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.

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.

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.

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.

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.

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.

A Pilot Randomized Clinical Trial of Pediatric Cystic Fibrosis Pulmonary Exacerbations Treatment Strategies.

Rationale: Despite the high prevalence and clear morbidity of cystic fibrosis (CF) pulmonary exacerbations (PEx), there have been no published clinical trials of outpatient exacerbation management. Objectives: To assess the feasibility of a pediatric clinical trial in which treatment of mild PEx is assigned randomly to immediate oral antibiotics or tailored therapy (increased airway clearance alone with oral antibiotics added only for prespecified criteria). The outcome on which sample size was based was the proportion of tailored therapy participants who avoided oral antibiotics during the 28 days after randomization. Methods: In this randomized, open-label, pilot feasibility study at 10 U.S. sites, children 6-18 years of age with CF were enrolled at their well baseline visits and followed through their first randomized PEx. Results: One hundred twenty-one participants were enrolled, of whom 94 (78%) reported symptoms of PEx at least once; of these, 81 (86%) had at least one exacerbation that met randomization criteria, of whom 63 (78%) were randomized. Feasibility goals were met, including enrollment, early detection of symptoms of PEx, and ability to randomize. Among the 33 participants assigned to tailored therapy, 10 (30%) received oral antibiotics, while 29 of 30 (97%) assigned to immediate antibiotics received oral antibiotics. The avoidance of oral antibiotics in 70% (95% confidence interval, 54-85%) was statistically significantly different from our null hypothesis that <10% of participants assigned to the tailored therapy arm would avoid antibiotics. Conclusions: Our pilot study demonstrates that conducting a randomized trial of oral antibiotic treatment strategies for mild PEx in children with CF is feasible and that assignment to a tailored therapy arm may reduce antibiotic exposure. Clinical trial registered with www.clinicaltrials.gov (NCT04608019).

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.

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.

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.

Can Multisystem Inflammatory Syndrome in Children Be Managed in the Outpatient Setting? An EHR-Based Cohort Study From the RECOVER Program.

Using electronic health record data combined with primary chart review, we identified seven children across nine participant pediatric medical centers with a diagnosis of Multisystem Inflammatory Syndrome in Children (MIS-C) managed exclusively as outpatients. These findings should raise awareness of mild presentations of MIS-C and the option of outpatient management.

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.

Systemic Corticosteroids in the Management of Pediatric Cystic Fibrosis Pulmonary Exacerbations.

Rationale: Pulmonary exacerbation (PEx) events contribute to lung function decline in people with cystic fibrosis (CF). CF Foundation PEx guidelines note that a short course of systemic corticosteroids may offer benefit without contributing to long-term adverse effects. However, insufficient evidence exists to recommend systemic corticosteroids for PEx treatment. Objectives: To determine if systemic corticosteroids for the treatment of in-hospital pediatric PEx are associated with improved clinical outcomes compared with treatment without systemic corticosteroids. Methods: We conducted a retrospective cohort study using the CF Foundation Patient Registry-Pediatric Health Information System linked database. People with CF were included if hospitalized for a PEx between 2006 and 2018 and were 6-21 years of age. Time to next PEx was assessed by Cox proportional hazards regression. Lung function outcomes were assessed by linear mixed-effect modeling and generalized estimating equations. To address confounding by indication, inverse probability treatment weighting was used. Results: A total of 3,471 people with CF contributed 9,787 PEx for analysis. Systemic corticosteroids were used in 15% of all PEx. In our primary analysis, systemic corticosteroids were not associated with better pre- to post-PEx percent predicted forced expiratory volume in 1 second responses (mean difference, -0.36; 95% confidence interval [CI], -1.14, 0.42; P = 0.4) or a higher odds of returning to lung function baseline (odds ratio, 0.97; 95% CI, 0.84-1.12; P = 0.7) but were associated with a reduced chance of future PEx requiring intravenous antibiotics (hazard ratio, 0.91; 95% CI, 0.85-0.96; P = 0.002). When restricting the analysis to one PEx per person, lung function outcomes remained no different among PEx treated with or without systemic corticosteroids, but, in contrast to our primary analysis, the use of systemic corticosteroids was no longer associated with a reduced chance of having a future PEx requiring intravenous antibiotics (hazard ratio, 0.96; 95% CI, 0.86, 1.07; P = 0.42). Conclusions: Systemic corticosteroid treatment for in-hospital pediatric PEx was not associated with improved lung function outcomes. Prospective trials are needed to better evaluate the risks and benefits of systemic corticosteroid use for PEx treatment in children with CF.

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

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.

Antimicrobial Stewardship in Cystic Fibrosis.

The chronic airway infection and inflammation characteristic of cystic fibrosis (CF) ultimately leads to progressive lung disease, the primary cause of death in persons with CF (pwCF). Despite many recent advances in CF clinical care, efforts to preserve lung function in many pwCF still necessitate frequent antimicrobial use. Incorporating antimicrobial stewardship (AMS) principles into management of pulmonary exacerbations (PEx) would facilitate development of best practices for antimicrobial utilization at CF care centers. However, AMS can be challenging in CF given the unique aspects of chronic, polymicrobial infection in the CF airways, lack of evidence-based guidelines for managing PEx, limited utility for antimicrobial susceptibility testing, and increased frequency of adverse drug events in pwCF. This article describes current evidence-based antimicrobial treatment strategies for pwCF, highlights the potential for AMS to beneficially impact CF care, and provides practical strategies for integrating AMS programs into the management of PEx in pwCF.

