Feeding level is associated with altered liver transcriptome and follicle selection in hen†.

Genetic selection for particular traits in domestic animals may have altered the optimal feedback regulation among systems regulating appetite, growth, and reproduction. Broiler breeder chickens have been selected for fast and efficient growth and, unless feed restricted, consume excessively resulting in poor reproductive efficiency. We examined the effect of dietary treatment in full-fed and restricted-fed broiler breeder hens on ovarian responses, liver morphology, and transcriptome associated with reproductive function. Although full-fed broiler breeder hens had lower egg production (P < 0.01), the total number of ovarian follicles >8 mm (P < 0.01), 6-8 mm (P < 0.03), and 3-5 mm (P < 0.04) were greater in full-fed hens compared to restricted-fed hens. There was a large amount of lipid accumulation in the liver of full-fed hens and differential gene analysis yielded 120 genes that were differentially expressed >2-fold in response to feeding level (P < 0.01; false discovery rate < 0.05). Elevated T3 may indicate that general metabolism was affected by diet and GHR (P < 0.01) and insulin like growth factor 1 (IGF1) (P < 0.04) mRNA expression were both greater in the liver of full-fed hens as compared to restricted-fed hens. It is likely that selection for increased growth, associated with enhanced activity of the IGF1 system, has altered nutritional coupling of feed intake to follicle development.

Bacteremia in Adults Admitted from the Emergency Department with Laboratory-Confirmed Respiratory Syncytial Virus.

BACKGROUND: Collecting blood cultures from patients admitted from the emergency department (ED) with acute respiratory infection (ARI) is common, but the rate of secondary bacteremia in adult patients admitted from the ED with ARI associated with respiratory syncytial virus (RSV) is unknown. Indiscriminate collection of blood cultures can be associated with contaminated blood cultures and increased inappropriate antimicrobial use and health care costs. OBJECTIVE: This study sought to determine the rate and etiology of secondary bacteremia, factors associated with secondary bacteremia, and factors associated with collecting blood cultures in the ED, in adults hospitalized with RSV. METHODS: We performed a retrospective substudy using data from a prospective study of adults admitted with RSV infections during two respiratory seasons (October 2017 to April 2018 and October 2018 to April 2019). Blood cultures were collected at the discretion of ED providers. We compared demographic and clinical characteristics among those with and without secondary bacteremia and among those with and without blood cultures collected using multivariate logistic regression models. RESULTS: Of the 365 hospitalized RSV-positive patients (mean age 68.8 years), 269 (73.7%) had blood cultures collected in the ED and 18 (6.7%) patients had secondary bacteremia, most commonly from a nonrespiratory source (n = 13). Patients with asthma and chronic obstructive pulmonary disease were significantly less likely to have secondary bacteremia. Patients who were immunocompromised, met systemic inflammatory response syndrome criteria, or had pneumonia described on chest x-ray reports were more likely to have blood cultures collected. CONCLUSIONS: Overall, 6.7% of adults hospitalized with RSV infections had secondary bacteremia, more commonly from nonrespiratory sources.

Impact of active surveillance and decolonization strategies for methicillin-resistant Staphylococcus aureus in a neonatal intensive care unit.

OBJECTIVE: To assess the impact of active surveillance and decolonization strategies on methicillin-resistant Staphylococcus aureus (MRSA) infection rates in a NICU. STUDY DESIGN: MRSA infection rates were compared before (2014-2016) and during (2017-2022) an active surveillance program. Eligible infants were decolonized with chlorohexidine gluconate (CHG) bathing and/or topical mupirocin. Successful decolonization and rates of recolonization were assessed. RESULTS: Fifty-two (0.57%) of 9 100 hospitalized infants had invasive MRSA infections from 2014 to 2022; infection rates declined non-significantly. During the 6-year surveillance program, the risk of infection was 16.9-times [CI95 8.4, 34.1] higher in colonized infants than uncolonized infants. Those colonized with mupirocin-susceptible MRSA were more likely successfully decolonized (aOR 9.7 [CI95 4.2, 22.5]). Of 57 infants successfully decolonized who remained hospitalized, 34 (60%) became recolonized. CONCLUSIONS: MRSA infection rates did not significantly decline in association with an active surveillance and decolonization program. Alternatives to mupirocin and CHG are needed to facilitate decolonization.

