Balanced on the Biggest Wave: Nirsevimab for Newborns.

Respiratory syncytial virus (RSV) is the leading cause of hospitalization in infancy in the United States. Nearly all infants are infected by 2 years of age, with bronchiolitis requiring hospitalization often occurring in previously healthy children and long-term consequences of severe disease including delayed speech development and asthma. Incomplete passage of maternal immunity and a high degree of genetic variability within the virus contribute to morbidity and have also prevented successful neonatal vaccine development. Monoclonal antibodies reduce the risk of hospitalization from severe RSV disease, with palivizumab protecting high-risk newborns with comorbidities including chronic lung disease and congenital heart disease. Unfortunately, palivizumab is costly and requires monthly administration of up to five doses during the RSV season for optimal protection.Rapid advances in the past two decades have facilitated the identification of antibodies with broad neutralizing activity and allowed manipulation of their genetic code to extend half-life. These advances have culminated with nirsevimab, a monoclonal antibody targeting the Ø antigenic site on the RSV prefusion protein and protecting infants from severe disease for an entire 5-month season with a single dose. Four landmark randomized controlled trials, the first published in July 2020, have documented the efficacy and safety of nirsevimab in healthy late-preterm and term infants, healthy preterm infants, and high-risk preterm infants and those with congenital heart disease. Nirsevimab reduces the risk of RSV disease requiring medical attention (number needed to treat [NNT] 14-24) and hospitalization (NNT 33-63) with rare mild rash and injection site reactions. Consequently, the Centers for Disease Control and Prevention has recently recommended nirsevimab for all infants younger than 8 months of age entering or born during the RSV season and high-risk infants 8-19 months of age entering their second season. Implementing this novel therapy in this large population will require close multidisciplinary collaboration. Equitable distribution through minimizing barriers and maximizing uptake must be prioritized.

Comparative Safety and Attributable Healthcare Expenditures Following Inappropriate Versus Appropriate Outpatient Antibiotic Prescriptions Among Adults With Upper Respiratory Infections.

BACKGROUND: Little is known about the clinical and financial consequences of inappropriate antibiotics. We aimed to estimate the comparative risk of adverse drug events and attributable healthcare expenditures associated with inappropriate versus appropriate antibiotic prescriptions for common respiratory infections. METHODS: We established a cohort of adults aged 18 to 64 years with an outpatient diagnosis of a bacterial (pharyngitis, sinusitis) or viral respiratory infection (influenza, viral upper respiratory infection, nonsuppurative otitis media, bronchitis) from 1 April 2016 to 30 September 2018 using Merative MarketScan Commercial Database. The exposure was an inappropriate versus appropriate oral antibiotic (ie, non-guideline-recommended vs guideline-recommended antibiotic for bacterial infections; any vs no antibiotic for viral infections). Propensity score-weighted Cox proportional hazards models were used to estimate the association between inappropriate antibiotics and adverse drug events. Two-part models were used to calculate 30-day all-cause attributable healthcare expenditures by infection type. RESULTS: Among 3 294 598 eligible adults, 43% to 56% received inappropriate antibiotics for bacterial and 7% to 66% for viral infections. Inappropriate antibiotics were associated with increased risk of several adverse drug events, including Clostridioides difficile infection and nausea/vomiting/abdominal pain (hazard ratio, 2.90; 95% confidence interval, 1.31-6.41 and hazard ratio, 1.10; 95% confidence interval, 1.03-1.18, respectively, for pharyngitis). Thirty-day attributable healthcare expenditures were higher among adults who received inappropriate antibiotics for bacterial infections ($18-$67) and variable (-$53 to $49) for viral infections. CONCLUSIONS: Inappropriate antibiotic prescriptions for respiratory infections were associated with increased risks of patient harm and higher healthcare expenditures, justifying a further call to action to implement outpatient antibiotic stewardship programs.

