Hospitalization and Mortality Due to Infection Among Children and Adolescents With Systemic Lupus Erythematosus in the United States.

OBJECTIVE: We aimed to determine the frequency and types of infections in hospitalized children with childhood-onset systemic lupus erythematosus (cSLE), and to identify risk factors for intensive care unit (ICU) admission and mortality. METHODS: We conducted a retrospective study of youth aged 2 to 21 years using International Classification of Diseases (ICD) codes for SLE assigned during admission to a hospital participating in the Pediatric Health Information System, a database of United States children's hospitals, from 2009 to 2021. Generalized linear mixed effects models were used to identify risk factors for ICU admission and mortality among children hospitalized with infection. RESULTS: We identified 8588 children with cSLE and ≥ 1 hospitalization. Among this cohort, there were 26,269 hospitalizations, of which 13% had codes for infections, a proportion that increased over time (P = 0.04). Bacterial pneumonia was the most common hospitalized infection. In-hospital mortality occurred in 0.4% (n = 103) of cSLE hospitalizations for any indication and 2% of hospitalizations for infection (n = 60). The highest mortality rates occurred with Pneumocystis jirovecii pneumonia (21%) and other fungal infections (21%). Lupus nephritis (LN) and endstage renal disease (ESRD) were associated with increased odds of ICU admission (odds ratio [OR] 1.47 [95% CI 1.2-1.8] and OR 2.40 [95% CI 1.7-3.4]) among children admitted for serious infection. ESRD was associated with higher mortality (OR 2.34 [95% CI 1.1-4.9]). CONCLUSION: Hospitalizations with ICD codes for infection comprised a small proportion of cSLE admissions but accounted for the majority of mortality. The proportion of hospitalizations for infection increased over time. LN and ESRD were risk factors for poor outcomes.

Management of Pediatric Pneumonia: A Decade After the Pediatric Infectious Diseases Society and Infectious Diseases Society of America Guideline.

BACKGROUND: Incomplete uptake of guidelines can lead to nonstandardized care, increased expenditures, and adverse clinical outcomes. The objective of this study was to evaluate the impact of the 2011 Pediatric Infectious Diseases Society and Infectious Diseases Society of America (PIDS/IDSA) pediatric community-acquired pneumonia (CAP) guideline that emphasized aminopenicillin use and de-emphasized the use of chest radiographs (CXRs) in certain populations. METHODS: This quasi-experimental study queried a national administrative database of children's hospitals to identify children aged 3 months-18 years with CAP who visited 1 of 28 participating hospitals from 2009 to 2021. PIDS/IDSA pediatric CAP guideline recommendations regarding antibiotic therapy, diagnostic testing, and imaging were evaluated. Segmented regression interrupted time series was used to measure guideline-concordant practices with interruptions for guideline publication and the Coronavirus Disease 2019 (COVID-19) pandemic. RESULTS: Of 315 384 children with CAP, 71 804 (22.8%) were hospitalized. Among hospitalized children, there was a decrease in blood culture performance (0.5% per quarter) and increase in aminopenicillin prescribing (1.1% per quarter). Among children discharged from the emergency department (ED), there was an increase in aminopenicillin prescription (0.45% per quarter), whereas the rate of obtaining CXRs declined (0.12% per quarter). However, use of CXRs rebounded during the COVID-19 pandemic (increase of 1.56% per quarter). Hospital length of stay, ED revisit rates, and hospital readmission rates remained stable. CONCLUSIONS: Guideline publication was associated with an increase of aminopenicillin prescribing. However, rates of diagnostic testing did not materially change, suggesting the need to consider implementation strategies to meaningfully change clinical practice for children with CAP.

Association of Intensity of Antipseudomonal Antibiotic Therapy With Risk of Treatment-Emergent Organisms in Children With Cystic Fibrosis and Newly Acquired Pseudomonas Aeruginosa.

