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.

Characteristics of antifungal utilization for hospitalized children in the United States.

Objective: To characterize antifungal prescribing patterns, including the indication for antifungal use, in hospitalized children across the United States. Design: We analyzed antifungal prescribing data from 32 hospitals that participated in the SHARPS Antibiotic Resistance, Prescribing, and Efficacy among Children (SHARPEC) study, a cross-sectional point-prevalence survey conducted between June 2016 and December 2017. Methods: Inpatients aged <18 years with an active systemic antifungal order were included in the analysis. We classified antifungal prescribing by indication (ie, prophylaxis, empiric, targeted), and we compared the proportion of patients in each category based on patient and antifungal characteristics. Results: Among 34,927 surveyed patients, 2,095 (6%) received at least 1 systemic antifungal and there were 2,207 antifungal prescriptions. Most patients had an underlying oncology or bone marrow transplant diagnosis (57%) or were premature (13%). The most prescribed antifungal was fluconazole (48%) and the most common indication for antifungal use was prophylaxis (64%). Of 2,095 patients receiving antifungals, 79 (4%) were prescribed >1 antifungal, most often as targeted therapy (48%). The antifungal prescribing rate ranged from 13.6 to 131.2 antifungals per 1,000 patients across hospitals (P < .001). Conclusions: Most antifungal use in hospitalized children was for prophylaxis, and the rate of antifungal prescribing varied significantly across hospitals. Potential targets for antifungal stewardship efforts include high-risk, high-utilization populations, such as oncology and bone marrow transplant patients, and specific patterns of utilization, including prophylactic and combination antifungal therapy.

A Veterans' Healthcare Administration (VHA) antibiotic stewardship intervention to improve outpatient antibiotic use for acute respiratory infections: A cost-effectiveness analysis.

OBJECTIVES: The Core Elements of Outpatient Antibiotic Stewardship provides a framework to improve antibiotic use, but cost-effectiveness data on implementation of outpatient antibiotic stewardship interventions are limited. We evaluated the cost-effectiveness of Core Element implementation in the outpatient setting. METHODS: An economic simulation model from the health-system perspective was developed for patients presenting to outpatient settings with uncomplicated acute respiratory tract infections (ARI). Effectiveness was measured as quality-adjusted life years (QALYs). Cost and utility parameters for antibiotic treatment, adverse drug events (ADEs), and healthcare utilization were obtained from the literature. Probabilities for antibiotic treatment and appropriateness, ADEs, hospitalization, and return ARI visits were estimated from 16,712 and 51,275 patient visits in intervention and control sites during the pre- and post-implementation periods, respectively. Data for materials and labor to perform the stewardship activities were used to estimate intervention cost. We performed a one-way and probabilistic sensitivity analysis (PSA) using 1,000,000 second-order Monte Carlo simulations on input parameters. RESULTS: The proportion of ARI patient-visits with antibiotics prescribed in intervention sites was lower (62% vs 74%) and appropriate treatment higher (51% vs 41%) after implementation, compared to control sites. The estimated intervention cost over a 2-year period was $133,604 (2018 US dollars). The intervention had lower mean costs ($528 vs $565) and similar mean QALYs (0.869 vs 0.868) per patient compared to usual care. In the PSA, the intervention was dominant in 63% of iterations. CONCLUSIONS: Implementation of the CDC Core Elements in the outpatient setting was a cost-effective strategy.

Duration of Outpatient Antibiotic Therapy for Common Outpatient Infections, 2017.

Our objective was to describe the duration of antibiotic therapy for the management of common outpatient conditions. The median duration of antibiotic courses for most common conditions, except for acute cystitis, was 10 days, in many cases exceeding guideline-recommended durations.

Oral Step-Down Therapy With Levofloxacin for Febrile Neutropenia in Children With Cancer.