Quantifying Procedure-level Prophylaxis Misutilization in Pediatric Surgery: Implications for the Prioritization of Antimicrobial Stewardship Efforts.

OBJECTIVE: To quantify procedure-level inappropriate antimicrobial prophylaxis utilization as a strategy to identify high-priority targets for stewardship efforts in pediatric surgery. BACKGROUND: Little data exist to guide the prioritization of antibiotic stewardship efforts as they relate to prophylaxis utilization in pediatric surgery. METHODS: This was a retrospective cohort analysis of children undergoing elective surgical procedures at 52 children's hospitals from October 2015 to December 2019 using the Pediatric Health Information System database. Procedure-level compliance with consensus guidelines for prophylaxis utilization was assessed for indication, antimicrobial spectrum, and duration. The relative contribution of each procedure to the overall burden of noncompliant cases was calculated to establish a prioritization framework for stewardship efforts. RESULTS: A total of 56,845 cases were included with an overall inappropriate utilization rate of 56%. The most common reason for noncompliance was unindicated utilization (43%), followed by prolonged duration (32%) and use of excessively broad-spectrum agents (25%). Procedures with the greatest relative contribution to noncompliant cases included cholecystectomy and repair of inguinal and umbilical hernias for unindicated utilization (63.2% of all cases); small bowel resections, gastrostomy, and colorectal procedures for use of excessively broad-spectrum agents (70.1%) and pectus excavatum repair and procedures involving the small and large bowel for prolonged duration (57.6%). More than half of all noncompliant cases were associated with 5 procedures (cholecystectomy, small bowel procedures, inguinal hernia repair, gastrostomy, and pectus excavatum). CONCLUSIONS: Cholecystectomy, inguinal hernia repair, and procedures involving the small and large bowel should be considered high-priority targets for antimicrobial stewardship efforts in pediatric surgery.

Utilization of nonguideline concordant antibiotic treatment following acute otitis media in children in the United States.

PURPOSE: Acute otitis media (AOM) is a common indication for antibiotics in children. We sought to characterize the frequency of nonguideline concordant antibiotic therapy for AOM in the United States, by agent and duration. METHODS: Using national administrative claims data (2016-2019), we identified children aged 6 months to 17 years with an oral antibiotic dispensed within 3 days of a new diagnosis of suppurative AOM. Use of nonguideline concordant agents and durations, defined based on national treatment guidelines, were summarized by age, race, rurality, region, and insurance type. Subsequent oral antibiotic dispensing within the year after AOM diagnosis was also evaluated. We created sunburst diagrams to visualize longitudinal patterns of within-person antibiotic utilization for AOM, by agent and duration. RESULTS: We identified 789 424 eligible commercially-insured and 502 239 medicaid-insured children. Among commercially insured children, 35% received nonguideline concordant agents for AOM, including cefdinir (16%), amoxicillin-clavulanate (12%), and azithromycin (7%). Fewer children age <2 years received a nonguideline concordant initial agent (27%) compared to age ≥6 years (41%). More children age <2 years received three or more antibiotics over the following year (34% vs. 3% for children age ≥6 years). The most common treatment duration was 10 days for all ages; treatment duration for the initial antibiotic was nonguideline concordant for 95% and 89% of children age 2-5 years and ≥6 years, respectively. Patterns were similar for medicaid-insured children. CONCLUSIONS: Nonguideline concordant antibiotic use is common when treating AOM in children, including use of broad-spectrum agents and longer-than-recommended antibiotic durations.