BACKGROUND: While Pseudomonas aeruginosa (Pa) eradication regimens have contributed to a decline in Pa prevalence in people with cystic fibrosis (CF), this antibiotic exposure might increase the risk of acquisition of drug-resistant organisms. This study evaluated the association between antipseudomonal antibiotic exposure intensity and acquisition risk of drug-resistant organisms among children with CF and new Pa infection. METHODS: We utilized data from the Early Pseudomonas Infection Control Clinical Trial (EPIC CT), a randomized controlled trial comparing Pa eradication strategies in children with CF and new Pa. The exposure was the number of weeks of oral or inhaled antipseudomonal antibiotics or ever versus never treatment with intravenous antipseudomonal antibiotics during the 18 months of EPIC CT participation. Primary outcomes were risks of acquisition of several respiratory organisms during 5 years of follow-up after EPIC CT estimated using Cox proportional hazards models separately for each specific organism. RESULTS: Among 249 participants, there was no increased acquisition risk of any organism associated with greater inhaled antibiotic exposure. With each additional week of oral antibiotics, there was an increased hazard of Achromobacter xylosoxidans acquisition (HR, 1.24; 95% CI: 1.02-1.50; P = .03). Treatment with intravenous antibiotics was associated with an increased hazard of acquisition of multidrug-resistant Pa (HR, 2.47; 95% CI: 1.28-4.78; P = .01) and MRSA (HR, 1.57; 95% CI: 1.03-2.40; P = .04). CONCLUSIONS: Results from this study illustrate the importance of making careful antibiotic choices to balance the benefits of antibiotics in people with CF while minimizing risk of acquisition of drug-resistant organisms.

Association Between Number of Intravenous Antipseudomonal Antibiotics and Clinical Outcomes of Pediatric Cystic Fibrosis Pulmonary Exacerbations.

BACKGROUND: Pulmonary exacerbations (PEx) in people with cystic fibrosis (PwCF) are associated with significant morbidity. While standard PEx treatment for PwCF with Pseudomonas aeruginosa infection includes two IV antipseudomonal antibiotics, little evidence exists to recommend this approach. This study aimed to compare clinical outcomes of single versus double antipseudomonal antibiotic use for PEx treatment. METHODS: Retrospective cohort study using the linked CF Foundation Patient Registry-Pediatric Health Information System dataset. PwCF were included if hospitalized between 2007 and 2018 and 6-21 years of age. Regression modeling accounting for repeated measures was used to compare lung function outcomes between single versus double IV antipseudomonal antibiotic regimens using propensity-score weighting to adjust for relevant confounding factors. RESULTS: Among 10,660 PwCF in the dataset, we analyzed 2,578 PEx from 1,080 PwCF, of which 455 and 2,123 PEx were treated with 1 versus 2 IV antipseudomonal antibiotics, respectively. We identified no significant differences between PEx treated with 1 versus 2 IV antipseudomonal antibiotics either in change between pre- and post-PEx percent predicted forced expiratory volume in one second (ppFEV1) (-0.84%, [95% CI -2.25, 0.56]; P = 0.24), odds of returning to ≥90% of baseline ppFEV1 within 3 months following PEx (Odds Ratio 0.83, [95% CI 0.61, 1.13]; P = 0.24) or time to next PEx requiring IV antibiotics (Hazard Ratio 1.04, [95% CI 0.87, 1.24]; P = 0.69). CONCLUSIONS: Use of 2 IV antipseudomonal antibiotics for PEx treatment in young PwCF was not associated with greater improvements in measured respiratory and clinical outcomes compared to treatment with 1 IV antipseudomonal antibiotic.

Pulmonary Outcomes Associated with Long-Term Azithromycin Therapy in Cystic Fibrosis.

Rationale: Chronic azithromycin is commonly used in cystic fibrosis based on short controlled clinical trials showing reductions in pulmonary exacerbations and improved FEV1. Long-term effects are unknown.Objectives: Examine pulmonary outcomes among chronic azithromycin users compared with matched controls over years of use and consider combined azithromycin use in cohorts using chronic inhaled tobramycin or aztreonam.Methods: This retrospective cohort study used the U.S. cystic fibrosis Foundation Patient Registry. Incident chronic azithromycin users were compared with matched controls by FEV1% predicted rate of decline and rates of intravenous antibiotic use to treat pulmonary exacerbations. Propensity score methods were utilized to address confounding by indication. Predefined sensitivity analyses based on lung function, Pseudomonas aeruginosa (PA) status, and follow-up time intervals were conducted.Measurements and Main Results: Across 3 years, FEV1% predicted per-year decline was nearly 40% less in those with PA using azithromycin compared with matched controls (slopes, -1.53 versus -2.41% predicted per yr; difference: 0.88; 95% confidence interval [CI], 0.30-1.47). This rate of decline did not differ based on azithromycin use in those without PA. Among all cohorts, use of intravenous antibiotics was no different between azithromycin users and controls. Users of inhaled tobramycin and azithromycin had FEV1% predicted per-year decline of -0.16 versus nonusers (95% CI, -0.44 to 0.13), whereas users of inhaled aztreonam lysine and azithromycin experienced a mean 0.49% predicted per year slower decline than matched controls (95% CI, -0.11 to 1.10).Conclusions: Results from this study provide additional rationale for chronic azithromycin use in PA-positive patients to reduce lung function decline.

