Trends in Prescribing Opioids, Benzodiazepines, and Both Among Adults with Alcohol Use Disorder in New York State.

BACKGROUND: Alcohol use disorder (AUD) is a highly prevalent public health problem that contributes to opioid- and benzodiazepine-related morbidity and mortality. Even though co-utilization of these substances is particularly harmful, data are sparse on opioid or benzodiazepine prescribing patterns among individuals with AUD. OBJECTIVE: To estimate temporal trends and disparities in opioid, benzodiazepine, and opioid/benzodiazepine co-prescribing among individuals with AUD in New York State (NYS). DESIGN/PARTICIPANTS: Serial cross-sectional study analyzing merged data from the NYS Office of Addiction Services and Supports (OASAS) and the NYS Department of Health Medicaid Data Warehouse. Subjects with a first admission to an OASAS treatment program from 2005-2018 and a primary AUD were included. A total of 148,328 subjects were identified. MEASURES: Annual prescribing rates of opioids, benzodiazepines, or both between the pre- (2005-2012) and post- (2013-2018) Internet System for Tracking Over-Prescribing (I-STOP) periods. I-STOP is a prescription monitoring program implemented in NYS in August 2013. Analyses were stratified based on sociodemographic factors (age, sex, race/ethnicity, and location). RESULTS: Opioid prescribing rates decreased between the pre- and post-I-STOP periods from 25.1% (95% CI, 24.9-25.3%) to 21.3% (95% CI, 21.2-21.4; P <.001), while benzodiazepine (pre: 9.96% [95% CI, 9.83-10.1%], post: 9.92% [95% CI, 9.83-10.0%]; P =.631) and opioid/benzodiazepine prescribing rates remained unchanged (pre: 3.01% vs. post: 3.05%; P =.403). After I-STOP implementation, there was a significant decreasing trend in opioid (change, -1.85% per year, P <.0001), benzodiazepine (-0.208% per year, P =.0184), and opioid/benzodiazepine prescribing (-0.267% per year, P <.0001). Opioid, benzodiazepine, and co-prescription rates were higher in females, White non-Hispanics, and rural regions. CONCLUSIONS: Among those with AUD, opioid prescribing decreased following NYS I-STOP program implementation. While both benzodiazepine and opioid/benzodiazepine co-prescribing rates remained high, a decreasing trend was evident after program implementation. Continuing high rates of opioid and benzodiazepine prescribing necessitate the development of innovative approaches to improve the quality of care.

A cohort of patients in New York State with an alcohol use disorder and subsequent treatment information - A merging of two administrative data sources.

OBJECTIVE: Despite the high prevalence of alcohol use disorder (AUD) in the United States, limited research is focused on the associations among AUD, pain, and opioids/benzodiazepine use. In addition, little is known regarding individuals with a history of AUD and their potential risk for pain diagnoses, pain prescriptions, and subsequent misuse. Moreover, the potential risk of pain diagnoses, prescriptions, and subsequent misuse among individuals with a history of AUD is not well known. The objective was to develop a tailored dataset by linking data from 2 New York State (NYS) administrative databases to investigate a series of hypotheses related to AUD and painful medical disorders. METHODS: Data from the NYS Office of Addiction Services and Supports (OASAS) Client Data System (CDS) and Medicaid claims data from the NYS Department of Health Medicaid Data Warehouse (MDW) were merged using a stepwise deterministic method. Multiple patient-level identifier combinations were applied to create linkage rules. We included patients aged 18 and older from the OASAS CDS who initially entered treatment with a primary substance use of alcohol and no use of opioids between January 1, 2003, and September 23, 2019. This cohort was then linked to corresponding Medicaid claims. RESULTS: A total of 177,685 individuals with a primary AUD problem and no opioid use history were included in the dataset. Of these, 37,346 (21.0%) patients had an OUD diagnosis, and 3,365 (1.9%) patients experienced an opioid overdose. There were 121,865 (68.6%) patients found to have a pain condition. CONCLUSION: The integrated database allows researchers to examine the associations among AUD, pain, and opioids/benzodiazepine use, and propose hypotheses to improve outcomes for at-risk patients. The findings of this study can contribute to the development of a prognostic prediction model and the analysis of longitudinal outcomes to improve the care of patients with AUD.