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

Antibiotic-associated diarrhea (AAD) is a common side effect of antibiotics. We examined the gastrointestinal microbiota in children treated with ß-lactams for community-acquired pneumonia. Data were from 66 children (n = 198 samples), aged 6-71 months, enrolled in the SCOUT-CAP trial (NCT02891915). AAD was defined as ≥1 day of diarrhea. Stool samples were collected on study days 1, 6-10, and 19-25. Samples were analyzed using 16S ribosomal RNA gene sequencing to identify associations between patient characteristics, microbiota characteristics, and AAD (yes/no). Nineteen (29%) children developed AAD. Microbiota compositional profiles differed between AAD groups (permutational multivariate analysis of variance, P < .03) and across visits (P < .001). Children with higher baseline relative abundances of 2 Bacteroides species were less likely to experience AAD. Higher baseline abundance of Lachnospiraceae and amino acid biosynthesis pathways were associated with AAD. Children in the AAD group experienced prolonged dysbiosis (P < .05). Specific gastrointestinal microbiota profiles are associated with AAD in children.

The impact of infectious diseases consultation for children with Staphylococcus aureus bacteremia.

BACKGROUND: Despite clear benefit of improved outcomes in adults, the impact of infectious diseases (ID) consultation for Staphylococcus aureus bacteremia in children remains understudied. METHODS: To assess the impact of pediatric ID consultation on management and outcomes, we conducted a cohort study of children with S. aureus bacteremia at St. Louis Children's Hospital from 2011 to 2018. We assessed adherence to six established quality-of-care indicators (QCIs). We applied propensity score methodology to examine the impact of ID consultation on risk of treatment failure, a composite of all-cause mortality or hospital readmission within 90 days. RESULTS: Of 306 patients with S. aureus bacteremia, 193 (63%) received ID consultation. ID consultation was associated with increased adherence to all QCIs, including proof-of-cure blood cultures, indicated laboratory studies, echocardiography, source control, targeted antibiotic therapy, and antibiotic duration. Obtaining proof-of-cure blood cultures and all indicated laboratory studies were associated with improved outcomes. In propensity score-weighted analyses, risk of treatment failure was similar among patients who did and did not receive ID consultation. However, the number of events was small and risk estimates were imprecise. CONCLUSIONS: For children with S. aureus bacteremia, ID consultation improved adherence to QCIs, some of which were associated with improved clinical outcomes. IMPACT: In children with Staphylococcus aureus bacteremia, consultation by an infectious diseases (ID) physician improved adherence to established quality-of-care indicators (QCIs). The current literature regarding ID consultation in pediatric S. aureus bacteremia is sparse. Three prior international studies demonstrated improved quality of care with ID consultation, though results were disparate regarding clinical outcomes. This article impacts the current literature by strengthening the evidence that ID consultation in children improves adherence to QCIs, and demonstrates that adherence to QCIs improves clinical outcomes.

Transmission risk of COVID-19 in high school and college water polo.

BACKGROUND: Concerns that athletes may be at a higher risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission has led to reduced participation in sports during the COVID-19 pandemic. We aimed to assess COVID-19 incidence and transmission during the spring 2021 high school and college water polo seasons across the United States. METHODS: This prospective observational study enrolled 1825 water polo athletes from 54 high schools and 36 colleges. Surveys were sent to coaches throughout the season, and survey data were collected and analyzed. RESULTS: We identified 17 COVID-19 cases among 1223 high school water polo athletes (1.4%) and 66 cases among 602 college athletes (11.0%). Of these cases, contact tracing suggested that three were water polo-associated in high school, and none were water polo-associated in college. Quarantine data suggest low transmission during water polo play as only three out of 232 (1.3%) high school athletes quarantined for a water polo-related exposure developed COVID-19. In college, none of the 54 athletes quarantined for exposure with an infected opponent contracted COVID-19. However, in both high school and college, despite the physical condition of water polo athletes, both high school (47%) and college athletes (21%) had prolonged return to play after contracting COVID-19, indicating the danger of COVID-19, even to athletes. CONCLUSIONS: While COVID-19 spread can occur during water polo play, few instances of spread occurred during the spring 2021 season, and transmission rates appear similar to those in other settings, such as school environments.

Dissemination and implementation science and antimicrobial stewardship in solid organ transplantation: A perspective.