A pilot study to assess short-term physiologic outcomes of transitioning infants with severe bronchopulmonary dysplasia from ICU to two subacute ventilators.

INTRODUCTION: This study was designed to evaluate short-term physiologic outcomes of transitioning neonates with bronchopulmonary dysplasia (BPD) from intensive care unit (ICU) ventilators to both the Trilogy 202 (Philips Healthcare, Andover, MA) and LTV 1200 (CareFusion, Yorba Linda, CA) subacute ventilators. METHODS: Six infants with BPD requiring tracheostomies for support with a neonatal-specific ICU ventilator underwent placement of esophageal balloon catheters, airway pressure transducers, flow sensors, oxygen saturation (SpO2), and end tidal carbon dioxide (PETCO2) monitors. Noninvasive gas exchange, airflow, and airway and esophageal pressures (PES) were recorded following 20 min on the ICU ventilator. The infants were placed on the Trilogy 202 and LTV 1200 ventilators in random order at identical settings as the ICU ventilator. We measured noninvasive gas exchange, pressure-rate product (respiratory rate × ΔPES), ventilator response times, and the percentage of spontaneous breaths that triggered the ventilator at 20 min in each subject while being supported with each of the different subacute ventilators. RESULTS: The mean (SD) weight of the six infants was 4.983 (0.56) kg. There were no differences in heart rate (p = 0.51) or SpO2 (p = 0.97) but lower PETCO2, ΔPES, respiratory rate, pressure rate-product, response times, and greater percentage of subject initiated breaths that triggered the ventilator (p < 0.05) was observed with the Trilogy 202 than the LTV 1200. All six infants transitioned successfully from the ICU ventilator to the Trilogy 202 ventilator. CONCLUSION: In this small group of infants with BPD, the Trilogy 202 ventilator performed better than the LTV 1200. The improved subject efforts, per cent subject triggering, and response times observed with the Trilogy are likely related to differences in triggering algorithms, location of triggering mechanisms, and gas delivery system performance within the ventilators. These pilot data may be useful for informing future clinical study design and understanding differences in the level of support provided by different subacute ventilators in infants with BPD.

Update on the diagnosis and management of cystic fibrosis pulmonary exacerbations.

Pulmonary exacerbations in people with cystic fibrosis are associated with significant morbidity and reduced quality of life. Pulmonary exacerbation treatment guidelines, published by an expert panel assembled by the Cystic Fibrosis Foundation nearly 15 years ago, were primarily consensus-based as there were several gaps in the evidence base. In particular, limited evidence existed regarding optimal pulmonary exacerbation treatment strategies, including duration of antibiotic therapy, treatment location, antibiotic selection, and the role of systemic corticosteroids. Over the last decade, results from observational studies and large multi-center randomized controlled trials have begun to answer important questions related to pulmonary exacerbation treatment. This review focuses on the diagnosis, etiology, and changing epidemiology of pulmonary exacerbations, and also summarizes the most recent and up-to-date studies describing pulmonary exacerbation treatment. Finally, this review provides consideration for future pulmonary exacerbation research priorities, particularly in the current highly effective modulator therapy era.

Hospitalised infections and rituximab administration among children and adolescents with systemic lupus erythematosus from 2009 to 2021.