Patient and social factors related to nebulizer use in COPD patients at the transition of care: a qualitative study.

BACKGROUND: Transition from hospital to home is a vulnerable period for patients with COPD exacerbations, with a high risk for readmission and mortality. Twenty percent of patients with an initial hospitalization for a COPD exacerbation are readmitted to a hospital within 30 days, costing the health care system over $15 billion annually. While nebulizer therapy directed at some high-risk COPD patients may improve the transition from hospital to home, patient and social factors are likely to contribute to difficulties with their use. Current literature describing the COPD patient's experience with utilizing nebulizer therapy, particularly during care transitions, is limited. Therefore, the objective of this study was to explore underlying COPD patient and social factors contributing to practical difficulties with nebulizer use at the care transition from hospital to home. METHODS: This was a qualitative study conducted between September 2020 and June 2022. Patients were included if they were ≥ 40 years old, had a current diagnosis of COPD, had an inpatient admission at a hospital, and were discharged directly to home with nebulizer therapy. Semi-structured, one-on-one interviews with patients were conducted covering a broad range of patient and social factors and their relationships with nebulizer use and readmission. Interviews were recorded and transcribed verbatim. A thematic analysis was performed using a mixed inductive and deductive approach. RESULTS: Twenty-one interviews were conducted, and subjects had a mean age of 64 ± 8.4 years, 62% were female, and 76% were White. The predominant interview themes were health care system interactions and medication management. The interviews highlighted that discharge counseling methods and depth of counseling from hospitals were inconsistent and were not always patient-friendly. They also suggested that patients could appropriately identify, set up, and utilize their nebulizer treatment without difficulties, but additional patient education is required for nebulizer clean up and maintenance. CONCLUSIONS: Our interviews suggest that there is room for improvement within the health care system for providing consistent, effective discharge counseling. Also, COPD patients discharged from a hospital on nebulizer therapy can access and understand their treatment but require additional education for nebulizer clean up and maintenance.

Integrating community health workers within a pharmacy to address health-related social needs.

BACKGROUND: Community pharmacies in the United States are beginning to serve as patient care service destinations addressing both clinical and health-related social needs (HRSN). Although there is support for integrating social determinant of health (SDoH) activities into community pharmacy practice, the literature remains sparse on optimal pharmacy roles and practice models. OBJECTIVE: To assess the feasibility of a community pharmacy HRSN screening and referral program adapted from a community health worker (CHW) model and evaluate participant perceptions and attitudes toward the program. METHODS: This feasibility study was conducted from January 2022 to April 2022 at an independent pharmacy in Buffalo, NY. Collaborative relationships were developed with 3 community-based organizations including one experienced in implementing CHW programs. An HRSN screening and referral intervention was developed and implemented applying a CHW practice model. Pharmacy staff screened subjects for social needs and referred to an embedded CHW, who assessed and referred subjects to community resources with as-needed follow-up. Post intervention, subjects completed a survey regarding their program experience. Descriptive statistics were used to report demographics, screening form, and survey responses. RESULTS: Eighty-six subjects completed screening and 21 (24.4%) an intervention and referral. Most participants utilized Medicaid (57%) and lived within a ZIP Code associated with the lowest estimated quartile for median household income (66%). Eighty-seven social needs were identified among the intervention subjects, with neighborhood and built environment (31%) and economic stability challenges (30%) being the most common SDoH domains. The CHW spent an average of 33 minutes per patient from initial case review through follow-up. All respondents had a positive perception of the program, and the majority agreed that community pharmacies should help patients with their social needs (70%). CONCLUSIONS: This feasibility study demonstrated that embedding a CHW into a community pharmacy setting can successfully address HRSN and that participants have a positive perception toward these activities.

Clinical and economic effectiveness of a pharmacy and primary care collaborative transition of care program.