BACKGROUND: Recipients of solid organ transplants (SOTs) have unique risks for infections, but providers are often hesitant to apply the principles of antimicrobial stewardship to this patient population due to perceived excess risk. The methods of implementation science may move the field forward to simultaneously improve patient outcomes and patient safety. METHODS: Perspective piece on implementation science in SOT patients. RESULTS: Herein, we provide explanation of implementation science as it relates to SOT patients. In addition, we provide examples of how implementation science can be applied to antimicrobial stewardship in SOT patients. CONCLUSION: Implementation science may offer insights and solutions to the challenges of implementing evidence-based antimicrobial stewardship interventions in patients with SOT, including uptake of new practices and the de-implementation of outdated or low-value practices.

Assessing COVID-19 testing strategies in K-12 schools in underserved populations: study protocol for a cluster-randomized trial.

BACKGROUND: Since March 2020, COVID-19 has disproportionately impacted communities of color within the United States. As schools have shifted from virtual to in-person learning, continual guidance is necessary to understand appropriate interventions to prevent SARS-CoV-2 transmission. Weekly testing of students and staff for SARS-CoV-2 within K-12 school setting could provide an additional barrier to school-based transmission, especially within schools unable to implement additional mitigation strategies and/or are in areas of high transmission. This study seeks to understand the role that weekly SARS-CoV-2 testing could play in K-12 schools. In addition, through qualitative interviews and listening sessions, this research hopes to understand community concerns and barriers regarding COVID-19 testing, COVID-19 vaccine, and return to school during the COVID-19 pandemic. METHODS/DESIGN: Sixteen middle and high schools from five school districts have been randomized into one of the following categories: (1) Weekly screening + symptomatic testing or (2) Symptomatic testing only. The primary outcome for this study will be the average of the secondary attack rate of school-based transmission per case. School-based transmission will also be assessed through qualitative contact interviews with positive contacts identified by the school contact tracers. Lastly, new total numbers of weekly cases and contacts within a school-based quarantine will provide guidance on transmission rates. Qualitative focus groups and interviews have been conducted to provide additional understanding to the acceptance of the intervention and barriers faced by the community regarding SARS-CoV-2 testing and vaccination. DISCUSSION: This study will provide greater understanding of the benefit that weekly screening testing can provide in reducing SARS-CoV-2 transmission within K-12 schools. Close collaboration with community partners and school districts will be necessary for the success of this and similar studies. TRIAL REGISTRATION: NCT04875520 . Registered May 6, 2021.

Pilot Investigation of SARS-CoV-2 Secondary Transmission in Kindergarten Through Grade 12 Schools Implementing Mitigation Strategies - St. Louis County and City of Springfield, Missouri, December 2020.

Many kindergarten through grade 12 (K-12) schools offering in-person learning have adopted strategies to limit the spread of SARS-CoV-2, the virus that causes COVID-19 (1). These measures include mandating use of face masks, physical distancing in classrooms, increasing ventilation with outdoor air, identification of close contacts,* and following CDC isolation and quarantine guidance† (2). A 2-week pilot investigation was conducted to investigate occurrences of SARS-CoV-2 secondary transmission in K-12 schools in the city of Springfield, Missouri, and in St. Louis County, Missouri, during December 7-18, 2020. Schools in both locations implemented COVID-19 mitigation strategies; however, Springfield implemented a modified quarantine policy permitting student close contacts aged ≤18 years who had school-associated contact with a person with COVID-19 and met masking requirements during their exposure to continue in-person learning.§ Participating students, teachers, and staff members with COVID-19 (37) from 22 schools and their school-based close contacts (contacts) (156) were interviewed, and contacts were offered SARS-CoV-2 testing. Among 102 school-based contacts who received testing, two (2%) had positive test results indicating probable school-based SARS-CoV-2 secondary transmission. Both contacts were in Springfield and did not meet criteria to participate in the modified quarantine. In Springfield, 42 student contacts were permitted to continue in-person learning under the modified quarantine; among the 30 who were interviewed, 21 were tested, and none received a positive test result. Despite high community transmission, SARS-CoV-2 transmission in schools implementing COVID-19 mitigation strategies was lower than that in the community. Until additional data are available, K-12 schools should continue implementing CDC-recommended mitigation measures (2) and follow CDC isolation and quarantine guidance to minimize secondary transmission in schools offering in-person learning.