BACKGROUND: Rituximab is associated with high infection rates, but studies of infections following rituximab in youth with childhood-onset SLE (cSLE) are limited. We conducted a retrospective longitudinal cohort study to assess the incidence of hospitalised infections following rituximab among children with cSLE and to assess changes in hospital-based rituximab administration over time. METHODS: Youth ages 2-21 years with an International Classification of Diseases (ICD) code for SLE who received rituximab during admission to a Pediatric Health Information System hospital from 2009 to 2021 were included. Incidence rates for infections requiring hospitalisation over the 12 months following first rituximab administration were calculated. Rituximab use by year of hospital discharge was tabulated. RESULTS: We identified 1567 children with cSLE who received rituximab. 219 children were admitted with an infection within 1 year after first rituximab administration, for an incidence rate of 140 cases per 1000 patient-years. Seven children (0.44%) died during a hospitalisation with an infection in the year following rituximab administration. The most common hospitalised infections were bacterial pneumonia, sepsis and cellulitis. 12 children were hospitalised with COVID-19, none of whom died. Hospitalisations with rituximab administered decreased from 2019 to 2021. CONCLUSIONS: In this cohort of patients with cSLE who received inpatient treatment with rituximab, we observed a 14% rate of hospitalisation with infection in the year following rituximab administration among youth with cSLE. Rituximab use declined during the COVID-19 pandemic. No fatalities with COVID-19 were observed. Given the lack of outpatient data, including doses of concomitant medications and disease activity measures, further research is needed to identify risk factors for infection following rituximab among children with cSLE.

Changes in factors associated with inhaled antibiotic prescriptions for people with cystic fibrosis over time in the U.S.

RATIONALE: CF care guidelines recommend chronic inhaled antibiotics for chronic Pseudomonas aeruginosa (Pa) lung infection. These medications are costly, time consuming and prescription needs may change with improved outcomes. OBJECTIVES: We determined the proportion of pwCF with chronic, intermittent or negative Pa infection categories, their clinical and demographic characteristics, factors associated with inhaled antibiotic prescription and changes between 2011 and 2019. METHODS: This cohort study using the U.S. CF Foundation patient registry for pwCF >2 years, no prior lung transplant, and with ≥3 respiratory cultures/year determined chronic inhaled antibiotics (≥3 months per calendar year) and Pa infection status from encounter level data. Outcomes and odds of prescription for relevant clinical factors were evaluated using generalized estimating equation models with additional interaction between the predictor and the calendar year to examine changes of predictors over time. RESULTS: Proportion of pwCF with chronic and intermittent Pa decreased and antibiotic prescription rates increased for these groups and decreased for Pa negative pwCF. Hispanic ethnicity, female sex, pancreatic insufficiency, CF diabetes, and ivacaftor/lumacaftor were associated with higher antibiotic prescriptions for each Pa status. Among Pa-negative pwCF prescriptions were higher with Burkholderia spp. (1.17, (CI95 1.03,1.34)) or MRSA (OR 1.45, (1.26,1.68)) but decreased between 2011 and 2019. For Aspergillus OR increased to 1.6,(1.3,1.8) in 2019. Prescriptions for pwCF on ivacaftor decreased, becoming lower in 2019 for chronic (OR 0.7, (0.5,0.8)) and Pa-negative pwCF (OR 0.7, (0.5,0.8)). CONCLUSIONS: Factors predicting inhaled antibiotic prescription differed between 2011 and 2019 indicating changes in health and care for pwCF even prior to triple-modulators.

Pediatric Resident and Program Director Views on Climate Change and Health Curricula: A Multi-Institution Study.

PURPOSE: The American Academy of Pediatrics emphasized in a 2007 policy statement the importance of educating trainees on the impacts of climate change on children's health, yet few studies have evaluated trainee knowledge and attitudes about climate change-related health effects in children. This multi-institution study assessed pediatric resident and program director (1) knowledge/attitudes on climate change and health, (2) perspectives on the importance of incorporating climate and health content into pediatric graduate medical education, and (3) preferred topics/activities to include in climate and health curricula. METHOD: This mixed-methods study employed an anonymous cross-sectional survey of pediatric residents and residency program directors from Association of Pediatric Program Directors (APPD) Longitudinal Educational Assessment Research Network (LEARN)-affiliated programs. Multivariable regression models and factor analyses were used to examine associations among resident demographics and resident knowledge, attitudes, and interest in a climate change curriculum. A conventional content analysis was conducted for the open-ended responses. RESULTS: Eighteen programs participated in the study with all program directors (100% response rate) and 663 residents (average response rate per program, 53%; overall response rate, 42%) completing respective surveys. Of the program directors, only 3 (17%) felt very or moderately knowledgeable about the association between climate change and health impacts. The majority of residents (n=423, 64%) agreed/strongly agreed that physicians should discuss global warming/climate change and its health effects with patients/families, while only 138 residents (21%) agreed/strongly agreed that they were comfortable talking with patients and families about these issues. Most residents (n=498, 76%) and program directors (n=15, 83%) agreed/strongly agreed that a climate change curriculum should be incorporated into their pediatrics training program. CONCLUSIONS: Pediatric residents and program directors support curricula that prepare future pediatricians to address the impact of climate change on children's health; however, few programs currently offer specific training, despite identified needs.

