A Multicenter Analysis of Changes in Pediatric Antibiotic Susceptibilities Among Staphylococcus aureus and Pseudomonas aeruginosa Isolates: 2014-2018.

OBJECTIVE: To describe antibiotic susceptibilities for Staphylococcus aureus and Pseudomonas aeruginosa among pediatric institutions in 2018. To assess correlations between antibiotic utilization and susceptibilities. METHODS: Institutional antibiograms from 2018 were compiled among 13 institutions via a survey. Resistant pathogens and antibiotic days of therapy/1000 patient days (PD) were collected from 6 institutions over 5 years. Correlations were assessed as pooled data among all institutions and relative changes within individual institutions. RESULTS: All 8552 S aureus isolates in 2018 were vancomycin susceptible and 40.1% were methicillin resistant (MRSA). Among MRSA, 96.3% and 78.8% were susceptible to trimethoprim/sulfamethoxazole and clindamycin, respectively. Pooled yearly MRSA/1000 PD decreased from 2014-2018 and correlated with pooled yearly decreases in vancomycin utilization (R = 0.983, p = 0.003). Institutional relative decreases in vancomycin utilization from 2014-2018 did not correlate with institutional relative decreases in MRSA susceptibility (R = -0.659, p = 0.16). Susceptibility to meropenem was 90.9% among 2315 P aeruginosa isolates in 2018. Antipseudomonal beta-lactam susceptibility ranged from 89.4% to 92.3%. Pooled yearly meropenem-resistant P aeruginosa/1000 PD and meropenem utilization did not significantly decrease over time or correlate (both p > 0.6). Institutional relative change in meropenem utilization from 2013-2017 correlated with the institutional relative change in P aeruginosa susceptibility to meropenem from 2014-2018 (Rs = -0.89, p = 0.019). CONCLUSIONS: Among included institutions, the burden of MRSA decreased over time. Institutional MRSA prevalence did not consistently correlate with institutional vancomycin utilization. Institutional changes in meropenem utilization correlated with P aeruginosa susceptibility the following year. Pooled analyses did not illustrate this correlation, likely owing to variability in utilization between institutions.

Changes in Metronidazole and Vancomycin Utilization for Nonsevere Clostridioides difficile Infection Among Institutions Caring for Children.

Clostridioides difficile infection guidelines were published in final format on April 1, 2018. Among 4962 and 3545 C. difficile infection cases in children the year before and after publication, oral metronidazole use decreased from 63.0% to 44.3% (P < 0.001) and oral vancomycin use increased from 27.3% to 47.7% (P < 0.001). Quarterly metronidazole utilization decreased postguidelines among 117 institutions, incidence rate ratios 0.86 (95% confidence intervals: 0.78-0.96).

Leapfrog Hospital Safety Score, Magnet Designation, and Healthcare-Associated Infections in United States Hospitals.

OBJECTIVE: Healthcare-associated infections (HAIs) pose a challenge to patient safety. Although studies have explored individual level, few have focused on organizational factors such as a hospital's safety infrastructure (indicated by Leapfrog Hospital Safety Score) or workplace quality (Magnet recognition). The aim of the study was to determine whether Magnet and hospitals with better Leapfrog Hospital Safety Scores have fewer HAIs. METHODS: Ordered probit regression analyses tested associations between Safety Score, Magnet status, and standardized infection ratios, depicting whether a hospital had a Clostridium difficile infection (CDI) and methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection standardized infection ratio that was "better," "no different," or "worse" than a National Benchmark as per Centers for Disease Control and Prevention's National Healthcare Safety Network definitions. RESULTS: Accounting for confounders, relative to "A" hospitals, "B" and "C" hospitals had significant and negative relationships with CDI (-0.16, P < 0.01, and -0.14, P < 0.05, respectively) but not MRSA bacteremia. Magnet hospitals had a significant and positive relationship with MRSA bloodstream infections (0.74, P < 0.001) but a significant negative relationship with CDI (-0.21, P < 0.01) compared with non-Magnet. CONCLUSIONS: A hospitals performed better on CDI but not MRSA bloodstream infections. In contrast, Magnet designation was associated with fewer than expected MRSA infections but more than expected CDIs. These mixed results indicate that hospital global assessments of safety and workplace quality differentially and imperfectly predict its level of HAIs, suggesting the need for more precise organizational measures of safety and more nuanced approaches to infection prevention and reduction.

