Feasibility of Core Antimicrobial Stewardship Interventions in Community Hospitals.

Importance: The feasibility of core Infectious Diseases Society of America-recommended antimicrobial stewardship interventions in community hospitals is unknown. Objective: To determine the feasibility and results of implementing 2 core stewardship intervention strategies in community hospitals. Design, Setting, and Participants: Three-stage, multicenter, prospective nonrandomized clinical trial with crossover design. The setting was 4 community hospitals in North Carolina (median bed size, 305; range, 102-425). Participants were all patients receiving targeted study antibacterial agents or alternative, nonstudy antibacterial agents. The study dates were October 2014 through October 2015. All statistical analyses were completed as of October 2016. Interventions: Two antimicrobial stewardship strategies targeted vancomycin hydrochloride, piperacillin-tazobactam, and the antipseudomonal carbapenems on formulary at the study hospitals: (1) modified preauthorization (PA), in which the prescriber had to receive pharmacist approval for continued use of the antibiotic after the first dose, and (2) postprescription audit and review (PPR), in which the pharmacist would engage the prescriber about antibiotic appropriateness after 72 hours of therapy. Two hospitals performed modified PA for 6 months, then PPR for 6 months after a 1-month washout. The other 2 hospitals performed the reverse. Main Outcomes and Measures: The primary outcome was the feasibility of implementing the interventions, determined by (1) approval by hospital administration and committees at each study hospital; (2) completion of pharmacist training; (3) initiation and implementation as determined by number, type, and outcomes of interventions performed; and (4) time required for interventions. Secondary outcomes included antimicrobial use (days of therapy) compared with matched historical periods and length of hospitalization. Results: A total of 2692 patients (median age, 65 years; interquartile range, 53-76 years) underwent a study intervention; 1413 (52.5%) were female, 1323 (49.1%) were white, and 1047 (38.9%) were African American. Intervention approvals took a median of 95 days (range, 56-119 days); during these discussions, strict PA was deemed not feasible. Instead, the modified PA intervention was used throughout the study. Pharmacists performed 1456 modified PA interventions (median per hospital, 350 [range, 129-628]) and 1236 PPR interventions (median per hospital, 298 [range, 273-366]). Study antimicrobials were determined to be inappropriate 2 times as often during the PPR period (41.0% [435 of 1060] vs 20.4% [253 of 1243]; P < .001). Pharmacists recommended dose change more often during the modified PA intervention (15.9% [232 of 1456] vs 9.6% [119 of 1236]; P < .001) and de-escalation during PPR (29.1% [360 of 1236] vs 13.0% [190 of 1456]; P < .001). The median time dedicated to the stewardship interventions varied by hospital (range of median hours per week, 5-19). Overall antibiotic use decreased during PPR compared with historical controls (mean [SD] days of therapy per 1000 patient-days, 925.2 [109.8] vs 965.3 [109.4]; mean difference, -40.1; 95% CI, -71.7 to -8.6), but not during modified PA (mean [SD] days of therapy per 1000 patient-days, 931.0 [102.0] vs 926.6 [89.7]; mean difference, 4.4; 95% CI, -55.8 to 64.7). Conclusions and Relevance: Strict PA was not feasible in the study hospitals. In contrast, PPR was a feasible and effective strategy for antimicrobial stewardship in settings with limited resources and expertise. Trial Registration: ClinicalTrials.gov identifier: NCT02212808.

China-United States Research Collaborations in Antimicrobial Resistance.

A strong synergy can result from China-US antimicrobial resistance (AMR) collaborations given similarities and differences between their respective healthcare systems and research infrastructures. The Antibacterial Resistance Leadership Group has employed a model of realistic growth, starting with a feasible, relatively low-resource observational study in a critical priority pathogen. This and other observational studies will provide vital scientific information required for the rational design of future interventional trials. In addition, it provides a mutual, low-risk opportunity for determining the strengths and opportunities of the research collaboration. Issues identified during the observational studies can be addressed prior to the initiation of high-resource interventional studies. Collaborative clinical AMR studies between China and the United States have tremendous potential to decrease AMR rates, improve responsible antibiotic use, and ultimately improve the lives of patients in both countries.

Transforming Concepts Into Clinical Trials and Creating a Multisite Network: The Leadership and Operations Center of the Antibacterial Resistance Leadership Group.

