs. post-implementation that were discordant with algorithm guidance and may have been avoidable. DESIGN: Retrospective evaluation 12 months pre- vs. post-quality improvement intervention. SETTING: Single-center academic PICU and pediatric cardiac ICU. SUBJECTS: All admitted patients. INTERVENTIONS: Implementing the "New Fever Algorithm" in July 2020. MEASUREMENTS AND MAIN RESULTS: Patient medical records were reviewed to categorize indications for all blood, respiratory, and urine cultures. Among cultures obtained for new fever or new clinical instability, we assessed specific testing patterns that were discordant from the algorithm's guidance such as blood cultures obtained without documented concern for sepsis without initiation of antibiotics, respiratory cultures without respiratory symptoms, urine cultures without a urinalysis or pyuria, and pan-cultures (concurrent blood, respiratory, and urine cultures). Among 2827 cultures, 1950 (69%) were obtained for new fever or instability. The proportion of peripheral blood cultures obtained without clinical concern for sepsis declined from 18.6% to 10.4% (p < 0.0007). Respiratory cultures without respiratory symptoms declined from 41.5% to 27.4% (p = 0.01). Urine cultures without a urinalysis did not decline (from 27.6% to 25.1%). Urine cultures without pyuria declined from 83.0% to 73.7% (p = 0.04). Pan-cultures declined from 22.4% to 10.6% (p < 0.0001). Overall, algorithm-discordant testing declined from 39% to 30% (p < 0.0001). CONCLUSIONS: The majority of cultures obtained were for new fever or instability and introduction of the "New Fever Algorithm" was associated with reductions in algorithm-discordant testing practices and pan-cultures. There remain opportunities for improvement and additional strategies are warranted to optimize testing practices for in this complex patient population.

Hospital-Onset Bacteremia Among Neonatal Intensive Care Unit Patients.

Importance: The Centers for Disease Control and Prevention plans to introduce hospital-onset bacteremia (HOB) as a health care-associated infection measure. The epidemiology and clinical characteristics of HOB among infants admitted to the neonatal intensive care unit (NICU) are unknown. Objective: To estimate the rate of HOB among infants admitted to the NICU, measure the association of HOB risk with birth weight group and postnatal age, and estimate HOB-attributable mortality. Design, Setting, and Participants: This retrospective multicenter cohort study and emulated trial from 2016 to 2021 included a convenience sample of 322 NICUs in the United States. Participants were infants admitted to participating NICUs for 4 or more days. Exposures: The primary exposures were birth weight and postnatal age. Additional exposures included small for gestational age and central line presence. Main Outcomes and Measures: The primary study outcomes were HOB and HOB-attributable mortality. Results: Of 451 443 included infants, 250 763 (55.6%) were male, 200 680 (44.4%) were female, and 62 091 (13.8%) were born 1500 g or less. Of 9015 HOB events that occurred among 8356 infants (2%) during 8 163 432 days at risk (unadjusted incidence rate, 1.1 per 1000 patient-days; 95% CI, 1.0-1.2), 4888 HOB events (54.2%) occurred in the absence of a central line. Within the first 2 weeks after birth, the HOB rate was 14.2 per 1000 patient-days (95% CI, 12.6-16.1) among infants born 750 g or less, to 0.4 events per 1000 patient-days among infants born more than 2500 g (95% CI, 0.4-0.5). Among infants born 750 g or less, the relative HOB risk decreased by 90% after day 42 compared with days 4 to 14 (incidence rate ratio [IRR], 0.10; 95% CI, 0.1-0.1). Conversely, among infants born more than 2500 g, the relative HOB risk increased by 50% after day 42 compared with days 4 to 14 (IRR, 1.5, 95% CI, 1.2-1.9). Compared with otherwise similar infants without HOB, infants with HOB had an absolute difference in attributable mortality of 5.5% (95% CI, 4.7-6.3). Conclusions and Relevance: This study found that HOB events in the NICU are associated with increased mortality. Birth weight is an important risk factor for HOB; however, the relative rate of HOB decreases over postnatal age among low-birth-weight infants and increases among infants born more than 2500 g. Identifying strategies to prevent HOB and programs to decrease HOB risk are urgently needed to reduce infant mortality.

Evaluation of hospital-onset bacteraemia and fungaemia in the USA as a potential healthcare quality measure: a cross-sectional study.