Association of Intrapartum Risk Factors and Infant Clinical Indicators with Culture Confirmed Early Onset Neonatal Sepsis in a Secondary Care Rural Hospital in India.

OBJECTIVE: The aim of this study is to determine the association of intrapartum risk factors and infant clinical indicators using the National Institute for Health and Care Excellence (NICE) criteria with culture-positive early-onset neonatal sepsis (EONS) from a rural secondary healthcare facility where intrapartum prophylactic antibiotics are routinely administered to high-risk mothers. METHODS: A single-center prospective observational study was conducted between July 2017 and September 2018. All intramural neonates with at least one NICE criteria at less than 72 h of life, were included. Univariate logistic regression and multivariable logistic backward elimination analyses were conducted to investigate individual risk factors and predictive models for culture proven EONS. RESULTS: Of 236 newborns who were at risk for EONS by NICE criteria, 32 (13.8%) had positive blood cultures. Klebsiella species (n = 13, 39.4%) and Acinetobacter species (n = 11, 33.3%) were the most common isolated bacteria. In univariate analysis, the number of infant clinical indicators were associated with culture positive EONS (OR 1.36; 95% CI 1.01-1.81), but not the number of intrapartum risk factors (OR 0.76; 95% CI 0.4-1.29). The multivariate logistic regression with backward elimination procedure suggested that a model including absolute neutrophil count [adjusted OR (aOR) 0.81; 95% CI 0.72-0.92], C-reactive protein (aOR 1.24; 95% CI 1.08-1.43) and the number of clinical indicators (aOR 1.29; 95% CI 0.93-1.80) could be useful to predict culture positive EONS in our setting. CONCLUSION: In this maternal and neonatal cohort, infant clinical indicators rather than intrapartum risk factors were associated with culture confirmed EONS.

Effect of Combined Clinical Practice Guideline and Electronic Order Set Implementation on Febrile Infant Evaluation and Management.

OBJECTIVE: Management of febrile infants 60 days and younger for suspected serious infection varies widely. Clinical practice guidelines (CPGs) are intended to improve clinician adherence to evidence-based practices. In 2011, a CPG for managing febrile infants was implemented in an urban children's hospital with simultaneous release of an electronic order set and algorithm to guide clinician decisions for managing infants for suspected serious bacterial infection. The objective of the present study was to determine the association of CPG implementation with order set use, clinical practices, and clinical outcomes. METHODS: Records of febrile infants 60 days and younger from February 1, 2009, to January 31, 2013, were retrospectively reviewed. Clinical documentation, order set use, clinical management practices, and outcomes were compared pre-CPG and post-CPG release. RESULTS: In total, 1037 infants pre-CPG and 930 infants post-CPG implementation were identified. After CPG release, more infants 29 to 60 days old underwent lumbar puncture (56% vs 62%, P = 0.02). Overall antibiotic use and duration of antibiotic use decreased for infants 29 to 60 days (57% vs 51%, P = 0.02). Blood culture and urine culture obtainment remained unchanged for older infants. Diagnosed infections, hospital readmissions, and length of stay were unchanged. Electronic order sets were used in 80% of patient encounters. CONCLUSIONS: Antibiotic use and lumbar puncture performance modestly changed in accordance with CPG recommendations provided in the electronic order set and algorithm, suggesting that the presence of embedded prompts may affect clinician decision-making. Our results highlight the potential usefulness of these decision aids to improve adherence to CPG recommendations.