BACKGROUND: Although febrile neutropenia (FN) is a frequent complication in children with cancer receiving chemotherapy, there remains significant variability in selection of route (intravenous [IV] vs oral) and length of therapy. We implemented a guideline with a goal to change practice from using IV antibiotics after hospital discharge to the use of step-down oral therapy with levofloxacin for most children with FN until absolute neutrophil count > 500. The objectives of this study were to determine the impact of this guideline on home IV antibiotic use, and to evaluate the safety of implementation of this guideline. METHODS: We performed a quasi-experimental, pre-post study of discharge FN treatment at a stand-alone children's hospital in patients without bacteremia discharged between January 2013 and October 2018. In January 2015, a multidisciplinary team created a guideline to switch most children with FN to oral levofloxacin, which was formally implemented as of September 2017. Discharges during the postintervention period (after September 2017) were compared to discharges in the preintervention period (between January 2013 and December 2014). RESULTS: In adjusted multivariable regression analyses, the postimplementation period was associated with a decrease in home IV antibiotics (adjusted risk ratio [aRR], 0.07 [95% confidence interval {CI}, .03-.13]) and fewer IV antibiotic initiations within 24 hours of a new healthcare encounter up to 7 days after discharge (aRR, 0.39 [95% CI, .17-.93]) compared to the preintervention time period. CONCLUSIONS: Step-down oral levofloxacin for children with FN who are afebrile with an ANC ≤ 500 at discharge is feasible and resulted in similar clinical outcomes compared to home IV antibiotics.

The Association of Antibiotic Duration With Successful Treatment of Community-Acquired Pneumonia in Children.

BACKGROUND: National guidelines recommend 10 days of antibiotics for children with community-acquired pneumonia (CAP), acknowledging that the outcomes of children hospitalized with CAP who receive shorter durations of therapy have not been evaluated. METHODS: We conducted a comparative effectiveness study of children aged ≥6 months hospitalized at The Johns Hopkins Hospital who received short-course (5-7 days) vs prolonged-course (8-14 days) antibiotic therapy for uncomplicated CAP between 2012 and 2018 using an inverse probability of treatment weighted propensity score analysis. Inclusion was limited to children with clinical and radiographic criteria consistent with CAP, as adjudicated by 2 infectious diseases physicians. Children with tracheostomies; healthcare-associated, hospital-acquired, or ventilator-associated pneumonia; loculated or moderate to large pleural effusion or pulmonary abscess; intensive care unit stay >48 hours; cystic fibrosis/bronchiectasis; severe immunosuppression; or unusual pathogens were excluded. The primary outcome was treatment failure, a composite of unanticipated emergency department visits, outpatient visits, hospital readmissions, or death (all determined to be likely attributable to bacterial pneumonia) within 30 days after completing antibiotic therapy. RESULTS: Four hundred and thirty-nine patients met eligibility criteria; 168 (38%) patients received short-course therapy (median, 6 days) and 271 (62%) received prolonged-course therapy (median, 10 days). Four percent of children experienced treatment failure, with no differences observed between patients who received short-course vs prolonged-course antibiotic therapy (odds ratio, 0.48; 95% confidence interval, .18-1.30). CONCLUSIONS: A short course of antibiotic therapy (approximately 5 days) does not increase the odds of 30-day treatment failure compared with longer courses for hospitalized children with uncomplicated CAP.

Multicenter Interim Guidance on Use of Antivirals for Children With Coronavirus Disease 2019/Severe Acute Respiratory Syndrome Coronavirus 2.

BACKGROUND: Although coronavirus disease 2019 (COVID-19) is a mild infection in most children, a small proportion develop severe or critical illness. Data describing agents with potential antiviral activity continue to expand such that updated guidance is needed regarding use of these agents in children. METHODS: A panel of pediatric infectious diseases physicians and pharmacists from 20 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a set of guidance statements was developed and refined based on review of the best available evidence and expert opinion. RESULTS: Given the typically mild course of COVID-19 in children, supportive care alone is suggested for most cases. For children with severe illness, defined as a supplemental oxygen requirement without need for noninvasive or invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO), remdesivir is suggested, preferably as part of a clinical trial if available. Remdesivir should also be considered for critically ill children requiring invasive or noninvasive mechanical ventilation or ECMO. A duration of 5 days is appropriate for most patients. The panel recommends against the use of hydroxychloroquine or lopinavir-ritonavir (or other protease inhibitors) for COVID-19 in children. CONCLUSIONS: Antiviral therapy for COVID-19 is not necessary for the great majority of pediatric patients. For children with severe or critical disease, this guidance offers an approach for decision-making regarding use of remdesivir.

An Evaluation of Vancomycin Area Under the Curve Estimation Methods for Children Treated for Acute Pulmonary Exacerbations of Cystic Fibrosis Due to Methicillin-Resistant Staphylococcus aureus.

