Risk Factors for Pediatric Critical COVID-19: A Systematic Review and Meta-Analysis.

BACKGROUND: Risk stratification is a cornerstone of the Pediatric Infectious Diseases Society COVID-19 treatment guidance. This systematic review and meta-analysis aimed to define the clinical characteristics and comorbidities associated with critical COVID-19 in children and adolescents. METHODS: Two independent reviewers screened the literature (Medline and EMBASE) for studies published through August 31, 2023, that reported outcome data on patients aged ≤21 years with COVID-19. Critical disease was defined as an invasive mechanical ventilation requirement, intensive care unit admission, or death. Random effects models were used to estimate pooled odds ratios (OR) with 95% confidence intervals (CI), and heterogeneity was explored through subgroup analyses. RESULTS: Among 10,178 articles, 136 studies met the inclusion criteria for review. Data from 70 studies, which collectively examined 172,165 children and adolescents with COVID-19, were pooled for meta-analysis. In previously healthy children, the absolute risk of critical disease from COVID-19 was 4% (95% CI, 1%-10%). Compared with no comorbidities, the pooled OR for critical disease was 3.95 (95% CI, 2.78-5.63) for the presence of one comorbidity and 9.51 (95% CI, 5.62-16.06) for ≥2 comorbidities. Key risk factors included cardiovascular and neurological disorders, chronic pulmonary conditions (excluding asthma), diabetes, obesity, and immunocompromise, all with statistically significant ORs >2.00. CONCLUSIONS: While the absolute risk for critical COVID-19 in children and adolescents without underlying health conditions is relatively low, the presence of one or more comorbidities was associated with markedly increased risk. These findings support the importance of risk stratification in tailoring pediatric COVID-19 management.

Guidance for prevention and management of COVID-19 in children and adolescents: A consensus statement from the Pediatric Infectious Diseases Society Pediatric COVID-19 Therapies Taskforce.

BACKGROUND: Since November 2019, the SARS-CoV-2 pandemic has created challenges for preventing and managing COVID-19 in children and adolescents. Most research to develop new therapeutic interventions or to repurpose existing ones has been undertaken in adults, and although most cases of infection in pediatric populations are mild, there have been many cases of critical and fatal infection. Understanding the risk factors for severe illness and the evidence for safety, efficacy, and effectiveness of therapies for COVID-19 in children is necessary to optimize therapy. METHODS: A panel of experts in pediatric infectious diseases, pediatric infectious diseases pharmacology, and pediatric intensive care medicine from 21 geographically diverse North American institutions was re-convened. Through a series of teleconferences and web-based surveys and a systematic review with meta-analysis of data for risk factors, a guidance statement comprising a series of recommendations for risk stratification, treatment, and prevention of COVID-19 was developed and refined based on expert consensus. RESULTS: There are identifiable clinical characteristics that enable risk stratification for patients at risk for severe COVID-19. These risk factors can be used to guide the treatment of hospitalized and non-hospitalized children and adolescents with COVID-19 and to guide preventative therapy where options remain available.

Risk Factors for Pediatric Critical COVID-19: A Systematic Review and Meta-Analysis.

Background: Risk stratification is a cornerstone of the Pediatric Infectious Diseases Society COVID-19 treatment guidance. This systematic review and meta-analysis aimed to define the clinical characteristics and comorbidities associated with critical COVID-19 in children and adolescents. Methods: Two independent reviewers screened the literature (Medline and EMBASE) for studies published through August 2023 that reported outcome data on patients aged ≤21 years with COVID-19. Critical disease was defined as an invasive mechanical ventilation requirement, intensive care unit admission, or death. Random effects models were used to estimate pooled odds ratios (OR) with 95% confidence intervals (CI), and heterogeneity was explored through subgroup analyses. Results: Among 10,178 articles, 136 studies met the inclusion criteria for review. Data from 70 studies, which collectively examined 172,165 children and adolescents with COVID-19, were pooled for meta-analysis. In previously healthy children, the absolute risk of critical disease from COVID-19 was 4% (95% CI, 1%-10%). Compared with no comorbidities, the pooled OR for critical disease was 3.95 (95% CI, 2.78-5.63) for presence of one comorbidity and 9.51 (95% CI, 5.62-16.06) for ≥2 comorbidities. Key risk factors included cardiovascular and neurological disorders, chronic pulmonary conditions (excluding asthma), diabetes, obesity, and immunocompromise, all with statistically significant ORs >2.00. Conclusions: While the absolute risk for critical COVID-19 in children and adolescents without underlying health conditions is relatively low, the presence of one or more comorbidities was associated with markedly increased risk. These findings support the importance of risk stratification in tailoring pediatric COVID-19 management.

