Real-World Effectiveness of BNT162b2 Against Infection and Severe Diseases in Children and Adolescents.

BACKGROUND: The efficacy of the BNT162b2 vaccine in pediatrics was assessed by randomized trials before the Omicron variant's emergence. The long-term durability of vaccine protection in this population during the Omicron period remains limited. OBJECTIVE: To assess the effectiveness of BNT162b2 in preventing infection and severe diseases with various strains of the SARS-CoV-2 virus in previously uninfected children and adolescents. DESIGN: Comparative effectiveness research accounting for underreported vaccination in 3 study cohorts: adolescents (12 to 20 years) during the Delta phase and children (5 to 11 years) and adolescents (12 to 20 years) during the Omicron phase. SETTING: A national collaboration of pediatric health systems (PEDSnet). PARTICIPANTS: 77 392 adolescents (45 007 vaccinated) during the Delta phase and 111 539 children (50 398 vaccinated) and 56 080 adolescents (21 180 vaccinated) during the Omicron phase. INTERVENTION: First dose of the BNT162b2 vaccine versus no receipt of COVID-19 vaccine. MEASUREMENTS: Outcomes of interest include documented infection, COVID-19 illness severity, admission to an intensive care unit (ICU), and cardiac complications. The effectiveness was reported as (1-relative risk)*100, with confounders balanced via propensity score stratification. RESULTS: During the Delta period, the estimated effectiveness of the BNT162b2 vaccine was 98.4% (95% CI, 98.1% to 98.7%) against documented infection among adolescents, with no statistically significant waning after receipt of the first dose. An analysis of cardiac complications did not suggest a statistically significant difference between vaccinated and unvaccinated groups. During the Omicron period, the effectiveness against documented infection among children was estimated to be 74.3% (CI, 72.2% to 76.2%). Higher levels of effectiveness were seen against moderate or severe COVID-19 (75.5% [CI, 69.0% to 81.0%]) and ICU admission with COVID-19 (84.9% [CI, 64.8% to 93.5%]). Among adolescents, the effectiveness against documented Omicron infection was 85.5% (CI, 83.8% to 87.1%), with 84.8% (CI, 77.3% to 89.9%) against moderate or severe COVID-19, and 91.5% (CI, 69.5% to 97.6%) against ICU admission with COVID-19. The effectiveness of the BNT162b2 vaccine against the Omicron variant declined 4 months after the first dose and then stabilized. The analysis showed a lower risk for cardiac complications in the vaccinated group during the Omicron variant period. LIMITATION: Observational study design and potentially undocumented infection. CONCLUSION: This study suggests that BNT162b2 was effective for various COVID-19-related outcomes in children and adolescents during the Delta and Omicron periods, and there is some evidence of waning effectiveness over time. PRIMARY FUNDING SOURCE: National Institutes of Health.

Dynamics and prognostic value of plasma cell-free DNA PCR in patients with invasive aspergillosis and mucormycosis.

Aspergillus species and Mucorales agents are the primary etiologies of invasive fungal disease (IFD). Biomarkers that predict outcomes are needed to improve care. Patients diagnosed with invasive aspergillosis and mucormycosis using plasma cell-free DNA (cfDNA) PCR were retested weekly for 4 weeks. The primary outcome included all-cause mortality at 6 weeks and 6 months based on baseline cycle threshold (CT) values and results of follow-up cfDNA PCR testing. Forty-five patients with Aspergillus and 30 with invasive Mucorales infection were retested weekly for a total of 197 tests. Using the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium (EORTC/MSG) criteria, 30.7% (23/75), 25.3% (19/75), and 38.7% (29/75) had proven, probable, and possible IFD, respectively. In addition, 97.3% (73/75) were immunocompromised. Baseline CT increased significantly starting at week 1 for Mucorales and week 2 for Aspergillus. Aspergillosis and mucormycosis patients with higher baseline CT (CT >40 and >35, respectively) had a nonsignificantly higher survival rate at 6 weeks, compared with patients with lower baseline CT. Mucormycosis patients with higher baseline CT had a significantly higher survival rate at 6 months. Mucormycosis, but not aspergillosis patients, with repeat positive cfDNA PCR results had a nonsignificantly lower survival rate at 6 weeks and 6 months compared with patients who reverted to negative. Aspergillosis patients with baseline serum Aspergillus galactomannan index <0.5 and <1.0 had significantly higher survival rates at 6 weeks when compared with those with index ≥0.5 and ≥1.0, respectively. Baseline plasma cfDNA PCR CT can potentially be used to prognosticate survival in patients with invasive Aspergillus and Mucorales infections. IMPORTANCE: We show that Aspergillus and Mucorales plasma cell-free DNA PCR can be used not only to noninvasively diagnose patients with invasive fungal disease but also to correlate the baseline cycle threshold with survival outcomes, thus potentially allowing the identification of patients at risk for poor outcomes, who may benefit from more targeted therapies.

