Risk of serious bacterial infections in pediatric patients with hyperpyrexia.

Objectives: Hyperpyrexia has been associated with a greater prevalence of bacterial infections in the pediatric population, which prior to routine childhood vaccinations, has led to invasive testing and empiric antibiotic use for urinary tract infections, bacterial pneumonia, bacteremia, and bacterial meningitis. Since the implementation of routine childhood vaccinations, the prevalence of serious bacterial infections (SBIs) has declined. This study aims to determine if there is an association between hyperpyrexia and serious bacterial infections in well-appearing febrile pediatric patients presenting to the emergency department (ED). Methods: This is a cross-sectional study conducted between January 1, 2019, and December 31, 2019, at a single urban tertiary care pediatric ED. Patients were included if they were between 61 days and ≤18 years old presenting with a chief complaint of fever. Patients were excluded if they received antibiotics within 3 days of presentation, underwent surgical procedures within 2 weeks of presentation, had an ED visit for febrile illness within 2 weeks of study visit, were transferred from another institution, or were ill appearing. Prevalence of SBI was described and compared by presence of hyperpyrexia, age group, chronic medical condition, gender, and vaccination status. Logistic regression was used to analyze the association between SBIs and hyperpyrexia. Results: Of the 3862 charts reviewed, 2565 patients were included. The prevalence of SBI was 5.6%. A total of 413 patients presented with hyperpyrexia. Of the patients with hyperpyrexia, 31 (7.5%) had a serious bacterial infection. Hyperpyrexia was not significantly associated with SBIs in our logistic regression models (adjusted Odds Ratio 1.40, 95% confidence interval 0.92-2.12). Conclusions: Serious bacterial infections were uncommon in our population. There is no statistically significant association between hyperpyrexia and SBIs in well-appearing pediatric patients presenting to the ED with fever. The lack of a statistically significant association between hyperpyrexia and SBIs argues that clinicians should be cautious using hyperpyrexia as an independent risk factor for SBIs. More research is needed to identify independent and grouped SBI risk factors in well-appearing pediatric patients presenting to the ED.

Characteristics and Clinical Outcomes of Vaccine-Eligible US Children Under-5 Years Hospitalized for Acute COVID-19 in a National Network.

BACKGROUND AND OBJECTIVES: In June 2022, the mRNA COVID-19 vaccination was recommended for young children. We examined clinical characteristics and factors associated with vaccination status among vaccine-eligible young children hospitalized for acute COVID-19. METHODS: We enrolled inpatients 8 months to <5 years of age with acute community-acquired COVID-19 across 28 US pediatric hospitals from September 20, 2022 to May 31, 2023. We assessed demographic and clinical factors, including the highest level of respiratory support, and vaccination status defined as unvaccinated, incomplete, or complete primary series [at least 2 (Moderna) or 3 (Pfizer-BioNTech) mRNA vaccine doses ≥14 days before hospitalization]. RESULTS: Among 597 children, 174 (29.1%) patients were admitted to the intensive care unit and 75 (12.6%) had a life-threatening illness, including 51 (8.5%) requiring invasive mechanical ventilation. Children with underlying respiratory and neurologic/neuromuscular conditions more frequently received higher respiratory support. Only 4.5% of children hospitalized for COVID-19 (n = 27) had completed their primary COVID-19 vaccination series and 7.0% (n = 42) of children initiated but did not complete their primary series. Among 528 unvaccinated children, nearly half (n = 251) were previously healthy, 3 of them required extracorporeal membrane oxygenation for acute COVID-19 and 1 died. CONCLUSIONS: Most young children hospitalized for acute COVID-19, including most children admitted to the intensive care unit and with life-threatening illness, had not initiated COVID-19 vaccination despite being eligible. Nearly half of these children had no underlying conditions. Of the small percentage of children who initiated a COVID-19 primary series, most had not completed it before hospitalization.

Infants Admitted to US Intensive Care Units for RSV Infection During the 2022 Seasonal Peak.