Creation of a CF-specific antibiotic spectrum index (ASI) as an antimicrobial stewardship initiative.

Antibiotics are frequently utilized for cystic fibrosis (CF)-related pulmonary exacerbation treatment. The antibiotic spectrum index (ASI) is an antimicrobial stewardship tool developed to compare the relative breadth of individual antibiotics. This study aimed to create two expanded CF-specific ASI scoring indices for use in antimicrobial stewardship research and clinical care. The first scoring index expanded the original ASI to include bacterial microorganisms common to CF airway infections (CF-ASI). The second scoring system only included scores for bacterial microorganisms classically identified in CF airway infections (CF-sASI). Sixty-two antibiotics were evaluated and included in the updated ASIs. When multiple antibiotics are prescribed, we proposed using an additive ASI approach whereby the sum of the individual prescribed antibiotic scores represents the total ASI score. The application of CF-focused ASIs into CF research and stewardship programs can help to optimize antibiotic benefits, minimize harms and allow for increased sustainability of antibiotic use in CF.

Factors associated with tracheostomy-associated infection treatment: A multicenter observational study.

OBJECTIVE: To characterize factors that influence the decision to treat suspected pediatric bacterial tracheostomy-associated respiratory infections (bTRAINs; e.g., pneumonia, tracheitis). METHODS: We conducted a multicenter, prospective cohort study of children with pre-existing tracheostomy hospitalized at six children's hospitals for a suspected bTRAIN (receipt of respiratory culture plus ≥1 doses of an antibiotic within 48 h). The primary predictor was respiratory culture growth categorized as Pseudomonas aeruginosa, P. aeruginosa + ≥1 other bacterium, other bacteria alone, or normal flora/no growth. Our primary outcome was bTRAIN treatment with a complete course of antibiotics as documented by the discharge team. We used logistic regression with generalized estimating equations to identify the association between our primary predictor and outcome and to identify demographic, clinical, and diagnostic testing factors associated with treatment. RESULTS: Of the 440 admissions among 289 patients meeting inclusion criteria, 307 (69.8%) had positive respiratory culture growth. Overall, 237 (53.9%) of admissions resulted in bTRAIN treatment. Relative to a negative culture, a culture positive for P. aeruginosa plus ≥1 other organism (adjusted odds ratio [aOR] 2.3; 95% confidence interval [CI] 1.02-5.0)] or ≥1 other organism alone (aOR: 2.8; 95% CI: 1.4-5.6)] was associated with treatment. Several clinical and diagnostic testing (respiratory Gram-stain and chest radiograph) findings were also associated with treatment. Positive respiratory viral testing was associated with reduced odds of treatment (aOR: 0.5; 95% CI: 0.2-0.9). CONCLUSIONS: Positive respiratory cultures as well as clinical indicators of acute illness and nonculture test results were associated with bTRAIN treatment. Clinicians may be more comfortable withholding antibiotics when a virus is identified during testing.

Antibiotic route and outcomes for children hospitalized with pneumonia.

