Risk factors for Clostridioides (Clostridium) difficile infection following solid organ transplantation in children.

BACKGROUND: Clostridioides (Clostridium) difficile infection (CDI) in pediatric solid organ transplant (SOT) recipients is a growing problem, though CDI risk factors in this population are poorly understood. Our objective was to characterize CDI risk factors in pediatric SOT recipients. METHODS: This retrospective case-control study, performed at a single freestanding academic children's hospital, included all SOT recipients age 1-22 years who were tested for C. difficile by toxin B gene PCR between August 2009 and August 2017. CDI risk factors were assessed by comparing PCR-positive and PCR-negative cases by generalized linear mixed models. RESULTS: Between August 2009 and August 2017, 409 SOTs were performed of which 138 (33.7%), 134 (32.8%), 131 (32.0%), and 6 (1.5%) were kidney, liver, heart, and small intestine transplants, respectively. Of 205 SOT recipients were tested for CDI, with 723 C. difficile PCR tests performed among these patients. 68/205 (33%) patients developed CDI at least once during the study period. Median (interquartile range) time to diagnosis of first CDI following SOT was 8.9 (1.2, 19.6) months. CDI was independently associated with calcineurin inhibitor use at time of C. difficile testing (odds ratio [OR] 2.38, 95% confidence interval [CI] 1.08, 5.24, P = 0.03) and systemic antibiotic exposure within 30 days of C. difficile testing (OR 1.74, 95% CI 1.08, 2.79, P = 0.02). CONCLUSIONS: CDI is a common, relatively late post-transplant complication and independently associated with calcineurin inhibitor and systemic antibiotic exposure. The potential impact of specific immunosuppressive drug and antibiotic selection on CDI risk reduction requires further investigation.

Clostridium difficile Whole Genome Sequencing Reveals Limited Transmission Among Symptomatic Children: A Single-Center Analysis.

Background: Although pediatric Clostridium difficile infections (CDIs) are increasing, C. difficile transmission patterns among children are poorly understood. Methods: We performed whole genome sequencing (WGS) on C. difficile isolates collected from children diagnosed with CDI between December 2012 and December 2013 at a single academic medical center. Genome sequences of isolates from CDIs diagnosed ≥8 weeks after study initiation were compared to all study isolate genome sequences. Among patients with isogenic isolates (≤2-3 core genome single nucleotide variants [SNVs] identified by pairwise SNV analyses), common inpatient and/or outpatient healthcare exposures were investigated. Results: Among 131 CDIs in 107 children, WGS identified 104 genetically distinct isolates. Of 84 incident CDIs occurring ≥8 weeks after study initiation, only 10 (11.9%) were caused by a strain isogenic to another cohort CDI isolate (putative transmission events). Proportions of each CDI class putatively associated with transmission were hospital-onset healthcare facility-associated (HCFA), 2/16 (12.5%); community-onset HCFA, 1/17 (5.9%); indeterminate, 1/11 (9.1%); community-associated (CA), 5/40 (12.5%); and recurrent, 1/21 (4.8%). Transmission events among CA and HCFA CDIs were similarly infrequent (5/40 [12.5%] vs 3/33 [9.1%]; P = .64). Shared healthcare facility exposures were only identified among 7/10 putative transmission events. Potential community transmission (same postal code) was not identified. Conclusions: WGS identified a highly diverse group of C. difficile isolates among children with CDI, including those with HCFA CDI. Clostridium difficile transmission among symptomatic children was very uncommon. Among putatively transmitted cases, investigation of shared healthcare exposures often did not identify a potential transmission source.

Whole-genome analysis reveals the evolution and transmission of an MDR DH/NAP11/106 Clostridium difficile clone in a paediatric hospital.