Successful enteral administration of crushed posaconazole delayed-release tablets in children.

Erratic absorption of posaconazole oral suspension necessitates frequent dosing and administration with meals or supplements. Alternative enteral formulations are desirable for patients intolerant to enteral nutrition. Crushed posaconazole delayed-release tablets (POS-DRT) show promise in adults; limited evidence exists in children. We used crushed POS-DRT in 10 encounters with nine pediatric patients, achieving target POS concentrations in 90% of encounters. This highlights crushed POS-DRT as a potential enteral option for pediatric antifungal prophylaxis and treatment.

Application of cell-free DNA fungal polymerase chain reaction for invasive fungal disease evaluation in pediatric oncology and stem cell transplant patients.

BACKGROUND: Molecular diagnostics may enable early, noninvasive detection of invasive fungal disease (IFD) in immunocompromised patients. Cell-free deoxyribonucleic acid (cfDNA) fungal polymerase chain reaction (PCR) assays were recently incorporated into institutional prolonged febrile neutropenia pathways. We aimed to evaluate the performance of plasma cfDNA PCR panels (mold and Candida panels) in pediatric oncology and hematopoietic stem cell transplant (HSCT) patients with clinical concern for IFD. METHODS: This single-center, observational study assessed plasma cfDNA fungal PCR performance for noninvasive IFD detection in hospitalized pediatric oncology and HSCT patients. The primary outcome was IFD diagnosis per published consensus definitions within 1 month. Positive and negative agreement between plasma cfDNA fungal PCR and consensus definitions were calculated. We also described test turnaround time and patient survival. RESULTS: From October 2021 to 2022, 54 patients underwent 60 evaluations with 11 proven/probable IFD cases. Comparing plasma cfDNA fungal PCRs to consensus definitions for proven/probable IFD, there was 73% positive agreement and 96% negative agreement. Two proven/probable cases with negative PCRs were caused by organisms not included on either panel. Median time to cfDNA fungal PCR result was 35 hours (interquartile range: 19-69) in eight proven/probable cases detected by cfDNA fungal PCR. There were 17 deaths among 54 patients, and IFD contributed to 45% of deaths in patients with proven/probable IFD. CONCLUSIONS: Plasma cfDNA fungal PCRs detected relevant molds or yeast in most cases classified as proven/probable IFD. However, this targeted approach missed some cases. More studies are required to determine optimal utilization of molecular diagnostics in pediatric patients.

Clinical Accuracy and Impact of Plasma Cell-Free DNA Fungal Polymerase Chain Reaction Panel for Noninvasive Diagnosis of Fungal Infection.