BACKGROUND: Primary care pharmacists are uniquely positioned to improve care quality by intervening within care transitions in the postdischarge period. However, additional evidence is required to demonstrate that pharmacist-led interventions can reduce health care utilization in a cost-effective manner. The study's objective was to evaluate the clinical and economic effectiveness of a pharmacy-led transition of care (TOC) program within a primary care setting. METHODS: This cluster randomized trial was conducted between 2019 and 2021 and included three primary care practices. Eligible patients were ≥18 years of age and at high risk of readmission. The multifaceted pharmacy intervention included medication reconciliation, comprehensive medication review, and patient and provider follow-up. The primary composite endpoint included hospital readmissions and emergency department (ED) visits within 30 days of discharge. Differences in outcomes were modeled using a generalized estimated equations approach and outcomes were assumed to be distributed as a Poisson random variable. A cost-benefit analysis was embedded within the study and estimated economic outcomes from a provider group/health system perspective. Cost measures included: net benefit, benefit to cost ratio (BCR), and return on investment (ROI). RESULTS: Of 300 eligible patients, 36 were in the intervention group and 264 in the control group. The intervention significantly reduced the primary composite outcome of all-cause readmissions and ED visits within 30 days (adjusted incidence rate ratio [aIRR], 0.54; 95% CI, 0.44-0.66; P < 0.001). There were significant reductions in both 30-day all-cause readmissions (aIRR, 0.64; 95% CI, 0.60-0.67; P < 0.001) and ED visits (aIRR, 0.25; 95% CI, 0.20, 0.31; P < 0.001) between groups. The net benefit of the intervention was $9,078, with a BCR of 2.11 and a ROI of 111%. Sensitivity analyses were robust to changes in economic inputs. CONCLUSION: This care transition program had positive clinical and economic benefits, providing further support for the essential role pharmacists demonstrate in providing TOC services.

Implementation and evaluation of social determinants of health practice models within community pharmacy.

BACKGROUND: While community pharmacies are an ideal setting for social needs screening and referral programs, information on social risk assessment within pharmacy practice is limited. OBJECTIVES: Our primary objective was to describe 2 social determinant of health (SDOH) practice models implemented within community pharmacies. The secondary objective was to evaluate implementation practices utilizing the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. PRACTICE DESCRIPTION: Two pharmacy groups participated in a 3-month study, one in New York (9 pharmacies) and another in Missouri (1 pharmacy). The New York pharmacies implemented an SDOH specialist practice model, in which pharmacy staff members facilitate the program. The Missouri pharmacy implemented a community health worker (CHW) model by cross training their technicians. Each pharmacy developed their program using the Community Pharmacy Enhanced Services Network Care Model. PRACTICE INNOVATION: Both programs expanded the technician role to take on additional responsibilities. The SDOH specialist model partnered with a local independent practice association to create a social needs referral program using a technology platform for closed-loop communication. All workflow steps of the self-contained CHW program were completed within the pharmacy, placing additional responsibility on the CHW and pharmacy staff. EVALUATION METHODS: RE-AIM framework dimensions of Reach, Effectiveness, and Adoption. RESULTS: Social challenges were identified in 49 of 76 (65%) generated SDOH screenings. The most prevalent social needs reported were affordability of daily needs (33%) and health care system navigation (15%). While most pharmacy staff indicated that workflow steps were clearly defined, assessments and referral tools were identified as potential gaps. While approximately 50% of pharmacy staff were comfortable with their assigned roles and in addressing SDOH challenges, physical and mental health concerns required additional education for intervention. CONCLUSION: The successful implementation of community pharmacy SDOH programs connected patients with local resources. Community pharmacies are ideally positioned to expand their public health footprint through SDOH interactions that consequently improve patient care.

Task difficulty and physiological measures of mental workload in air traffic control: a scoping review.

This study provides a systematic synthesis of empirical research on mental workload (MWL) in air traffic control (ATC). MWL is a key concept in research on innovative technologies, because the assessment of MWL is crucial to the evaluation of such technologies. Our specific focus was on physiological measures of MWL. The used search strategy identified 39 peer-reviewed publications that analysed ATC tasks, examined different levels of difficulty of the ATC task, and considered at least one physiological measure of MWL. Positive relations between measures of MWL and task difficulty were observed most frequently, indicating that the measures indeed allowed the assessment of MWL. The most commonly used physiological measures were brain measures (EEG and fNIR) and heart rate measures. The review revealed a need for more precise descriptions of crucial experimental parameters in order to permit a transition of the field towards more interactive and dynamic types of analysis. Practitioner summary: Research on innovative technology in air traffic control (ATC) depends on assessments of mental workload (MWL). We reviewed empirical research on MWL in ATC. Brain and heart measures often allow assessments of MWL. Better descriptions of experiments are needed to allow comparisons among studies and more dynamic and interactive analyses.