Background: Clostridium difficile strain DH/NAP11/106, a relatively antibiotic-susceptible strain, is now the most common cause of C. difficile infection (CDI) among adults in the USA. Objectives: To identify mechanisms underlying the evolution and transmission of an MDR DH/NAP11/106 clone. Methods: WGS (Illumina MiSeq), restriction endonuclease analysis (REA) and antibiotic susceptibility testing were performed on 134 C. difficile isolates collected from paediatric patients with CDI over a 2 year period. Results: Thirty-one of 134 (23%) isolates were REA group DH. Pairwise single-nucleotide variant (SNV) analyses identified a DH clone causing seven instances of CDI in two patients. During the 337 days between the first and second CDI, Patient 1 (P1) received 313 days of antibiotic therapy. Clindamycin and rifaximin resistance, and reduced vancomycin susceptibility (MIC 0.5-2 mg/L), were newly identified in the relapsed isolate. This MDR clone was transmitted to Patient 2 (P2) while P1 and P2 received care in adjacent private rooms. P1 and P2 each developed two additional CDI relapses. Comparative genomics analyses demonstrated SNVs in multiple antibiotic resistance genes, including rpoB (rifaximin resistance), gyrB and a gene encoding PBP; gyrB and PBP mutations did not consistently confer a resistance phenotype. The clone also acquired a 46 000 bp genomic element, likely a conjugative plasmid, which contained ermB (clindamycin resistance). The element shared 99% identity with the genomic sequence of Faecalibacterium prausnitzii, an enteric commensal. Conclusions: These data highlight the emergence of MDR in C. difficile strain DH/NAP11/106 through multiple independent mechanisms probably as a consequence of profound antibiotic pressure.

Variability in Antibiotic Use Across PICUs.

OBJECTIVES: To characterize and compare antibiotic prescribing across PICUs to evaluate the degree of variability. DESIGN: Retrospective analysis from 2010 through 2014 of the Pediatric Health Information System. SETTING: Forty-one freestanding children's hospital. SUBJECTS: Children aged 30 days to 18 years admitted to a PICU in children's hospitals contributing data to Pediatric Health Information System. INTERVENTIONS: To normalize for potential differences in disease severity and case mix across centers, a subanalysis was performed of children admitted with one of the 20 All Patient Refined-Diagnosis Related Groups and the seven All Patient Refined-Diagnosis Related Groups shared by all PICUs with the highest antibiotic use. RESULTS: The study included 3,101,201 hospital discharges from 41 institutions with 386,914 PICU patients. All antibiotic use declined during the study period. The median-adjusted antibiotic use among PICU patients was 1,043 days of therapy/1,000 patient-days (interquartile range, 977-1,147 days of therapy/1,000 patient-days) compared with 893 among non-ICU children (interquartile range, 805-968 days of therapy/1,000 patient-days). For PICU patients, the median adjusted use of broad-spectrum antibiotics was 176 days of therapy/1,000 patient-days (interquartile range, 152-217 days of therapy/1,000 patient-days) and was 302 days of therapy/1,000 patient-days (interquartile range, 220-351 days of therapy/1,000 patient-days) for antimethicillin-resistant Staphylococcus aureus agents, compared with 153 days of therapy/1,000 patient-days (interquartile range, 130-182 days of therapy/1,000 patient-days) and 244 days of therapy/1,000 patient-days (interquartile range, 203-270 days of therapy/1,000 patient-days) for non-ICU children. After adjusting for potential confounders, significant institutional variability existed in antibiotic use in PICU patients, in the 20 All Patient Refined-Diagnosis Related Groups with the highest antibiotic usage and in the seven All Patient Refined-Diagnosis Related Groups shared by all 41 PICUs. CONCLUSIONS: The wide variation in antibiotic use observed across children's hospital PICUs suggests inappropriate antibiotic use.

Differences in the Molecular Epidemiology and Antibiotic Susceptibility of Clostridium difficile Isolates in Pediatric and Adult Patients.