The prevalence of pulmonary methicillin-resistant Staphylococcus aureus infections in patients with cystic fibrosis (CF) has increased over the last 2 decades. Two concentrations-a postdistributive and a trough-are currently used to estimate the area under the curve (AUC) of vancomycin, an antibiotic routinely used to treat these infections, to achieve the target AUC/minimum inhibitory concentration of ≥400 mg·h/L in ensuring optimal dosing of this drug. This study evaluated precision and bias in estimating vancomycin AUCs obtained either from a population pharmacokinetic (PK) model by using a single trough concentration or from standard PK equation-based 2-point monitoring approach. AUCs were either obtained from a single trough concentration-fitted model or derived from a model fitted by 2 concentration points. Children ≥2 years of age with CF received intravenous vancomycin at 2 centers from June 2012 to December 2014. A population PK model was developed in Pmetrics to quantify the between-subject variability in vancomycin PK parameters, define the sources of PK variability, and leverage information from the population to improve individual AUC estimates. Twenty-three children with CF received 27 courses of vancomycin. The median age was 12.3 (interquartile range [IQR] 8.5-16.6) years. From the individual vancomycin PK parameter estimates from the population PK model, median AUC was 622 (IQR 529-680) mg·h/L. Values were not significantly different from the AUC calculated using the standard PK equation-based approach (median 616 [IQR 540-663] mg·h/L) (P = .89). A standard PK equation-based approach using 2 concentrations and a population PK model-based approach using a single trough concentration yielded unbiased and precise AUC estimates. Findings suggest that options exist to implement AUC-based pediatric vancomycin dosing in patients with CF. The findings of this study reveal that several excellent options exist for centers to implement AUC-based pediatric vancomycin dosing for patients with CF.

Trends in Intravenous Antibiotic Duration for Urinary Tract Infections in Young Infants.

OBJECTIVES: To assess trends in the duration of intravenous (IV) antibiotics for urinary tract infections (UTIs) in infants ≤60 days old between 2005 and 2015 and determine if the duration of IV antibiotic treatment is associated with readmission. METHODS: Retrospective analysis of infants ≤60 days old diagnosed with a UTI who were admitted to a children's hospital and received IV antibiotics. Infants were excluded if they had a previous surgery or comorbidities, bacteremia, or admission to the ICU. Data were analyzed from the Pediatric Health Information System database from 2005 through 2015. The primary outcome was readmission within 30 days for a UTI. RESULTS: The proportion of infants ≤60 days old receiving 4 or more days of IV antibiotics (long IV treatment) decreased from 50% in 2005 to 19% in 2015. The proportion of infants ≤60 days old receiving long IV treatment at 46 children's hospitals varied between 3% and 59% and did not correlate with readmission (correlation coefficient 0.13; P = .37). In multivariable analysis, readmission for a UTI was associated with younger age and female sex but not duration of IV antibiotic therapy (adjusted odds ratio for long IV treatment: 0.93 [95% confidence interval 0.52-1.67]). CONCLUSIONS: The proportion of infants ≤60 days old receiving long IV treatment decreased substantially from 2005 to 2015 without an increase in hospital readmissions. These findings support the safety of short-course IV antibiotic therapy for appropriately selected neonates.

Variability in Antifungal and Antiviral Use in Hospitalized Children.

We analyzed antifungal and antiviral prescribing among high-risk children across freestanding children's hospitals. Antifungal and antiviral days of therapy varied across hospitals. Benchmarking antifungal and antiviral use and developing antimicrobial stewardship strategies to optimize use of these high cost agents is needed. Infect Control Hosp Epidemiol 2017;38:743-746.

Extended- Versus Narrower-Spectrum Antibiotics for Appendicitis.