Trends in fall-related mortality and fall risk increasing drugs among older individuals in the United States,1999-2017.

BACKGROUND: Previous studies have demonstrated increasing mortality due to falls among older adults. The objective of this study was to determine whether there was an increase in fall risk increasing drug prescribing and if this is concurrent with an increase in fall-related mortality in persons 65 years and older in the United States. METHODS: The study is a serial cross-sectional analysis utilizing data from both the National Vital Statistics System (NVSS) and the medical expenditure panel survey (MEPS) for years 1999-2017. Adults aged 65 years and older were evaluated for death due to falls from the NVSS and for prescription fills of fall risk increasing drugs per the Stopping Elderly Accidents, Deaths, and Injuries-Rx (STEADI-Rx) fall checklist from the MEPS. RESULTS: The analysis included 374 972 fall-related mortalities and 7 858 177 122 fills of fall risk increasing drugs. 563 037 964 persons age 65 and older received at least one fall risk increasing drug. Age-adjusted mortality due to falls increased from 29.40 per 100 000 in 1999 to 63.27 per 100 000 in 2017. The percent of persons who received at least one prescription for a fall risk increasing drug increased from 57% in 1999 to 94% in 2017 (p for trend <.0001). CONCLUSIONS AND RELEVANCE: Both use of fall risk increasing drugs and mortality due to falls are on the rise. Fall risk increasing drugs may partially explain the increase in mortality due to falls; this cannot be firmly concluded from the current study. Future research examining the potential relationship between fall risk increasing drugs and fall-related mortality utilizing nationally representative person-level data are needed.

Socio-demographic and -economic factors associated with 30-day readmission for conditions targeted by the hospital readmissions reduction program: a population-based study.

BACKGROUND: Early hospital readmissions remain common in patients with conditions targeted by the CMS Hospital Readmission Reduction Program (HRRP). There is still no consensus on whether readmission measures should be adjusted based on social factors, and there are few population studies within the U.S. examining how social characteristics influence readmissions for HRRP-targeted conditions. The objective of this study was to determine if specific socio-demographic and -economic factors are associated with 30-day readmissions in HRRP-targeted conditions: acute exacerbation of chronic obstructive pulmonary disease, pneumonia, acute myocardial infarction, and heart failure. METHODS: The Nationwide Readmissions Database was used to identify patients admitted with HRRP-targeted conditions between January 1, 2010 and September 30, 2015. Stroke was included as a control condition because it is not included in the HRRP. Multivariate models were used to assess the relationship between three social and economic characteristics (gender, urban/rural hospital designation, and estimated median household income within the patient's zip code) and 30-day readmission rates using a hierarchical two-level logistic model. Age-adjusted models were used to assess relationship differences between Medicare vs. non-Medicare populations. RESULTS: There were 19,253,997 weighted index hospital admissions for all diagnoses and 3,613,488 30-day readmissions between 2010 and 2015. Patients in the lowest income quartile (≤$37,999) had an increased odds of 30-day readmission across all conditions (P < 0.0001). Female gender and rural hospital designation were associated with a decreased odds of 30-day readmission for most targeted conditions (P < 0.05). Similar findings were also seen in patients ≥65 years old. CONCLUSIONS: Socio-demographic and -economic factors are associated with 30-day readmission rates and should be incorporated into tools or interventions to improve discharge planning and mitigate against readmission.

Readmissions and costs among younger and older adults for targeted conditions during the enactment of the hospital readmission reduction program.