Monoclonal Antibodies for COVID-19 in Children: Case Series Should be Just the Start.

Two new articles describe the use and implementation of monoclonal antibodies to treat COVID-19 in children. While these studies provide valuable guidance for pediatric clinicians, more studies of monoclonal antibodies and other COVID-19 therapies in children are needed.

Updated Guidance on Use and Prioritization of Monoclonal Antibody Therapy for Treatment of COVID-19 in Adolescents.

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.

Evaluation of the Infectious Diseases Society of America's Core Antimicrobial Stewardship Curriculum for Infectious Diseases Fellows.

BACKGROUND: Antimicrobial stewardship (AS) programs are required by Centers for Medicare and Medicaid Services and should ideally have infectious diseases (ID) physician involvement; however, only 50% of ID fellowship programs have formal AS curricula. The Infectious Diseases Society of America (IDSA) formed a workgroup to develop a core AS curriculum for ID fellows. Here we study its impact. METHODS: ID program directors and fellows in 56 fellowship programs were surveyed regarding the content and effectiveness of their AS training before and after implementation of the IDSA curriculum. Fellows' knowledge was assessed using multiple-choice questions. Fellows completing their first year of fellowship were surveyed before curriculum implementation ("pre-curriculum") and compared to first-year fellows who complete the curriculum the following year ("post-curriculum"). RESULTS: Forty-nine (88%) program directors and 105 (67%) fellows completed the pre-curriculum surveys; 35 (64%) program directors and 79 (50%) fellows completed the post-curriculum surveys. Prior to IDSA curriculum implementation, only 51% of programs had a "formal" curriculum. After implementation, satisfaction with AS training increased among program directors (16% to 68%) and fellows (51% to 68%). Fellows' confidence increased in 7/10 AS content areas. Knowledge scores improved from a mean of 4.6 to 5.1 correct answers of 9 questions (P = .028). The major hurdle to curriculum implementation was time, both for formal teaching and for e-learning. CONCLUSIONS: Effective AS training is a critical component of ID fellowship training. The IDSA Core AS Curriculum can enhance AS training, increase fellow confidence, and improve overall satisfaction of fellows and program directors.

Pediatric antimicrobial stewardship practices at discharge: A national survey.

We surveyed pediatric antimicrobial stewardship program (ASP) site leaders within the Sharing Antimicrobial Reports for Pediatric Stewardship collaborative regarding discharge stewardship practices. Among 67 sites, 13 (19%) reported ASP review of discharge antimicrobial prescriptions. These findings highlight discharge stewardship as a potential opportunity for improvement during the hospital-to-home transition.

A National Survey of Outpatient Parenteral Antibiotic Therapy Practices.

We conducted a national survey of pediatric infectious diseases (ID) clinicians on outpatient parenteral antibiotic therapy (OPAT) practices and post-discharge ID follow-up. Only 15% of sites required ID consultation for all OPAT. ID division resources for post-discharge care varied. Opportunities exist to increase ID involvement in post-discharge management of serious infections.

Investing in the Future: A Role for Professional Societies to Prepare the Next Generation of Healthcare Leaders Through Curriculum Development and Dissemination.

Professional societies serve many functions that benefit constituents; however, few professional societies have undertaken the development and dissemination of formal, national curricula to train the future workforce while simultaneously addressing significant healthcare needs. The Infectious Diseases Society of America (IDSA) has developed 2 curricula for the specific purpose of training the next generation of clinicians to ensure the future infectious diseases (ID) workforce is optimally trained to lead antimicrobial stewardship programs and equipped to meet the challenges of multidrug resistance, patient safety, and healthcare quality improvement. A core curriculum was developed to provide a foundation in antimicrobial stewardship for all ID fellows, regardless of career path. An advanced curriculum was developed for ID fellows specifically pursuing a career in antimicrobial stewardship. Both curricula will be broadly available in the summer of 2021 through the IDSA website.