The rising incidence of Clostridium difficile infections (CDIs) in adults is partly related to the global spread of fluoroquinolone-resistant strains, namely, BI/NAP1/027. Although CDIs are also increasingly diagnosed in children, BI/NAP1/027 is relatively uncommon in children. Little is known about the antibiotic susceptibility of pediatric CDI isolates. C. difficile was cultured from tcdB-positive stools collected from children diagnosed with CDI between December 2012 and December 2013 at an academic children's hospital. CDI isolates were grouped by restriction endonuclease analysis (REA). MICs were measured by agar dilution method for 7 antibiotics. Susceptibility breakpoints were based on guidelines from CLSI and/or the European Committee on Antimicrobial Susceptibility Testing (EUCAST). MICs and REA groupings of C. difficile isolates from 74 adult patients (29 isolates underwent REA) from a temporally and geographically similar adult cohort were compared to those of pediatric isolates. Among 122 pediatric and 74 adult isolates, respectively, the rates of resistance were as follows: metronidazole, 0% and 0%; vancomycin, 0% and 8% (P = 0.003); rifaximin, 1.6% and 6.7% (P = 0.11); clindamycin, 18.9% and 25.3% (P = 0.29); and moxifloxacin, 2.5% and 36% (P = <0.0001). Only 1 of 122 (0.8%) BI/NAP1/027 isolates was identified among the children, compared to 9 of 29 (31%) isolates identified among the adults (P = <0.0001). The 3 moxifloxacin-resistant pediatric isolates were of REA groups BI and CF and a nonspecific group. The 2 rifaximin-resistant pediatric isolates were of REA groups DH and Y. The 21 clindamycin-resistant pediatric isolates were distributed among 9 REA groups (groups A, CF, DH, G, L, M, and Y and 2 unique nonspecific REA groups). These data suggest that a diverse array of relatively antibiotic-susceptible C. difficile strains predominate in a cohort of children with CDI compared to adults.

Risk Factors for Recurrent Clostridium difficile Infection in Children: A Nested Case-Control Study.

OBJECTIVE: To identify risk factors for recurrent Clostridium difficile infection (RCDI) in children. STUDY DESIGN: A nested case-control study was performed to identify RCDI risk factors using a pediatric cohort of inpatients and outpatients diagnosed with Clostridium difficile infection by tcdB polymerase chain reaction (PCR) at an academic children's hospital between December 9, 2012, and June 30, 2014. Strict inclusion criteria were adopted to limit selection bias related to inappropriate inclusion of patients with probable C difficile colonization. RESULTS: Thirty children with RCDI were compared with 94 children with non-RCDI. Statistically significant associations were identified between RCDI and malignancy (OR 2.8, 95% CI 1.0-7.4, P = .044), tracheostomy tube dependence (OR 5.2, 95% CI 1.1-24.7, P = .037), and tcdB PCR cycle threshold (OR 0.87, 95% CI 0.78-0.97, P = .01) using multivariable logistic regression modeling. The receiver operator characteristic curve for PCR cycle threshold as a predictor of RCDI demonstrated area under the curve = 0.67. The highest predictive rate (75%) for RCDI was demonstrated at cycle threshold cutpoint ≤ 20. The difference between sensitivity (64%) and specificity (68%) was minimized at cycle threshold cutpoint ≤ 23. Compared with controls with non-RCDI, children excluded because of probable C difficile colonization had a similar cycle threshold value (27.5 vs 27.2, P = .77). CONCLUSIONS: Malignancy and tracheostomy tube dependence were identified as RCDI risk factors. Although RCDI was associated with positivity at a lower tcdB PCR cycle threshold, the clinical utility of cycle threshold as a tool to predict recurrence was limited. Better methods to predict RCDI are needed to prioritize pediatric populations to target for RCDI prevention efforts.

Post-Exposure Prophylaxis for Varicella-Zoster Virus Exposure in High-Risk Children.