Importance: Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections (LRTIs) and infant hospitalization worldwide. Objective: To evaluate the characteristics and outcomes of RSV-related critical illness in US infants during peak 2022 RSV transmission. Design, Setting, and Participants: This cross-sectional study used a public health prospective surveillance registry in 39 pediatric hospitals across 27 US states. Participants were infants admitted for 24 or more hours between October 17 and December 16, 2022, to a unit providing intensive care due to laboratory-confirmed RSV infection. Exposure: Respiratory syncytial virus. Main Outcomes and Measures: Data were captured on demographics, clinical characteristics, signs and symptoms, laboratory values, severity measures, and clinical outcomes, including receipt of noninvasive respiratory support, invasive mechanical ventilation, vasopressors or extracorporeal membrane oxygenation, and death. Mixed-effects multivariable log-binomial regression models were used to assess associations between intubation status and demographic factors, gestational age, and underlying conditions, including hospital as a random effect to account for between-site heterogeneity. Results: The first 15 to 20 consecutive eligible infants from each site were included for a target sample size of 600. Among the 600 infants, the median (IQR) age was 2.6 (1.4-6.0) months; 361 (60.2%) were male, 169 (28.9%) were born prematurely, and 487 (81.2%) had no underlying medical conditions. Primary reasons for admission included LRTI (594 infants [99.0%]) and apnea or bradycardia (77 infants [12.8%]). Overall, 143 infants (23.8%) received invasive mechanical ventilation (median [IQR], 6.0 [4.0-10.0] days). The highest level of respiratory support for nonintubated infants was high-flow nasal cannula (243 infants [40.5%]), followed by bilevel positive airway pressure (150 infants [25.0%]) and continuous positive airway pressure (52 infants [8.7%]). Infants younger than 3 months, those born prematurely (gestational age <37 weeks), or those publicly insured were at higher risk for intubation. Four infants (0.7%) received extracorporeal membrane oxygenation, and 2 died. The median (IQR) length of hospitalization for survivors was 5 (4-10) days. Conclusions and Relevance: In this cross-sectional study, most US infants who required intensive care for RSV LRTIs were young, healthy, and born at term. These findings highlight the need for RSV preventive interventions targeting all infants to reduce the burden of severe RSV illness.

Community-Onset Bacterial Coinfection in Children Critically Ill With Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

Background: Community-onset bacterial coinfection in adults hospitalized with coronavirus disease 2019 (COVID-19) is reportedly uncommon, though empiric antibiotic use has been high. However, data regarding empiric antibiotic use and bacterial coinfection in children with critical illness from COVID-19 are scarce. Methods: We evaluated children and adolescents aged <19 years admitted to a pediatric intensive care or high-acuity unit for COVID-19 between March and December 2020. Based on qualifying microbiology results from the first 3 days of admission, we adjudicated whether patients had community-onset bacterial coinfection. We compared demographic and clinical characteristics of those who did and did not (1) receive antibiotics and (2) have bacterial coinfection early in admission. Using Poisson regression models, we assessed factors associated with these outcomes. Results: Of the 532 patients, 63.3% received empiric antibiotics, but only 7.1% had bacterial coinfection, and only 3.0% had respiratory bacterial coinfection. In multivariable analyses, empiric antibiotics were more likely to be prescribed for immunocompromised patients (adjusted relative risk [aRR], 1.34 [95% confidence interval {CI}, 1.01-1.79]), those requiring any respiratory support except mechanical ventilation (aRR, 1.41 [95% CI, 1.05-1.90]), or those requiring invasive mechanical ventilation (aRR, 1.83 [95% CI, 1.36-2.47]) (compared with no respiratory support). The presence of a pulmonary comorbidity other than asthma (aRR, 2.31 [95% CI, 1.15-4.62]) was associated with bacterial coinfection. Conclusions: Community-onset bacterial coinfection in children with critical COVID-19 is infrequent, but empiric antibiotics are commonly prescribed. These findings inform antimicrobial use and support rapid de-escalation when evaluation shows coinfection is unlikely.

A Description of COVID-19-Directed Therapy in Children Admitted to US Intensive Care Units 2020.