Drugs, Drugs, Drugs: Current Treatment Paradigms in Cystic Fibrosis Airway Infections.

Airway infections have remained a prominent feature in persons living with cystic fibrosis (CF) despite the dramatic improvements in survival in the past decades. Antimicrobials are a cornerstone of infection management for both acute and chronic maintenance indications. Historic clinical trials of antimicrobials in CF have led to the adoption of consensus guidelines for their use in clinical care. More recently, however, there are efforts to re-think the optimal use of antimicrobials for care with the advent of novel and highly effective CF transmembrane conductance regulator modulator therapies. Encouragingly, however, drug development has remained active concurrently in this space. Our review focuses on the evidence for and perspectives regarding antimicrobial use in both acute and maintenance settings in persons with CF. The therapeutic innovations in CF and how this may affect antimicrobial approaches are also discussed.

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

BACKGROUND: Despite the increased availability of diagnostic tests for respiratory viruses, their clinical utility for children with community-acquired pneumonia (CAP) remains uncertain. OBJECTIVE: To identify patterns of respiratory virus testing across children's hospitals prior to the COVID-19 pandemic and to determine whether hospital-level rates of viral testing were associated with clinical outcomes. DESIGN, SETTING, AND PARTICIPANTS: Multicenter retrospective cohort study of children hospitalized for CAP at 19 children's hospitals in the United States from 2010-2019. MAIN OUTCOMES AND MEASURES: Using a novel method to identify the performance of viral testing, we assessed time trends in the use of viral tests, both overall and stratified by testing method. Adjusted proportions of encounters with viral testing were compared across hospitals and were correlated with length of stay, antibiotic and oseltamivir use, and performance of ancillary laboratory testing. RESULTS: There were 46,038 hospitalizations for non-severe CAP among children without complex chronic conditions. The proportion with viral testing increased from 38.8% to 44.2% during the study period (p < .001). Molecular testing increased (27.2% to 40.0%, p < .001) and antigen testing decreased (33.2% to 7.8%, p < .001). Hospital-specific adjusted proportions of testing ranged from 10.0% to 83.5% and were not associated with length of stay, antibiotic use, or antiviral use. Hospitals that performed more viral testing did not have lower rates of ancillary laboratory testing. CONCLUSIONS: Viral testing practices varied widely across children's hospitals and were not associated with clinically important process or outcome measures. Viral testing may not influence clinical management for many children hospitalized with CAP.

Clinical Outcomes of Antipseudomonal versus Other Antibiotics among Children with Cystic Fibrosis without Pseudomonas aeruginosa.

Rationale: Antibiotic selection for pulmonary exacerbation (PEx) management in children with cystic fibrosis is typically guided by prior respiratory culture results. Although antipseudomonal antibiotics are often used in children with chronic Pseudomonas aeruginosa (Pa) airway infection, no data exist to guide antibiotic selection in children who are culture negative for Pa for ≥1 year. Objectives: To determine among children classified as 1, 2, or 3 years' Pa negative if PEx treatment with at least one oral and/or intravenous antipseudomonal antibiotic is associated with improved clinical outcomes compared with treatment with antibiotics not effective against Pa. Methods: A retrospective cohort study was conducted using the linked Cystic Fibrosis Foundation Patient Registry-Pediatric Health Information System database. We included children 6-21 years old hospitalized between 2008 and 2018 consistently culture negative for Pa 1 year before a study PEx. Children were classified as 1 or 2 years' Pa negative if their last Pa-positive culture occurred in the 13-24 months or 25-36 months before a study PEx, respectively, with all subsequent cultures negative for Pa. Children classified as 3 years' Pa negative had no Pa-positive cultures in the 36 months before a study PEx. Inverse probability of treatment weighted linear or logistic regression models were used to compare clinical outcomes (pre- to post-PEx forced expiratory volume in 1 s, odds of returning to ≥90% of baseline lung function, and odds of having a future PEx) between antipseudomonal and non-antipseudomonal antibiotic strategies. Results: Among all children included in the linked data set, 1,290 children with 2,347 PExs were eligible for analysis. Among all study PExs, 530, 326, and 1,491 were classified as 1, 2, and 3 years' Pa negative, respectively, and antipseudomonal antibiotics were administered in 79%, 67%, and 66% of all PExs classified as 1, 2, and 3 years' Pa negative, respectively. For all Pa-negative groups, when compared with non-antipseudomonal antibiotic regimens, antipseudomonal antibiotic treatment was not associated with greater improvement in any studied clinical outcome. Conclusions: Despite their common use, including antibiotics effective against Pa may provide no additional benefit for PEx treatment among children who are Pa negative for at least 1 year prior. Prospective trials are warranted to directly test this hypothesis.