BACKGROUND: Post-exposure prophylaxis (PEP) with varicella immunoglobulin is recommended to minimize risk of varicella complications for high-risk children. However, providers frequently use alternatives like acyclovir or intravenous immunoglobulin. METHODS: A retrospective cohort study was conducted of PEP for varicella in children from January 2009 to December 2019. Data were provided by 47 children's hospitals who participate in the Pediatric Health Information Systems database. Patients with clinical encounters for varicella exposure were reviewed. Choice of varicella PEP regimens, including differences by underlying condition and institution, and incidence of varicella disease were determined. RESULTS: A total of 1704 patients with first clinical encounters for varicella met inclusion criteria. Of these patients, 509 (29.9%) were prescribed PEP after varicella exposure, and 65 (3.8%) ultimately had a subsequent encounter for varicella disease. Of 509 patients who received PEP, acyclovir was most frequently prescribed (n = 195, 38.3%), followed by varicella immunoglobulin (n = 146, 28.7%), IVIG (n = 115, 22.6%), and combination therapy (n = 53, 10.4%). The highest proportion of varicella immunoglobulin use (10/20, 50%) was amongst children with diagnoses of rheumatological/gastrointestinal conditions. The highest proportion of acyclovir use (29/684, 4.2%) was amongst children with diagnoses of oncology/stem cell transplant conditions. The proportion of patients who subsequently had clinical encounters for varicella disease was highest for Acyclovir (30/195, 15.4%) followed by varicella immunoglobulin (5/146, 3.4%), combination therapy (2/53, 3.8%), and intravenous immunoglobulin alone (0/115) (P < .0001). CONCLUSIONS: Varicella PEP in high-risk children was highly varied among children's hospitals. In our dataset, use of acyclovir was associated with a higher rate of subsequent encounters for Varicella disease.

Percutaneous Drainage of Pediatric Pulmonary Abscesses: An Effective Therapy.

INTRODUCTION: Pulmonary abscess is a complication of lung infection with localized necrosis and purulent cavity formation. Pulmonary abscesses are typically managed using antibiotic therapy with anatomic surgical resection reserved as a rescue. Percutaneous drainage is considered relatively contraindicated in some centers due to perceived risk of bronchopleural fistula. However, drain placement has been frequently employed at our institution. The purpose of this study was to review and describe our longitudinal experience. METHODS: Medical records of children diagnosed with lung abscess and treated with percutaneous drainage from 2005 through 2023 were reviewed. Patient clinical parameters, follow-up imaging, and clinical outcomes were evaluated. RESULTS: Percutaneous drainage (n = 24) or aspiration alone (n = 4) under imaging guidance was performed by interventional radiologists for 28 children with lung abscesses. A single catheter (8-12 Fr) was deployed in the pulmonary abscess cavity and remained for a median of 6 days (IQR: 6-8 days). The median hospital stay was 10 days (IQR: 8.8-14.8 days). The technical success rate for percutaneous drainage or aspiration of primary pulmonary abscesses was 100% (26/26). Two children were later diagnosed with secondarily infected congenital pulmonary airway malformations that were both successfully drained and ultimately surgically resected. The abscess cavities resolved in all patients and catheters were removed upon clinical, radiographic, and laboratory improvement. Complications included the presence of two bronchopleural fistula, both of which were treated with immediate pleural drain placement. CONCLUSION: Percutaneous drainage of pulmonary abscesses is an effective therapeutic option in children and can be considered alongside antibiotics as part of the initial treatment for pulmonary abscesses. Bronchopleural fistula can occur, but at a lower frequency than previously reported. LEVEL OF EVIDENCE: Level V.

Ambulatory amoxicillin use for common acute respiratory infections during a national shortage: Results from the SHARPS-OP benchmarking collaborative.

We quantified antibiotic prescribing for ambulatory pediatric acute respiratory illness at 22 institutions in "pre-shortage" (Jan 2019-Sep 2022) and "shortage" (Oct 2022-Mar 2023) periods for amoxicillin. While acute respiratory illness prescribing increased across settings, the proportion of amoxicillin prescriptions decreased. Variation was seen within and between institutions.