BACKGROUND: It is unclear how acute coronavirus disease 2019 (COVID-19)-directed therapies are used in children with life-threatening COVID-19 in US hospitals. We described characteristics of children hospitalized in the intensive care unit or step-down unit (ICU/SDU) who received COVID-19-directed therapies and the specific therapies administered. METHODS: Between March 15, 2020 and December 27, 2020, children <18 years of age in the ICU/SDU with acute COVID-19 at 48 pediatric hospitals in the United States were identified. Demographics, laboratory values, and clinical course were compared in children who did and did not receive COVID-19-directed therapies. Trends in COVID-19-directed therapies over time were evaluated. RESULTS: Of 424 children in the ICU/SDU, 235 (55%) received COVID-19-directed therapies. Children who received COVID-19-directed therapies were older than those who did not receive COVID-19-directed therapies (13.3 [5.6-16.2] vs 9.8 [0.65-15.9] years), more had underlying medical conditions (188 [80%] vs 104 [55%]; difference = 25% [95% CI: 16% to 34%]), more received respiratory support (206 [88%] vs 71 [38%]; difference = 50% [95% CI: 34% to 56%]), and more died (8 [3.4%] vs 0). Of the 235 children receiving COVID-19-directed therapies, 172 (73%) received systemic steroids and 150 (64%) received remdesivir, with rising remdesivir use over the study period (14% in March/April to 57% November/December). CONCLUSION: Despite the lack of pediatric data evaluating treatments for COVID-19 in critically ill children, more than half of children requiring intensive or high acuity care received COVID-19-directed therapies.

Severe Acute Respiratory Syndrome Coronavirus 2 Clinical Syndromes and Predictors of Disease Severity in Hospitalized Children and Youth.

OBJECTIVE: To characterize the demographic and clinical features of pediatric severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) syndromes and identify admission variables predictive of disease severity. STUDY DESIGN: We conducted a multicenter, retrospective, and prospective study of pediatric patients hospitalized with acute SARS-CoV-2 infections and multisystem inflammatory syndrome in children (MIS-C) at 8 sites in New York, New Jersey, and Connecticut. RESULTS: We identified 281 hospitalized patients with SARS-CoV-2 infections and divided them into 3 groups based on clinical features. Overall, 143 (51%) had respiratory disease, 69 (25%) had MIS-C, and 69 (25%) had other manifestations including gastrointestinal illness or fever. Patients with MIS-C were more likely to identify as non-Hispanic black compared with patients with respiratory disease (35% vs 18%, P = .02). Seven patients (2%) died and 114 (41%) were admitted to the intensive care unit. In multivariable analyses, obesity (OR 3.39, 95% CI 1.26-9.10, P = .02) and hypoxia on admission (OR 4.01; 95% CI 1.14-14.15; P = .03) were predictive of severe respiratory disease. Lower absolute lymphocyte count (OR 8.33 per unit decrease in 109 cells/L, 95% CI 2.32-33.33, P = .001) and greater C-reactive protein (OR 1.06 per unit increase in mg/dL, 95% CI 1.01-1.12, P = .017) were predictive of severe MIS-C. Race/ethnicity or socioeconomic status were not predictive of disease severity. CONCLUSIONS: We identified variables at the time of hospitalization that may help predict the development of severe SARS-CoV-2 disease manifestations in children and youth. These variables may have implications for future prognostic tools that inform hospital admission and clinical management.

Preparing for an Influenza Pandemic: Hospital Acceptance Study of Filtering Facepiece Respirator Decontamination Using Ultraviolet Germicidal Irradiation.

OBJECTIVES: Predictions estimate supplies of filtering facepiece respirators (FFRs) would be limited in the event of a severe influenza pandemic. Ultraviolet decontamination and reuse (UVDR) is a potential approach to mitigate an FFR shortage. A field study sought to understand healthcare workers' perspectives and potential logistics issues related to implementation of UVDR methods for FFRs in hospitals. METHODS: Data were collected at three hospitals using a structured guide to conduct 19 individual interviews, 103 focus group interviews, and 285 individual surveys. Data were then evaluated using thematic analysis to reveal key themes. RESULTS: Data revealed noteworthy variation in FFR use across the sample, along with preferences and requirements for the use of UVDR, unit design, and FFR reuse. Based on a scale of 1 (low) to 10 (high), the mean perception of safety in a high mortality pandemic wearing no FFR was 1.25 of 10, wearing an FFR for an extended period without decontamination was 4.20 of 10, and using UVDR was 7.72 of 10. CONCLUSIONS: In addition to technical design and development, preparation and training will be essential to successful implementation of a UVDR program. Ultraviolet decontamination and reuse program design and implementation must account for actual clinical practice, compliance with regulations, and practical financial considerations to be successfully adopted so that it can mitigate potential FFR shortages in a pandemic.

Two Neonates With Postnatally Acquired Tickborne Infections.

