The Leaders in Epidemiology, Antimicrobial Stewardship, and Public Health (LEAP) Fellowship, a Novel Training Program in Public Health for Infectious Diseases Physicians.

The severe acute respiratory syndrome coronavirus 2 pandemic demonstrated a critical need for partnerships between practicing infectious diseases (ID) physicians and public health departments. The soon-to-launch combined ID and Epidemic Intelligence Service fellowship can only address a fraction of this need, and otherwise US ID training lacks development pathways for physicians aiming to make careers working with public health departments. The Leaders in Epidemiology, Antimicrobial Stewardship, and Public Health (LEAP) fellowship is a model compatible with the current training paradigm with a proven track record of developing careers of long-term collaboration. Established in 2017 by the ID Society of America, Society for Healthcare Epidemiology of America, Pediatric ID Society, and supported by the Centers for Disease Control and Prevention, LEAP is a single-year in-place, structured training for senior trainees and early career ID physicians. In this viewpoint, we describe the LEAP fellowship, its outcomes, and how it could be adapted into ID training.

Durability of Original Monovalent mRNA Vaccine Effectiveness Against COVID-19 Omicron-Associated Hospitalization in Children and Adolescents - United States, 2021-2023.

Pediatric COVID-19 vaccination is effective in preventing COVID-19-related hospitalization, but duration of protection of the original monovalent vaccine during SARS-CoV-2 Omicron predominance merits evaluation, particularly given low coverage with updated COVID-19 vaccines. During December 19, 2021-October 29, 2023, the Overcoming COVID-19 Network evaluated vaccine effectiveness (VE) of ≥2 original monovalent COVID-19 mRNA vaccine doses against COVID-19-related hospitalization and critical illness among U.S. children and adolescents aged 5-18 years, using a case-control design. Too few children and adolescents received bivalent or updated monovalent vaccines to separately evaluate their effectiveness. Most case-patients (persons with a positive SARS-CoV-2 test result) were unvaccinated, despite the high frequency of reported underlying conditions associated with severe COVID-19. VE of the original monovalent vaccine against COVID-19-related hospitalizations was 52% (95% CI = 33%-66%) when the most recent dose was administered <120 days before hospitalization and 19% (95% CI = 2%-32%) if the interval was 120-364 days. VE of the original monovalent vaccine against COVID-19-related hospitalization was 31% (95% CI = 18%-43%) if the last dose was received any time within the previous year. VE against critical COVID-19-related illness, defined as receipt of noninvasive or invasive mechanical ventilation, vasoactive infusions, extracorporeal membrane oxygenation, and illness resulting in death, was 57% (95% CI = 21%-76%) when the most recent dose was received <120 days before hospitalization, 25% (95% CI = -9% to 49%) if it was received 120-364 days before hospitalization, and 38% (95% CI = 15%-55%) if the last dose was received any time within the previous year. VE was similar after excluding children and adolescents with documented immunocompromising conditions. Because of the low frequency of children who received updated COVID-19 vaccines and waning effectiveness of original monovalent doses, these data support CDC recommendations that all children and adolescents receive updated COVID-19 vaccines to protect against severe COVID-19.

Pediatric SARS-CoV-2 Seroprevalence, Oregon, USA, November 1, 2020-June 30, 2022.

We estimated SARS-CoV-2 seroprevalence in children in Oregon, USA, at 6 time points. Seroprevalence increased linearly during November 2020-December 2021 and peaked in February 2022 at 38.8% (95% CI 32.8%-46.5%). We observed no increase in the seroprevalence trend after widespread school reopening. Seroprevalence estimates complement case-based cumulative incidence.

Knowledge, Attitudes, and Perceptions about Antibiotic Stewardship Programs among Neonatology Trainees.

