First name
Jeffrey
Middle name
S
Last name
Gerber

Title

Developing Consensus on Clinical Outcomes for Children with Mild Pneumonia: A Delphi Study.

Year of Publication

2023

Date Published

01/2023

ISSN Number

2048-7207

Abstract

BACKGROUND: The absence of consensus for outcomes in pediatric antibiotic trials is a major barrier to research harmonization and clinical translation. We sought to develop expert consensus on study outcomes for clinical trials of children with mild community-acquired pneumonia (CAP).

METHODS: Applying the Delphi method, a multispecialty expert panel ranked the importance of various components of clinical response and treatment failure outcomes in children with mild CAP for use in research. During Round 1, panelists suggested additional outcomes in open-ended responses that were added to subsequent rounds of consensus building. For Rounds 2 and 3, panelists were provided their own prior responses and summary statistics for each item in the previous round. The consensus was defined by >70% agreement.

RESULTS: The expert panel determined that response to and failure of treatment should be addressed at a median of 3 days after initiation. Complete or substantial improvement in fever, work of breathing, dyspnea, tachypnea when afebrile, oral intake, and activity should be included as components of adequate clinical response outcomes. Clinical signs and symptoms including persistent or worsening fever, work of breathing, and reduced oral intake should be included in treatment failure outcomes. Interventions including receipt of parenteral fluids, supplemental oxygen, need for high-flow nasal cannula oxygen therapy, and change in prescription of antibiotics should also be considered in treatment failure outcomes.

CONCLUSIONS: Clinical response and treatment failure outcomes determined by the consensus of this multidisciplinary expert panel can be used for pediatric CAP studies to provide objective data translatable to clinical practice.

DOI

10.1093/jpids/piac123

Alternate Title

J Pediatric Infect Dis Soc

PMID

36625856

Title

Comparison of Maternal and Neonatal Antibody Levels After COVID-19 Vaccination vs SARS-CoV-2 Infection.

Year of Publication

2022

Number of Pages

e2240993

Date Published

11/2022

ISSN Number

2574-3805

Abstract

Importance: Pregnant persons are at an increased risk of severe COVID-19 from SARS-CoV-2 infection, and COVID-19 vaccination is currently recommended during pregnancy.

Objective: To ascertain the association of vaccine type, time from vaccination, gestational age at delivery, and pregnancy complications with placental transfer of antibodies to SARS-CoV-2.

Design, Setting, and Participants: This cohort study was conducted in Pennsylvania Hospital in Philadelphia, Pennsylvania, and included births at the study site between August 9, 2020, and April 25, 2021. Maternal and cord blood serum samples were available for antibody level measurements for maternal-neonatal dyads.

Exposures: SARS-CoV-2 infection vs COVID-19 vaccination.

Main Outcomes and Measures: IgG antibodies to the receptor-binding domain of the SARS-CoV-2 spike protein were measured by quantitative enzyme-linked immunosorbent assay. Antibody concentrations and transplacental transfer ratios were measured after SARS-CoV-2 infection or receipt of COVID-19 vaccines.

Results: A total of 585 maternal-newborn dyads (median [IQR] maternal age, 31 [26-35] years; median [IQR] gestational age, 39 [38-40] weeks) with maternal IgG antibodies to SARS-CoV-2 detected at the time of delivery were included. IgG was detected in cord blood from 557 of 585 newborns (95.2%). Among 169 vaccinated persons without SARS-CoV-2 infection, the interval from first dose of vaccine to delivery ranged from 12 to 122 days. The geometric mean IgG level among 169 vaccine recipients was significantly higher than that measured in 408 persons after infection (33.88 [95% CI, 27.64-41.53] arbitrary U/mL vs 2.80 [95% CI, 2.50-3.13] arbitrary U/mL). Geometric mean IgG levels were higher after vaccination with the mRNA-1273 (Moderna) vaccine compared with the BNT162b2 (Pfizer/BioNTech) vaccine (53.74 [95% CI, 40.49-71.33] arbitrary U/mL vs 25.45 [95% CI, 19.17-33.79] arbitrary U/mL; P < .001). Placental transfer ratios were lower after vaccination compared with after infection (0.80 [95% CI, 0.68-0.93] vs 1.06 [95% CI, 0.98-1.14]; P < .001) but were similar between the mRNA vaccines (mRNA-1273: 0.70 [95% CI, 0.55-0.90]; BNT162b2: 0.85 [95% CI, 0.69-1.06]; P = .25). Time from infection or vaccination to delivery was associated with transfer ratio in models that included gestational age at delivery and maternal hypertensive disorders, diabetes, and obesity. Placental antibody transfer was detectable as early as 26 weeks' gestation. Transfer ratio that was higher than 1.0 was present for 48 of 51 (94.1%) births at 36 weeks' gestation or later by 8 weeks after vaccination.