Neonatal tick bites place infants at risk for acquiring infections that have rarely or never been documented in this age group. We describe 2 rare cases of tickborne infection in neonates. The first patient presented with multiple erythema migrans and fever, leading to a diagnosis of early disseminated Lyme disease. The second patient presented with irritability, fever, and worsening anemia due to babesiosis. Both infants had been bitten by arthropods fitting the description of ticks before the onset of symptoms. Our cases demonstrate the clinical course of 2 common tickborne infections occurring at an atypical age, opening the door to new, complex questions for which little guiding data exists. As tickborne infections become more prevalent, we expect other clinicians will be faced with similarly challenging neonatal cases. Providers must use past experience and a keen eye to identify neonates with tickborne infections and sort through their optimal diagnosis and management. In this article, we raise some of the questions we faced and discuss our conclusions.

Provider Knowledge, Attitudes, and Practices Regarding Bronchiolitis and Pneumonia Guidelines.

BACKGROUND AND OBJECTIVES: Practice guidelines have been published for bronchiolitis and community-acquired pneumonia (CAP), but little is known about pediatricians' knowledge of and attitudes toward these guidelines since their publication. METHODS: We surveyed pediatric providers at 6 children's hospitals in the New York City area. Two vignettes, an infant with bronchiolitis and a child with CAP, were provided, and respondents were asked about management. Associations between respondent characteristics and their reported practices were examined using χ2 and Fisher's exact tests. Associations between questions probing knowledge and attitude barriers relevant to guideline adherence and reported practices were examined using Cochran-Mantel-Haenszel relative risk estimates. RESULTS: Of 283 respondents, 58% were trainees; 57% of attending physician respondents had finished training within 10 years. Overall, 76% and 45% of respondents reported they had read the bronchiolitis and CAP guidelines, respectively. For the bronchiolitis vignette, 40% reported ordering a chest radiograph (CXR), and 38% prescribed bronchodilators (neither recommended). For the CAP vignette, 38% prescribed ceftriaxone (not recommended). Study site, level of training, and practice locations were associated with nonrecommended practices. Site-adjusted knowledge and attitude barriers were used to identify that those who agreed CXRs were useful in managing bronchiolitis were more likely to order CXRs, and those who felt bronchodilators shortened length of stay were more likely to prescribe them. Concerns about ampicillin resistance and lack of confidence using local susceptibility patterns to guide prescribing were associated with ordering ceftriaxone. CONCLUSIONS: Provider-level factors and knowledge gaps were associated with ordering nonrecommended treatments for bronchiolitis and CAP.

Antimicrobial Stewardship Barriers and Goals in Pediatric Oncology and Bone Marrow Transplantation: A Survey of Antimicrobial Stewardship Practitioners.

We undertook a cross-sectional survey of antimicrobial stewardship clinicians in North America and Australasia regarding practices, goals, and barriers to implementation of stewardship for pediatric oncology patients. Goals and barriers were similar regardless of clinician or institutional characteristics and geographic location. Strategies addressing these factors could help optimize antimicrobial use.

Congenital candidiasis: an uncommon skin eruption presenting at birth.

We present the case of a preterm neonate who was born with respiratory distress and a papulovesicular rash that was diagnosed as congenital candidiasis (CC). The mother was asymptomatic. The cutaneous eruption and respiratory distress improved following treatment with systemic antifungals. Congenital candidiasis ranges in presentation from isolated cutaneous involvement to severe multisystem disease. Given its rarity among neonatal skin eruptions, heightened suspicion is required for prompt diagnosis and treatment.

Bordetella holmesii: initial genomic analysis of an emerging opportunist.

Bordetella holmesii is an emerging opportunistic pathogen that causes respiratory disease in healthy individuals and invasive infections among patients lacking splenic function. We used 16S rRNA gene analysis to confirm B. holmesii as the cause of bacteremia in a child with sickle cell disease. Semiconductor-based draft genome sequencing provided insight into B. holmesii phylogeny and potential virulence mechanisms and also identified a toluene-4-monoxygenase locus unique among bordetellae.

Genome Sequence of the Human Abscess Isolate Streptococcus intermedius BA1.

Streptococcus intermedius is a human pathogen with a propensity for abscess formation. We report a high-quality draft genome sequence of S. intermedius strain BA1, an isolate from a human epidural abscess. This sequence provides insight into the biology of S. intermedius and will aid investigations of pathogenicity.