Appropriateness of Antibiotic Prescribing in United States Children's Hospitals: A National Point Prevalence Survey.

BACKGROUND: Studies estimate that 30%-50% of antibiotics prescribed for hospitalized patients are inappropriate, but pediatric data are limited. Characterization of inappropriate prescribing practices for children is needed to guide pediatric antimicrobial stewardship. METHODS: Cross-sectional analysis of antibiotic prescribing at 32 children's hospitals in the United States. Subjects included hospitalized children with ≥ 1 antibiotic order at 8:00 am on 1 day per calendar quarter, over 6 quarters (quarter 3 2016-quarter 4 2017). Antimicrobial stewardship program (ASP) physicians and/or pharmacists used a standardized survey to collect data on antibiotic orders and evaluate appropriateness. The primary outcome was the percentage of antibiotics prescribed for infectious use that were classified as suboptimal, defined as inappropriate or needing modification. RESULTS: Of 34 927 children hospitalized on survey days, 12 213 (35.0%) had ≥ 1 active antibiotic order. Among 11 784 patients receiving antibiotics for infectious use, 25.9% were prescribed ≥ 1 suboptimal antibiotic. Of the 17 110 antibiotic orders prescribed for infectious use, 21.0% were considered suboptimal. Most common reasons for inappropriate use were bug-drug mismatch (27.7%), surgical prophylaxis > 24 hours (17.7%), overly broad empiric therapy (11.2%), and unnecessary treatment (11.0%). The majority of recommended modifications were to stop (44.7%) or narrow (19.7%) the drug. ASPs would not have routinely reviewed 46.1% of suboptimal orders. CONCLUSIONS: Across 32 children's hospitals, approximately 1 in 3 hospitalized children are receiving 1 or more antibiotics at any given time. One-quarter of these children are receiving suboptimal therapy, and nearly half of suboptimal use is not captured by current ASP practices.

Reductions in Parent Interest in Receiving Antibiotics following a 90-Second Video Intervention in Outpatient Pediatric Clinics.

OBJECTIVES: To assess the impact of a 90-second animated video on parents' interest in receiving an antibiotic for their child. STUDY DESIGN: This pre-post test study enrolled English and Spanish speaking parents (n = 1051) of children ages 1-5 years presenting with acute respiratory tract infection symptoms. Before meeting with their provider, parents rated their interest in receiving an antibiotic for their child, answered 6 true/false antibiotic knowledge questions, viewed the video, and then rated their antibiotic interest again. Parents rated their interest in receiving an antibiotic using a visual analogue scale ranging from 0 to 100, with 0 being "I definitely do not want an antibiotic," 50 "Neutral," and 100 "I absolutely want an antibiotic." RESULTS: Parents were 84% female, with a mean age of 32 ± 6.0, 26.0% had a high school education or less, 15% were black, and 19% were Hispanic. After watching the video, parents' average antibiotic interest ratings decreased by 10 points (mean, 57.0 ± 20 to M ± 21; P < .0001). Among parents with the highest initial antibiotic interest ratings (≥60), even greater decreases were observed (83.0 ± 12.0 to 63.4 ± 22; P < .0001) with more than one-half (52%) rating their interest in the low or neutral ranges after watching the video. CONCLUSIONS: A 90-second video can decrease parents' interest in receiving antibiotics, especially among those with higher baseline interest. This scalable intervention could be used in a variety of settings to reduce parents' interest in receiving antibiotics. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03037112.

The Infectious Diseases Society of America's 10 × '20 Initiative (10 New Systemic Antibacterial Agents US Food and Drug Administration Approved by 2020): Is 20 × '20 a Possibility?