BACKGROUND: Emerging evidence suggests that initial oral and intravenous (IV) antibiotics have similar efficacy in pediatric community-acquired pneumonia (CAP), but further data are needed. OBJECTIVE: We determined the association between hospital-level initial oral antibiotic rates and outcomes in pediatric CAP. DESIGNS, SETTINGS, AND PARTICIPANTS: This retrospective cohort study included children hospitalized with CAP at 43 hospitals in the Pediatric Health Information System (2016-2022). Hospitals were grouped by whether initial antibiotics were given orally in a high, moderate, or low proportion of patients. MAIN OUTCOME AND MEASURES: Regression models examined associations between high versus low oral-utilizing hospitals and length of stay (LOS, primary outcome), intensive care unit (ICU) transfers, escalated respiratory care, complicated CAP, cost, readmissions, and emergency department (ED) revisits. RESULTS: Initial oral antibiotics were used in 16% (interquartile range: 10%-20%) of 30,207 encounters, ranging from 1% to 68% across hospitals. Comparing high versus low oral-utilizing hospitals (oral rate: 32% [27%-47%] and 10% [9%-11%], respectively), there were no differences in LOS, intensive care unit, complicated CAP, cost, or ED revisits. Escalated respiratory care occurred in 1.3% and 0.5% of high and low oral-utilizing hospitals, respectively (relative ratio [RR]: 2.96 [1.12, 7.81]), and readmissions occurred in 1.5% and 0.8% (RR: 1.68 [1.31, 2.17]). Initial oral antibiotics varied across hospitals without a difference in LOS. While high oral-utilizing hospitals had higher escalated respiratory care and readmission rates, these were rare, the clinical significance of these small differences is uncertain, and there were no differences in other clinically relevant outcomes. This suggests some children may benefit from initial IV antibiotics, but most would probably do well with oral antibiotics.

Outpatient Antibiotic Use and Treatment Failure Among Children With Pneumonia.

Importance: Although a viral etiology can be detected in most cases of pediatric pneumonia, antibiotic treatment is common. The effectiveness of antibiotics in the outpatient setting for children diagnosed with pneumonia is not known. Objective: To compare outcomes among children diagnosed with pneumonia who were and were not treated with oral antibiotics. Design, Setting, and Participants: This retrospective cohort study identified Medicaid-insured children and adolescents 17 years or younger diagnosed with pneumonia and discharged from ambulatory settings in a multistate claims database from January 1, 2017, to December 31, 2019. Propensity score matching was used to mitigate confounding. Data were analyzed from August 31, 2023, to August 16, 2024. Exposures: Antibiotic receipt, defined as an oral antibiotic dispensed from a pharmacy on the day of the index visit or on the subsequent day. Children who did not receive antibiotics included those who were not prescribed antibiotics and those who were prescribed antibiotics but did not fill the prescription. Main Outcomes and Measures: Treatment failure and severe outcomes within 2 to 14 days after the index visit. Treatment failure included hospitalization or ambulatory revisits for pneumonia, new antibiotic dispensation with a same-day ambulatory visit, or complicated pneumonia. Severe outcomes included hospitalization for pneumonia or complicated pneumonia. Results: Among the 103 854 children with pneumonia included in the analysis, the median age was 5 (IQR, 2-9) years, and 54 665 (52.6%) were male. Overall, 20 435 children (19.7%) did not receive an antibiotic within 1 day. The propensity score-matched analysis included 40 454 children (20 227 per group). Treatment failure occurred in 2167 children (10.7%) who did not receive antibiotics and 1766 (8.7%) who received antibiotics (risk difference, 1.98 [95% CI, 1.41-2.56] percentage points). Severe outcomes occurred in 234 of 20 435 children (1.1%) who did not receive antibiotics and in 133 of 83 419 (0.7%) who did (risk difference, 0.46 [95% CI, 0.28-0.64] percentage points). Conclusions and Relevance: In this cohort study of children diagnosed with pneumonia in ambulatory settings, almost 20% did not receive antibiotics within a day of diagnosis. Although not receiving antibiotics was associated with a small increase in the risk of treatment failure, severe outcomes were uncommon regardless of whether antibiotics were received. These results suggest that some children diagnosed with pneumonia can likely be managed without antibiotics and highlight the need for prospective studies to identify these children.

Pediatric Nirmatrelvir/Ritonavir Prescribing Patterns During the COVID-19 Pandemic.