BACKGROUND: Invasive fungal infection (IFI) is a growing cause of morbidity and mortality in oncology and transplant patients. Diagnosis of IFI is often delayed due to need for invasive biopsy and low sensitivity of conventional diagnostic methods. Fungal cell-free DNA (cfDNA) detection in plasma is a novel testing modality for the noninvasive diagnosis of IFI. METHODS: A novel bioinformatic pipeline was created to interrogate fungal genomes and identify multicopy sequences for cfDNA polymerase chain reaction (PCR) targeting. A real-time PCR panel was developed for 12 genera and species most commonly causing IFI. Sensitivity and specificity of the fungal PCR panel were determined using plasma samples from patients with IFI and non-IFI controls. Clinical impact of the fungal PCR panel was evaluated prospectively based on the treating team's interpretation of the results. RESULTS: Overall, the sensitivity and specificity were 56.5% (65/115; 95% confidence interval [CI], 47.4-65.2) and 99.5% (2064/2075; 95% CI, 99.0-99.7), respectively. In the subset of patients with an optimized plasma volume (2 mL), sensitivity was 69.6% (48/69; 95% CI, 57.9-79.2). Sensitivity was 91.7% (11/12; 95% CI, 62.5-100) for detection of Mucorales agents, 56.3% (9/16; 95% CI, 33.2-76.9) for Aspergillus species, and 84.6% (11/13; 95% CI, 56.5-96.9) for Candida albicans. In a prospective evaluation of 226 patients with suspected IFI, cfDNA testing was positive in 47 (20.8%) patients and resulted in a positive impact on clinical management in 20 of 47 (42.6%). CONCLUSIONS: The fungal cfDNA PCR panel offers a noninvasive approach to early diagnosis of IFI, providing actionable results for personalized care.

Recent advances in Clostridioides difficile infection epidemiology, diagnosis and treatment in children.

PURPOSE OF REVIEW: The US Centers for Disease Control and Prevention (CDC) classified Clostridioides difficile as an 'urgent' public health threat that requires 'urgent and aggressive action'. This call to action has led to new discoveries that have advanced C. difficile infection (CDI) epidemiology, diagnosis and treatment, albeit predominantly in adults. In 2017, the Infectious Diseases Society of America and Society for Healthcare Epidemiology of America published clinical practice guidelines for both adults and children. At that time, recommendations in children were generally limited to relatively low-quality evidence. RECENT FINDINGS: Since publication of this guidance, there have been many advancements in the understanding of CDI in children. These include better understanding of healthcare settings as uncommon sources of C. difficile acquisition in children; risk factors for recurrent and community-associated CDI; performance of diagnostic tests in children and strategies for optimizing their use; and a more rigorous evidence base for CDI treatment in children, including the first-ever randomized controlled trial of CDI treatment in children and the largest study of fecal microbiota transplantation in children. SUMMARY: This review highlights the most recent salient advancements in paediatric CDI knowledge and practice that supplement published clinical guidance provided prior to these advancements.

Reducing Piperacillin and Tazobactam Use for Pediatric Perforated Appendicitis.

BACKGROUND: Although perforated appendicitis is associated with infectious complications, the choice of antibiotic therapy is controversial. We assess the effectiveness and safety of an intervention to reduce piperacillin and tazobactam (PT) use for pediatric acute perforated appendicitis. METHODS: This is a single-center, retrospective cohort study of children 18 y of age or younger who underwent primary appendectomy for perforated appendicitis between January 01, 2016 and June 30, 2019. An intervention to decrease PT use was implemented: the first phase was provider education (April 19, 2017) and the second phase was modification of electronic antibiotic orders to default to ceftriaxone and metronidazole (July 06, 2017). Preintervention and postintervention PT exposure, use of PT ≥ half of intravenous antibiotic days, and clinical outcomes were compared. RESULTS: Forty children before and 109 after intervention were included and had similar baseline characteristics. PT exposure was 31 of 40 (78%) and 20 of 109 (18%) (P < 0.001), and use ≥ half of intravenous antibiotic days was 31 of 40 (78%) and 14 of 109 (13%) (P < 0.001), in the preintervention and postintervention groups, respectively. There was no significant difference in mean duration of antibiotic therapy (10.8 versus 9.8 d), mean length of stay (6.2 versus 6.5 d), rate of surgical site infection (10% versus 11%), or rate of 30-d readmission and emergency department visit (20% versus 20%) between the preintervention and postintervention periods, respectively. CONCLUSIONS: Provider education and modification of electronic antibiotic orders safely reduced the use of PT for pediatric perforated appendicitis.