BACKGROUND: Infections caused by antibiotic-resistant bacteria, including carbapenem-resistant Enterobacteriaceae, have increased in frequency, resulting in significant patient morbidity and mortality. The Infectious Diseases Society of America continues to propose legislative, regulatory, and funding solutions to address this escalating crisis. This report updates the status of development and approval of systemic antibiotics in the United States as of late 2018. METHODS: We performed a review of the published literature and on-line clinical trials registry at www.clinicaltrials.gov to identify new systemically acting orally and/or intravenously administered antibiotic drug candidates in the development pipeline, as well as agents approved by the US Food and Drug Administration since 2012. RESULTS: Since our 2013 pipeline status report, the number of new antibiotics annually approved for marketing in the United States has reversed its previous decline, likely influenced by new financial incentives and increased regulatory flexibility. Although our survey demonstrates progress in development of new antibacterial drugs that target infections caused by resistant bacterial pathogens, the majority of recently approved agents have been modifications of existing chemical classes of antibiotics, rather than new chemical classes. Furthermore, larger pharmaceutical companies continue to abandon the field, and smaller companies face financial difficulties as a consequence. CONCLUSIONS: Unfortunately, if 20 × '20 is achieved due to efforts embarked upon in decades past, it could mark the apex of antibiotic drug development for years to come. Without increased regulatory, governmental, industry, and scientific support and collaboration, durable solutions to the clinical, regulatory, and economic problems posed by bacterial multidrug resistance will not be found.

Can a Septic Hip Decision Rule Aid in the Evaluation of Suspected Pediatric Musculoskeletal Infections?

BACKGROUND: Musculoskeletal (MSK) infections can be difficult to diagnose in acute care settings. The utility of clinical decision tools for pediatric MSK infections in an emergency department has not been well studied. OBJECTIVE: Our aim was to evaluate the performance of a septic hip clinical decision rule (CDR) in the evaluation of pediatric musculoskeletal infections. METHODS: We performed a retrospective study of children evaluated for an MSK infection in our emergency department from 2014 to 2016. Data collection included demographics, discharge diagnoses, and clinical/laboratory predictors from the CDR. A χ2 analysis and Wilcoxon rank-sum tests compared patients with and without MSK infections. Logistic regression analysis examined the predictors for MSK infections. A receiver operating characteristic (ROC) curve was calculated to evaluate the performance of the predictors. RESULTS: Of 996 evaluations included in the final analysis, 109 (10.9%) had MSK infections. In a multivariable model, an adjusted odds ratio (OR) was significant for fever (OR 3.9, 95% confidence interval [CI] 2.4-6.4), refusal to bear weight/pseudoparalysis (OR 4.4, 95% CI 2.7-7.1), and C-reactive protein (CRP) > 2.0 mg/dL (OR 5.4, 95% CI 3.2-9.1). The probability of infection was 75.1% with five predictors present, 1.9% for zero predictors, and 5.1% if one predictor was present. An ROC curve showed an area under the curve of 0.82, indicating moderate accuracy. CONCLUSIONS: A septic hip CDR demonstrates a low predicted probability of an MSK infection with zero or one clinical predictor present and moderate predictability with all five predictors. Fever, refusal to bear weight/pseudoparalysis, and CRP > 2.0 mg/dL performed best and should alert providers to consider other MSK infections in addition to septic arthritis.

Experience With a Care Process Model in the Evaluation of Pediatric Musculoskeletal Infections in a Pediatric Emergency Department.