OBJECTIVES: This study seeks to identify demographic and clinical factors prompting clinician prescribing of nirmatrelvir/ritonavir to pediatric patients for management of coronavirus disease 2019 (COVID-19) infection. METHODS: Patients aged 12 to 17 years with a COVID-19 infection and nirmatrelvir/ritonavir prescription during an outpatient clinical encounter within a PEDSnet-affiliated institution between January 2022 and August 2023 were identified using electronic health record data. A multivariate logistic regression analysis was used to estimate odds of nirmatrelvir/ritonavir prescription after adjusting for various factors. RESULTS: A total of 20 959 patients aged 12 to 17 years were diagnosed with a COVID-19 infection on the basis of an electronic health record-documented positive polymerase chain reaction or antigen test or diagnosis during an outpatient clinical visit. Of these patients, 408 received a nirmatrelvir/ritonavir prescription within 5 days of diagnosis. Higher odds of nirmatrelvir/ritonavir treatment were associated with having chronic or complex chronic disease (chronic: odds ratio [OR] 2.50 [95% confidence interval (CI) 1.83-3.38]; complex chronic: OR 2.21 [95% CI 1.58-3.08]). Among patients with chronic disease, each additional body system conferred 1.18 times higher odds of treatment (95% CI 1.10-1.26). Compared with non-Hispanic white patients, Hispanic patients (OR 0.61 [95% CI 0.44-0.83]) had lower odds of treatment. CONCLUSIONS: Children with chronic conditions are more likely than those without to receive nirmatrelvir/ritonavir prescriptions. However, nirmatrelvir/ritonavir prescribing to children with chronic conditions remains infrequent. Pediatric data concerning nirmatrelvir/ritonavir safety and effectiveness in preventing severe disease and hospitalization are critical optimizing clinical decision-making and use among children.

Polymicrobial infections and antibiotic treatment patterns for cystic fibrosis pulmonary exacerbations.

BACKGROUND: No data exist to guide antibiotic selection among people with CF (PwCF) with respiratory cultures positive for multiple CF-related bacteria (polymicrobial infections). This study aimed to describe the number of polymicrobial in-hospital treated pulmonary exacerbations (PEx), to determine the proportion of polymicrobial PEx where antibiotics were prescribed with activity against all bacteria detected (termed complete antibiotic coverage), and to determine clinical and demographic factors associated with complete antibiotic coverage. METHODS: Retrospective cohort study using the CF Foundation Patient Registry-Pediatric Health Information System dataset. Children aged 1-21 years with an in-hospital treated PEx from 2006 to 2019 were eligible for inclusion. Bacterial culture positivity was based on any positive respiratory culture in the 12 months prior to a study PEx. RESULTS: A total of 4,923 children contributed 27,669 total PEx of which 20,214 were polymicrobial; of these, 68% of PEx had complete antibiotic coverage. In regression modeling, a prior PEx with complete antibiotic coverage for MRSA was associated with a higher likelihood of having complete antibiotic coverage at a subsequent study PEx (OR (95% CI) 3.48 (2.50, 4.83)). CONCLUSIONS: The majority of children with CF hospitalized for polymicrobial PEx were prescribed complete antibiotic coverage. Prior PEx treatment with complete antibiotic coverage predicted complete antibiotic coverage at a future PEx for all bacteria studied. Studies are needed comparing outcomes of polymicrobial PEx treated with different antibiotic coverages to optimize PEx antibiotic selection.

Antibiotic Regimen Changes during Cystic Fibrosis Pediatric Pulmonary Exacerbation Treatment.

Rationale/Objectives: Antibiotic selection for in-hospital treatment of pulmonary exacerbations (PEx) in people with cystic fibrosis (CF) is typically guided by previous respiratory culture results or past PEx antibiotic treatment. In the absence of clinical improvement during PEx treatment, antibiotics are frequently changed in search of a regimen that better alleviates symptoms and restores lung function. The clinical benefits of changing antibiotics during PEx treatment are largely uncharacterized. Methods: This was a retrospective cohort study using the Cystic Fibrosis Foundation Patient Registry Pediatric Health Information System. PEx were included if they occurred in children with CF from 6 to 21 years old who had been treated with intravenous antibiotics between January 1, 2006, and December 31, 2018. PEx with lengths of stay <5 or >21 days or for which treatment was delivered in an intensive care unit were excluded. An antibiotic change was defined as the addition or subtraction of any intravenous antibiotic between Hospital Day 6 and the day before hospital discharge. Inverse probability of treatment weighting was used to adjust for disease severity and indication bias, which might influence a decision to change antibiotics. Results: In all, 4,099 children with CF contributed 18,745 PEx for analysis, of which 8,169 PEx (43.6%) included a change in intravenous antibiotics on or after Hospital Day 6. The mean change in pre- to post-treatment percent predicted forced expiratory volume in 1 second (ppFEV1) was 11.3 (standard error, 0.21) among events in which an intravenous antibiotic change occurred versus 12.2 (0.18) among PEx without an intravenous antibiotic change (P = 0.001). Similarly, the odds of return to ⩾90% of baseline ppFEV1 were less for PEx with antibiotic changes than for those without changes (odds ratio [OR], 0.89 [95% confidence interval (CI), 0.80-0.98]). The odds of returning to ⩾100% of baseline ppFEV1 did not differ between PEx with versus without antibiotic changes (OR, 0.94 [95% CI, 0.86-1.03]). In addition, PEx treated with intravenous antibiotic changes were associated with higher odds of future PEx (OR, 1.17 [95% CI, 1.12-1.22]). Conclusions: In this retrospective study, changing intravenous antibiotics during PEx treatment in children with CF was common and not associated with improved clinical outcomes.