Outpatient Fluoroquinolone Use in Children, 2000-2018.

BACKGROUND: While fluoroquinolones are commonly used in adults, the use in children has been low. Since 2000, there were 3 US Food and Drug Administration (FDA) Boxed warnings regarding fluoroquinolones (2008, 2013, and 2016). Our objective was to describe the use of fluoroquinolones in children and assess the impact of 3 recent FDA warnings on fluoroquinolone use. METHODS: From 2000 to 2018, we assessed claims for all outpatient prescription fills to measure the use of systemic fluoroquinolones and other broad-spectrum antibiotics in children  less than 18 years old in the MarketScan Commercial Claims and Encounters database. We describe demographics, indication for antibiotic, and clinical characteristics. To assess the impact of FDA warnings on fill rates, we conducted an interrupted time-series analysis. RESULTS: The cohort included 34.6 million unique beneficiaries less than 18 years old with 441 062 fluoroquinolone fills (5.5 fills per 1000 person-years). The fluoroquinolone fill rate was highest among children > 11 years old. Urinary tract infection was the most common associated diagnosis (21.8%). Since 2008, the fluoroquinolone fill rate has declined. By the end of the study period in December 2018, in the (counterfactual) absence of the FDA warnings, fluoroquinolone fill rate would have been 7.5 (95% confidence interval [CI]: 5.2-9.7); however, the corresponding rate in observed data was 2.8 (95% CI: 1.7-3.9). CONCLUSIONS: Fluoroquinolone use was low compared with other common broad-spectrum antibiotics and declining trends over time were associated with FDA warnings, even though these warnings were not pediatric specific. Future work should assess the adverse events at issue in these warnings in children.

An Ambulatory Antimicrobial Stewardship Initiative to Improve Diagnosis and Treatment of Urinary Tract Infections in Children.

BACKGROUND: Antibiotic stewardship efforts should standardize treatment of common infections when possible. Urinary tract infections (UTIs) are common in children and require appropriate diagnostic methods and treatment. A pediatric emergency department (ED) identified an opportunity to improve care by standardizing uncomplicated UTI diagnostic testing and treatment according to local bacterial resistance patterns from January 2017 to December 2018. METHODS: Using the Model for Improvement, researchers undertook a quality improvement (QI) initiative to standardize the diagnosis and treatment of uncomplicated UTI in children ages 3 months to 12 years in a pediatric ED. Multiple Plan-Do-Study-Act (PDSA) cycles were used, engaging both nurses and physicians, to implement an evidence-based clinical algorithm. Primary aims were to achieve 100% of targeted patients with suspected UTI having appropriately ordered and collected specimens and to increase the frequency of targeted patients receiving algorithm-recommended antibiotics at discharge to 80%. Balancing measures included ED length of stay and revisits to the ED related to UTI. RESULTS: During this initiative, 458 children were assessed for UTI, of whom 75 received a UTI diagnosis. Guideline-concordant urine collection procedure improved from 54.7% to 96.2%. After project initiation, 100% of all antibiotic prescriptions for UTI were guideline-concordant. These changes have been sustained for 19 months since the initiative began. There was no change in UTI-related ED revisits or ED length of stay. CONCLUSIONS: This QI initiative achieved standardization of specimen collection and treatment for pediatric UTI in the ED setting, and no adverse outcomes were observed at the institution.

Intensity of Therapy for Malignancy and Risk for Recurrent and Complicated Clostridium difficile Infection in Children.