BACKGROUND AND OBJECTIVES: Appendicitis guidelines recommend either narrower- or extended-spectrum antibiotics for treatment of complicated appendicitis. The goal of this study was to compare the effectiveness of extended-spectrum versus narrower-spectrum antibiotics for children with appendicitis. METHODS: We performed a retrospective cohort study of children aged 3 to 18 years discharged between 2011 and 2013 from 23 freestanding children's hospitals with an appendicitis diagnosis and appendectomy performed. Subjects were classified as having complicated appendicitis if they had a postoperative length of stay ≥3 days, a central venous catheter placed, major or severe illness classification, or ICU admission. The exposure of interest was receipt of systemic extended-spectrum antibiotics (piperacillin ± tazobactam, ticarcillin ± clavulanate, ceftazidime, cefepime, or a carbapenem) on the day of appendectomy or the day after. The primary outcome was 30-day readmission for wound infection or repeat abdominal surgery. Multivariable logistic regression, propensity score weighting, and subgroup analyses were used to control for confounding by indication. RESULTS: Of 24 984 patients, 17 654 (70.7%) had uncomplicated appendicitis and 7330 (29.3%) had complicated appendicitis. Overall, 664 (2.7%) patients experienced the primary outcome, 1.1% among uncomplicated cases and 6.4% among complicated cases (P < .001). Extended-spectrum antibiotic exposure was significantly associated with the primary outcome in complicated (adjusted odds ratio, 1.43 [95% confidence interval, 1.06 to 1.93]), but not uncomplicated, (adjusted odds ratio, 1.32 [95% confidence interval, 0.88 to 1.98]) appendicitis. These odds ratios remained consistent across additional analyses. CONCLUSIONS: Extended-spectrum antibiotics seem to offer no advantage over narrower-spectrum agents for children with surgically managed acute uncomplicated or complicated appendicitis.

Risk Factors for Recurrent Clostridium difficile Infection in Pediatric Inpatients.

OBJECTIVE: The purpose of this study was to identify the risk factors during the incident Clostridium difficile infection (CDI) episode, associated with developing recurrent CDI within 60 days, among hospitalized children that may be amenable to intervention. METHODS: This was a retrospective cohort study of pediatric patients hospitalized at a freestanding children's hospital from January 1, 2003, to December 31, 2010. Patients were eligible if they were <18 years of age at admission and had a new diagnosis of CDI. Patients <1 year of age and those with a history of CDI in the previous 60 days were excluded. Age, gender, race, complex chronic conditions, and other information were collected. Multivariable logistic regression was used to evaluate predictors of recurrent CDI. RESULTS: During the study period, there were 612 unique patients with an incident CDI episode; 65 (10.6%) experienced at least 1 recurrence. Patients with any complex chronic condition were 4.0 (95% confidence interval [CI]: 1.2-13.9) times more likely to experience recurrence. Patients with a malignancy and those who received non-CDI antibiotics at any time during CDI treatment were 2.3 (95% CI: 1.3-4.0) and 2.8 (95% CI: 1.2-6.9) times more likely to experience recurrence, respectively. CONCLUSIONS: The presence of underlying comorbidities, malignancies, and treatment with non-CDI antibiotics during CDI treatment were the most important risk factors for recurrence. Efforts to reduce unnecessary courses of non-CDI antibiotics could lower the risk of CDI recurrence.

Use of Concomitant Antibiotics During Treatment for Clostridium difficile Infection (CDI) in Pediatric Inpatients: An Observational Cohort Study.

Concomitant antibiotic use during treatment for Clostridium difficile infection (CDI) increases the risk of recurrence. Across a network of children's hospitals, 46% of patients treated for CDI received concomitant antibiotics for a median of 7 days. Concomitant antibiotic use was more common among patients with malignancies, and solid organ or bone marrow transplant. Unnecessary concomitant antibiotic use in CDI patients is a potential target for pediatric antimicrobial stewardship.

Identifying Antimicrobial Stewardship Targets for Pediatric Surgical Patients.

BACKGROUND: More than 80% of surgical inpatients at US children's hospitals receive antibiotics, accounting for >40% of all inpatient pediatric antibiotic use. We aimed to examine the collective pool of all systemic antibiotics prescribed to children hospitalized for surgical conditions and identify common surgical conditions with highly variable and potentially unnecessary antibiotic use, because these conditions may represent antimicrobial stewardship priorities. METHODS: We conducted a retrospective cross-sectional study of surgical inpatients discharged in 2012 at 37 freestanding children's hospitals. We captured all systemic antibiotic use as days of therapy (DOT), and we reported surgical conditions by frequency and contribution to overall antibiotic use. We used multivariable logistic and Poisson regression with marginal standardization to estimate (1) the standardized proportion and (2) DOT of condition-specific targeted antibiotic use among top surgical condition patients. RESULTS: Among 151 345 surgical inpatients, 82.9% received antimicrobials for a median 2 DOT per subject (interquartile range, 1-5; range, 1-958). The most commonly received antibiotics were cefazolin (16.7% of all DOT), vancomycin (12.5%), and piperacillin/tazobactam (6.9%). The top 10 conditions contributing most to antibiotic use accounted for 51.3% of all antibiotic use. Among these, adjusted use of postoperative and perioperative vancomycin varied across hospitals among craniotomy and cardiothoracic surgery subjects (all P < .001); adjusted use of broad-spectrum antipseudomonal agents varied across hospitals among gastrointestinal surgery subjects (all P < .001). CONCLUSIONS: Use of (1) vancomycin for pediatric cardiothoracic and neurosurgical patients and (2) broad-spectrum antipseudomonal agents for gastrointestinal surgery patients represent potentially high-yield targets for stewardship efforts to reduce unnecessary antimicrobial use.