Fluoroquinolone Use Among Hospitalized Children: Diagnosis-Based Stratification to Identify Stewardship Targets.

Background: As FQ (fluoroquinolone) use has shifted in pediatric populations, better metrics are needed to guide targeted antibiotic stewardship interventions and limit development of adverse events and resistance, particularly in medically complex children. In this study, we identify high-utilization groups based on underlying medical conditions and describe their relative FQ use over time. Methods: This study is a retrospective analysis of data from the Pediatric Health Information System database from 2016 to 2020. We identify high-utilization groups based on underlying medical conditions using International Classification of Diseases, Ninth or Tenth Revision codes. We delineate overall trends in the use of FQs in the inpatient setting, including rate and proportional use by each patient group. Results: Patients with an oncology diagnosis represent a large (25%-44%) and rising proportion (+4.8%/year, P = .001) of national FQ use over the study period. Patients with intra-abdominal infections, including appendicitis, have had a significant increase in both their relative proportional use of FQs (+0.6%/year, P = .037) and proportion of FQ use per admission encounter over the study period (+0.6%/year, P = .008). Patients with cystic fibrosis represent a decreasing proportion of overall use (-2.1%/year, P = .011) and have decreasing FQ use per inpatient encounter (-0.8%/year, P = .001). Conclusions: Patients with an oncology diagnosis and patients with an intra-abdominal infection appear to be targets for FQ stewardship. Patients with cystic fibrosis have decreasing inpatient FQ use. Key Points: This study describes fluoroquinolone use among hospitalized children from 2016 to 2020, stratified by underlying diagnoses. These trends are used to identify high-yield antibiotic stewardship targets.

Antimicrobial stewardship for nurse practitioners and physician assistants: enhancing patient safety through education.

Background: As nurse practitioners and physician assistants (APPs) become more prevalent in delivering pediatric care, their involvement in antimicrobial stewardship efforts increases in importance. This project aimed to create and assess the efficacy of a problem-based learning (PBL) approach to teaching APPs antimicrobial stewardship principles. Methods: A PBL education initiative was developed after communication with local APP leadership and focus group feedback. It was offered to all APPs associated with Lurie Children's Hospital of Chicago. Participants completed a survey which assessed opinions on antimicrobial stewardship and included knowledge-based questions focused on antimicrobial stewardship. Prescriptions for skin and soft tissue infections associated with APPs were recorded via chart review before and after the education campaign. Results: Eighty APPs participated in the initial survey and teaching initiative with 44 filling out the 2-week follow-up and 29 filling out the 6-month follow-up. Subjective opinions of antimicrobial stewardship and comfort with basic principles of AS increased from pre-intervention. Correct responses to knowledge-based assessments increased from baseline after 2-week follow-up (p < 0.01) and were maintained at the 6-month follow-up (p = 0.03). Simple skin and soft tissue infection prescriptions for clindamycin went from 44.4% pre-intervention to 26.5% (p = 0.2) post-intervention. Conclusions: A PBL approach for APP education on antimicrobial stewardship can be effective in increasing knowledge and comfort with principles of antimicrobial stewardship. These changes are maintained in long-term follow-up. Changes in prescribing habits showed a strong trend towards recommended empiric therapy choice. Institutions should develop similar education campaigns for APPs.

Prospective evaluation of a pediatric urodynamics protocol before and after limiting urine cultures.