Clostridium difficile infection (CDI) is common in pediatric oncology patients and is often associated with recurrences and complications. We hypothesized that higher intensity of chemotherapy would be associated with these outcomes. We conducted a retrospective cohort study including all cases of primary CDI in children with malignancy in our institution for over 7 years. Intensity of chemotherapy was measured by the Intensity of Treatment Rating Scale, third edition, ranging from level 1 (minimal) to 4 (highest). Outcomes included recurrence within both 56 and 180 days, CDI-associated complications, and primary treatment failure (PTF). Risk of recurrence was compared using Cox proportional hazards regression. Among 192 patients with CDI and malignancy, 122 met inclusion criteria. CDI recurred in 27% (31/115) of patients followed for 56 days and 46% (48/104) of patients followed for 180 days. Fourteen patients (11.4%) had a CDI-associated complication, including 4 intensive care unit admissions and 3 surgical procedures, but no deaths. Ten patients (8.2%) had PTF. Although PTF and severe complications were infrequent, recurrence was common in our cohort. None of these outcomes were associated with level of treatment intensity. More research is required to assess oncologic and nononcologic risk factors for CDI recurrence, PTF, and severe CDI-associated complications.

Improvements in Antimicrobial Prescribing and Outcomes in Pediatric Complicated Appendicitis.

BACKGROUND: Complicated appendicitis, characterized by perforation and/or peritonitis, is common in children, and late infectious complications are frequent. The best antibiotic treatment approach is unknown, resulting in substantial variation in care. We evaluated the effects of 2 successive interventions, an antimicrobial stewardship program (ASP) and a condition-specific clinical practice guideline (CPG), on antimicrobial utilization and patient outcomes in these patients. METHODS: The ASP at our institution was begun in March 2012. The CPG, a standardized antibiotic treatment, was implemented in July 2013. We reviewed every case of complicated appendicitis managed with early appendectomy between January 2011 and October 2014. Patients were thus divided into 3 eras based on their exposure to the following: (1) neither intervention, (2) ASP only or (3) both ASP and CPG. We compared measures of antibiotic utilization and clinical outcomes among the 3 eras. RESULTS: A total of 313 patients were included in the study: 91 exposed to neither intervention; 100 exposed to only the ASP; and 122 exposed to both interventions. With ASP implementation, there were declines in the use of unnecessarily broad or toxic antibiotic regimens. With CPG implementation, there was a decrease in total antibiotic utilization and discharges with intravenous antibiotics. Compliance with CPG-recommended antibiotics exceeded 90%. There was no significant change in overall adverse events; there was a decline in the incidence of surgical-site infections in patients exposed to both interventions. CONCLUSIONS: Complicated appendicitis is an important target for antimicrobial stewardship and quality improvement efforts. A condition-specific CPG can improve both antimicrobial utilization and clinical outcomes.

Reducing Antimicrobial Use in an Academic Pediatric Institution: Evaluation of the Effectiveness of a Prospective Audit With Real-Time Feedback.

INTRODUCTION: Antimicrobial use is decreasing across freestanding children's hospitals, predominantly in institutions with antimicrobial stewardship programs (ASPs) in place. A highly effective ASP should effect a greater decrease in use than predicted by existing trends. Antimicrobial stewardship programs depend on clinician adherence to program recommendations, but little is known about factors associated with adherence. METHODS: Parenteral antimicrobial-use data for our institution and 43 additional freestanding children's hospitals were obtained and normalized for patient census. Segmental linear regression was used to compare rates of change of parenteral antimicrobial use before and after ASP implementation. Time-series models were developed to predict use in the absence of intervention. The odds of adherence to ASP recommendations were determined based on provider characteristics and recommendation type. RESULTS: In the 38 months before ASP implementation, parenteral antimicrobial use was decreasing at our hospital by 3.7%/year, similar to the 3.4%/year found across children's hospitals. The rate of change after implementation of the ASP at our hospital was 11.1%/year, compared to 5.6%/year for other hospitals over the same period. Of 643 interventions, teams adhered with recommendations in 495 cases (77.0%). According to adjusted analysis, primary service was not associated with adherence (P = .356). There was an association between adherence and the role of the clinician receiving a recommendation (P = .009) and the recommendation type (P = .009). CONCLUSIONS: Understanding factors associated with adherence to ASP recommendations can help those who administer such programs to strategize interventions for maximizing efficacy. Our findings reveal the value of a formal ASP in reducing use when controlling for secular trends.