BACKGROUND: The Hospital Readmissions Reduction Program (HRRP) was introduced to reduce readmission rates among Medicare beneficiaries, however little is known about readmissions and costs for HRRP-targeted conditions in younger populations. The primary objective of this study was to examine readmission trends and costs for targeted conditions during policy implementation among younger and older adults in the U.S. METHODS: We analyzed the Nationwide Readmission Database from January 2010 to September 2015 in younger (18-64 years) and older (≥65 years) patients with acute myocardial infarction (AMI), heart failure (HF), pneumonia, and acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Pre- and post-HRRP periods were defined based on implementation of the policy for each condition. Readmission rates were evaluated using an interrupted time series with difference-in-difference analyses and hospital cost differences between early and late readmissions (≤30 vs. > 30 days) were evaluated using generalized linear models. RESULTS: Overall, this study included 16,884,612 hospitalizations with 3,337,266 readmissions among all age groups and 5,977,177 hospitalizations with 1,104,940 readmissions in those aged 18-64 years. Readmission rates decreased in all conditions. In the HRRP announcement period, readmissions declined significantly for those aged 40-64 years for AMI (p < 0.0001) and HF (p = 0.003). Readmissions decreased significantly in the post-HRRP period for those aged 40-64 years at a slower rate for AMI (p = 0.003) and HF (p = 0.05). Readmission rates among younger patients (18-64 years) varied within all four targeted conditions in HRRP announcement and post-HRRP periods. Adjusted models showed a significantly higher readmission cost in those readmitted within 30 days among younger and older populations for AMI (p < 0.0001), HF (p < 0.0001), pneumonia (p < 0.0001), and AECOPD (p < 0.0001). CONCLUSION: Readmissions for targeted conditions decreased in the U.S. during the enactment of the HRRP policy and younger age groups (< 65 years) not targeted by the policy saw a mixed effect. Healthcare expenditures in younger and older populations were significantly higher for early readmissions with all targeted conditions. Further research is necessary evaluating total healthcare utilization including emergency department visits, observation units, and hospital readmissions in order to better understand the extent of the HRRP on U.S. healthcare.

Addressing social determinants of health in community pharmacy: Innovative opportunities and practice models.

Social determinants of health (SDoH) account for up to 90% of health outcomes, whereas medical care accounts for only 10%-15%; despite this disparity, only 24% of hospitals and 16% of physician practices screen for the 5 social needs. Community-embedded and highly accessible, pharmacies are uniquely positioned to connect individuals to local community and social resources and thereby address SDoH. In this article, we explore novel community pharmacy practice models that address SDoH, provide real-world examples of these models, and discuss pathways for reimbursement and sustainability. A number of innovative community pharmacy practice models that focus on social issues are currently being explored. These include integrating community health workers (CHWs) or SDoH specialists, wherein CHWs are frontline public health workers who can effectively bridge the health care system and their community, whereas SDoH specialists are pharmacy team members trained with substantial SDoH knowledge and how to use it to connect pharmacy patients to community resources. Three community pharmacy networks have implemented pilot programs using either a CHW or SDoH specialist model. An essential component for program success in all cases has been partnership development and increased interdependence between the pharmacies, local community organizations, and the public health sector. New payment models and financial incentives will be necessary to expand and sustain these programs. A potential Approach may be the use of Z codes, a subset of ICD-10-CM codes specific to assessing SDoH. Although opportunities are developing for community pharmacies to play a major role in sustainably addressing SDoH, additional work is needed before there is a widespread acceptance of pharmacies becoming service referral destinations for patients with social needs. Evaluation of these models on a wider scale will be necessary to fully evaluate their effectiveness, costs, and implementation within different community pharmacy settings.

Pharmacist-led transitions-of-care services in primary care settings: Opportunities, experiences, and challenges.

OBJECTIVE: To initiate a call to action for ambulatory care pharmacists to play a more active role in transitional care management within primary care settings by discussing relevant opportunities, experiences, and challenges. SUMMARY: With the shift to value-based health care, greater emphasis is being placed on improving patient care quality at the lowest cost. This represents an opportunity for pharmacist integration into primary care teams to address medication management challenges in the postdischarge period. Primary care pharmacists are uniquely positioned to close gaps in care not typically addressed by hospital-based programs. These pharmacists can provide complex transition interventions tailored toward individual patients, including comprehensive medication review, patient counseling, and direct collaboration with providers. For broad acceptance of these services, current challenges include identifying and prioritizing high-risk patients, establishing the cost-effectiveness of these strategies, and ultimately applying dissemination and implementation methodologies to increase the potential impact of these interventions. CONCLUSION: Opportunities are expanding for primary care pharmacists to play a more substantial role in transitional care management in sustainable ways. For widespread implementation of these strategies, additional research is necessary to determine their clinical effectiveness as well as cost-effectiveness and to understand better the barriers and facilitators to adopting these interventions.