Conclusions and Relevance: This study found that maternal and cord blood IgG antibody levels were higher after COVID-19 vaccination compared with after SARS-CoV-2 infection, with slightly lower placental transfer ratios after vaccination than after infection. The findings suggest that time from infection or vaccination to delivery was the most important factor in transfer efficiency.

DOI

10.1001/jamanetworkopen.2022.40993

Alternate Title

JAMA Netw Open

PMID

36350652

Title

Ribavirin Use in Hospitalized Children.

Year of Publication

2022

Number of Pages

386-387

Date Published

06/2022

ISSN Number

2048-7207

DOI

10.1093/jpids/piac039

Alternate Title

J Pediatric Infect Dis Soc

PMID

35699489

Title

Respiratory virus testing and clinical outcomes among children hospitalized with pneumonia.

Year of Publication

2022

Number of Pages

693-701

Date Published

06/2022

ISSN Number

1553-5606

Abstract

BACKGROUND: Despite the increased availability of diagnostic tests for respiratory viruses, their clinical utility for children with community-acquired pneumonia (CAP) remains uncertain.

OBJECTIVE: To identify patterns of respiratory virus testing across children's hospitals prior to the COVID-19 pandemic and to determine whether hospital-level rates of viral testing were associated with clinical outcomes.

DESIGN, SETTING, AND PARTICIPANTS: Multicenter retrospective cohort study of children hospitalized for CAP at 19 children's hospitals in the United States from 2010-2019.

MAIN OUTCOMES AND MEASURES: Using a novel method to identify the performance of viral testing, we assessed time trends in the use of viral tests, both overall and stratified by testing method. Adjusted proportions of encounters with viral testing were compared across hospitals and were correlated with length of stay, antibiotic and oseltamivir use, and performance of ancillary laboratory testing.

RESULTS: There were 46,038 hospitalizations for non-severe CAP among children without complex chronic conditions. The proportion with viral testing increased from 38.8% to 44.2% during the study period (p < .001). Molecular testing increased (27.2% to 40.0%, p < .001) and antigen testing decreased (33.2% to 7.8%, p < .001). Hospital-specific adjusted proportions of testing ranged from 10.0% to 83.5% and were not associated with length of stay, antibiotic use, or antiviral use. Hospitals that performed more viral testing did not have lower rates of ancillary laboratory testing.

CONCLUSIONS: Viral testing practices varied widely across children's hospitals and were not associated with clinically important process or outcome measures. Viral testing may not influence clinical management for many children hospitalized with CAP.

DOI

10.1002/jhm.12902

Alternate Title

J Hosp Med

PMID

35747928

Title

COVID-19 booster vaccination during pregnancy enhances maternal binding and neutralizing antibody responses and transplacental antibody transfer to the newborn (DMID 21-0004).

Year of Publication

2022

Date Published

06/2022

Abstract

Importance: COVID-19 vaccination is recommended during pregnancy for the protection of the mother. Little is known about the immune response to booster vaccinations during pregnancy.

Objective: To measure immune responses to COVID-19 primary and booster mRNA vaccination during pregnancy and transplacental antibody transfer to the newborn.

Design: Prospective cohort study of pregnant participants enrolled from July 2021 to January 2022, with follow up through and up to 12 months after delivery.

Setting: Multicenter study conducted at 9 academic sites.

Participants: Pregnant participants who received COVID-19 vaccination during pregnancy and their newborns.

Exposures: Primary or booster COVID-19 mRNA vaccination during pregnancy.

Main Outcomes and Measures: SARS-CoV-2 binding and neutralizing antibody (nAb) titers after primary or booster COVID-19 mRNA vaccination during pregnancy and antibody transfer to the newborn. Immune responses were compared between primary and booster vaccine recipients in maternal sera at delivery and in cord blood, after adjusting for days since last vaccination.

Results: In this interim analysis, 167 participants received a primary 2-dose series and 73 received a booster dose of mRNA vaccine during pregnancy. Booster vaccination resulted in significantly higher binding and nAb titers, including to the Omicron BA.1 variant, in maternal serum at delivery and cord blood compared to a primary 2-dose series (range 0.55 to 0.88 log higher, p<0.0001 for all comparisons). Although levels were significantly lower than to the prototypical D614G variant, nAb to Omicron were present at delivery in 9% (GMT ID50 12.7) of Pfizer and 22% (GMT ID50 14.7) of Moderna recipients, and in 73% (GMT ID50 60.2) of boosted participants (p<0.0001). Transplacental antibody transfer was efficient regardless of vaccination regimen (median transfer ratio range: 1.55-1.77 for binding IgG and 1.00-1.78 for nAb).