BACKGROUND: Hospital-onset bacteraemia and fungaemia (HOB) is being explored as a surveillance and quality metric. The objectives of the current study were to determine sources and preventability of HOB in hospitalised patients in the USA and to identify factors associated with perceived preventability. METHODS: We conducted a cross-sectional study of HOB events at 10 academic and three community hospitals using structured chart review. HOB was defined as a blood culture on or after hospital day 4 with growth of one or more bacterial or fungal organisms. HOB events were stratified by commensal and non-commensal organisms. Medical resident physicians, infectious disease fellows or infection preventionists reviewed charts to determine HOB source, and infectious disease physicians with training in infection prevention/hospital epidemiology rated preventability from 1 to 6 (1=definitely preventable to 6=definitely not preventable) using a structured guide. Ratings of 1-3 were collectively considered 'potentially preventable' and 4-6 'potentially not preventable'. RESULTS: Among 1789 HOB events with non-commensal organisms, gastrointestinal (including neutropenic translocation) (35%) and endovascular (32%) were the most common sources. Overall, 636/1789 (36%) non-commensal and 238/320 (74%) commensal HOB events were rated potentially preventable. In logistic regression analysis among non-commensal HOB events, events attributed to intravascular catheter-related infection, indwelling urinary catheter-related infection and surgical site infection had higher odds of being rated preventable while events with neutropenia, immunosuppression, gastrointestinal sources, polymicrobial cultures and previous positive blood culture in the same admission had lower odds of being rated preventable, compared with events without those attributes. Of 636 potentially preventable non-commensal HOB events, 47% were endovascular in origin, followed by gastrointestinal, respiratory and urinary sources; approximately 40% of those events would not be captured through existing healthcare-associated infection surveillance. DISCUSSION: Factors identified as associated with higher or lower preventability should be used to guide inclusion, exclusion and risk adjustment for an HOB-related quality metric.

New Vibrio cholerae sequences from Eastern and Southern Africa alter our understanding of regional cholera transmission.

Despite ongoing containment and vaccination efforts, cholera remains prevalent in many countries in sub-Saharan Africa. Part of the difficulty in containing cholera comes from our lack of understanding of how it circulates throughout the region. To better characterize regional transmission, we generated and analyzed 118 Vibrio cholerae genomes collected between 2007-2019 from five different countries in Southern and Eastern Africa. We showed that V. cholerae sequencing can be successful from a variety of sample types and filled in spatial and temporal gaps in our understanding of circulating lineages, including providing some of the first sequences from the 2018-2019 outbreaks in Uganda, Kenya, Tanzania, Zambia, and Malawi. Our results present a complex picture of cholera transmission in the region, with multiple lineages found to be co-circulating within several countries. We also find evidence that previously identified sporadic cases may be from larger, undersampled outbreaks, highlighting the need for careful examination of sampling biases and underscoring the need for continued and expanded cholera surveillance across the African continent.

Medical education during the COVID-19 pandemic: a reflection on the JHUSOM experience.

BACKGROUND: We sought to understand the relative risk of COVID-19 infection and identify risk factors for infection to identify targets for mitigation among medical students. METHODS: An observational cohort study of Johns Hopkins School of Medicine students was conducted from June 2020 to July 2021. Blood samples were collected and tested at three visits to assess for antibodies against SARS-CoV-2. Additionally, a questionnaire was administered at each visit to collect demographic information and assess potential social and behavioral risk factors. RESULTS: 264 students enrolled in the study, and 38 participants completed all study requirements by study end. Roughly 6% of the first- and second-year classes had a reported positive COVID-19 test compared to 5% of third- and fourth-year students. By visit 3, 92% of medical students had detectable antibodies against COVID-19 compared to 4% during the study enrollment period. From study enrollment to visit 3, there was a 10-fold increase in the percentage of students reporting attending large social gatherings and dining in restaurants. CONCLUSIONS: Overall, few COVID-19 cases were found among medical students, even those on clinical rotations. As the study progressed, students reported engaging in higher-risk social behaviors in conjunction with increasing vaccination rates among students.

Association of Nirmatrelvir/Ritonavir Treatment and COVID-19-Neutralizing Antibody Titers in a Longitudinal Health Care Worker Cohort.

Nirmatrelvir/ritonavir (NMV/r) is used for the treatment of coronavirus disease 2019 (COVID-19) infection. However, rebound COVID-19 infections can occur after taking NMV/r. We examined neutralizing antibodies to the severe acute respiratory syndrome coronavirus 2 spike protein before and after infection in people who did and did not take NMV/r to determine if NMV/r impedes the humoral immune response.

Diagnostic stewardship to improve patient outcomes and healthcare-associated infection (HAI) metrics.

Diagnostic stewardship seeks to improve ordering, collection, performance, and reporting of tests. Test results play an important role in reportable HAIs. The inclusion of HAIs in public reporting and pay for performance programs has highlighted the value of diagnostic stewardship as part of infection prevention initiatives. Inappropriate testing should be discouraged, and approaches that seek to alter testing solely to impact a reportable metric should be avoided. HAI definitions should be further adapted to new testing technologies, with focus on actionable and clinically relevant test results that will improve patient care.