Primary care physician smoking screening and counseling for patients with chronic disease.

BACKGROUND: Evidence-based guidelines recommend smoking cessation treatment, including screening and counseling, for all smokers, including those with chronic diseases exacerbated by smoking. Physician treatment improves smoking cessation. Little data describes smoking treatment guideline uptake for patients with chronic cardiopulmonary smoking-sensitive diseases. OBJECTIVE: Describe U.S. primary care physician (PCP) smoking cessation treatment during patient visits for chronic cardiopulmonary smoking-sensitive diseases. METHODS: The National (Hospital) Ambulatory Medical Care Survey captured PCP visits. We examined smoking screening and counseling time trends for smokers with chronic diseases. Multivariable logistic regression assessed factors associated with smoking counseling for smokers with chronic smoking-sensitive diseases. RESULTS: From 2001-2009 smoking screening and counseling for smokers with chronic smoking-sensitive cardiopulmonary diseases were unchanged. Among smokers with chronic smoking-sensitive diseases, 50%-72% received no counseling. Smokers with chronic obstructive pulmonary disease (COPD) (odds ratio (OR)=6.54, 95% confidence interval (CI) 4.85-8.83) and peripheral vascular disease (OR=4.50, 95% CI 1.72-11.75) were more likely to receive smoking counseling at chronic/preventive care visits, compared with patients without smoking-sensitive diseases. Other factors associated with increased smoking counseling included non-private insurance, preventive and longer visits, and an established PCP. Asthma and cardiovascular disease showed no association with counseling. CONCLUSIONS: Smoking cessation counseling remains infrequent for smokers with chronic smoking-sensitive cardiopulmonary diseases. New strategies are needed to encourage smoking cessation counseling.

Linezolid use in hospitalized children.

We used the Pediatric Health Information System to evaluate linezolid use among hospitalized children. From 2003 to 2007, use increased 5-fold, including wide interhospital variation, then stabilized through 2011. Linezolid was responsible for 3% of total antibiotic expenditures. Children with respiratory, oncologic or transplant conditions were the most frequently treated with linezolid.

Identifying targets for antimicrobial stewardship in children's hospitals.

OBJECTIVE: Antimicrobial stewardship programs (ASPs) are recommended to optimize antimicrobial use for hospitalized patients. Although mechanisms for the implementation of ASPs have been described, data-driven approaches to prioritize specific conditions and antimicrobials for intervention have not been established. We aimed to develop a strategy for identifying high-impact targets for antimicrobial stewardship efforts. DESIGN: Retrospective cross-sectional study. SETTING AND PATIENTS: Children admitted to 32 freestanding children's hospitals in the United States in 2010. METHODS: We identified the conditions with the largest proportional contribution to the total days of antibiotic therapy prescribed to all hospitalized children. For the 4 highest-using conditions, we examined variability between hospitals in antibiotic selection patterns for use of either first- or second-line therapies depending on the condition. Antibiotic use was determined using standardized probability of exposure to selected agents and standardized days of therapy per 1,000 patient-days, adjusting for patient demographics and severity of illness. RESULTS: In 2010, 524,364 children received 2,082,929 days of antibiotic therapy. Surgical patients received 43% of all antibiotics. The 4 highest-using conditions-pneumonia, appendicitis, cystic fibrosis, and skin and soft-tissue infection-represent 1% of all conditions yet accounted for more than 10% of all antibiotic use. Wide variability in antibiotic use occurred for 3 of these 4 conditions. CONCLUSIONS: Antibiotic use in children's hospitals varied broadly across institutions when examining diagnoses individually and adjusting for severity of illness. Identifying conditions with both frequent and variable antimicrobial use informs the prioritization of high-impact targets for future antimicrobial stewardship interventions.