Impact of the Centers for Medicare and Medicaid Services Sepsis Core Measure on Antibiotic Use.

BACKGROUND: The Centers for Medicare and Medicaid Services (CMS) implemented a core measure sepsis (SEP-1) bundle in 2015. One element was initiation of broad-spectrum antibiotics within 3 hours of diagnosis. The policy has the potential to increase antibiotic use and Clostridioides difficile infection (CDI). We evaluated the impact of SEP-1 implementation on broad-spectrum antibiotic use and CDI occurrence rates. METHODS: Monthly adult antibiotic data for 4 antibiotic categories (surgical prophylaxis, broad-spectrum for community-acquired infections, broad-spectrum for hospital-onset/multidrug-resistant [MDR] organisms, and anti-methicillin-resistant Staphylococcus aureus [MRSA]) from 111 hospitals participating in the Clinical Data Base Resource Manager were evaluated in periods before (October 2014-September 2015) and after (October 2015-June 2017) policy implementation. Interrupted time series analyses, using negative binomial regression, evaluated changes in antibiotic category use and CDI rates. RESULTS: At the hospital level, there was an immediate increase in the level of broad-spectrum agents for hospital-onset/MDR organisms (+2.3%, P = .0375) as well as a long-term increase in trend (+0.4% per month, P = .0273). There was also an immediate increase in level of overall antibiotic use (+1.4%, P = .0293). CDI rates unexpectedly decreased at the time of SEP-1 implementation. When analyses were limited to patients with sepsis, there was a significant level increase in use of all antibiotic categories at the time of SEP-1 implementation. CONCLUSIONS: SEP-1 implementation was associated with immediate and long-term increases in broad-spectrum hospital-onset/MDR organism antibiotics. Antimicrobial stewardship programs should evaluate sepsis treatment for opportunities to de-escalate broad therapy as indicated.

Economic burden of pediatric prescription opioid poisonings in the United States.

BACKGROUND: Among the different drugs involved in pediatric exposures and poisonings, opioids are the most important, given their rise in nonmedical use. Opioid poisonings in children can result in serious symptoms or complications, including respiratory disorders such as apnea, respiratory failure, and respiratory depression; psychiatric or nervous system disorders such as agitation, seizures, and coma; and cardiac disorders such as tachycardia, bradycardia, and cardiac arrest. Opioid poisonings in children can have delayed onset of symptoms as well as severe and prolonged toxic effects. Many studies have examined the economic burden of opioid poisoning in the general population, but very little is known about the pediatric population. OBJECTIVE: To estimate the economic burden associated with pediatric prescription opioid poisonings. METHODS: This study examined opioid poisonings in pediatric patients, defined as patients aged less than 18 years, for the 2012 base year. Costs were estimated using the 2012 Nationwide Emergency Department Sample (NEDS), Kids' Inpatient Database (KID), Multiple Cause-of-Death (MCOD) file, and other published sources, while applying a societal perspective. The Bottom Up approach was used to estimate the total cost of pediatric prescription opioid poisonings. Direct costs included costs associated with emergency department (ED) visits, hospitalizations, and ambulance transports. Indirect costs were estimated using the human capital method and included productivity costs due to caregivers' absenteeism and premature mortality among children. Descriptive statistics were employed in calculating costs. RESULTS: The total costs of pediatric prescription opioid poisonings and exposure in the United States were $230.8 million in 2012. Total direct costs were estimated to be over $21.1 million, the majority resulting from prescription opioid poisoning-related inpatient stays. Total indirect (productivity) costs were calculated at $209.7 million, and 98.6% of these costs were attributed to opioid poisoning-related mortality. Pediatric prescription opioid poisoning-related ED visits, inpatient stays, and deaths were most common in patients aged 13-17 years and those in mid to large urban areas. Most were unintentional. CONCLUSIONS: Pediatric prescription opioid poisonings resulted in direct and indirect costs of $230.8 million in 2012. While these costs are low in comparison with the costs of prescription opioid poisoning in the general population, the number of pediatric poisonings represents only a small fraction of total poisonings. Quantified costs associated with pediatric prescription opioid poisonings can help decision makers to understand the economic trade-offs in planning interventions. DISCLOSURES: This research had no external funding but was funded by an unrestricted research grant made to the Department of Pharmacotherapy & Outcomes Science by kaléo Pharma, maker of a naloxone product. The authors declare no conflicts of interest or financial interests. Portions of this study were presented as an abstract at the 22nd Annual ISPOR Meeting; May 22, 2017; Boston, MA.

