Infants admitted to the neonatal intensive care unit, particularly those born preterm, are at high risk for infection due to the combination of an immature immune system, prolonged hospitalization, ...and frequent use of invasive devices. Emerging evidence suggests that multidrug-resistant gram-negative (MDR-GN) infections are increasing in neonatal settings, which directly threatens recent and ongoing advances in contemporary neonatal care. A rising prevalence of antibiotic resistance among common neonatal pathogens compounds the challenge of optimal management of suspected and confirmed neonatal infection. We review the epidemiology of MDR-GN infections in neonates in the United States and internationally, with a focus on extended-spectrum β-lactamase (ESBL)-producing Enterobacterales and carbapenem-resistant Enterobacterales (CRE). We include published single-center studies, neonatal collaborative reports, and national surveillance data. Risk factors for and mechanisms of resistance are discussed. In addition, we discuss current recommendations for empiric antibiotic therapy for suspected infections, as well as definitive treatment options for key MDR organisms. Finally, we review best practices for prevention and identify current knowledge gaps and areas for future research. IMPACT: Surveillance and prevention of MDR-GN infections is a pediatric research priority. A rising prevalence of MDR-GN neonatal infections, specifically ESBL-producing Enterobacterales and CRE, compounds the challenge of optimal management of suspected and confirmed neonatal infection. Future studies are needed to understand the impacts of MDR-GN infection on neonatal morbidity and mortality, and studies of current and novel antibiotic therapies should include a focus on the pharmacokinetics of such agents among neonates.
Sepsis is responsible for a substantial proportion of global childhood morbidity and mortality. However, evidence demonstrates major inaccuracies in the use of the term "sepsis" in clinical practice, ...coding, and research. Current and previous definitions of sepsis have been developed using expert consensus but the specific criteria used to identify children with sepsis have not been rigorously evaluated. Therefore, as part of the Society of Critical Care Medicine's Pediatric Sepsis Definition Taskforce, we will conduct a systematic review to synthesize evidence on individual factors, clinical criteria, or illness severity scores that may be used to identify children with infection who have or are at high risk of developing sepsis-associated organ dysfunction and separately those factors, criteria, and scores that may be used to identify children with sepsis who are at high risk of progressing to multiple organ dysfunction or death.
We will identify eligible studies by searching the following databases: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials.
We will include all randomized trials and cohort studies published between January 1, 2004, and March 16, 2020.
Data extraction will include information related to study characteristics, population characteristics, clinical criteria, and outcomes.
We will calculate sensitivity and specificity of each criterion for predicting sepsis and conduct a meta-analysis if the data allow. We will also provide pooled estimates of overall hospital mortality.
The potential risk factors, clinical criteria, and illness severity scores from this review which identify patients with infection who are at high risk of developing sepsis-associated organ dysfunction and/or progressing to multiple organ dysfunction or death will be used to inform the next steps of the Pediatric Sepsis Definition Taskforce.
Abstract
Background
Starting in November 2020, the US Food and Drug Administration (FDA) has issued Emergency Use Authorizations (EUAs) for multiple novel virus-neutralizing monoclonal antibody ...therapies, including bamlanivimab monotherapy (now revoked), bamlanivimab and etesivimab, casirivimab and imdevimab (REGEN-COV), and sotrovimab, for treatment or postexposure prophylaxis of Coronavirus disease 2019 (COVID-19) in adolescents (≥12 years of age) and adults with certain high-risk conditions. Previous guidance is now updated based on new evidence and clinical experience.
Methods
A panel of experts in pediatric infectious diseases, pediatric infectious diseases pharmacotherapy, and pediatric critical care medicine from 18 geographically diverse US institutions was convened. Through a series of teleconferences and web-based surveys, a guidance statement was developed and refined based on a review of the best available evidence and expert opinion.
Results
The course of COVID-19 in children and adolescents is typically mild, though more severe disease is occasionally observed. Evidence supporting risk stratification is incomplete. Randomized controlled trials have demonstrated the benefit of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-specific monoclonal antibody therapies in adults, but data on safety and efficacy in children or adolescents are limited. Potential harms associated with infusion reactions or anaphylaxis are reportedly low in adults.