Standardization of post-operative antimicrobials reduced exposure while maintaining good outcomes in pediatric liver transplant recipients.

Infections following orthotopic liver transplant (OLT) result in significant morbidity and mortality, warranting careful consideration of risks associated with antibiotic overuse and benefits of infection prevention. In the absence of specific guidelines for antimicrobial prophylaxis in pediatric OLT, we developed a standardized approach to post-operative (post-op) antimicrobial therapy including 48 hours of antibiotics, no vancomycin for post-op fever within the first 48 hours, and caspofungin only for certain situations. The goal was to reduce antimicrobial utilization and adverse outcomes associated with longer duration of and broader treatment while maintaining good outcomes. The impact of this standardization on antimicrobial utilization and clinical outcomes at the largest pediatric liver transplant center in the United States is described. All individuals receiving an OLT from 1/1/17-9/30/17 (N = 38) and 3/14/18-12/13/18 (N = 27) were included in the pre-intervention (PreI) and post-intervention (PostI) groups, respectively. The intervention resulted in a significant reduction in individuals receiving post-op broad-spectrum gram-negative antibiotics for >48 hours (76% PreI vs 44% PostI OLT recipients, P = .01) and post-op vancomycin use (50% PreI, vs 7.4% PostI, P < .001). There were no statistically significant differences between groups for post-op fever, positive pre-/post-operative cultures, receipt of massive transfusion, or hospital length of stay. In conclusion, following the implementation of a standardized approach to post-op prophylaxis, antimicrobial exposure was significantly reduced without affecting OLT recipient outcomes.

Use of Prospective Audit and Feedback to Reduce Antibiotic Exposure in a Pediatric Cardiac ICU.

OBJECTIVES: We sought to determine whether a prospective audit and feedback intervention decreased antibiotic utilization in a pediatric cardiac ICU and to describe the characteristics of prospective audit and feedback audits and recommendations. DESIGN: Before-after study. SETTING: Pediatric cardiac ICU of a freestanding children's hospital. PATIENTS: All patients admitted to the cardiac ICU. INTERVENTIONS: A prospective audit and feedback program was established in our hospital's pediatric cardiac ICU on December 7, 2015. The antimicrobial stewardship program audited IV antibiotics, communicated prospective audit and feedback recommendations to the cardiac ICU, and regularly reviewed recommendation adherence. Mean monthly antibiotic utilization 18 months before ("preprospective audit and feedback"; from June 1, 2014 to November 30, 2015) and 24 months after ("prospective audit and feedback"; from January 1, 2016 to December 31, 2017) prospective audit and feedback implementation was compared. Antibiotic audit data during the prospective audit and feedback period were reviewed to capture the characteristics of prospective audit and feedback audits, recommendations, and adherence. MEASUREMENTS AND MAIN RESULTS: Mean cardiac ICU IV antibiotic use decreased 20% (701 vs 880 days of therapy per 1,000 patient days, p = 0.001) during the prospective audit and feedback period compared with the preprospective audit and feedback period. There was no difference in mean cardiac ICU length of stay (p = 0.573), mean hospital length of stay (p = 0.722), or the rate of discharge due to death (p = 0.541). There were 988 antibiotic audits and 370 prospective audit and feedback recommendations (37% recommendation rate) during the study period. The most commonly audited antibiotic category was broad-spectrum gram-negative agents and the most common indication for use was sepsis. Broad-spectrum gram-positive agents were more likely to be associated with a recommendation. CONCLUSIONS: There was a significant reduction in antibiotic use following implementation of a prospective audit and feedback program in our pediatric cardiac ICU. Over one-third of antibiotics audited in our cardiac ICU were associated with a prospective audit and feedback recommendation, revealing important targets for future antimicrobial stewardship efforts in this population.

