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

2022

08/2022

1873-5010

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.

10.1016/j.jcf.2022.08.001

J Cyst Fibros

35945130

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

2022

08/2022

1097-6833

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.

10.1016/j.jpeds.2022.07.053

J Pediatr

35944719

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

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

2022

2022 Apr 05

1476-5543

<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>

10.1038/s41372-022-01380-y

J Perinatol

35383276

Fidelity evaluation of the dialogue around respiratory illness treatment (DART) program communication training.

2022

2022 Mar 14

1873-5134

<p><strong>OBJECTIVE: </strong>To evaluate receipt fidelity of communication training content included in a multifaceted intervention known to reduce antibiotic over-prescribing for pediatric acute respiratory tract infections (ARTIs), by examining the degree to which clinicians implemented the intended communication behavior changes.</p>

<p><strong>METHODS: </strong>Parents were surveyed regarding clinician communication behaviors immediately after attending 1026 visits by children 6 months to &lt;&nbsp;11 years old diagnosed with ARTIs by 53 clinicians in 18 pediatric practices. Communication outcomes analyzed were whether clinicians: (A) provided both a combined (negative + positive) treatment recommendation and a contingency plan (full implementation); (B) provided either a combined treatment recommendation or a contingency plan (partial implementation); or (C) provided neither (no implementation). We used mixed effects multinomial logistic regression to determine whether these 3 communication outcomes changed between baseline and the time periods following each of 3 training modules.</p>

<p><strong>RESULTS: </strong>After completing the communication training, the adjusted probability of clinicians fully implementing the intended communication behavior changes increased by an absolute 8.1% compared to baseline (95% Confidence Interval [CI]: 2.4%, 13.8%, p&nbsp;=&nbsp;.005).</p>

<p><strong>CONCLUSIONS: </strong>Our findings support the receipt fidelity of the intervention's communication training content.</p>

<p><strong>PRACTICAL IMPLICATIONS: </strong>Clinicians can be trained to implement communication behaviors that may aid in reducing antibiotic over-prescribing for ARTIs.</p>

10.1016/j.pec.2022.03.011

Patient Educ Couns

35341612

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

Comparison of the Respiratory Resistomes and Microbiota in Children Receiving Short versus Standard Course Treatment for Community-Acquired Pneumonia.

2022

e0019522

2022 Mar 24

2150-7511

<p>Pediatric community-acquired pneumonia (CAP) is often treated with 10 days of antibiotics. Shorter treatment strategies may be effective and lead to less resistance. The impact of duration of treatment on the respiratory microbiome is unknown. Data are from children ( = 171), ages 6 to 71 months, enrolled in the SCOUT-CAP trial (NCT02891915). Children with CAP were randomized to a short (5 days) versus standard (10 days) beta-lactam treatment strategy. Throat swabs were collected at enrollment and the end of the study and used for shotgun metagenomic sequencing. The number of beta-lactam and multidrug efflux resistance genes per prokaryotic cell (RGPC) was significantly lower in children receiving the short compared to standard treatment strategy at the end of the study (Wilcoxon rank sum test,  &lt; 0.05 for each). Wilcoxon effect sizes were small for beta-lactam (: 0.15; 95% confidence interval [CI], 0.01 to 0.29) and medium for multidrug efflux RGPC (: 0.23; 95% CI, 0.09 to 0.37). Analyses comparing the resistome at the beginning and end of the trial indicated that in contrast to the standard strategy group, the resistome significantly differed in children receiving the short course strategy. Relative abundances of commensals such as Neisseria subflava were higher in children receiving the standard strategy, and species and Veillonella parvula were higher in children receiving the short course strategy. We conclude that children receiving 5 days of beta-lactam therapy for CAP had a significantly lower abundance of antibiotic resistance determinants than those receiving standard 10-day treatment. These data provide an additional rationale for reductions in antibiotic use when feasible. Antibiotic resistance is a major threat to public health. Treatment strategies involving shorter antibiotic courses have been proposed as a strategy to lower the potential for antibiotic resistance. We examined relationships between the duration of antibiotic treatment and its impact on resistance genes and bacteria in the respiratory microbiome using data from a randomized controlled trial of beta-lactam therapy for pediatric pneumonia. The randomized design provides reliable evidence of the effectiveness of interventions and minimizes the potential for confounding. Children receiving 5 days of therapy for pneumonia had a lower prevalence of two different types of resistance genes than did those receiving the 10-day treatment. Our data also suggest that children receiving longer durations of therapy have a greater abundance of antibiotic resistance genes for a longer period of time than do children receiving shorter durations of therapy. These data provide an additional rationale for reductions in antibiotic use.</p>

10.1128/mbio.00195-22

mBio

35323040

Characterizing Neurocognitive Impairment in Juvenile Fibromyalgia Syndrome: Subjective and Objective Measures of Dyscognition.