Clinical impact of healthcare-associated respiratory syncytial virus in hospitalized adults.

OBJECTIVE: To describe the clinical impact of healthcare-associated (HA) respiratory syncytial virus (RSV) in hospitalized adults. DESIGN: Retrospective cohort study within a prospective, population-based, surveillance study of RSV-infected hospitalized adults during 3 respiratory seasons: October 2017-April 2018, October 2018-April 2019, and October 2019-March 2020. SETTING: The study was conducted in 2 academically affiliated medical centers. PATIENTS: Each HA-RSV patient (in whom RSV was detected by PCR test ≥4 days after hospital admission) was matched (age, sex, season) with 2 community-onset (CO) RSV patients (in whom RSV was detected ≤3 days of admission). METHODS: Risk factors and outcomes were compared among HA-RSV versus CO-RSV patients using conditional logistic regression. Escalation of respiratory support associated with RSV detection (day 0) from day -2 to day +4 was explored among HA-RSV patients. RESULTS: In total, 84 HA-RSV patients were matched to 160 CO-RSV patients. In HA-RSV patients, chronic kidney disease was more common, while chronic respiratory conditions and obesity were less common. HA-RSV patients were not more likely to be admitted to an ICU or require mechanical ventilation, but they more often required a higher level of care at discharge compared with CO-RSV patients (44% vs 14%, respectively). Also, 29% of evaluable HA-RSV patients required respiratory support escalation; these patients were older and more likely to have respiratory comorbidities, to have been admitted to intensive care, and to die during hospitalization. CONCLUSIONS: HA-RSV in adults may be associated with escalation in respiratory support and an increased level of support in living situation at discharge. Infection prevention and control strategies and RSV vaccination of high-risk adults could mitigate the risk of HA-RSV.

Surveillance for Acute Respiratory Illnesses in Pediatric Chronic Care Facilities.

Overall, 119 (33%) of 364 pediatric chronic care facility residents experienced 182 acute respiratory illnesses (ARIs) that met the surveillance definition which led to 31 (17%) emergency room visits, 34 (19%) acute care hospitalizations, and/or 25 (14%) ICU admissions. Continued PCR-positivity was observed in 35% of ARIs during follow-up testing.

Successful diagnostic stewardship for Clostridioides difficile testing in pediatrics.

OBJECTIVE: To reduce both inappropriate testing for and diagnosis of healthcare-onset (HO) Clostridioides difficile infections (CDIs). DESIGN: We performed a retrospective analysis of C. difficile testing from hospitalized children before (October 2017-October 2018) and after (November 2018-October 2020) implementing restrictive computerized provider order entry (CPOE). SETTING: Study sites included hospital A (a ∼250-bed freestanding children's hospital) and hospital B (a ∼100-bed children's hospital within a larger hospital) that are part of the same multicampus institution. METHODS: In October 2018, we implemented CPOE. No testing was allowed for infants aged ≤12 months, approval of the infectious disease team was required to test children aged 13-23 months, and pathology residents' approval was required to test all patients aged ≥24 months with recent laxative, stool softener, or enema use. Interrupted time series analysis and Mann-Whitney U test were used for analysis. RESULTS: An interrupted time series analysis revealed that from October 2017 to October 2020, the numbers of tests ordered and samples sent significantly decreased in all age groups (P < .05). The monthly median number of HO-CDI cases significantly decreased after implementation of the restrictive CPOE in children aged 13-23 months (P < .001) and all ages combined (P = .003). CONCLUSION: Restrictive CPOE for CDI in pediatrics was successfully implemented and sustained. Diagnostic stewardship for CDI is likely cost-saving and could decrease misdiagnosis, unnecessary antibiotic therapy, and overestimation of HO-CDI rates.

Cost determinants among adults hospitalized with respiratory syncytial virus in the United States, 2017-2019.