Educational Outcomes Resulting From Restructuring a Scholarship Course for Doctor of Pharmacy Students.

Objective. To compare educational outcomes between two iterations of a scholarship and research course for Doctor of Pharmacy (PharmD) students at Virginia Commonwealth University's School of Pharmacy. Methods. The first iteration of a course intended to teach pharmacy students the knowledge and skills necessary to design and conduct research involved lectures and application exercises, including limited guided questions about different aspects of the research process. In the fall of 2015, multiple structured activities and accompanying grading rubrics, each designed around the structure and content of a section of a research proposal, were introduced to the course to supplement lectures. Both iterations of the course culminated with students submitting a research proposal. After establishing interrater reliability, faculty members graded a random sample of 20 research proposals, 10 from each version of the course, and section-specific and overall proposal scores were compared. Results. In the proposals submitted after the course revisions, significant improvements in three areas were identified: the overall score, the section-specific scores for research hypothesis/specific aims, and institutional review board (IRB) discussion/informed consent. Nominal, though not statistically significant, improvements were observed in other sections. Conclusion. Additional research is needed regarding the best instructional strategies to reinforce data analysis and statistical testing knowledge and skills in PharmD students. Overall, our findings support the hypothesis that a more formalized, guided approach for teaching research methods improves learning outcomes for PharmD students.

Association between meeting core elements for inpatient antimicrobial stewardship and antibiotic utilization.

We used multivariable analyses to assess whether meeting core elements was associated with antibiotic utilization. Compliance with 7 elements versus not doing so was associated with higher use of broad-spectrum agents for community-acquired infections [days of therapy per 1,000 patient days: 155 (39) vs 133 (29), P = .02] and anti-methicillin-resistant S. aureus agents [days of therapy per 1,000 patient days: 145 (37) vs 124 (30), P = .03].

Prevalence and Characteristics of Pediatric Opioid Exposures and Poisonings in the United States.

OBJECTIVE: To examine the prevalence and characteristics of pediatric opioid exposures and poisonings in the US. STUDY DESIGN: This was a retrospective, cross-sectional analysis using the National Poison Data System from January 1, 2010 to December 31, 2014. Records of children aged <18 years with exposure to opioid-containing medications were identified. Standardized prevalence rates were calculated, and the annual trend was examined. Pediatric opioid exposures were characterized descriptively, and logistic regression was performed to estimate the association between various clinical and sociodemographic characteristics and exposures with serious (ie, moderate, major, or death) outcomes. The association of pediatric opioid exposures and area-level socioeconomic status factors at 5-digit ZIP code level was examined descriptively. RESULTS: The prevalence of opioid exposures was 22.6 per 100 000 children and was particularly high among ≤5-year-olds. Prevalence declined from 25.5 to 20 per 100 000 children from 2010 to 2014. There were 83 418 pediatric opioid exposures over the 5-year period and nearly one-half resulted in poisoning. Over 60% of exposures were among children ≤5 years of age, 73.4% were unintentional, and over 90% occurred at home. One in every 2 pediatric opioid exposures was evaluated in a healthcare facility. Annually 4912 children aged ≤5 years were treated in the emergency department or admitted for care. Older age, nonaccidental intent, and single-substance opioid, especially buprenorphine and methadone, were associated with serious outcomes (P < .05). Positive correlations were observed for area-level socioeconomic status factors including proportion of adults and pediatric opioid exposures. CONCLUSIONS: Pediatric opioid exposures and poisonings decreased from 2010 to 2014 but morbidity remains high. The epidemiology of opioid exposures differed considerably by age.

High-risk medication use for Clostridium difficile infection among hospitalized patients with cancer.

Patients with cancer are vulnerable to Clostridium difficile infection (CDI); hospitals with larger oncology populations may have worse CDI performance. Among 71 academic hospitals studied, there were significant differences in oncology patient-days per 1,000 admissions across CDI standardized infection ratio categories of better, no different, and worse; worse hospitals had the greatest number of patient-days. Oncology patients' most commonly used high-risk CDI medications were quinolones, third- and fourth-generation cephalosporins, and proton pump inhibitors.

Learning Activities to Build Population Health Management Skills for Pharmacy Students.