2022

848009

2022

2296-2360

<p><strong>Objectives: </strong>Our understanding of brain fog, or dyscognition, among youth with juvenile fibromyalgia syndrome is limited. We aimed to determine the prevalence of subjective (self-reported) and objective dyscognition, as well as factors associated with subjective dyscognition in juvenile fibromyalgia syndrome.</p>

<p><strong>Methods: </strong>A cross-sectional cohort study of patients ( = 31) 12-17 years old diagnosed with primary juvenile fibromyalgia syndrome and one of their parents from 2017 to 2019. Subjects completed a series of survey measures and patients completed a brief neurocognitive battery. Subjective dyscognition was determined based on scores on the Pediatric Quality of Life Inventory (PedsQL) Cognitive Functioning Scale and Behavior Rating Inventory of Executive Function (BRIEF-2) global executive composite (GEC). Objective dyscognition was defined as impairment of more than two standard deviations in any of the neurocognitive domains. We used Fisher's exact test or Wilcoxon rank-sum test, as appropriate, to compare clinical patients based on the presence of dyscognition. Multivariable logistic regression modeling was performed to determine factors associated with subjective dyscognition.</p>

<p><strong>Results: </strong>Of the 31 subjects, 65% reported subjective dyscognition and 39% had objective dyscognition, primarily in the domains of psychomotor speed (23%), executive function (23%), and attention (3%). Subjective dyscognition was not indicative of objective dyscognition. Subjective dyscognition was independently associated with functional disability (OR: 1.19 [95% CI: 1.02-1.40]) and anxiety (OR: 1.12 [95% CI: 1.02-1.24]).</p>

<p><strong>Discussion: </strong>Adolescents with fibromyalgia predominantly experience subjective dyscognition but more than 1/3 also experience objective dyscognition. Future research should explore the impact of interdisciplinary rehabilitation programs on the treatment of dyscognition in youth with JFMS.</p>

10.3389/fped.2022.848009

Front Pediatr

35281242

Factors Associated With Penicillin Allergy Labels in Electronic Health Records of Children in 2 Large US Pediatric Primary Care Networks.

2022

e222117

2022 Mar 01

2574-3805

<p><strong>Importance: </strong>Penicillin allergy labels influence clinical decision-making, yet most children who are labeled do not have type 1 hypersensitivity allergic reactions and instead have a history of predictable adverse reactions or unspecified illness symptoms while receiving penicillin for viral infections. Studies describing penicillin allergy labeling in the pediatric outpatient setting are lacking.</p>

<p><strong>Objective: </strong>To describe the epidemiology and factors associated with penicillin allergy labels across 2 large US pediatric primary care networks.</p>

<p><strong>Design, Setting, and Participants: </strong>This retrospective, longitudinal birth cohort study was conducted in 90 primary care pediatric practices serving a diverse population of children across Houston, Texas, Austin, Texas, Philadelphia, Pennsylvania, and parts of New Jersey. Participants were children born between January 2010 and June 2020 who had a health care visit in the first 14 days of life and at least 2 additional visits in the first year of life at one of 90 primary care pediatric practices. Censoring criteria were additionally applied to exclude data from children no longer seeking health care in the 90 clinics over time. Statistical analysis was performed from February to May 2021.</p>

<p><strong>Exposures: </strong>Basic patient demographics, health care utilization, penicillin exposure, and primary clinic location.</p>

<p><strong>Main Outcomes and Measures: </strong>Addition of penicillin allergy label in the electronic medical record.</p>

<p><strong>Results: </strong>Among 334 465 children in the birth cohort, 164 173 (49.1%) were female; 72 831 (21.8%) were Hispanic, 59 598 (17.8%) were non-Hispanic Black, and 148 534 (44.4%) were non-Hispanic White; the median (IQR) age at censoring was 3.8 (1.7-6.6) years; 18 015 (5.4%) were labeled as penicillin allergic, but the prevalence of penicillin allergy labeling ranged from 0.9% to 10.2% across practices. Children were labeled at a median (IQR) age of 1.3 (0.9-2.3) years. Non-Hispanic White children were more likely to be labeled compared with non-Hispanic Black children after controlling for potential confounders (adjusted odds ratio, 1.7 [95% CI, 1.6-1.8]). There were 6797 allergic children (37.7%) labeled after receiving 1 penicillin prescription and 1423 (7.9%) labeled after receiving 0 penicillin prescriptions.</p>

<p><strong>Conclusions and Relevance: </strong>In this cohort study of more than 330 000 children, penicillin allergy labeling was common and varied widely across practices. Children were labeled early in life, and almost half were labeled after receiving 1 or 0 penicillin prescriptions. These findings raise questions regarding the validity of penicillin allergy labels. Future work exploring the fidelity of and outcomes associated with penicillin allergy-labeling in children is warranted.</p>

10.1001/jamanetworkopen.2022.2117

JAMA Netw Open

35285918

Gastrointestinal Microbiome Disruption and Antibiotic-Associated Diarrhea in Children Receiving Antibiotic Therapy for Community-Acquired Pneumonia.

2022

2022 Mar 06

1537-6613

<p>Antibiotic-associated diarrhea (AAD) is a common side effect of antibiotics. We examined the gastrointestinal microbiota in children treated with beta-lactams for community-acquired pneumonia. Data were from 66 children (n=198 samples), ages 6-71 months, enrolled in the SCOUT-CAP trial (NCT02891915). AAD was defined as ≥1 day of diarrhea. Stool samples were collected on study days 1, 6-10, and 19-25. Samples were analyzed using 16s-rRNA gene sequencing to identify associations between patient characteristics, microbiota characteristics, and AAD (yes/no). Nineteen (29%) children developed AAD. Microbiota compositional profiles differed between AAD groups (PERMANOVA, P &lt; 0.03) and across visits (P &lt; 0.001). Children with higher baseline relative abundances of two Bacteroides species were less likely to experience AAD. Higher baseline abundance of Lachnospiraceae and amino acid biosynthesis pathways were associated with AAD. Children in the AAD group experienced prolonged dysbiosis (P &lt; 0.05). Specific gastrointestinal microbiota profiles are associated with AAD in children.</p>

10.1093/infdis/jiac082

J Infect Dis

35249113