Conclusions and Relevance: COVID-19 mRNA vaccination during pregnancy elicited robust immune responses in mothers and efficient transplacental antibody transfer to the newborn. A booster dose during pregnancy significantly increased maternal and cord blood antibody levels, including against Omicron.Findings support continued use of COVID-19 vaccines during pregnancy, including booster doses.

Trial Registration: clinical trials.gov; Registration Number: NCT05031468 ; https://clinicaltrials.gov/ct2/show/NCT05031468.

Key Points: What is the immune response after COVID-19 booster vaccination during pregnancy and how does receipt of a booster dose impact transplacental antibody transfer to the newborn? Receipt of COVID-19 mRNA vaccines during pregnancy elicited robust binding and neutralizing antibody responses in the mother and in the newborn. Booster vaccination during pregnancy elicited significantly higher antibody levels in mothers at delivery and cord blood than 2-dose vaccination, including against the Omicron BA.1 variant. COVID-19 vaccines, especially booster doses, should continue to be strongly recommended during pregnancy.

DOI

10.1101/2022.06.13.22276354

Alternate Title

medRxiv

PMID

35734087

Title

Development of an Electronic Algorithm to Target Outpatient Antimicrobial Stewardship Efforts for Acute Bronchitis and Pharyngitis.

Year of Publication

2022

Number of Pages

ofac273

Date Published

07/2022

ISSN Number

2328-8957

Abstract

Background: A major challenge for antibiotic stewardship programs is the lack of accurate and accessible electronic data to target interventions. We developed and validated separate electronic algorithms to identify inappropriate antibiotic use for adult outpatients with bronchitis and pharyngitis.

Methods: We used International Classification of Diseases, 10th Revision, diagnostic codes to identify patient encounters for acute bronchitis and pharyngitis at outpatient practices between 3/15/17 and 3/14/18. Exclusion criteria included immunocompromising conditions, complex chronic conditions, and concurrent infections. We randomly selected 300 eligible subjects each with bronchitis and pharyngitis. Inappropriate antibiotic use based on chart review served as the gold standard for assessment of the electronic algorithm, which was constructed using only data in the electronic data warehouse. Criteria for appropriate prescribing, choice of antibiotic, and duration were based on established guidelines.

Results: Of 300 subjects with bronchitis, 167 (55.7%) received an antibiotic inappropriately based on chart review. The electronic algorithm demonstrated 100% sensitivity and 95.3% specificity for detection of inappropriate prescribing. Of 300 subjects with pharyngitis, 94 (31.3%) had an incorrect prescribing decision. Among 29 subjects with a positive rapid streptococcal antigen test, 27 (93.1%) received an appropriate antibiotic and 29 (100%) received the correct duration. The electronic algorithm demonstrated very high sensitivity and specificity for all outcomes.

Conclusions: Inappropriate antibiotic prescribing for bronchitis and pharyngitis is common. Electronic algorithms for identifying inappropriate prescribing, antibiotic choice, and duration showed excellent test characteristics. These algorithms could be used to efficiently assess prescribing among practices and individual clinicians. Interventions based on these algorithms should be tested in future work.

DOI

10.1093/ofid/ofac273

Alternate Title

Open Forum Infect Dis

PMID

35854991

Title

Antibiotics and outcomes of CF pulmonary exacerbations in children infected with MRSA and Pseudomonas aeruginosa.

Year of Publication

2022

Date Published

08/2022

ISSN Number

1873-5010

Abstract

BACKGROUND: Limited data exist to inform antibiotic selection among people with cystic fibrosis (CF) with airway infection by multiple CF-related microorganisms. This study aimed to determine among children with CF co-infected with methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (Pa) if the addition of anti-MRSA antibiotics to antipseudomonal antibiotic treatment for pulmonary exacerbations (PEx) would be associated with improved clinical outcomes compared with antipseudomonal antibiotics alone.

METHODS: Retrospective cohort study using data from the CF Foundation Patient Registry-Pediatric Health Information System linked dataset. The odds of returning to baseline lung function and having a subsequent PEx requiring intravenous antibiotics were compared between PEx treated with anti-MRSA and antipseudomonal antibiotics and those treated with antipseudomonal antibiotics alone, adjusting for confounding by indication using inverse probability of treatment weighting.