Objective. To describe the implementation and evaluation of population health management learning activities in a second-year Doctor of Pharmacy (PharmD) course. Methods. Population health learning sessions were implemented in a step-wise manner: population needs assessment activity to identify priority programs for implementation given a specific patient population; didactic materials to introduce program evaluation foundational knowledge; program evaluation design activity to evaluate implemented programs using the Centers for Disease Control and Prevention's Program Evaluation Framework; and evaluation of program outcome data. Students' self-rated abilities (grouped into Bloom's Taxonomy classifications) and perceptions before and after program evaluation activities were assessed. Qualitative analyses evaluated student feedback on learning sessions. Results. Students' self-rated abilities for all Bloom's classifications increased after the learning sessions. Student perceptions on importance of program evaluation also improved (from 71% reporting "agree" or "strongly agree" pre-activities to 79% post-activities). Students found the application to case scenarios and the opportunity to integrate each component of program evaluation into a complete process useful. Conclusion. Step-wise population health management learning sessions were implemented, culminating in skill-based program evaluation activities. The activities improved students' self-rated abilities and perceptions regarding program evaluation. Areas for improvement for the learning sessions were also identified and will inform future instructional design.

Variability in antifungal utilization among neonatal, pediatric, and adult inpatients in academic medical centers throughout the United States of America.

BACKGROUND: Identification of factors associated with antifungal utilization in neonatal, pediatric, and adult patient groups is needed to guide antifungal stewardship initiatives in academic medical centers. METHODS: For this hospital-level analysis, we analyzed antifungal use in hospitals across the United States of America, excluding centers only providing care for hematology/oncology patients. Analysis of variance was used to compare antifungal use between patient groups. Three multivariable linear regression models were used to determine independent factors associated with antifungal use in the neonatal, pediatric, and adult patient groups. RESULTS: For the neonatal, pediatric, and adult patient groups, 54, 44, and 60 hospitals were included, respectively. Total antifungal use was significantly lower in the neonatal patient group (14 days of therapy (DOT)/1000 patient days (PDs) versus 76 in pediatrics and 74 in adults, p < 0.05). There were no significant associations identified with total antifungal DOT/1000 PDs in the neonatal patient group (model R2 = 0.11). In the pediatric patient group (model R2 = 0.55), admission to immunosuppressed service lines and total broad-spectrum antibiotic use were positively associated with total antifungal use (coefficients of 1.95 and 0.41, both p < 0.05). In the adult patient group (model R2 = 0.79), admission to immunosuppressed service lines, total invasive fungal infections, and total broad-spectrum antibiotic use were positively associated with total antifungal use (coefficients of 5.08, 5.17, and 0.137, all p < 0.05). CONCLUSIONS: Variability in antifungal use in the neonatal group could not be explained well, whereas factors were associated with antifungal use in the adult and pediatric patient groups. These data can help guide antifungal stewardship initiatives.

Pediatric Antimicrobial Stewardship: State of the Art.

PURPOSE OF REVIEW: We aim to systematically review the literature on the effectiveness of pediatric antimicrobial stewardship programs (ASPs) and antimicrobial stewardship (AS) strategies in the United States (US) inpatient setting. Furthermore, we review current gaps and challenges for unique pediatric populations and those in ambulatory settings. RECENT FINDINGS: Misuse and overuse of antimicrobials have been identified as key factors for antimicrobial resistance (AR). Multiple professional organizations support the implementation of hospital-based ASPs to decrease antimicrobial consumption, improve patient outcomes, and reduce healthcare costs. There is limited data on the effectiveness of inpatient pediatric ASPs and AS strategies in unique populations. Furthermore, there is a paucity of evidence on ASPs in ambulatory settings. This review contributes to the growing body of evidence that supports the use of pediatric ASPs to optimize antimicrobial therapy in the inpatient setting as well as in unique patient populations and ambulatory settings. Active stewardship is critical and antimicrobial consumption is a key outcome metric for programs.

Performance of a Novel Antipseudomonal Antibiotic Consumption Metric Among Academic Medical Centers in the United States.

A metric was developed to identify hospital proportion of carbapenem consumption (PoCC) among antipseudomonal antibiotics. The PoCC varied significantly among academic medical centers by Census Bureau geographic division after adjusting for patient mix. This metric may be useful in identifying disproportionate carbapenem use and potential carbapenem overuse. Infect Control Hosp Epidemiol 2018;39:229-232.

Treatment of Vancomycin-Resistant Enterococci: Focus on Daptomycin.