A multifaceted quality improvement project improves intraoperative redosing of surgical antimicrobial prophylaxis during pediatric surgery.

BACKGROUND: Accurate intraoperative antibiotic redosing contributes to prevention of surgical site infections in pediatric patients. Ensuring compliance with evolving national guidelines of weight-based, intraoperative redosing of antibiotics is challenging to pediatric anesthesiologists. AIMS: Our primary aim was to increase compliance of antibiotic redoses at the appropriate time and appropriate weight-based dose to 70%. Secondary aims included a subset analysis of time compliance and dose compliance individually, and compliance based on order entry method of the first dose (verbal or electronic). METHODS: At a freestanding, academic pediatric hospital, we reviewed surgical cases between May 1, 2014, and October 31, 2017 requiring antibiotic redoses. After an institutional change in cefazolin dosing in May 2015, phased interventions to improve compliance included electronic countermeasures to display previous and next dose timing, an alert 5 minutes prior to next dose, and weight-based dose recommendation (September 2015). Physical countermeasures include badge cards, posting of guidelines, and updates to housestaff manual (September 2015). Statistical process control charts were used to assess overall antibiotic redose compliance, time compliance, and dose compliance. The chi-square test was used to analyze group differences. RESULTS: A total of 3015 antibiotic redoses were administered during 2341 operative cases between May 1, 2014, and October 31, 2017. Mean monthly compliance with redosing was 4.3% (May 2014-April 2015) and 73% (November 2015-October 2017) (P < 0.001). Dose-only compliance increased from 76% to 89% (P < 0.001), and time-only compliance increased from 4.9% to 82% (P < 0.001). After implementation of countermeasures, electronic order entry compared with verbal order was associated with higher dose compliance, 90% vs 86% (P = 0.015). CONCLUSION: This quality improvement project, utilizing electronic and physical interventions, was effective in improving overall prophylactic antibiotic redosing compliance in accordance with institutional redosing guidelines.

A quality improvement initiative to optimize dosing of surgical antimicrobial prophylaxis.

BACKGROUND: The risk of surgical site infections is reduced with appropriate timing and dosing of preoperative antimicrobials. Based on evolving national guidelines, we increased the preoperative dose of cefazolin from 25 to 30 mg·kg-1 . This quality improvement project describes an improvement initiative to develop standard work processes to ensure appropriate dosing. AIMS: The primary aim was to deliver cefazolin 30 mg·kg-1 to at least 90% of indicated patients. The secondary aim was to determine differences between accuracy of cefazolin doses when given as an electronic order compared to a verbal order. METHODS: Data were collected from January 1, 2012 to May 31, 2016. A quality improvement team of perioperative physicians, nurses, and pharmacists implemented a series of interventions including new electronic medical record order sets, personal provider antibiotic dose badges, and utilization of pharmacists to prepare antibiotics to increase compliance with the recommended dose. Process compliance was measured using a statistical process control chart, and dose compliance was measured through electronic analysis of the electronic medical record. Secondary aim data were displayed as percentage of dose compliance. An unpaired t-test was used to determine differences between groups. RESULTS: Between January 1, 2012 and May 31, 2016, cefazolin was administered to 9086 patients. The mean compliance of cefazolin at 30 mg·kg-1 from May 2013 to March 2014 was 40%, which prompted initiation of this project. From April 2014 to May 2016, a series of interventions were deployed. The mean compliance from September 2015 to May 2016 was 93% with significantly reduced variation and no special cause variation, indicating that the process was in control at the target primary aim. There were 649 cefazolin administrations given verbally and 1929 given with an electronic order between October 1, 2014 and May 31, 2016. During this time period, the rate of compliance of administering cefazolin at 30 mg·kg-1 was significantly higher when given after an electronic order than when given verbally, 94% vs 76%. CONCLUSION: This comprehensive quality improvement project improved practitioner compliance with evidence-based preoperative antimicrobial dosing recommendations to reduce the risk of surgical site infections.