BACKGROUND: Respiratory syncytial virus (RSV) infections are common in adults, but data describing the cost of RSV-associated hospitalization are lacking due to inconsistency in diagnostic coding and incomplete case ascertainment. We evaluated costs of RSV-associated hospitalization in adult patients with laboratory-confirmed, community-onset RSV. METHODS: We included adults ≥ 18 years of age admitted to three hospital systems in New York during two RSV seasons who were RSV-positive by polymerase chain reaction (PCR) and had more than or equal to two acute respiratory infection symptoms or exacerbation of underlying cardiopulmonary disease. We abstracted costs from hospital finance systems or converted hospital charges to cost using cost-charge ratios. We converted cost into 2020 US dollars and extrapolated to the United States. We used a generalized linear model to determine predictors of hospitalization cost, stratified by admission to intensive care units (ICU). RESULTS: Cost data were available for 79% (601/756) of eligible patients. The mean total cost of hospitalization was $8403 (CI95 $7240-$9741). The highest costs were those attributed to ICU services $7885 (CI95 $5877-$10,240), whereas the lowest were radiology $324 (CI95 $275-$376). Other than longer length of stay, predictors of higher cost included having chronic liver disease (odds ratio [OR] 1.38 [CI95 1.05-1.80]) for patients without ICU admission and antibiotic use (OR 1.49 [CI95 1.10-2.03]) for patients with ICU admission. The annual US cost was estimated to be $1.2 (CI95 0.9-1.4) billion. CONCLUSION: The economic burden of RSV hospitalization of adults ≥ 18 years of age in the United States is substantial. RSV vaccine programs may be useful in reducing this economic burden.

Genomic and Epidemiological Features of Two Dominant Methicillin-Susceptible Staphylococcus aureus Clones from a Neonatal Intensive Care Unit Surveillance Effort.

Methicillin-susceptible Staphylococcus aureus (MSSA) is a more prevalent neonatal intensive care unit (NICU) pathogen than methicillin-resistant S. aureus (MRSA). However, the introduction and spread of MSSA, the role of systematic decolonization, and optimal infection prevention and control strategies remain incompletely understood. We previously screened infants hospitalized in a university-affiliated level III to IV NICU twice monthly over 18 months for S. aureus colonization and identified several prevalent staphylococcal protein A (spa) types. Here, we performed whole-genome sequencing (WGS) and phylogenetic comparisons of 140 isolates from predominant spa types t279, t1451, and t571 to examine possible transmission routes and identify genomic and epidemiologic features associated with the spread of dominant clones. We identified two major MSSA clones: sequence type 398 (ST398), common in the local community, and ST1898, not previously encountered in the region. ST398 NICU isolates formed distinct clusters with closely related community isolates from previously published data sets, suggesting multiple sources of acquisition, such as family members or staff, including residents of the local community. In contrast, ST1898 isolates were nearly identical, pointing to clonal expansion within the NICU. Almost all ST1898 isolates harbored plasmids encoding mupirocin resistance (mupA), suggesting an association between the proliferation of this clone and decolonization efforts with mupirocin. Comparative genomics indicated genotype-specific pathways of introduction and spread of MSSA via community-associated (ST398) or health care-associated (ST1898) sources and the potential role of mupirocin resistance in dissemination of ST1898. Future surveillance efforts could benefit from routine genotyping to inform clone-specific infection prevention strategies. IMPORTANCE Methicillin-susceptible Staphylococcus aureus (MSSA) is a significant pathogen in neonates. However, surveillance efforts in neonatal intensive care units (NICUs) have focused primarily on methicillin-resistant S. aureus (MRSA), limiting our understanding of colonizing and infectious MSSA clones which are prevalent in the NICU. Here, we identify two dominant colonizing MSSA clones during an 18-month surveillance effort in a level III to IV NICU, ST398 and ST1898. Using genomic surveillance and phylogenetic analysis, coupled with epidemiological investigation, we found that these two sequence types had distinct modes of spread, namely the suggested exchange with community reservoirs for ST398 and the contribution of antibiotic resistance to dissemination of ST1898 in the health care setting. This study highlights the additional benefits of whole-genome surveillance for colonizing pathogens, beyond routine species identification and genotyping, to inform targeted infection prevention strategies.

Spa Typing of Staphylococcus aureus in a Neonatal Intensive Care Unit During Routine Surveillance.

