BNT162b2 mRNA Vaccination Against COVID-19 is Associated with Decreased Likelihood of Multisystem Inflammatory Syndrome in U.S. Children Ages 5-18 Years.

2022

08/2022

1537-6591

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C), linked to antecedent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is associated with considerable morbidity. Prevention of SARS-CoV-2 infection or coronavirus disease 2019 (COVID-19) by vaccination might also decrease MIS-C likelihood.

METHODS: In a multicenter case-control public health investigation of children ages 5-18 years hospitalized from July 1, 2021 to April 7, 2022, we compared the odds of being fully vaccinated (two doses of BNT162b2 vaccine ≥28 days before hospital admission) between MIS-C case-patients and hospital-based controls who tested negative for SARS-CoV-2. These associations were examined by age group, timing of vaccination, and periods of Delta and Omicron variant predominance using multivariable logistic regression.

RESULTS: We compared 304 MIS-C case-patients (280 [92%] unvaccinated) with 502 controls (346 [69%] unvaccinated). MIS-C was associated with decreased likelihood of vaccination (aOR, 0.16 95% CI, 0.10-0.26), including among children ages 5-11 years (aOR, 0.22 95% CI, 0.10-0.52), ages 12-18 years (aOR, 0.10 95% CI, 0.05-0.19), and during the Delta (aOR, 0.06 95% CI, 0.02-0.15) and Omicron (aOR, 0.22 95% CI, 0.11-0.42) variant-predominant periods. This association persisted beyond 120 days after the second dose (aOR, 0.08, 95% CI, 0.03-0.22) in 12-18 year-olds. Among all MIS-C case-patients, 187 (62%) required intensive care unit admission and 280 (92%) vaccine-eligible patients were unvaccinated.

CONCLUSIONS: Vaccination with two doses of BNT162b2 is associated with reduced likelihood of MIS-C in children ages 5-18 years. Most vaccine eligible hospitalized patients with MIS-C were unvaccinated.

10.1093/cid/ciac637

Clin Infect Dis

35924406

Antibiotic indications and appropriateness in the pediatric intensive care unit: a ten-center point prevalence study.

2022

09/2022

1537-6591

BACKGROUND: Antibiotics are prescribed to most pediatric intensive care unit (PICU) patients, but data evaluating indications and appropriateness of antibiotic orders in this population are lacking.

METHODS: We performed a multicenter point prevalence study including children admitted to 10 geographically diverse PICUs over four study days in 2019. Antibiotic orders were reviewed for indication, and appropriateness was assessed using a standardized rubric.

RESULTS: Of 1462 patients admitted to participating PICUs, 843 (58%) had at least one antibiotic order. A total of 1277 antibiotic orders were reviewed. Common indications were empiric therapy for suspected bacterial infections without sepsis or septic shock (260 orders, 21%), non-operative prophylaxis (164 orders, 13%), empiric therapy for sepsis or septic shock (155 orders, 12%), community acquired pneumonia (CAP) (118 orders, 9%), and post-operative prophylaxis (94 orders, 8%). Appropriateness was assessed for 985 orders for which an evidence-based rubric for appropriateness could be created. Of these, 331 (34%) were classified as inappropriate. Indications with the most orders classified as inappropriate were empiric therapy for suspected bacterial infection without sepsis or septic shock (78 orders, 24%), sepsis or septic shock (55 orders, 17%), CAP (51 orders, 15%), ventilator-associated infections (47 orders, 14%), and post-operative prophylaxis (44 orders, 14%). The proportion of antibiotics classified as inappropriate varied across institutions (range: 19%-43%).

CONCLUSIONS: Most PICU patients receive antibiotics, and based on our study, we estimate that one-third of antibiotic orders are inappropriate. Improved antibiotic stewardship and research focused on strategies to optimize antibiotic use in critically ill children are needed.

10.1093/cid/ciac698

Clin Infect Dis

36048543

Administration of a β-lactam Prior to Vancomycin as the First Dose of Antibiotic Therapy Improves Survival in Patients with Bloodstream Infections.

2021

2021 Oct 04

1537-6591

OBJECTIVE: Prompt initiation of antibiotic therapy improves the survival of patients with bloodstream infections (BSI). We sought to determine if the sequence of administration of the first dose of antibiotic therapy (i.e., β-lactam or vancomycin, if both cannot be administered simultaneously) impacts early mortality for patients with BSI.

METHODS: We conducted a multicenter, observational study of patients ≥13 years with BSIs to evaluate the association of the sequence of antibiotic administration with 7-day mortality using inverse probability of treatment weighting (IPTW) incorporating propensity scores. Propensity scores were generated based on: demographics, Pitt bacteremia score, ICU status, highest lactate, highest WBC count, Charlson Comorbidity index, severe immunocompromise, administration of active empiric therapy, combination therapy, and time from emergency department arrival to first antibiotic dose.