Subacute Sclerosing Panencephalitis: The Foothold in Undervaccination.

Subacute sclerosing panencephalitis (SSPE) is a fatal complication of measles infection. We present a case of a fully vaccinated 3-year-old boy who was diagnosed with and treated for autoimmune encephalitis before arriving at a diagnosis of SSPE. We discuss the challenges of diagnosing SSPE in developed countries.

Indication-driven order entry decreases stewardship and pharmacist interventions.

Indication-driven order entry (IDOE) was implemented at our pediatric institution for cefazolin, piperacillin-tazobactam, and meropenem; the 3 most intervened upon antibiotics during prospective audit and feedback (PAF) by the antimicrobial stewardship program (ASP). IDOE was associated with a significant reduction in both ASP PAF recommendations and clinical pharmacist interventions.

Prescribing Patterns of Nonrecommended Medications for Children With Acute COVID-19.

OBJECTIVE: Repurposed medications for acute coronavirus disease 2019 (COVID-19) continued to be prescribed after results from rigorous studies and national guidelines discouraged use. We aimed to describe prescribing rates of nonrecommended medications for acute COVID-19 in children, associations with demographic factors, and provider type and specialty. METHODS: In this retrospective cohort of children <18 years in a large United States all-payer claims database, we identified prescriptions within 2 weeks of an acute COVID-19 diagnosis. We calculated prescription rate, performed multivariable logistic regression to identify risk factors, and described prescriber type and specialty during nonrecommended periods defined by national guidelines. RESULTS: We identified 3 082 626 COVID-19 diagnoses in 2 949 118 children between March 7, 2020 and December 31, 2022. Hydroxychloroquine (HCQ) and ivermectin were prescribed in 0.03% and 0.14% of COVID-19 cases, respectively, during nonrecommended periods (after September 12, 2020 for HCQ and February 5, 2021 for ivermectin) with considerable variation by state. Prescription rates were 4 times the national average in Arkansas (HCQ) and Oklahoma (ivermectin). Older age, nonpublic insurance, and emergency department or urgent care visit were associated with increased risk of either prescription. Additionally, residence in nonurban and low-income areas was associated with ivermectin prescription. General practitioners had the highest rates of prescribing. CONCLUSIONS: Although nonrecommended medication prescription rates were low, the overall COVID-19 burden translated into high numbers of ineffective and potentially harmful prescriptions. Understanding overuse patterns can help mitigate downstream consequences of misinformation. Reaching providers and parents with clear evidence-based recommendations is crucial to children's health.

EHR-based Case Identification of Pediatric Long COVID: A Report from the RECOVER EHR Cohort.

Objective: Long COVID, marked by persistent, recurring, or new symptoms post-COVID-19 infection, impacts children's well-being yet lacks a unified clinical definition. This study evaluates the performance of an empirically derived Long COVID case identification algorithm, or computable phenotype, with manual chart review in a pediatric sample. This approach aims to facilitate large-scale research efforts to understand this condition better. Methods: The algorithm, composed of diagnostic codes empirically associated with Long COVID, was applied to a cohort of pediatric patients with SARS-CoV-2 infection in the RECOVER PCORnet EHR database. The algorithm classified 31,781 patients with conclusive, probable, or possible Long COVID and 307,686 patients without evidence of Long COVID. A chart review was performed on a subset of patients (n=651) to determine the overlap between the two methods. Instances of discordance were reviewed to understand the reasons for differences. Results: The sample comprised 651 pediatric patients (339 females, M age = 10.10 years) across 16 hospital systems. Results showed moderate overlap between phenotype and chart review Long COVID identification (accuracy = 0.62, PPV = 0.49, NPV = 0.75); however, there were also numerous cases of disagreement. No notable differences were found when the analyses were stratified by age at infection or era of infection. Further examination of the discordant cases revealed that the most common cause of disagreement was the clinician reviewers' tendency to attribute Long COVID-like symptoms to prior medical conditions. The performance of the phenotype improved when prior medical conditions were considered (accuracy = 0.71, PPV = 0.65, NPV = 0.74). Conclusions: Although there was moderate overlap between the two methods, the discrepancies between the two sources are likely attributed to the lack of consensus on a Long COVID clinical definition. It is essential to consider the strengths and limitations of each method when developing Long COVID classification algorithms.