BACKGROUND: Staphylococcus aureus protein A (spa) typing can be used to expand characterization of the epidemiology of methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) in neonatal intensive care units (NICU). METHODS: From January 2017 to June 2018, twice-monthly surveillance for S. aureus was performed in an academically affiliated NICU. Decolonization of infants colonized with S. aureus included chlorhexidine gluconate bathing and/or mupirocin for those with mupirocin-susceptible strains. Spa typing and mupirocin-resistance testing were performed. Demographic and clinical characteristics were compared between infants colonized with MSSA vs MRSA and infants with and without the most common MSSA spa type, MSSA-t279. RESULTS: Overall, 14% and 2% of 1556 hospitalized infants had positive surveillance cultures for MSSA and MRSA, respectively. Thirty-six infants harbored unique MSSA spa types, 5 infants harbored unique MRSA spa types, and 30 MSSA and 6 MRSA spa types were identified in ≥2 infants. No outbreaks were identified during the study period. MSSA-t279 was isolated from 3% of infants and largely detected from infants hospitalized in one section of the NICU; 96% of t279 isolates were mupirocin resistant. Infection rates, length of hospitalization, and mortality were similar among infants initially colonized with t279 vs other MSSA spa types. CONCLUSIONS: The MSSA colonization burden was 5-fold larger than that of MRSA. Numerous unique spa types were identified. The most common spa type, MSSA-t279, was not associated with increased morbidity or mortality but was mupirocin resistant and associated with clustered NICU beds. This suggests potential transmission from the environment, shared staff, and/or workflow issues requiring further study. Other decolonization strategies for S. aureus in the NICU are needed.

Knowledge, Attitudes, and Practices of Pediatric Long-term Care Facility Staff Regarding Infection Control for Acute Respiratory Infections and Influenza Vaccination.

We surveyed clinical staff and on-site teachers working at pediatric long-term care facilities regarding prevention and control of acute respiratory infections and influenza in staff and residents. We uncovered knowledge gaps, particularly among teachers and clinical staff working <5 years at sites, thereby elucidating areas for targeted staff education.

Infection prevention and control and antibiotic stewardship practices in pediatric long-term care facilities.

Pediatric long-term care facilities were surveyed to assess infection control and antimicrobial stewardship practices. Policies mandated by the Centers of Medicare and Medicaid Services (CMS) were included. Only 40% of sites reported implementing >90% of surveyed CMS policies. The survey also identified several gaps in non-CMS-mandated policies.

Using the "Who, What, and When" of free text documentation to improve hospital infectious disease surveillance.

We demonstrate a novel method of using unstructured health data for infectious disease surveillance. A model incorporating the dynamics of documentation of a test diagnosis (UTI) in free text, without using grammatical or syntactic analysis, achieved performance comparable to ICD-10 codes (sensitivity 57.3, positive predictive value 69.5%, negative predictive value 95.9%) and detected missed cases (15% of total).

Epidemiology of Staphylococcus aureus in neonates on admission to a Chinese neonatal intensive care unit.

PURPOSE: Little is known about the molecular epidemiology of Staphylococcus aureus in Chinese neonatal intensive care units (NICUs). We describe the molecular epidemiology of S. aureus isolated from neonates on admission to Beijing Children's Hospital. METHODS: From May 2015-March 2016, nasal swabs were obtained on admission from 536 neonates. Cultures were also obtained from body sites with suspected infections. S. aureus isolates were characterized by staphylococcal chromosomal cassette (SCCmec) type, staphylococcal protein A (spa) type, multilocus sequence type (MLST), sasX gene, antimicrobial susceptibility and cytotoxicity. Logistic regression assessed risk factors for colonization. RESULTS: Overall, 92 (17%) infants were colonized with S. aureus and 20 (3.7%) were diagnosed with culture-positive S. aureus infection. Of the colonized infants, 70% (64/92) harbored methicillin-susceptible S. aureus (MSSA), 30% (28/92) harbored methicillin-resistant S. aureus (MRSA) while 70% (14/20) of infected infants were culture-positive for MRSA, 30% (6/20) were culture-positive for MSSA. Risk factors for colonization included female sex, age 7-28 days, higher birthweight (3270 IQR [2020-3655] grams) and vaginal delivery (p<0.05). The most common MRSA and MSSA clones were community-associated ST59-SCCmecIVa-t437 (60%) and ST188-t189 (15%), respectively. The sasX gene was not detected. Some MSSA isolates (16%) were penicillin-susceptible and some MRSA isolates (18%) were oxacillin-susceptible. MRSA and MSSA had similar cytotoxicity, but colonizing strains were less cytotoxic than strains associated with infections. CONCLUSIONS: S. aureus colonization was common in infants admitted to our NICU and two community-associated clones predominated. Several non-modifiable risk factors for S. aureus colonization were identified. These results suggest that screening infants for S. aureus upon admission and targeting decolonization of high-risk infants and/or those colonized with high-risk clones could be useful to prevent transmission.