OBJECTIVE: Antibiotic stewardship should be an essential component of neonatology training as neonatal intensive care units (NICU) have unique stewardship needs. Our aim was to assess neonatology fellowship trainees' knowledge, attitudes, and perceptions about antibiotic stewardship to inform sustainable curriculum development. STUDY DESIGN: We distributed an electronic survey to neonatology fellows in the United States over 4 months (January-April 2018) via Accreditation Council for Graduate Medical Education program directors. RESULTS: Of 99 programs in the United States with an estimated 700 fellows, 159 (23%) fellows from 52 training programs (53%) responded to the survey and 139 (87%) provided analyzed responses. Majority of respondents were training in southern (59; 42%) and northeastern (43; 31%) regions and were equally spread across all 3 years of training. One hundred (72%) respondents reported an antibiotic stewardship program (ASP) in their institution. While 86% (120/139) were able to identify the components of an ASP, 59% (82/139) either did not or were unsure if they had received antibiotic stewardship training during fellowship.Furthermore, while answering case studies, 124 (89%) respondents identified the optimal antibiotic for methicillin susceptible Staphylococcus aureus (MSSA) infection and 69 (50%) respondents chose appropriate empiric antibiotics for neonatal meningitis. Notably, fellowship training year was not significantly related to the proportion of incorrect knowledge responses (p = 0.40). Most survey respondents (81; 59%) identified small group sessions as the most useful teaching format, while others chose audit and feedback of individual prescribing behavior (52; 38%) and didactic lectures (52; 38%). Finally, ninety-five (69%) respondents preferred trainee-led ASP interventions targeting focal areas such as antifungal and surgical prophylaxis. CONCLUSION: Antibiotic stewardship is a critical part of neonatology training. Neonatology fellows report variation in access to ASP during their training. Fellows prefer dedicated trainee-led interventions and stewardship curriculum taught within small group settings to promote targeted NICU ASP. KEY POINTS: · Most neonatology programs expose trainees to internal or external antibiotic stewardship programs.. · Over half of fellow trainees are unsure about receiving targeted antibiotic stewardship training.. · Most neonatology fellows prefer a trainee-led antibiotic stewardship intervention..

Risk Factors for SARS-CoV-2 Infection Among US Healthcare Personnel, May-December 2020.

To determine risk factors for coronavirus disease (COVID-19) among US healthcare personnel (HCP), we conducted a case-control analysis. We collected data about activities outside the workplace and COVID-19 patient care activities from HCP with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test results (cases) and from HCP with negative test results (controls) in healthcare facilities in 5 US states. We used conditional logistic regression to calculate adjusted matched odds ratios and 95% CIs for exposures. Among 345 cases and 622 controls, factors associated with risk were having close contact with persons with COVID-19 outside the workplace, having close contact with COVID-19 patients in the workplace, and assisting COVID-19 patients with activities of daily living. Protecting HCP from COVID-19 may require interventions that reduce their exposures outside the workplace and improve their ability to more safely assist COVID-19 patients with activities of daily living.

Notes from the Field: Subacute Sclerosing Panencephalitis Death - Oregon, 2015.

In 2015, the Oregon Health Authority was notified of the death of a boy with subacute sclerosing panencephalitis (SSPE), a rare and fatal complication of measles. The patient, aged 14 years, had reportedly been vaccinated against measles in the Philippines at age 8 months. However, the patient contracted measles at age 1 year while still in the Philippines. He had been well until 2012, when his neurodegenerative symptoms began. After the diagnosis of SSPE was made, the patient remained in home hospice care until his death. Investigators from the Oregon Health Authority and the Oregon Health and Science University reviewed the patient's medical records and interviewed the parents. Vaccination against measles can prevent not only acute measles and its complications, but also SSPE.

Variation in antibiotic susceptibility of uropathogens by age among ambulatory pediatric patients.

We compared uropathogen antibiotic susceptibility across age groups of ambulatory pediatric patients. For Escherichia coli (n=5,099) and other Gram-negative rods (n=626), significant differences (p<0.05) existed across age groups for ampicillin, cefazolin, and trimethoprim/sulfamethoxazole susceptibility. In E. coli, differences in trimethoprim/sulfamethoxazole susceptibility varied from 79% in children under 2 to 88% in ages 16-18 (p<0.001), while ampicillin susceptibility varied from 30% in children under 2 to 53% in ages 2-5 (p=0.015). Uropathogen susceptibility to common urinary anti-infectives may be lower in the youngest children. Further investigation into these differences is needed to facilitate appropriate and prudent treatment of urinary tract infections.

Cefepime-induced Acute Liver Injury in a 5-Year-old Boy.

Cephalosporins are frequently used to treat pediatric infections and are overall well tolerated. Cefepime, a fourth-generation cephalosporin, has an excellent safety profile in pediatrics. We report a rare case of cefepime-induced acute liver injury in a pediatric patient, which resolved after antibiotic discontinuation.