PURPOSE: While our institution has historically obtained a urine culture (UCx) from every child at the time of urodynamics (UDS), no consensus exists on UDS UCx utility, and practice varies widely. This study aims to prospectively study our symptomatic post-UDS UTI rate before and after implementing a targeted UCx protocol. MATERIALS AND METHODS: A 2-part prospective study of patients undergoing UDS at one pediatric hospital was undertaken, divided into Phase 1 (7/2016-6/2017) with routine UCx at the time of UDS and Phase 2 (7/2019-6/2020) after implementation of a protocol limiting UCx at the time of UDS to only a targeted subset of patients. The primary outcome was symptomatic post-UDS UTI, defined as positive UCx ≥10ˆ4 CFU/mL and fever ≥38.5 °C or new urinary symptoms within seven days of UDS. RESULTS: A total of 1,154 UDS were included: 553 in 483 unique patients during Phase 1 and 601 in 533 unique patients during Phase 2. Age, sex, race, ethnicity, and bladder management did not differ significantly between phases. All 553 UDS in Phase 1 had UCx at the time of UDS, compared to 34% (204/601) in Phase 2. The rate of positive UCx decreased from 39% in Phase 1-35% in Phase 2. Three patients developed symptomatic post-UDS UTI in each study period, resulting in a stable post-UDS UTI rate of 0.5% (3/553) in Phase 1 and 0.5% (3/601) in Phase 2. These patients varied in age, sex, UDS indication, and bladder management. Four of the six (67%) patients had positive UCx at the time of UDS, one had a negative UCx, and one had no UCx under the targeted UCx protocol. Predictors of symptomatic post-UDS UTI could not be evaluated. DISCUSSION: In the largest prospective study to date, we found that symptomatic post-UDS UTI was <1% and that UCx at the time of UDS can safely be limited at our hospital. This reduction has important implications for cost containment and antibiotic stewardship. We will continue iterative modifications to our protocol, which may eventually include the elimination of UCx at the time of UDS in all groups. CONCLUSIONS: This 2-part prospective evaluation at one pediatric hospital determined that the symptomatic post-UDS UTI rate remained <1% with no identifiable predictors after limiting previously universal UCx at the time of UDS to only a targeted subset of patients.

Benchmarking of Outpatient Pediatric Antibiotic Prescribing: Results of a Multicenter Collaborative.

BACKGROUND: Most antibiotic use occurs in ambulatory settings. No benchmarks exist for pediatric institutions to assess their outpatient antibiotic use and compare prescribing rates to peers. We aimed to share pediatric outpatient antibiotic use reports and benchmarking metrics nationally. METHODS: We invited institutions from the Sharing Antimicrobial Reports for Pediatric Stewardship OutPatient (SHARPS-OP) Collaborative to contribute quarterly aggregate reports on antibiotic use from January 2019 to June 2022. Outpatient settings included emergency departments (ED), urgent care centers (UCC), primary care clinics (PCC) and telehealth encounters. Benchmarking metrics included the percentage of: (1) all acute encounters resulting in antibiotic prescriptions; (2) acute respiratory infection (ARI) encounters resulting in antibiotic prescriptions; and among ARI encounters receiving antibiotics, (3) the percentage receiving amoxicillin ("Amoxicillin index"); and (4) the percentage receiving azithromycin ("Azithromycin index"). We collected rates of antibiotic prescriptions with durations ≤7 days and >10 days from institutions able to provide validated duration data. RESULTS: Twenty-one institutions submitted aggregate reports. Percent ARI encounters receiving antibiotics were highest in the UCC (40.2%), and lowest in telehealth (19.1%). Amoxicillin index was highest for the ED (76.2%), and lowest for telehealth (55.8%), while the azithromycin index was similar for ED, UCC, and PCC (3.8%, 3.7%, and 5.0% respectively). Antibiotic duration of ≤7 days varied substantially (46.4% for ED, 27.8% UCC, 23.7% telehealth, and 16.4% PCC). CONCLUSIONS: We developed a benchmarking platform for key pediatric outpatient antibiotic use metrics drawing data from multiple pediatric institutions nationally. These data may serve as a baseline measurement for future improvement work.

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

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.

Utilizing Google trends to monitor coronavirus vaccine interest and hesitancies.