Adjuvant ß-Lactam Therapy Combined with Vancomycin for Methicillin-Resistant Staphylococcus aureus Bacteremia: Does ß-Lactam Class Matter?

We analyzed the impact of vancomycin (VAN) combined with adjuvant ß-lactam therapy (Combo) on persistent (≥5 days) methicillin-resistant Staphylococcus aureus bacteremia versus VAN alone by using pooled data from two previously published observational studies (n = 156). Combo was inversely associated with persistent bacteremia (adjusted odds ratio, 0.460; 95% confidence interval, 0.229 to 0.923). Acute kidney injury was more common with Combo than with VAN (18.9% and 7.6%, respectively; P = 0.062).

Acute exacerbations in chronic obstructive pulmonary disease: should we use antibiotics and if so, which ones?

PURPOSE OF REVIEW: Acute exacerbations are a major cause of morbidity and mortality in chronic obstructive pulmonary disease (COPD) with evidence suggesting at least 50% of exacerbations involve bacteria that benefit from antibiotic treatment. Here, we review the most relevant data regarding the use of antibiotics in exacerbations of COPD and provide insights on the selection of initial antibiotic therapy for their treatment. RECENT FINDINGS: Identification of bacterial exacerbations still relies on clinical assessment rather than laboratory biomarkers. Several recent studies, including a meta-analysis and placebo-controlled trials, demonstrate improved outcomes with antibiotics in all but mild exacerbations of COPD, including both inpatient and outpatient. A broader antibiotic regimen should be used for patients who have risk factors for poor outcomes. A risk-stratification approach can guide antibiotic choice, although the stratification algorithm still needs to be validated in a randomized controlled trial. SUMMARY: The use of antibiotics for the treatment of moderate-to-severe suspected bacterial exacerbations in COPD is supported by published trials and evidence-based systematic reviews. Recent trials also show differences in outcomes based on antibiotic choice. More research is necessary to evaluate risk stratification approaches when selecting initial antibiotic therapy.

A systematic review of the impact of antifungal stewardship interventions in the United States.

BACKGROUND: Antimicrobial resistance is a widely recognized public health threat, and stewardship interventions to combat this problem are well described. Less is known about antifungal stewardship (AFS) initiatives and their influence within the United States. The purpose of this study was to evaluate evidence on the impact of AFS interventions on clinical and performance measures. METHODS: A systematic review of English language studies identified in the PubMed and EMBASE databases was performed through November 2017. The review was conducted in accordance with PRISMA. Search terms included antifungal stewardship, antimicrobial stewardship, Candida, candidemia, candiduria, and invasive fungal disease. Eligible studies were those that described an AFS program or intervention occurring in the US and evaluated clinical or performance measures. RESULTS: Fifty-four articles were identified and 13 were included. Five studies evaluated AFS interventions and reported clinical outcomes (mortality and length of stay) and performance measures (appropriate antifungal choice and time to therapy). The remaining eight studies evaluated general stewardship interventions and reported data on antifungal consumption. All studies were single center, quasi-experimental with varying interventions across studies. AFS programs had no impact on mortality (3 of 3 studies), with an overall rate of 27% in the intervention group and 23% in the non-intervention group. Length of stay (5 of 5) was also similar between groups (range, 9-25 vs. 11-22). Time to antifungal therapy improved in 2 of 5 studies, and appropriate choice of antifungal increased in 2 of 2 studies. Antifungal consumption was significantly blunted or reduced following stewardship initiation (8 of 8), although a direct comparison between studies was not possible due to a lack of common units. CONCLUSION: The available evidence suggests that AFS interventions can improve performance measures and decrease antifungal consumption. Although this review did not detect improvements in clinical outcomes, significant adverse outcomes were not reported.

Antibiotic prescribing for acute respiratory tract infections in the United States outpatient setting.