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.

Safety and efficacy of CMX001 as salvage therapy for severe adenovirus infections in immunocompromised patients.

No therapeutic agent has yet been established as the definitive therapy for adenovirus infections. We describe the clinical experience of 13 immunocompromised patients who received CMX001 (hexadecyloxypropyl cidofovir), an orally bioavailable lipid conjugate of cidofovir, for adenovirus disease. We retrospectively analyzed 13 patients with adenovirus disease and viremia treated with CMX001; data were available for ≥ 4 weeks after initiation of CMX001 therapy. Virologic response (VR) was defined as a 99% drop from baseline or undetectable adenovirus DNA in serum. The median age of the group was 6 years (range, 0.92-66 years). One patient had severe combined immunodeficiency, 1 patient was a small bowel transplant recipient, and 11 were allogeneic stem cell transplant recipients. Adenovirus disease was diagnosed at a median of 75 days (range, 15-720 days) after transplantation. All patients received i.v. cidofovir for a median of 21 days (range, 5-90 days) before CMX001 therapy. The median absolute lymphocyte count at CMX001 initiation was 300 cells/µL (range, 7-1500 cells/µL). Eight patients (61.5%) had a ≥ 1 log10 drop in viral load after the first week of therapy. By week 8, 9 patients (69.2%) demonstrated a VR, with a median time to achieve VR of 7 days (range, 3-35 days). The change in absolute lymphocyte count was inversely correlated with the change in log10 viral load only at week 6 (r = -0.74; P = .03). Patients with VR had longer survival than those without VR (median 196 days versus 54.5 days; P = .04). No serious adverse events were attributed to CMX001 during therapy. CMX001 may be a promising therapeutic option for the treatment of severe adenovirus disease in immunocompromised patients.

National Healthcare Safety Network 2018 Baseline Neonatal Standardized Antimicrobial Administration Ratios.

BACKGROUND: The microbiologic etiologies, clinical manifestations, and antimicrobial treatment of neonatal infections differ substantially from infections in adult and pediatric patient populations. In 2019, the Centers for Disease Control and Prevention developed neonatal-specific (Standardized Antimicrobial Administration Ratios SAARs), a set of risk-adjusted antimicrobial use metrics that hospitals participating in the National Healthcare Safety Network's (NHSN's) antimicrobial use surveillance can use in their antibiotic stewardship programs (ASPs). METHODS: The Centers for Disease Control and Prevention, in collaboration with the Vermont Oxford Network, identified eligible patient care locations, defined SAAR agent categories, and implemented neonatal-specific NHSN Annual Hospital Survey questions to gather hospital-level data necessary for risk adjustment. SAAR predictive models were developed using 2018 data reported to NHSN from eligible neonatal units. RESULTS: The 2018 baseline neonatal SAAR models were developed for 7 SAAR antimicrobial agent categories using data reported from 324 neonatal units in 304 unique hospitals. Final models were used to calculate predicted antimicrobial days, the SAAR denominator, for level II neonatal special care nurseries and level II/III, III, and IV NICUs. CONCLUSIONS: NHSN's initial set of neonatal SAARs provides a way for hospital ASPs to assess whether antimicrobial agents in their facility are used at significantly higher or lower rates compared with a national baseline or whether an individual SAAR value is above or below a specific percentile on a given SAAR distribution, which can prompt investigations into prescribing practices and inform ASP interventions.

Practices and activities among healthcare personnel with severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection working in different healthcare settings-ten Emerging Infections Program sites, April-November 2020.

Healthcare personnel with severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection were interviewed to describe activities and practices in and outside the workplace. Among 2,625 healthcare personnel, workplace-related factors that may increase infection risk were more common among nursing-home personnel than hospital personnel, whereas selected factors outside the workplace were more common among hospital personnel.

Symptomatic Acute Myocarditis in 7 Adolescents After Pfizer-BioNTech COVID-19 Vaccination.