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.

Vaccine Effectiveness Against Long COVID in Children.

OBJECTIVES: Vaccination reduces the risk of acute coronavirus disease 2019 (COVID-19) in children, but it is less clear whether it protects against long COVID. We estimated vaccine effectiveness (VE) against long COVID in children aged 5 to 17 years. METHODS: This retrospective cohort study used data from 17 health systems in the RECOVER PCORnet electronic health record program for visits after vaccine availability. We examined both probable (symptom-based) and diagnosed long COVID after vaccination. RESULTS: The vaccination rate was 67% in the cohort of 1 037 936 children. The incidence of probable long COVID was 4.5% among patients with COVID-19, whereas diagnosed long COVID was 0.8%. Adjusted vaccine effectiveness within 12 months was 35.4% (95 CI 24.5-44.7) against probable long COVID and 41.7% (15.0-60.0) against diagnosed long COVID. VE was higher for adolescents (50.3% [36.6-61.0]) than children aged 5 to 11 (23.8% [4.9-39.0]). VE was higher at 6 months (61.4% [51.0-69.6]) but decreased to 10.6% (-26.8% to 37.0%) at 18-months. CONCLUSIONS: This large retrospective study shows moderate protective effect of severe acute respiratory coronavirus 2 vaccination against long COVID. The effect is stronger in adolescents, who have higher risk of long COVID, and wanes over time. Understanding VE mechanism against long COVID requires more study, including electronic health record sources and prospective data.

Vancomycin Use for Pediatric Clostridium difficile Infection Is Increasing and Associated with Specific Patient Characteristics.

In adults with Clostridium difficile infection (CDI), enteral vancomycin is considered the preferred initial regimen for severe disease; however, patterns of antimicrobial use for children with CDI are unknown. We sought to describe trends in and predictors of vancomycin use for the treatment of children with CDI admitted to tertiary-care children's hospitals in the United States. We used a database of freestanding children's hospitals to identify patients 1 to 18 years old with CDI between January 2006 and June 2011. The first hospitalization with a diagnosis of CDI for each patient was identified, and CDI-directed therapy was assessed. Generalized estimating equations were used to identify predictors of vancomycin receipt, controlling for clustering within hospitals. Vancomycin use has increased significantly (P = 0.005), with substantial variability between hospitals (0 to 16%). In multivariate analyses, vancomycin use was more common in children age 7 to 13 years old (versus children 1 to 2 years old: adjusted odds ratio [AOR] = 1.57; 95% confidence interval [CI] = 1.13 to 2.18), 14 to 18 years old (AOR = 1.40; 95% CI = 1.11 to 1.76), in an ICU (AOR = 1.37; 95% CI = 1.05 to 1.80), or with chronic gastrointestinal conditions (AOR = 2.01; 95% CI = 1.44 to 2.81). Vancomycin use was less common in black (AOR = 0.53; 95% CI = 0.39 to 0.73) and Hispanic (AOR = 0.63; 95% CI = 0.47 to 0.84) patients and in children with malignancies (AOR = 0.57; 95% CI = 0.36 to 0.89). Despite a lack of empirical evidence to suggest superiority, vancomycin use for pediatric CDI is increasing. Furthermore, there is substantial variability in vancomycin use between hospitals. Further studies are needed to explore potential racial and ethnic differences in CDI management and to investigate clinicians' rationale for using vancomycin for initial therapy in selected populations.