BACKGROUND: Acute respiratory tract infections (ARIs) are common in the outpatient setting. Although they are predominantly viral, antibiotics are often prescribed for the treatment of ARIs. METHODS: Using the U.S. Medical Expenditure Panel Survey (MEPS; 2010-2015), we estimated the national prevalence and predictors of outpatient antibiotic prescribing for ARIs by provider type. We categorized the trends of antibiotic prescriptions (overall or broad-spectrum) for ARIs by provider type (physician and advanced practice provider [APP] which includes nurse practitioner [NP], and physician assistant [PA]). The outcome variable was defined as receipt of an antibiotic prescription during a consultation with a provider for an ARI (including outpatient clinic visit or doctor's office visit). RESULTS: There were 64,081,892 ARI antibiotic prescriptions written, with a decrease from 10.9 (2010) to 9.7 million (2015) during the study interval (p < 0.0001). Associations of patient- and provider-level variables with antibiotics prescription were examined using binary logistic regression. Blacks were more likely to receive antibiotics than whites (OR 1.51; 95% CI 1.25, 1.84; p < 0.001), and antibiotic prescription was more likely if the patient-provider race was concordant (OR 5.41; 95% CI 4.65, 6.29, p < 0.0001). Although the majority of patients with ARI were cared for by physicians, APPs were seeing an increasing number of ARI patients. CONCLUSIONS: Antibiotic prescribing for ARIs though declining, remains high. More research is needed to better understand the drivers of ARI antibiotic prescribing and to develop targeted interventions for both patients and providers.

Overtreatment of Asymptomatic Candiduria among Hospitalized Patients: a Multi-institutional Study.

Candiduria is common in hospitalized patients, and asymptomatic candiduria contributes to antifungal overuse. The guidelines for management of asymptomatic candiduria do not recommend antifungal use, but rather the elimination of predisposing factors. It is unknown whether these recommendations are being followed. The primary objective of this study was to characterize candiduria management among hospitalized patients. This was a retrospective cohort study of a random sample of 305 hospitalized patients with candiduria at four U.S. medical centers from January 2010 to December 2013. Patients were classified as asymptomatic or symptomatic based on established criteria, and data were collected by chart review. Infectious Diseases Society of America (IDSA) treatment guideline adherence and its association with clinical outcomes, including candiduria recurrence (short- and long-term) and 30-day readmission, were assessed. Eighty percent of patients were classified as having asymptomatic candiduria. Overall, 143 (47%) patients were not managed according to recommended guidelines, including 105/243 (43%) in the asymptomatic candiduria group and 38/62 (61%) in the symptomatic group (P = 0.01). Discordance among asymptomatic patients was driven by overtreatment with an antifungal (98/105 [93%]). Thirty-three percent of patients with asymptomatic candiduria not managed according to the guidelines were treated for over 7 days, and 5% received over 14 days of therapy. Fluconazole was the most commonly used empirical antifungal among asymptomatic candiduria patients (96%), followed by micafungin (4%). Asymptomatic candiduria patients not managed according to the guidelines had a trend toward higher 30-day readmission (35% versus 26%, P = 0.27). Inappropriate management of candiduria among hospitalized patients was high, leading to overtreatment with antifungal therapy.

Lower Airway Bacterial Colonization Patterns and Species-Specific Interactions in Chronic Obstructive Pulmonary Disease.

Little is known about interactions between nontypeable Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, and Pseudomonas aeruginosa in the lower respiratory tract in chronic obstructive pulmonary disease (COPD) patients. We characterized colonization by these four bacterial species, determined species-specific interactions, and estimated the effects of host factors on bacterial colonization among COPD patients. We conducted a prospective cohort study in veterans with COPD that involved monthly clinical assessment and sputum cultures with an average duration of follow-up of 4.5 years. Cultures were used for bacterial identification. We analyzed bacterial interactions using generalized linear mixed models after controlling for clinical and demographic variables. The outcomes of interest were the relationships between bacteria based on clinical status (stable or exacerbation). One hundred eighty-one participants completed a total of 8,843 clinic visits, 30.8% of which had at least one of the four bacteria isolated. H. influenzae was the most common bacterium isolated (14.4%), followed by P. aeruginosa (8.1%). In adjusted models, S. pneumoniae colonization was positively associated with H. influenzae colonization (odds ratio [OR], 2.79; 95% confidence interval [CI], 2.03 to 3.73). We identified negative associations between P. aeruginosa and H. influenzae (OR, 0.15; 95% CI, 0.10 to 0.22) and P. aeruginosa and M. catarrhalis (OR, 0.51; 95% CI, 0.35 to 0.75). Associations were similar during stable and exacerbation visits. Recent antimicrobial therapy was associated with a lower prevalence of S. pneumoniae, H. influenzae, and M. catarrhalis, but not P. aeruginosa Our findings support the presence of specific interspecies interactions between common bacteria in the lower respiratory tracts of COPD patients. Further work is necessary to elucidate the mechanisms of these complex interactions that shift bacterial species.