RESULTS: 943 children with CF co-infected with MRSA and Pa contributed 2,989 PEx for analysis. Of these, 2,331 (78%) PEx were treated with both anti-MRSA and antipseudomonal antibiotics and 658 (22%) PEx were treated with antipseudomonal antibiotics alone. Compared with PEx treated with antipseudomonal antibiotics alone, the addition of anti-MRSA antibiotics to antipseudomonal antibiotic therapy was not associated with a higher odds of returning to ≥90% or ≥100% of baseline lung function or a lower odds of future PEx requiring intravenous antibiotics.

CONCLUSIONS: Children with CF co-infected with MRSA and Pa may not benefit from the addition of anti-MRSA antibiotics for PEx treatment. Prospective studies evaluating optimal antibiotic selection strategies for PEx treatment are needed to optimize clinical outcomes following PEx treatment.

DOI

10.1016/j.jcf.2022.08.001

Alternate Title

J Cyst Fibros

PMID

35945130

Title

Amoxicillin versus other antibiotic agents for the treatment of acute otitis media in children.

Year of Publication

2022

Date Published

08/2022

ISSN Number

1097-6833

Abstract

OBJECTIVES: The objective of the study was to compare the antibiotic treatment failure and recurrence rates between antibiotic agents (amoxicillin, amoxicillin-clavulanate, cefdinir, and azithromycin) for children with uncomplicated acute otitis media (AOM).

STUDY DESIGN: We completed a retrospective cohort study of children 6 months-12 years of age with uncomplicated AOM identified in a nationwide claims database. The primary exposure was the antibiotic agent, and the primary outcomes were treatment failure and recurrence. Logistic regression was used to estimate ORs, and analyses were stratified by primary exposure, patient age, and antibiotic duration.

RESULTS: Among the 1 051 007 children included in the analysis, 56.6% were prescribed amoxicillin, 13.5% were prescribed amoxicillin-clavulanate, 20.6% were prescribed cefdinir, and 9.3% were prescribed azithromycin. Most prescriptions (93%) were for 10 days, and 98% were filled within 1 day of the medical encounter. Treatment failure and recurrence occurred in 2.2% (95% CI: 2.1, 2.2) and 3.3% (3.2, 3.3) of children, respectively. Combined failure and recurrence rates were low for all agents including amoxicillin (1.7%; 1.7, 1.8), amoxicillin-clavulanate (11.3%; 11.1, 11.5), cefdinir (10.0%; 9.8, 10.1), and azithromycin (9.8%; 9.6, 10.0).

CONCLUSIONS: Despite microbiologic changes in AOM etiology, treatment failure and recurrence were uncommon for all antibiotic agents and were lower for amoxicillin than for other agents. These findings support the continued use of amoxicillin as a first-line agent for AOM when antibiotics are prescribed.

DOI

10.1016/j.jpeds.2022.07.053

Alternate Title

J Pediatr

PMID

35944719

Title

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

Year of Publication

2022

Date Published

09/2022

ISSN Number

1537-6591

Abstract

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.

DOI

10.1093/cid/ciac698

Alternate Title

Clin Infect Dis

PMID

36048543

Title

Early childhood antibiotic utilization for infants discharged from the neonatal intensive care unit.

Year of Publication

2022

Date Published

2022 Apr 05

ISSN Number

1476-5543

Abstract

<p><strong>OBJECTIVE: </strong>To determine antibiotic utilization for NICU infants, as compared to non-NICU infants, in the first 3 years after birth hospital discharge.</p>

<p><strong>STUDY DESIGN: </strong>Retrospective observational study using data from Medicaid Analytic Extract including 667 541 newborns discharged from 2007-2011. Associations between NICU admission and antibiotic prescription were assessed using regression models, adjusting for confounders, and stratified by gestational age and birth weight.</p>

<p><strong>RESULTS: </strong>596 999 infants (89.4%) received ≥1 antibiotic, with a median of 4 prescriptions per 3 person-years (IQR 2-8). Prescribed antibiotics and associated indication were similar between groups. Compared to non-NICU infants (N = 586 227), NICU infants (N = 81 314) received more antibiotic prescriptions (adjusted incidence rate ratio 1.08, 95% confidence interval [CI] (1.08,1.08)). Similar results were observed in all NICU subgroups.</p>

<p><strong>CONCLUSIONS: </strong>Antibiotic utilization in early childhood was higher among infants discharged from NICUs compared to non-NICU infants.</p>

DOI

10.1038/s41372-022-01380-y

Alternate Title

J Perinatol

PMID

35383276

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