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).

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.

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.

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.

A Payer Perspective of the Costs of Urinary Tract and Skin and Soft Tissue Infections in Adults with Diabetes and the Relationship to Oral Antidiabetic Medication Nonadherence.

BACKGROUND: Controlling costs and improving quality outcomes are important considerations of the triple aim in health care. Medication adherence to oral antidiabetic (OAD) medications is an outcome measure for those with diabetes. However, there is little research reporting the costs associated with OAD medication adherence among adults with diabetes and comorbid infections. OBJECTIVE: To provide nationally representative cost and utilization estimates from a payer perspective of 2 common comorbid infections: urinary tract infection (UTI) and skin and soft tissue infection (SSTI) among adults with diabetes in relation to OAD medication nonadherence to quantify cost per outcome. METHODS: A retrospective observational study for years 2010-2015 used longitudinal panel data in the public domain from the Medical Expenditure Panel Survey (MEPS). The study included individuals aged ≥ 18 years with diabetes (excluding gestational diabetes) who were prescribed OAD medications and then stratified by infection status, that is, without infection versus with UTI and/or SSTI. Outcomes measured included medication adherence, defined as medication possession ratio (MPR); treated prevalence of UTI and SSTI; and associated direct medical costs paid by insurers. RESULTS: 4,633 adults with diabetes were included; of those, 12% reported a UTI or SSTI, with the weighted sample representing 2.2 million U.S. residents. The mean MPR was 0.61 and 0.63 in the infection and noninfection groups, respectively. Less than 35% in each group were adherent to OAD medications. Having a UTI or SSTI increased the adjusted total health expenses by 53.7% (P < 0.001), but adherence to OAD medications did not significantly affect total health care costs. CONCLUSIONS: In adults with diabetes, a UTI or SSTI diagnosis did not influence medication adherence to OAD medication but increased health care utilization and costs significantly. DISCLOSURES: This study was supported by the Virginia Commonwealth University Presidential Research Quest Fund (PeRQ Fund). The authors have no financial conflicts of interest to disclose.

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].

The impact of formulary restriction on the relative consumption of carbapenems in intensive care units at an academic medical center.

Antipseudomonal carbapenems are an important target for antimicrobial stewardship programs. We evaluated the impact of formulary restriction and preauthorization on relative carbapenem use for medical and surgical intensive care units at a large, urban academic medical center using interrupted time-series analysis.

Adequacy of empiric gram-negative coverage for septic patients at an academic medical center.

BACKGROUND: Gram-negative organisms (GNOs) have increasing resistance rates to levofloxacin at Virginia Commonwealth University Health System (VCUHS), where levofloxacin is the most common agent added to provide double coverage of gram-negative infections. The goal of this study was to determine the adequacy of empiric gram-negative coverage for septic patients at our institution. METHODS: A retrospective review of patients admitted to VCUHS, from January 1, 2014, to December 31, 2014, with a diagnosis of sepsis, severe sepsis, or septic shock and documented infection, was performed to determine the adequacy of various empiric antibiotic combinations. RESULTS: Of 219 patients who met the inclusion criteria, 56% of patients received monotherapy and 21% of patients received combination therapy (2 antibiotics) covering GNOs. GNOs (84%) were susceptible to piperacillin-tazobactam. When used in combination with cefepime and meropenem, levofloxacin did not increase coverage. However, levofloxacin provided an 8% increase in coverage and gentamicin provided an additional 13% increase in coverage, respectively, when used in combination with piperacillin-tazobactam. CONCLUSIONS: Among septic patients at VCUHS, gentamicin provided increased gram-negative coverage when compared with levofloxacin. Although susceptibility to piperacillin-tazobactam alone was relatively low, the combination of piperacillin-tazobactam and gentamicin provided nearly equivalent coverage to meropenem and gentamicin.

The effectiveness of formulary restriction and preauthorization at an academic medical center.

The impact of formulary restriction and preauthorization (FRPA) on prescribing trends was examined over a 5-year period at an academic medical center. Ordinary least squares regression was used to identify hospital units demonstrating statistically significant trends in prescription of restricted agents. Significant decreases in restricted drug use were seen on 2 of 7 medicine units subject to FRPA, whereas a significant increase was seen in 1 of 4 surgical units subject to FRPA.

Effect of carbapenem restriction on prescribing trends for immunocompromised wards at an academic medical center.

The recently described proportion of carbapenem consumption metric was used to assess the effectiveness of formulary restriction for carbapenems for 2 units housing predominantly immunocompromised patients at a large academic medical center. Interrupted time series analysis revealed a significant decrease in meropenem use for hematology-oncology and bone marrow transplant units after restriction.

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.

Knowledge, attitudes, and practices of bedside nursing staff regarding antibiotic stewardship: A cross-sectional study.

BACKGROUND: Nursing engagement in antibiotic stewardship programs (ASPs) remains suboptimal. The purpose of this study was to determine the knowledge, attitudes, and practices of nursing staff members regarding ASPs and identify barriers to their participation in such programs. METHODS: This cross-sectional study was conducted at Virginia Commonwealth University Health System, an 860-bed tertiary care academic center located in Richmond, Virginia, where a well-resourced ASP has been in place for 2 decades. A survey consisting of 12 questions was administered to nursing staff via REDCap (Research Electronic Data Capture) in February 2018. RESULTS: A total of 159 survey responses were included in the study. The results demonstrated gaps in knowledge regarding antibiotic stewardship (AS) and highlighted the importance of improving communication between nurses and ASPs. Overall, 102 (64.15%) of the study participants indicated familiarity with AS. Time constraints and concerns over physician pushback were identified as major barriers to participation. CONCLUSIONS: Many nurses were unaware of our center's ASP. Nurses identified activities falling within their daily workflow as potential areas for contribution to ASPs. Key barriers to participation were also identified. These data will inform efforts to engage nursing in AS activities at our medical center.

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.