Polymyxin B in Combination with Rifampin and Meropenem against Polymyxin B-Resistant KPC-Producing Klebsiella pneumoniae.

Safe and effective therapies are urgently needed to treat polymyxin-resistant KPC-producing Klebsiella pneumoniae infections and suppress the emergence of resistance. We investigated the pharmacodynamics of polymyxin B, rifampin, and meropenem alone and as polymyxin B-based double and triple combinations against KPC-producing K. pneumoniae isolates. The rates and extents of killing with polymyxin B (1 to 128 mg/liter), rifampin (2 to 16 mg/liter), and meropenem (10 to 120 mg/liter) were evaluated against polymyxin B-susceptible (PBs) and polymyxin B-resistant (PBr) clinical isolates using 48-h static time-kill studies. Additionally, humanized triple-drug regimens of polymyxin B (concentration at steady state [Css] values of 0.5, 1, and 2 mg/liter), 600 mg rifampin every 12 or 8 h, and 1 or 2 g meropenem every 8 h dosed as an extended 3-h infusion were simulated over 48 h by using a one-compartment in vitro dynamic infection model. Serial bacterial counts were performed to quantify the pharmacodynamic effect. Population analysis profiles (PAPs) were used to assess the emergence of polymyxin B resistance. Monotherapy was ineffective against both isolates. Polymyxin B with rifampin demonstrated early bactericidal activity against the PBs isolate, followed by regrowth by 48 h. Bactericidal activity was sustained at all polymyxin B concentrations of ≥2 mg/liter in combination with meropenem. No two-drug combinations were effective against the PBr isolate, but all simulated triple-drug regimens showed early bactericidal activity against both strains by 8 h that was sustained over 48 h. PAPs did not reveal the emergence of resistant subpopulations. The triple-drug combination of polymyxin B, rifampin, and meropenem may be a viable consideration for the treatment of PBr KPC-producing K. pneumoniae infections. Further investigation is warranted to optimize triple-combination therapy.

Triple combination antibiotic therapy for carbapenemase-producing Klebsiella pneumoniae: a systematic review.

BACKGROUND: The spread of carbapenemase-producing K. pneumoniae (CPKP) has become a significant problem worldwide. Combination therapy for CPKP is encouraging, but polymyxin resistance to many antibiotics is hampering effective treatment. Combination therapy with three or more antibiotics is being increasingly reported, therefore we performed a systematic review of triple combination cases in an effort to evaluate their clinical effectiveness for CPKP infections. METHODS: The PubMed database was searched to identify all published clinical outcomes of CPKP infections treated with triple combination therapy. Articles were stratified into two tiers depending on the level of clinical detail provided. A tier 1 study included: antibiotic regimen, regimen-specific outcome, patient status at onset of infection, and source of infection. Articles not reaching these criteria were considered tier 2. RESULTS: Thirty-three studies were eligible, 23 tier 1 and ten tier 2. Among tier 1 studies, 53 cases were included in this analysis. The most common infection was pneumonia (31%) followed by primary or catheter-related bacteremia (21%) and urinary tract infection (17%). Different combinations of antibiotic classes were utilized in triple combinations, the most common being a polymyxin (colistin or polymyxin B, 86.8%), tigecycline (73.6%), aminoglycoside (43.4%), or carbapenem (43.4%). Clinical and microbiological failure occurred in 14/39 patients (35.9%) and 22/42 patients (52.4%), respectively. Overall mortality for patients treated with triple combination therapy was 35.8% (19/53 patients). CONCLUSIONS: Triple combination therapy is being considered as a treatment option for CPKP. Polymyxin-based therapy is the backbone antibiotic in these regimens, but its effectiveness needs establishing in prospective clinical trials.