DNase inhibits Gardnerella vaginalis biofilms in vitro and in vivo.

Bacterial vaginosis is a highly prevalent and poorly understood polymicrobial disorder of the vaginal microbiota, with significant adverse sequelae. Gardnerella vaginalis predominates in bacterial vaginosis. Biofilms of G. vaginalis are present in human infections and are implicated in persistent disease, treatment failure, and transmission. Here we demonstrate that G. vaginalis biofilms contain extracellular DNA, which is essential to their structural integrity. Enzymatic disruption of this DNA specifically inhibits biofilms, acting on both newly forming and established biofilms. DNase liberates bacteria from the biofilm to supernatant fractions and potentiates the activity of metronidazole, an antimicrobial agent used in the treatment of bacterial vaginosis. Using a new murine vaginal colonization model for G. vaginalis, we demonstrate >10-fold inhibition of G. vaginalis colonization by DNase. We conclude that DNase merits investigation as a potential nonantibiotic adjunct to existing bacterial vaginosis therapies in order to decrease the risk of chronic infection, recurrence, and associated morbidities.

Retrocyclin inhibits Gardnerella vaginalis biofilm formation and toxin activity.

BACKGROUND: Retrocyclins are cyclic antimicrobial peptides that have been shown to be both broadly active and safe in animal models. RC-101, a synthetic retrocyclin, targets important human pathogens and is a candidate vaginal microbicide. Its activity against microbes associated with bacterial vaginosis is unknown. METHODS: We investigated the effect of RC-101 on toxin activity, bacterial growth and biofilm formation of Gardnerella vaginalis in vitro. RESULTS: RC-101 potently inhibits the cytolytic activity of vaginolysin, the Gardnerella vaginalis toxin, on both erythrocytes and nucleated cells. RC-101 lacks inhibitory activity against planktonic G. vaginalis but markedly decreases biofilm formation. CONCLUSIONS: These dual properties, toxin inhibition and biofilm retardation, justify further exploration of RC-101 as a candidate agent for bacterial vaginosis prevention.

Comparing the clinical severity of the first versus second wave of 2009 Influenza A (H1N1) in a New York City pediatric healthcare facility.

OBJECTIVE: We previously reported the epidemiology of 2009 Influenza A (H1N1) in our pediatric healthcare facility in New York City during the first wave of illness (May-July 2009). We hypothesized that compared with the first wave, the second wave would be characterized by increased severity of illness and mortality. DESIGN: : Case series conducted from May 2009 to April 2010. SETTING: Pediatric emergency departments and inpatient facilities of New York-Presbyterian Hospital. PATIENTS: All hospitalized patients ÷ 18 yrs of age with positive laboratory tests for influenza A. MEASUREMENTS AND MAIN RESULTS: We compared severity of illness during the first and second wave assessed by the number of hospitalized children, including those in the pediatric intensive care unit, bacterial superinfections, and mortality rate. Compared to the first wave, fewer children were hospitalized during the second wave (n = 115 vs. 76), but a comparable portion were admitted to the pediatric intensive care unit (30.4% vs. 19.7%; p = .10). Pediatric Risk of Mortality III scores, length of hospitalization in the pediatric intensive care unit, incidence of respiratory failure and pneumonia, and peak oxygenation indices were similar during both waves. Bacterial superinfections were comparable in the first vs. second wave (3.5% vs. 1.3%). During the first wave, no child received extracorporeal membrane oxygenation and one died, while during the second wave, one child received extracorporeal membrane oxygenation and there were no deaths. CONCLUSIONS: At our pediatric healthcare facility in New York City, fewer children were hospitalized with 2009 Influenza A (H1N1) during the second wave, but both waves had a similar spectrum of illness severity and low mortality rate.

Ineffectiveness of handwashing with lotion soap to remove nosocomial bacterial pathogens persisting on fingertips: a major link in their intrahospital spread.

The effectiveness of five 30-second handwashes with a non-antiseptic lotion soap to remove nosocomial pathogens (10(8) CFU) applied to fingertips was studied. CFU for all species dropped rapidly after the first handwash; persistence (10 to 15 CFU) was maintained thereafter. Wiping hands with an antiseptic (70% isopropyl or 10% povidone-iodine) sponge removed persisters.