Trials of coronavirus disease 2019 (COVID-19) vaccination included limited numbers of children, so they may not have detected rare but important adverse events in this population. We report 7 cases of acute myocarditis or myopericarditis in healthy male adolescents who presented with chest pain all within 4 days after the second dose of Pfizer-BioNTech COVID-19 vaccination. Five patients had fever around the time of presentation. Acute COVID-19 was ruled out in all 7 cases on the basis of negative severe acute respiratory syndrome coronavirus 2 real-time reverse transcription polymerase chain reaction test results of specimens obtained by using nasopharyngeal swabs. None of the patients met criteria for multisystem inflammatory syndrome in children. Six of the 7 patients had negative severe acute respiratory syndrome coronavirus 2 nucleocapsid antibody assay results, suggesting no previous infection. All patients had an elevated troponin. Cardiac MRI revealed late gadolinium enhancement characteristic of myocarditis. All 7 patients resolved their symptoms rapidly. Three patients were treated with nonsteroidal antiinflammatory drugs only, and 4 received intravenous immunoglobulin and corticosteroids. In this report, we provide a summary of each adolescent's clinical course and evaluation. No causal relationship between vaccine administration and myocarditis has been established. Continued monitoring and reporting to the US Food and Drug Administration Vaccine Adverse Event Reporting System is strongly recommended.

Using NHSN's Antimicrobial Use Option to Monitor and Improve Antibiotic Stewardship in Neonates.

BACKGROUND: The Antimicrobial Use (AU) Option of the Centers for Disease Control and Prevention's National Healthcare Safety Network (NHSN) is a surveillance resource that can provide actionable data for antibiotic stewardship programs. Such data are used to enable measurements of AU across hospitals and before, during, and after stewardship interventions. METHODS: We used monthly AU data and annual facility survey data submitted to the NHSN to describe hospitals and neonatal patient care locations reporting to the AU Option in 2017, examine frequencies of most commonly reported agents, and analyze variability in AU rates across hospitals and levels of care. We used results from these analyses in a collaborative project with Vermont Oxford Network to develop neonatal-specific Standardized Antimicrobial Administration Ratio (SAAR) agent categories and neonatal-specific NHSN Annual Hospital Survey questions. RESULTS: As of April 1, 2018, 351 US hospitals had submitted data to the AU Option from at least 1 neonatal unit. In 2017, ampicillin and gentamicin were the most frequently reported antimicrobial agents. On average, total rates of AU were highest in level III NICUs, followed by special care nurseries, level II-III NICUs, and well newborn nurseries. Seven antimicrobial categories for neonatal SAARs were created, and 6 annual hospital survey questions were developed. CONCLUSIONS: A small but growing percentage of US hospitals have submitted AU data from neonatal patient care locations to NHSN, enabling the use of AU data aggregated by NHSN as benchmarks for neonatal antimicrobial stewardship programs and further development of the SAAR summary measure for neonatal AU.

Identification of adenoviruses in specimens from high-risk pediatric stem cell transplant recipients and controls.

Adenovirus infection is an important cause of morbidity and mortality in stem cell transplant recipients. We report species and type-specific analysis from a prospective study of high-risk adenovirus infections following hematopoietic progenitor cell transplantation prior to, during, and after treatment with cidofovir, as well as species analysis of contemporaneously collected samples from control patients. Nine different adenovirus types representing all six recognized species were identified, and mixed infections were commonly found in this group of patients.

High-risk adenovirus-infected pediatric allogeneic hematopoietic progenitor cell transplant recipients and preemptive cidofovir therapy.

ADV has emerged as an important pathogen in children undergoing allogeneic HPCT. A prospective study of the epidemiology of ADV infection and preemptive therapy of high risk ADV infections in children undergoing HPCT was undertaken. Cultures of throat, urine, and stool for viral pathogens and plasma for ADV PCR were obtained prior to transplantation, weekly for the first 100 days, and then monthly for one yr. Children developing high-risk ADV infections were treated preemptively with cidofovir 1 mg/kg/day given three times weekly for three wk. A case-controlled study was performed to identify risk factors for high-risk ADV infections. Seven (18%) of the 38 subjects developed high-risk ADV infections usually within 100 days of HPCT and were preemptively treated with i.v. cidofovir at a dose of 1 mg/kg/dose three times weekly for nine doses. High-risk ADV infections resolved in all seven patients without renal toxicity. CMV viremia occurred in two of seven patients during or shortly after therapy with cidofovir. A case-control study did not identify any risk factors that achieved statistical significance. Treatment with a modified dosing regimen of cidofovir was well-tolerated and high-risk ADV infections resolved in all patients.