INTRODUCTION: Vaccine hesitancy remains a serious challenge for ending the coronavirus disease 2019 (COVID-19) pandemic. Digital media has played an immense role in the spread of information during the pandemic. One method to gauge public interest in COVID-19 related information is to examine patterns of online search queries. METHODS: Google Trends (GT) was used to analyze results for search terms relating to COVID-19 vaccine misinformation, information, and accessibility from October 1st, 2020 to May 27th, 2021. GT allows you to compare multiple queries at one time. The resultant relative search volumes (RSVs)range from 0 to 100. The search term andpoint in time on the graph that has the greatest search volume is given a score of 100 and all other terms and times are given values relative to that maximum. Search interest peaks were analyzed by subgroups (misinformation, information seeking, and access seeking) and across key time points throughout the pandemic. RESULTS: GT analysis revealed that search interest related to vaccine misinformation, general information, and access seeking changed in relation to events taking place throughout the pandemic. The most commonly searched terms in each subgroup were: "Covid vaccine infertility", "Covid vaccine side effects", and "Covid vaccine appointment". Searches related to misinformation peaked in December 2020. Search terms in the general information category peaked in April 2021. RSVs for access seeking terms peaked in March 2021 and have decreased since April 2021. CONCLUSION: Misinformation RSVs were highest after FDA authorization and have multiple repeated spikes after subsequent vaccine announcements. General information seeking terms peaked concurrently with increased vaccination uptake in the United States. Search interest has decreased with wider vaccine availability, despite many individuals in the United States remaining unvaccinated. GT can be used to monitor trends in public attitudes and misinformation regarding COVID-19 vaccines and further target education.

Drivers of Prolonged Outpatient Antibiotic Therapy for Urinary Tract Infections and Community-Acquired Pneumonia.

BACKGROUND: Variability exists in treatment duration for community-acquired pneumonia (CAP) and urinary tract infection (UTI) in children and may be associated with non-clinical factors. METHODS: A retrospective study was conducted of patients treated for outpatient CAP and UTI in a children's hospital network from 2016 to 2019. Multivariable logistic regression was performed to identify predictors of long antibiotic duration (≥10 days). Hospitalization within 30 days was determined. RESULTS: Overall, 2124 prescriptions for CAP and 1116 prescriptions for UTI were included. Prescriptions were ≥10 days in 59.9% and 47.6% for CAP and UTI, respectively. Long durations were more common in the emergency department (ED) than in clinics for UTI's (P = .0082), and more common in convenient care for CAP (P = .045). In UTI's, Asian and Hispanic patients received shorter durations than white patients. Younger children had greater odds of long duration for both diagnoses. Medicaid insurance was associated with long therapy for UTI (OR: 1.660, P = .0042) and CAP (OR: 1.426, P = .0169). Residents and fellows were less likely to give long durations than attending physicians (P < .0001). APNs were more likely to administer long therapies in CAP (P = .0062). Subsequent hospitalizations were uncommon for UTI (n = 10) and CAP (n = 20). CONCLUSIONS: Younger age, Medicaid insurance, ED, and convenient care visits were associated with a long duration of therapy. Residents and fellows were less likely to give long durations.

Sociodemographic Comparison of Children With High-risk Medical Conditions Referred vs Identified Through Screening Plus Outreach for COVID-19 Therapeutics.