Microbiome dysbiosis: a modifiable state and target to prevent Staphylococcus aureus infections and other diseases in neonates.

Bacterial infections present a significant threat to neonates. Increasingly, studies demonstrate associations between human diseases and the microbiota, the communities of microorganisms on or in the body. A "healthy" microbiota with a great diversity and balance of microorganisms can resist harmful pathogens and protect against infections, whereas a microbiota suffering from dysbiosis, can predispose to pathogen colonization and subsequent infection. For decades, strategies such as bacterial interference, decolonization, prebiotics, and probiotics have been tested to reduce Staphylococcus aureus disease and other infections in neonates. More recently, microbiota transplant has emerged as a strategy to broadly correct dysbiosis, promote colonization resistance, and prevent infections. This paper discusses the benefits of a healthy neonate's microbiota, exposures that alter the microbiota, associations of dysbiosis and neonatal disease, strategies to prevent dysbiosis, such as microbiota transplantation, and presents a framework of microbiome manipulation to reduce Staphylococcus aureus (S. aureus) and other infections in neonates.

A Survey of PICU Clinician Practices and Perceptions regarding Respiratory Cultures in the Evaluation of Ventilator-Associated Infections in the BrighT STAR Collaborative.

OBJECTIVES: To characterize respiratory culture practices for mechanically ventilated patients, and to identify drivers of culture use and potential barriers to changing practices across PICUs. DESIGN: Cross-sectional survey conducted May 2021-January 2022. SETTING: Sixteen academic pediatric hospitals across the United States participating in the BrighT STAR Collaborative. SUBJECTS: Pediatric critical care medicine physicians, advanced practice providers, respiratory therapists, and nurses. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We summarized the proportion of positive responses for each question within a hospital and calculated the median proportion and IQR across hospitals. We correlated responses with culture rates and compared responses by role. Sixteen invited institutions participated (100%). Five hundred sixty-eight of 1,301 (44%) e-mailed individuals completed the survey (median hospital response rate 60%). Saline lavage was common, but no PICUs had a standardized approach. There was the highest variability in perceived likelihood (median, IQR) to obtain cultures for isolated fever (49%, 38-61%), isolated laboratory changes (49%, 38-57%), fever and laboratory changes without respiratory symptoms (68%, 54-79%), isolated change in secretion characteristics (67%, 54-78%), and isolated increased secretions (55%, 40-65%). Respiratory cultures were likely to be obtained as a "pan culture" (75%, 70-86%). There was a significant correlation between higher culture rates and likelihood to obtain cultures for isolated fever, persistent fever, isolated hypotension, fever, and laboratory changes without respiratory symptoms, and "pan cultures." Respondents across hospitals would find clinical decision support (CDS) helpful (79%) and thought that CDS would help align ICU and/or consulting teams (82%). Anticipated barriers to change included reluctance to change (70%), opinion of consultants (64%), and concern for missing a diagnosis of ventilator-associated infections (62%). CONCLUSIONS: Respiratory culture collection and ordering practices were inconsistent, revealing opportunities for diagnostic stewardship. CDS would be generally well received; however, anticipated conceptual and psychologic barriers to change must be considered.

Three doses of COVID-19 mRNA vaccine induce class-switched antibody responses in inflammatory arthritis patients on immunomodulatory therapies.

Patients with inflammatory arthritis (IA) are at increased risk of severe COVID-19 due to medication-induced immunosuppression that impairs host defenses. The aim of this study was to assess antibody and B cell responses to COVID-19 mRNA vaccination in IA patients receiving immunomodulatory therapies. Adults with IA were enrolled through the Johns Hopkins Arthritis Center and compared with healthy controls (HC). Paired plasma and peripheral blood mononuclear cell (PBMC) samples were collected prior to and 30 days or 6 months following the first two doses of mRNA vaccines (D2; HC=77 and IA=31 patients), or 30 days following a third dose of mRNA vaccines (D3; HC=11 and IA=96 patients). Neutralizing antibody titers, total binding antibody titers, and B cell responses to vaccine and Omicron variants were analyzed. Anti-Spike (S) IgG and S-specific B cells developed appropriately in most IA patients following D3, with reduced responses to Omicron variants, and negligible effects of medication type or drug withholding. Neutralizing antibody responses were lower compared to healthy controls after both D2 and D3, with a small number of individuals demonstrating persistently undetectable neutralizing antibody levels. Most IA patients respond as well to mRNA COVID-19 vaccines as immunocompetent individuals by the third dose, with no evidence of improved responses following medication withholding. These data suggest that IA-associated immune impairment may not hinder immunity to COVID-19 mRNA vaccines in most individuals.