OBJECTIVES: Care process models (CPMs) for certain conditions have improved clinical outcomes in children. This study describes the implementation and impact of a CPM for the evaluation of musculoskeletal infections in a pediatric emergency department (ED). METHODS: A retrospective pre-post intervention study was performed to analyze the impact of a musculoskeletal infection CPM. Patients were identified retrospectively through electronic order history for imaging of an extremity or joint and recommended laboratory tests. Clinical outcomes evaluated included hospital length of stay (LOS), time to magnetic resonance imaging (MRI), time to administration of antibiotics, hospital admission rate, and 30-day readmission rate. RESULTS: Musculoskeletal infection evaluations completed in the ED were reviewed from 1 year before implementation (n = 383) and 2 years after implementation (n = 1219) of the CPM. A significant improvement in the time to antibiotic administration for all patients (4.3 vs 3.7 hours, P < 0.05) and for patients with confirmed musculoskeletal infections (9.5 vs 4.9 hours, P < 0.05) was observed after the implementation of the CPM. The overall time to MRI (13.2 vs 10.3 hours, P = 0.29) and hospital LOS (4.7 vs 3.7 days, P = 0.11) were improved for all patients but were not statistically significant. The admission rate and 30-day readmission were similar before and after the implementation of the CPM. CONCLUSIONS: The implementation of a musculoskeletal infection CPM has standardized the approach to the evaluation and diagnosis of musculoskeletal infections resulting in a significant decrease in the time to administer antibiotics and a downward trend in time to MRI and hospital LOS.

Essential Resources and Strategies for Antibiotic Stewardship Programs in the Acute Care Setting.

Background: Antibiotic stewardship programs improve clinical outcomes and patient safety and help combat antibiotic resistance. Specific guidance on resources needed to structure stewardship programs is lacking. This manuscript describes results of a survey of US stewardship programs and resultant recommendations regarding potential staffing structures in the acute care setting. Methods: A cross-sectional survey of members of 3 infectious diseases subspecialty societies actively involved in antibiotic stewardship was conducted. Survey responses were analyzed with descriptive statistics. Logistic regression models were used to investigate the relationship between stewardship program staffing levels and self-reported effectiveness and to determine which strategies mediate effectiveness. Results: Two-hundred forty-four respondents from a variety of acute care settings completed the survey. Prior authorization for select antibiotics, antibiotic reviews with prospective audit and feedback, and guideline development were common strategies. Eighty-five percent of surveyed programs demonstrated effectiveness in at least 1 outcome in the prior 2 years. Each 0.50 increase in pharmacist and physician full-time equivalent (FTE) support predicted a 1.48-fold increase in the odds of demonstrating effectiveness. The effect was mediated by the ability to perform prospective audit and feedback. Most programs noted significant barriers to success. Conclusions: Based on our survey's results, we propose an FTE-to-bed ratio that can be used as a starting point to guide discussions regarding necessary resources for antibiotic stewardship programs with executive leadership. Prospective audit and feedback should be the cornerstone of stewardship programs, and both physician leadership and pharmacists with expertise in stewardship are crucial for success.

Variability in Antibiotic Use Across PICUs.

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

Antimicrobial Stewardship in Neonates: Challenges and Opportunities.

Neonatal infections result in significant morbidity and mortality. Antibiotics are vital for the treatment of infections but disrupt the neonatal microbiome, put the infant at risk for an adverse drug reaction, and may lead to the development of antibiotic resistance. Immediately after birth, clinicians must determine which infants require empiric antibiotics. Online risk stratification tools may provide a superior approach to decision trees. In infants who require empiric therapy for early-onset sepsis, ampicillin and an aminoglycoside with dosing based on recent pharmacokinetic studies represents the most appropriate first-line agents; third-generation cephalosporins should be reserved for patients with a high likelihood of Gram-negative meningitis. An antistaphylococcal penicillin and gentamicin should be utilized for suspected late-onset sepsis. Vancomycin and other broad-spectrum agents are reserved for patients with a history of resistant organisms. Antibiotic duration should be guided by understanding the clinical indications and obtaining the necessary cultures appropriately (i.e., adequate volume blood cultures). In the absence of a positive culture, antibiotic duration should often be limited. Individual institutions should leverage a multidisciplinary, interprofessional team to identify opportunities for antimicrobial stewardship. A collaborative, transparent system is required to change unit culture and generate a sustained impact on antibiotic utilization with optimal patient outcomes.