Conclusions
Based on evidence available as of August 31, 2021, the panel suggests a risk-based approach to administration of SARS-CoV-2 monoclonal antibody therapy. Therapy is suggested for the treatment of mild to moderate COVID-19 in adolescents (≥12 years of age) at the highest risk of progression to hospitalization or severe disease. Therapeutic decision-making about those at moderate risk of severe disease should be individualized. Use as postexposure prophylaxis could be considered for those at the highest risk who have a high-risk exposure but are not yet diagnosed with COVID-19. Clinicians and health systems should ensure safe and timely implementation of these therapeutics that does not exacerbate existing healthcare disparities.
Monoclonal antibody therapies currently available under Emergency Use Authorization for the treatment of COVID-19 are suggested for adolescents with the highest risk of severe COVID-19 and could be considered with shared decision-making for those at moderate risk of severe COVID-19.
Background:
Community-acquired pneumonia (CAP) is a common indication for antibiotic use in hospitalized children and is a key target for pediatric antimicrobial stewardship programs (ASPs). Building ...upon prior work, we developed and refined an electronic algorithm to identify children hospitalized with CAP and to evaluate the appropriateness of initial antibiotic choice and duration.
Methods:
We performed a cross-sectional study including children 6 months to 17 years hospitalized for CAP between January 1, 2019, and October 31, 2022, at a tertiary-care children’s hospital. CAP was defined electronically as an
International Classification of Disease, Tenth Revision
(ICD-10) code for pneumonia, a chest radiograph or chest computed tomography scan (CT) performed within 48 hours of admission, and systemic antibiotics administered within the first 48 hours of hospitalization and continued for at least 2 days. We applied the following exclusion criteria: patients transferred from another healthcare setting, those who died within 48 hours of hospitalization, children with complex chronic conditions, and those with intensive care unit stays >48 hours. Criteria for appropriate antibiotic choice and duration were defined based on established guidelines. Two physicians performed independent medical record reviews of 80 randomly selected patients (10% sample) to evaluate the performance of the electronic algorithm in (1) identifying patients treated for clinician-diagnosed CAP and (2) classifying antibiotic choice and duration as appropriate. A third physician resolved discrepancies. The electronic algorithm was compared to this medical record review, which served as the reference standard.
Results:
Of 80 children identified by the electronic algorithm, 79 (99%) were diagnosed with CAP based on medical record review. Antibiotic use was classified as the appropriate choice in 75 (94%) of 80 cases, and appropriate duration in 16 (20%) of 80 cases. The sensitivity of the electronic algorithm for identifying appropriate initial antibiotic choice was 94%; specificity could not be calculated because no events of inappropriate antibiotic choice were identified based on chart review. The sensitivity and specificity for determining appropriate duration were 88% and 97%, respectively (Table 1).
Conclusions:
The electronic algorithm accurately identified children hospitalized with CAP and demonstrated acceptable performance for identifying appropriate antibiotic choice and duration. Use of this electronic algorithm may improve the efficiency of stewardship activities and could facilitate alignment with updated accreditation standards. Future studies validating this algorithm at other centers are needed.
Disclosures:
None
Disseminated toxoplasmosis is an uncommon but highly lethal cause of hyperferritinemic sepsis after hematopoietic cell transplantation (HCT). We report two cases of disseminated toxoplasmosis from ...two centers in critically ill adolescents after HCT: a 19-year-old who developed fever and altered mental status on day +19 after HCT and a 20-year-old who developed fever and diarrhea on day +52 after HCT. Both patients developed hyperferritinemia with multiple organ dysfunction syndrome and profound immune dysregulation, which progressed to death despite maximal medical therapies. Because disseminated toxoplasmosis is both treatable and challenging to diagnose, it is imperative that intensivists maintain a high index of suspicion for
Toxoplasma gondii
infection when managing immunocompromised children, particularly in those with known positive
T. gondii
serologies.
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