RESULTS: Of 3,376 eligible patients, 2,685 (79.5%) received a β-lactam and 691 (20.5%) received vancomycin as their initial antibiotic. In the IPTW cohort, exposed and unexposed patients were similar on all baseline variables. Administration of a β-lactam agent prior to vancomycin protected against 7-day mortality (aOR 0.48 (95% CI: 0.33-0.69)]. Similar results were observed when evaluating 48-hour mortality (aOR 0.45 [95% CI: 0.24-0.83]). Administration of vancomycin prior to a β-lactam was not associated with improved survival in the subgroup of 524 patients with methicillin-resistant Staphylococcus aureus BSI (aOR 0.93 [95% CI: 0.33-2.63]).

CONCLUSIONS: For ill-appearing patients likely to be experiencing a BSI, prioritizing administration of a β-lactam over vancomycin may reduce early mortality, underscoring the significant impact of a relatively simple practice change on improving patient survival.

10.1093/cid/ciab865

Clin Infect Dis

34606585

COVID-19 FAQs in Pediatric Cardiac Surgery: 2022 Perspective and Updates.

2022

21501351221085966

2022 Mar 28

2150-136X

10.1177/21501351221085966

World J Pediatr Congenit Heart Surg

35341384

BNT162b2 Protection against the Omicron Variant in Children and Adolescents.

2022

2022 Mar 30

1533-4406

<p><strong>BACKGROUND: </strong>Spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.529 (omicron) variant, which led to increased U.S. hospitalizations for coronavirus disease 2019 (Covid-19), generated concern about immune evasion and the duration of protection from vaccines in children and adolescents.</p>

<p><strong>METHODS: </strong>Using a case-control, test-negative design, we assessed vaccine effectiveness against laboratory-confirmed Covid-19 leading to hospitalization and against critical Covid-19 (i.e., leading to receipt of life support or to death). From July 1, 2021, to February 17, 2022, we enrolled case patients with Covid-19 and controls without Covid-19 at 31 hospitals in 23 states. We estimated vaccine effectiveness by comparing the odds of antecedent full vaccination (two doses of BNT162b2 messenger RNA vaccine) at least 14 days before illness among case patients and controls, according to time since vaccination for patients 12 to 18 years of age and in periods coinciding with circulation of B.1.617.2 (delta) (July 1, 2021, to December 18, 2021) and omicron (December 19, 2021, to February 17, 2022) among patients 5 to 11 and 12 to 18 years of age.</p>

<p><strong>RESULTS: </strong>We enrolled 1185 case patients (1043 [88%] of whom were unvaccinated, 291 [25%] of whom received life support, and 14 of whom died) and 1627 controls. During the delta-predominant period, vaccine effectiveness against hospitalization for Covid-19 among adolescents 12 to 18 years of age was 93% (95% confidence interval [CI], 89 to 95) 2 to 22 weeks after vaccination and was 92% (95% CI, 80 to 97) at 23 to 44 weeks. Among adolescents 12 to 18 years of age (median interval since vaccination, 162 days) during the omicron-predominant period, vaccine effectiveness was 40% (95% CI, 9 to 60) against hospitalization for Covid-19, 79% (95% CI, 51 to 91) against critical Covid-19, and 20% (95% CI, -25 to 49) against noncritical Covid-19. During the omicron period, vaccine effectiveness against hospitalization among children 5 to 11 years of age was 68% (95% CI, 42 to 82; median interval since vaccination, 34 days).</p>

<p><strong>CONCLUSIONS: </strong>BNT162b2 vaccination reduced the risk of omicron-associated hospitalization by two thirds among children 5 to 11 years of age. Although two doses provided lower protection against omicron-associated hospitalization than against delta-associated hospitalization among adolescents 12 to 18 years of age, vaccination prevented critical illness caused by either variant. (Funded by the Centers for Disease Control and Prevention.).</p>

10.1056/NEJMoa2202826

N Engl J Med

35353976

Improving Vancomycin Stewardship in Critically Ill Children.

2022

2022 Apr 01

1098-4275

<p><strong>BACKGROUND AND OBJECTIVES: </strong>Inappropriate vancomycin use is common in children's hospitals. We report a quality improvement (QI) intervention to reduce vancomycin use in our tertiary care PICU.</p>

<p><strong>METHODS: </strong>We retrospectively quantified the prevalence of infections caused by organisms requiring vancomycin therapy, including methicillin-resistant Staphylococcus aureus (MRSA), among patients with suspected bacterial infections. Guided by these data, we performed 3 QI interventions over a 3-year period, including (1) stakeholder education, (2) generation of a consensus-based guideline for empiric vancomycin use, and (3) implementation of this guideline through clinical decision support. Vancomycin use in days of therapy (DOT) per 1000 patient days was measured by using statistical process control charts. Balancing measures included frequency of bacteremia due to an organism requiring vancomycin not covered with empiric therapy, 30-day mortality, and cardiovascular, respiratory, and renal organ dysfunction.</p>

<p><strong>RESULTS: </strong>Among 1276 episodes of suspected bacterial infection, a total of 19 cases of bacteremia (1.5%) due to organisms requiring vancomycin therapy were identified, including 6 MRSA bacteremias (0.5%). During the 3-year QI project, overall vancomycin DOT per 1000 patient days in the PICU decreased from a baseline mean of 182 DOT per 1000 patient days to 109 DOT per 1000 patient days (a 40% reduction). All balancing measures were unchanged, and all cases of MRSA bacteremia were treated empirically with vancomycin.</p>

<p><strong>CONCLUSION: </strong>Our interventions reduced overall vancomycin use in the PICU without evidence of harm. Provider education and consensus building surrounding indications for empiric vancomycin use were key strategies.</p>

10.1542/peds.2021-052165

Pediatrics

35362066

Cutaneous manifestations of hospitalized COVID-19 patients in the VIRUS COVID-19 registry.