The impact of elexacaftor/tezacaftor/ivacaftor on fat-soluble vitamin levels in people with cystic fibrosis.

BACKGROUND: While elexacaftor/tezacaftor/ivacaftor (ETI) has improved the pulmonary health of many people with cystic fibrosis (PwCF), less is known about ETI effectiveness for extra-pulmonary manifestations, including fat-soluble vitamin malabsorption. This study aims to evaluate ETI's impact on vitamin A, D, E, and international normalized ratio (INR, an indirect marker for Vitamin K) serum levels. METHODS: Retrospective cohort study of PwCF ≥12 years receiving ETI. Vitamin levels up to four years preceding and up to two years following ETI initiation were collected. Pairwise comparisons of vitamin levels pre/post-ETI initiation were made using Wilcoxon signed rank and McNemar's tests. Linear mixed effect models were used to regress vitamin levels on time since starting ETI, ETI use (yes/no), the interaction between time and ETI use, and age. RESULTS: Two hundred and sixty-four participants met study inclusion, and 169 (64%) had post-ETI initiation vitamin levels. Median vitamin A levels increased from 422.0 to 471.0 mcg/L (p < 0.001), median vitamin D levels increased from 28.5 to 30.8 ng/mL (p = 0.003), and there were no significant changes in median vitamin E or INR. Vitamin A levels rose at a rate of 40.7 mcg/L/year (CI 11.3, 70.2) after ETI start. CONCLUSIONS: ETI initiation is associated with increased median vitamin A and vitamin D levels, but no change in median vitamin E or INR levels. Ongoing monitoring of vitamin levels after ETI initiation is needed to screen for potential deficiencies and toxicities, particularly in light of case reports of hypervitaminosis A following ETI initiation.

Seroprevalence and clinical characteristics of SARS-CoV-2 infection in children with cystic fibrosis.

BACKGROUND: People with cystic fibrosis (PwCF) have chronic lung disease and may be at increased risk of coronavirus disease 2019 (COVID-19)-related morbidity and mortality. This study aimed to determine seroprevalence and clinical characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children with cystic fibrosis (CF), and to assess antibody responses following SARS-CoV-2 infection or vaccination. METHODS: Children and adolescents with CF followed at Seattle Children's Hospital were enrolled between July 20, 2020 and February 28, 2021. SARS-CoV-2 serostatus was determined on enrollment at 6 and 11 months (±2 months) for nucleocapsid and spike IgG. Participants completed intake and weekly surveys inquiring about SARS-CoV-2 exposures, viral/respiratory illnesses, and symptoms. RESULTS: Of 125 PwCF enrolled, 14 (11%) had positive SARS-CoV-2 antibodies consistent with recent or past infection. Seropositive participants were more likely to identify as Hispanic (29% vs. 8%, p = 0.04) and have pulmonary exacerbations requiring oral antibiotics in the year prior (71% vs. 41%, p = 0.04). Five seropositive individuals (35.7%) were asymptomatic, while six (42.9%) reported mild symptoms, primarily cough and nasal congestion. Antispike protein IgG levels were approximately 10-fold higher in participants following vaccination compared with participants who had natural infection alone (p < 0.0001) and resembled levels previously reported in the general population. CONCLUSIONS: A majority of PwCF have mild or no symptoms of SARS-CoV-2 making it difficult to distinguish from baseline respiratory symptoms. Hispanic PwCF may be disproportionately impacted, consistent with racial and ethnic COVID-19 disparities among the general US population. Vaccination in PwCF generated antibody responses similar to those previously reported in the general population.