Medical Education during the COVID-19 Pandemic: A Reflection on the JHUSOM Experience.

Background: We sought to understand the relative risk of COVID-19 infection and identify risk factors for infection to identify targets for mitigation among medical students. Methods: An observational cohort study of Johns Hopkins School of Medicine students was conducted from June 2020 to July 2021. Blood samples were collected and tested at three visits to assess for the presence of antibodies against SARS-CoV-2. Additionally, a questionnaire was administered at each visit to collect demographic information and assess potential social and behavioral risk factors. Results: 264 students enrolled in the study, and 38 participants completed all study requirements by study end. Roughly 6% of the first- and second-year classes had a reported positive COVID-19 test compared to 5% of third- and fourth-year students. By visit 3, 92% of medical students had detectable antibodies against COVID-19 compared to 4% during the study enrollment period. From study enrollment to visit 3, there was a 10-fold increase in the percentage of students reporting attending large social gatherings and dining in restaurants. Conclusions: Overall, few COVID-19 cases were found among medical students, even those on clinical rotations. As the study progressed, students reported engaging in higher-risk social behaviors in conjunction with increasing vaccination rates among students.

Strategies to reduce hospital-associated bloodstream infections in a limited resource setting: Preventing Infections in Neonates (PIN) collaborative.

Background: Hospitalized neonates are at high risk for hospital-associated bloodstream infections (HA-BSI) and require locally contextualized interventions to prevent HA-BSI. Methods: The Preventing Infections in Neonates (PIN) collaborative aimed to reach a 50% decrease in neonatal HA-BSI rates for a 27-bed Level IV neonatal intensive care unit (NICU). Using quality improvement (QI) methodologies, a multidisciplinary cross-cultural collaborative implemented phased and bundled interventions from July 2017 to September 2019. Descriptive statistics and statistical process control charts were used to analyze infection rates. Results: There were 916 admissions, 19,812 patient-days, and 4264 central line days in the NICU during the project period. Monthly baseline preintervention HA-BSI median rate was 3.95/1000 patient-days and decreased to 1.73/1000 patient-days (56% change) during the bundled interventions. Quarterly HA-BSI rates also decreased from the preintervention median of 4.5/1000 patient-days to 3.3/1000 patient-days during the intervention period (IRR 0.73; 95%CI 0.39, 1.36). Staff were highly compliant with hand hygiene and environmental cleaning. Through project efforts, compliance with bundle elements increased from 25% at baseline to a peak of 97% for central line (CL) insertion checklists and from 13% to a peak of 56% for CL maintenance checklists. Conclusions: Unit-based bundled interventions can reduce neonatal HA-BSI in limited resource settings. Future studies can assess similar practices in other units and the impact of the pandemic on interventions to reduce HA-BSIs.

Sustainability of the Bright STAR Diagnostic Stewardship Program to Reduce Blood Culture Rates Among Critically Ill Children.

This quality improvement study evaluates whether pediatric intensive care units sustained reduced blood culture rates after participation in the Bright STAR collaborative from 2017 to 2020.

Application of Participatory Ergonomics to the Dissemination of a Quality Improvement Program for Optimizing Blood Culture Use.

BACKGROUND: Blood cultures are overused in pediatric ICUs (PICUs), which may lead to unnecessary antibiotic use and antibiotic resistance. Using a participatory ergonomics (PE) approach, the authors disseminated a quality improvement (QI) program for optimizing blood culture use in PICUs to a national 14-hospital collaborative. The objective of this study was to evaluate the dissemination process and its impact on blood culture reduction. METHODS: The PE approach emphasized three key principles (stakeholder participation, application of human factors and ergonomics knowledge and tools, and cross-site collaboration) with a six-step dissemination process. Data on interactions between sites and the coordinating team and site experiences with the dissemination process were collected using site diaries and semiannual surveys with local QI teams, respectively, and correlated with the site-specific change in blood culture rates. RESULTS: Overall, participating sites were able to successfully implement the program and reduced their blood culture rates from 149.4 blood cultures per 1,000 patient-days/month before implementation to 100.5 blood cultures per 1,000 patient-days/month after implementation, corresponding to a 32.7% relative reduction (p < 0.001). Variations in the dissemination process, as well as in local interventions and implementation strategies, were observed across sites. Site-specific changes in blood culture rates were weakly negatively correlated with the number of preintervention interactions with the coordinating team (p = 0.057) but not correlated with their experiences with the six domains of the dissemination process or their interventions. CONCLUSIONS: The authors applied a PE approach to disseminate a QI program for optimizing PICU blood culture use to a multisite collaborative. Working with local stakeholders, participating sites tailored their interventions and implementation processes and achieved the goal of reducing blood culture use.