2022

2022 Feb 19

1365-4632

10.1111/ijd.16134

Int J Dermatol

35182396

Increasing Cefazolin Use for Perioperative Antibiotic Prophylaxis in Penicillin-Allergic Children.

2022

2022 Mar 01

1098-4275

<p><strong>BACKGROUND AND OBJECTIVES: </strong>Cefazolin, a first-generation cephalosporin, is the most commonly recommended antibiotic for perioperative prophylaxis to reduce surgical site infections. Children with a reported penicillin allergy often receive an alternative antibiotic because of a common misunderstanding of the cross-reactivity between these antibiotics. This use of alternative antibiotics in surgical populations have been associated with increased infections, antibiotic resistance, and health care costs. We aimed to increase the percentage of patients with nonsevere penicillin-class allergies who receive cefazolin for antibiotic prophylaxis.</p>

<p><strong>METHODS: </strong>A multidisciplinary team conducted this quality improvement initiative, with a series of 3 plan-do-study-act cycles aimed at children with nonsevere penicillin-class allergies undergoing surgical procedures that require antibiotic prophylaxis. The primary outcome measure was the percentage of surgical encounters among patients with nonsevere penicillin-class allergies who received cefazolin as antibiotic prophylaxis. Statistical process control charts were used to measure improvement over time.</p>

<p><strong>RESULTS: </strong>Approximately 400 children were involved in this project. There was special cause variation and a shift in the center line from 60% to 80% of eligible patients receiving cefazolin for antibiotic prophylaxis, which was sustained for the duration of the project. In the last month, 90% of eligible patient received cefazolin, surpassing our goal of 85%. This improvement has been sustained in the 5 months after project completion. We had no cases of severe allergic reactions in the operating room.</p>

<p><strong>CONCLUSIONS: </strong>Our multidisciplinary education-focused interventions were associated with a significant increase in the use of cefazolin for perioperative antibiotic prophylaxis in patient with penicillin allergies.</p>

10.1542/peds.2021-050694

Pediatrics

35229120

Effectiveness of Maternal Vaccination with mRNA COVID-19 Vaccine During Pregnancy Against COVID-19-Associated Hospitalization in Infants Aged <6 Months - 17 States, July 2021-January 2022.

2022

264-270

2022 Feb 18

1545-861X

<p>COVID-19 vaccination is recommended for persons who are pregnant, breastfeeding, trying to get pregnant now, or who might become pregnant in the future, to protect them from COVID-19. Infants are at risk for life-threatening complications from COVID-19, including acute respiratory failure (1). Evidence from other vaccine-preventable diseases suggests that maternal immunization can provide protection to infants, especially during the high-risk first 6 months of life, through passive transplacental antibody transfer (2). Recent studies of COVID-19 vaccination during pregnancy suggest the possibility of transplacental transfer of SARS-CoV-2-specific antibodies that might provide protection to infants (3-5); however, no epidemiologic evidence currently exists for the protective benefits of maternal immunization during pregnancy against COVID-19 in infants. The Overcoming COVID-19 network conducted a test-negative, case-control study at 20 pediatric hospitals in 17 states during July 1, 2021-January 17, 2022, to assess effectiveness of maternal completion of a 2-dose primary mRNA COVID-19 vaccination series during pregnancy against COVID-19 hospitalization in infants. Among 379 hospitalized infants aged &lt;6 months (176 with COVID-19 [case-infants] and 203 without COVID-19 [control-infants]), the median age was 2 months, 21% had at least one underlying medical condition, and 22% of case- and control-infants were born premature (&lt;37 weeks gestation). Effectiveness of maternal vaccination during pregnancy against COVID-19 hospitalization in infants aged &lt;6 months was 61% (95% CI&nbsp;=&nbsp;31%-78%). Completion of a 2-dose mRNA COVID-19 vaccination series during pregnancy might help prevent COVID-19 hospitalization among infants aged &lt;6 months.</p>

10.15585/mmwr.mm7107e3

MMWR Morb Mortal Wkly Rep

35176002

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

2022

2022 Feb 02

2048-7207

<p><strong>BACKGROUND: </strong>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.</p>

<p><strong>METHODS: </strong>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.</p>

<p><strong>RESULTS: </strong>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.</p>

<p><strong>CONCLUSIONS: </strong>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.</p>

10.1093/jpids/piab124

J Pediatric Infect Dis Soc

35107571