Importance: Minoritized groups are less likely to receive COVID-19 therapeutics, but few studies have identified potential methods to reduce disparities. Objective: To determine whether screening plus outreach, when compared with referral alone, increases identification of vulnerable pediatric patients at high risk for severe disease eligible for COVID-19 therapeutics from low-resourced communities. Design, Setting, and Participants: A retrospective cohort study of COVID-19 medication allocation between January 1, 2022, and February 15, 2022, at Lurie Children's Hospital, a quaternary care children's hospital, in Chicago, Illinois. The cohorts were pediatric patients referred for COVID-19 therapeutics or with a positive SARS-CoV-2 polymerase chain reaction within the hospital system followed by outreach. Screening involved daily review of positive cases of SARS-CoV-2, followed by medical record review for high-risk conditions, and communication with clinicians and/or patients and families to offer therapy. Exposures: Diagnosis of COVID-19. Main Outcomes and Measures: The primary measure was difference in child opportunity index (COI) scores between the 2 cohorts. Secondary measures included presence and duration of symptoms at diagnosis, medication uptake, race and ethnicity, insurance type, qualifying medical condition, sex, primary language, and age. Results: Of 145 total patients, the median (IQR) age was 15 (13-17) years, and most were male (87 participants [60.0%]), enrolled in public insurance (83 participants [57.2%]), and members of minoritized racial and ethnic groups (103 participants [71.0%]). The most common qualifying conditions were asthma and/or obesity (71 participants [49.0%]). From 9869 SARS-CoV-2 tests performed, 94 eligible patients were identified via screening for COVID-19 therapeutics. Fifty-one patients were identified via referral. Thirty-two patients received medication, of whom 8 (25%) were identified by screening plus outreach alone. Compared with referred patients, patients in the screening plus outreach group were more likely to have moderate, low, or very low COI composite scores (70 patients [74.5%] vs 27 patients [52.9%]); public insurance (65 patients [69.1%] vs 18 patients [35.3%]); and asthma or obesity (60 patients [63.8%] vs 11 patients [21.6%]). Patients in the referral group were more likely to be non-Hispanic White (23 patients [45.1%] vs 19 patients [20.2%]) and receive medication (24 patients [47.1%] vs 8 patients [8.5%]). Conclusions and Relevance: Compared with referral patients, screening plus outreach patients for COVID-19 medications were more socially vulnerable, with lower COI scores, and more likely to have asthma or obesity. Future studies should investigate communication strategies to improve uptake of these medications after outreach.

Amphotericin-Associated Infusion-Related Reactions: A Narrative Review of Pre-Medications.

PURPOSE: Amphotericin B has been reported to cause infusion-related adverse effects (IRAEs). To prevent IRAEs, pre-medications may be administered prior to the administration of amphotericin B. The effects of different formulations of amphotericin B (amphotericin B deoxycholate and lipid formulations), duration of infusion, and utility of pre-medications in preventing IRAEs are reviewed. METHODS: PubMed, Ovid Medline, Embase, Web of Science, the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, and the Scopus databases were searched with the following search terms: pre-medication, amphotericin B, and its related compounds. Upon review, a total of 39 publications were considered for inclusion. FINDINGS: In vitro and in vivo studies have reported that amphotericin B deoxycholate stimulates pro-inflammatory cytokine genes causing IRAEs. Nonetheless, the clinical literature has reported that IRAEs occur among patients who received pre-medications. In comparison to amphotericin B deoxycholate, lipid-based formulations of amphotericin may result in a lower or similar risk for IRAEs. IMPLICATIONS: The routine use of pre-medications to prevent IRAEs after the administration of amphotericin B (amphotericin B deoxycholate or lipid formulations) would not be warranted.

SARS-CoV-2 Monoclonal Antibodies in Children: Ethical Considerations.

The use of monoclonal antibodies in children with certain conditions and at high risk for severe COVID-19 has been approved by the US Food and Drug Administration under the Emergency Use Authorization mechanism of the Federal Food, Drug, and Cosmetic Act. No data on the tolerability or efficacy of these therapies in persons <18 years of age are available; there is risk. Whether they will work is unknown, but they could. A disproportionate number of these children who meet the criteria for treatment with mAbs are from communities of black, Native American, and other race. How should health systems, hospitals, and clinicians balance the tensions between being seen as experimenting with an untested drug as opposed to withholding a potentially life-saving treatment? This article identifies, analyzes, and makes recommendations on the methods by which health systems, hospitals, and individual clinicians can ethically balance these tensions.