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.

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.

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.

An evaluation of the association between an antimicrobial stewardship score and antimicrobial usage.

OBJECTIVES: To determine whether an antimicrobial stewardship 'intensity' score predicts hospital antimicrobial usage. METHODS: An antimicrobial stewardship score for 44 academic medical centres was developed that comprised two main categories: resources (antimicrobial stewardship programme personnel and automated surveillance software) and strategies (preauthorization, audit with intervention and feedback, education, guidelines and clinical pathways, parenteral to oral therapy programmes, de-escalation of therapy, antimicrobial order forms and dose optimization). Multiple regression analyses were used to assess whether the composite score and also the categories were associated with either total or antimicrobial stewardship programme-target antimicrobial use as measured in days of therapy. RESULTS: The mean antimicrobial stewardship programme score was 55 (SD 21); the total composite score was not significantly associated with total or target antimicrobial use [estimate -0.49 (95% CI -2.30 to 0.89)], while the category strategies was significantly and negatively associated with target antimicrobial use [-5.91 (95% CI -9.51 to -2.31)]. CONCLUSIONS: The strategy component of a score developed to measure the intensity of antimicrobial stewardship was associated with the amount of antimicrobials used. Thus, the number and types of strategies employed by antimicrobial stewardship programmes may be of particular importance in programme effectiveness.

Medication risk factors associated with healthcare-associated Clostridium difficile infection: a multilevel model case-control study among 64 US academic medical centres.

OBJECTIVES: The main objective of this study was to determine patient- and hospital-level medication risk factors associated with Clostridium difficile infection (CDI) occurrence among patients clustered within hospitals using a multilevel model. METHODS: Patients with healthcare-associated (HA)-CDI were identified from among 64 academic medical centres in 2009. A frequency match was conducted; for each case, up to two controls were selected, matched on similar pre-infection length of stay and clinical service line. Patient- and hospital-level medication use, including antibacterial and gastric acid-suppressant agents, was assessed using a two-level logistic regression model. RESULTS: A total of 5967 CDI cases and 8167 controls were included in the analysis. The odds of acquiring HA-CDI increased with the following medications [OR (95% CI)]: anti-methicillin-resistant Staphylococcus aureus agents [1.38 (1.22-1.56)]; third- or fourth-generation cephalosporins [1.75 (1.62-1.89)]; carbapenems [1.60 (1.44-1.79)]; ß-lactam/ß-lactamase inhibitor combinations [1.49 (1.36-1.64)]; vancomycin [1.73 (1.57-1.89)]; and proton pump inhibitors [1.43 (1.30-1.57)]. The odds of acquiring HA-CDI decreased with the following medications: clindamycin [0.74 (0.63-0.87)]; and macrolides [0.88 (0.77-0.99)]. Controlling for patient-level covariates, no hospital-level medication covariates that we analysed had statistically significant effects on HA-CDI. The odds of acquiring HA-CDI increased with the hospital proportion of patients aged ≥ 65 years [1.01 (1.00-1.02)]. CONCLUSIONS: We found several medications that were associated with the risk of patients developing HA-CDI, including ß-lactam/ß-lactamase inhibitor combinations, third- or fourth-generation cephalosporins, carbapenems, vancomycin, proton pump inhibitors and anti-methicillin-resistant S. aureus agents. There were no medication effects significant at the hospital level.

Statin use and the risk of Clostridium difficile in academic medical centres.

OBJECTIVES: To estimate the possible relationship between statin use and the risk of healthcare facility onset Clostridium difficile. METHODS: Patients over 18 years of age admitted to hospitals contributing data to the University HealthSystem Consortium between 2002 and 2009 were eligible. Patients with the ICD-9-CM code 008.45 who received a minimum 3-day course of either metronidazole or oral vancomycin on/after day 5 of admission were considered incident cases of C difficile infection. 31,472 incident cases of C difficile infection were identified and matched to five controls, on hospital, year/quarter of admission date, and age ±10 years (N=78,096). Patients who were administered one drug in the statin class (atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin or simvastatin) before the index date were considered to be exposed. Conditional logistic regression modelling provided adjusted odds ratios and 95% CI. RESULTS: Compared with non-users, users of any drug within the statin class were 0.78 times less likely to develop C difficile infection in the hospital (95% CI 0.75 to 0.81) adjusting for potential confounders. Differences in estimates for specific statins were minimal. Niacin, fibrates and selective cholesterol absorption inhibitors showed no association with the risk of C difficile infection. CONCLUSIONS: Our data were consistent with a growing body of literature demonstrating a reduced risk of infections with statin use. Statins' pleiotropic properties may provide protection against C difficile infection.

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.

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.

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).

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.

Relationship of carbapenem restriction in 22 university teaching hospitals to carbapenem use and carbapenem-resistant Pseudomonas aeruginosa.

Many hospital antimicrobial stewardship programs restrict the availability of selected drugs by requiring prior approval. Carbapenems may be among the restricted drugs, but it is unclear if hospitals that restrict availability actually use fewer carbapenems than hospitals that do not restrict use. Nor is it clear if restriction is related to resistance. We evaluated the relationship between carbapenem restriction and the volume of carbapenem use and both the incidence rate and proportion of carbapenem-resistant Pseudomonas aeruginosa isolates from 2002 through 2006 in a retrospective, longitudinal, multicenter analysis among a consortium of academic health centers. Carbapenem use was measured from billing records as days of therapy per 1,000 patient days. Hospital antibiograms were used to determine both the incidence rate and proportion of carbapenem-resistant P. aeruginosa isolates. A survey inquired about restriction policies for antibiotics, including carbapenems. General linear mixed models were used to examine study outcomes. Among 22 hospitals with sufficient data for analysis, overall carbapenem use increased significantly over the 5 years of study (P < 0.0001), although overall carbapenem resistance in P. aeruginosa did not change. Hospitals that restricted carbapenems (n = 8; 36%) used significantly fewer carbapenems (P = 0.04) and reported lower incidence rates of carbapenem-resistant P. aeruginosa (P = 0.01) for all study years. Fluoroquinolone use was a potential confounder of these relationships, but hospitals that restricted carbapenems actually used fewer fluoroquinolones than those that did not. Restriction of carbapenems is associated with both lower use and lower incidence rates of carbapenem resistance in P. aeruginosa.

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.

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.

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.

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.

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].

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.