Active surveillance for acute respiratory infections among pediatric long-term care facility staff.

BACKGROUND: Transmission of respiratory viruses between staff and residents of pediatric long-term care facilities (pLTCFs) can occur. We assessed the feasibility of using text or email messages to perform surveillance for acute respiratory infections (ARIs) among staff. METHODS: From December 7, 2016 to May 7, 2017, 50 staff participants from 2 pLTCFs received weekly text or email requests to report the presence or absence of ARI symptoms. Those who fulfilled the ARI case definition (≥2 symptoms) had respiratory specimens collected to detect viruses by reverse transcriptase polymerase chain reaction assays. Pre- and postsurveillance respiratory specimens were collected to assess subclinical viral shedding. RESULTS: The response rate to weekly electronic messages was 93%. Twenty-one ARIs reported from 20 (40%) participants fulfilled the case definition. Respiratory viruses were detected in 29% (5/17) of specimens collected at symptom onset (influenza B, respiratory syncytial virus, coronavirus [CoV] 229E, rhinovirus [RV], and dual detection of CoV OC43 and bocavirus). Four participants had positive presurveillance (4 RV), and 6 had positive postsurveillance specimens (3 RV, 2 CoV NL63, and 1 adenovirus). CONCLUSIONS: Electronic messaging to conduct ARI surveillance among pLTCF staff was feasible.

Perceptions of safety monitoring in CF clinical studies and potential impact on future study participation.

BACKGROUND: Individuals with CF and their parents cite safety concerns as barriers to participating in clinical studies. We assessed whether a brochure/infographic describing patient safety monitoring processes could reduce knowledge and attitude barriers regarding safety monitoring. We also identified factors associated with likely participation in future CF studies. METHODS: Respondents from three CF centers in the U.S. were randomly assigned to receive the safety monitoring brochure/infographic or an unrelated brochure. Fifty parents of children with CF <16, 50 adolescents with CF 16-21, and 50 adults with CF ≥22 years old were recruited to complete the study survey. Factors associated with survey responses and with reported likelihood of participating in future studies were assessed. RESULTS: Overall the safety monitoring brochure/infographic was associated with increased likelihood of future participation in non-drug studies (aOR 2.30, CI95 1.01-5.28), but not in drug studies. Non-Hispanic respondents reported greater likelihood of participating in a future drug study than Hispanic respondents (aOR 3.18, CI95 1.30-7.74). Adults with CF (aOR 2.62, CI95 1.05-6.51) and parents (aOR 4.49, CI95 1.66-12.15) were more likely than adolescents to report they would ask their care team about clinical trials. Confidence in safety monitoring was associated with reported likelihood of future participation in drug studies. CONCLUSIONS: Potential future participation in CF drug and/or non-drug studies was associated with respondent age and ethnicity, receiving the safety monitoring brochure/infographic, and confidence in safety monitoring. Our findings underscore the need for education about safety monitoring, with targeted approaches for the Hispanic CF population and adolescents.

Impact of respiratory viruses in the neonatal intensive care unit.

OBJECTIVE: To describe the epidemiology and clinical impact of respiratory viruses in a neonatal intensive care unit (NICU). STUDY DESIGN: We conducted a retrospective observational study of infants with respiratory viruses detected by multiplex reverse-transcriptase PCR from May 2012 to May 2017. The proportion of symptomatic vs. asymptomatic infants and associated morbidity were assessed. The association of infection prevention and control (IP&C) strategies and transmission was ascertained. RESULTS: Respiratory viruses were detected in 83 infants representing 86 unique episodes during which infants remained asymptomatic in 15 (17%). Of the 71 symptomatic episodes, only 45% were associated with increased respiratory and/or nutritional support. Rhinovirus/enteroviruses were most common (69%) and involved nine of 12 transmission events. IP&C strategies including restricting visitors <12 years of age and screening exposed infants were associated with decreased transmission rates. CONCLUSIONS: NICU patients can be asymptomatic carriers of respiratory viruses. Identification of such infants is important to prevent transmission in the NICU.