PURPOSE OF REVIEW: Vancomycin-resistant Enterococci (VRE) infections are problematic due to limited availability of anti-VRE agents and their potential for adverse effects and drug interactions. This review focuses on the role of daptomycin in treating VRE infections by summarizing key points of relevant clinical studies. RECENT FINDINGS: Higher doses of daptomycin (≥ 6 mg/kg), as compared to standard doses, were found to be safe in terms of creatinine phosphokinase elevation and associated with successful infection outcomes and microbiological clearance. High doses are especially important in treatment of infections involving elevated daptomycin minimum inhibitory concentration (MIC) values (3-4 µg/mL). Daptomycin, especially in higher doses, has been shown to be an effective and safe VRE agent for a variety of serious infection types, such as catheter-associated bloodstream and intra-abdominal infections, and for different populations including oncology. Infections involving higher daptomycin MIC values were associated with previous daptomycin use and prosthetic devices.

Associations between antimicrobial stewardship program elements and Clostridium difficile infection performance.

Hospitals are categorized as better, no different, or worse at a national level based on their Clostridium difficile infection performance. Institutional antimicrobial stewardship programs seek to decrease the occurrence of C difficile by implementing strategies to address antibiotic usage; however, optimal structure and strategies for accomplishing this remain largely unknown. We found that a higher proportion of hospitals with either a worse or no different rank used a postprescription audit and feedback strategy than hospitals with a better rank.

Identifying Hospital Antimicrobial Resistance Targets via Robust Ranking.

We develop a robust ranking procedure to uncover trends in variation in antibiotic resistance (AR) rates across hospitals for some antibiotic-bacterium pairs over several years. We illustrate how the method can be used to detect potentially dangerous trends and to direct attention to hospitals' management practices. A robust method is indicated due to the fact that some unusual reported resistance rates may be due to measurement protocol differences and not any real difference in AR rates. Our proposed method is less sensitive to outlier observations than other robust methods. The application on real AR data shows how a dangerous trend in a particular AR rate would be detected. Our results indicate the potential benefits of systematic AR rate collection and AR reporting systems across hospitals.

Virtual Pediatric Patient Activities With Randomized Scenarios as an Instructional Tool for Pharmacy Students.

OBJECTIVES: To assess student pharmacist best activity scores and related exam question performance based on the number of pediatric virtual patient activity (VPA) attempts. METHODS: A 40-point asthma VPA was implemented and included three possible randomized scenarios. A 60-point meningitis VPA was implemented and included three possible randomized scenarios followed by an additional three possible randomized scenarios only if the first scenario was correctly completed. Points were awarded in the VPA based on appropriateness of treatment decisions. Students were allowed unlimited VPA attempts individually and as a group in class. Three exam questions were based on a fourth scenario of each randomized portion of the VPAs. The Kruskal-Wallis test, Mann-Whitney U test, and T-test were used for statistical comparisons when appropriate. RESULTS: Of 132 students, median individual best asthma VPA scores were 15.25, 22, and 30 for those with 1, 2, and ≥3 asthma attempts, respectively (p < 0.001). Median individual best meningitis VPA scores were 4, 5, 7, and 45.5 for those with 1, 2, 3 to 4, and ≥5 attempts, respectively (p < 0.001). Median number of group VPA attempts was higher among students who correctly answered the exam question related to the first randomized meningitis scenario (10 versus 4, p = 0.015), although no differences in attempts were found for the other related questions (all p > 0.05). CONCLUSIONS: Students who completed the VPAs more times achieved greater individual best scores. Students who correctly answered related exam questions had a higher number of group VPA attempts only when continuation of the VPA required correct randomized scenario completion.

Antimicrobial Stewardship Program Members' Perspectives on Program Goals and National Metrics.

PURPOSE: This study compares antimicrobial stewardship program (ASP)-stated goals and outcomes collected as well as opinions regarding national metric establishment. METHODS: Twenty-one ASP members underwent telephone interviews answering open-ended questions about ASP goals, outcomes collected, and opinions about national metrics. Content analysis was used to code responses into predefined ASP-metric categories. FINDINGS: The most common ASP goal was antimicrobial appropriateness (76%), outcomes tracked were use and microbial outcomes (both 71%), and desired national metric was use (67%). IMPLICATIONS: Stated-goals, outcomes tracked, and opinions regarding national metric establishment did not fully align. With ASP-related regulations looming, it is important that alignment is increased.