The Leadership and Operations Center (LOC) is responsible for facilitating, coordinating, and implementing the Antibacterial Resistance Leadership Group (ARLG) scientific agenda by engaging thought leaders; soliciting research proposals; and developing the processes, tools, and infrastructure required to operationalize studies and create and sustain the ARLG network. These efforts are ongoing as new projects are developed and the network expands and grows to address the ever-changing priorities in antibacterial resistance. This article describes the innovations, accomplishments, and opportunities of the LOC since the inception of the ARLG in 2013.

Characteristics of depression remission and its relation with cardiovascular outcome among patients with chronic heart failure (from the SADHART-CHF Study).

Depression is prevalent in patients with heart failure and is associated with a significant increase in hospitalizations and death. Primary results of the Sertraline Against Depression and Heart Disease in Chronic Heart Failure (SADHART-CHF) trial revealed that sertraline and placebo had comparable effects on depression and cardiovascular outcomes. In this study, we explored whether remission from depression was associated with better survival and aimed to characterize participants who remitted during the trial. Based on depression response during the 12-week treatment phase, SADHART-CHF participants were divided into 2 groups: (1) remission, defined as participants whose last measured Hamilton Depression Rating Scale (HDRS) score was <8, and (2) nonremission, defined as participants whose last measured HDRS score was ≥8. Patients who dropped out before having any repeat HDRS were not included. Baseline characteristics and survival differences up to 5 years were evaluated between the remission and nonremission groups. Of the 469 SADHART-CHF participants, 208 (44.3%) achieved remission, 194 (41.4%) remained depressed, and 67 (14.3%) dropped out or died without any repeat HDRS assessment. Patients in the remission group had significantly fewer cardiovascular events than those in the nonremission group (1.34 ± 1.86 vs 1.93 ± 2.71, adjusted p = 0.01). Men patients were more likely to remit than women patients (56.5 vs 44.8%, p = 0.02). The remission group had milder depressive symptoms at baseline compared to the nonremission group (HDRS 17.0 ± 5.4 vs 19.6 ± 5.5, Beck Depression Inventory scale 17.9 ± 6.5 vs 20.3 ± 7.2, p <0.001 for the 2 comparisons). In conclusion, this study indicates that remission from depression may improve the cardiovascular outcome of patients with heart failure.

Safety and efficacy of sertraline for depression in patients with heart failure: results of the SADHART-CHF (Sertraline Against Depression and Heart Disease in Chronic Heart Failure) trial.

OBJECTIVES: The objective was to test the hypothesis that heart failure (HF) patients treated with sertraline will have lower depression scores and fewer cardiovascular events compared with placebo. BACKGROUND: Depression is common among HF patients. It is associated with increased hospitalization and mortality. METHODS: The SADHART-CHF (Sertraline Against Depression and Heart Disease in Chronic Heart Failure) trial was a randomized, double-blind, placebo-controlled trial of sertraline 50 to 200 mg/day versus matching placebo for 12 weeks. All participants also received nurse-facilitated support. Eligible patients were age 45 years or older with HF (left ventricular ejection fraction < or =45%, New York Heart Association functional class II to IV) and clinical depression (Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition criteria for current major depressive disorder). Those with significant cognitive impairment, psychosis, recent alcohol or drug dependence, bipolar or severe personality disorder, active suicidal ideation, and current antipsychotic or antidepressant medications were excluded. Primary end points were change in depression severity (Hamilton Depression Rating Scale total score) and composite cardiovascular status at 12 weeks. RESULTS: A total of 469 patients were randomized (n = 234 sertraline, n = 235 placebo). The mean +/- SE change from baseline to 12 weeks in the Hamilton Depression Rating Scale total score was -7.1 +/- 0.5 (sertraline) and -6.8 +/- 0.5 (placebo) (p < 0.001 from baseline, p = 0.89 between groups, mean change between groups -0.4; 95% confidence interval: -1.7 to 0.92). The proportions whose composite cardiovascular score worsened, improved, or was unchanged were 29.9%, 40.6%, and 29.5%, respectively, in the sertraline group and 31.1%, 43.8%, and 25.1%, respectively, in the placebo group (p = 0.78). CONCLUSIONS: Sertraline was safe in patients with significant HF. However, treatment with sertraline compared with placebo did not provide greater reduction in depression or improved cardiovascular status among patients with HF and depression. (Antidepressant Medication Treatment for Depression in Individuals With Chronic Heart Failure [SADHART-CHF]; NCT00078286).

Safety and efficacy of sertraline for depression in patients with CHF (SADHART-CHF): a randomized, double-blind, placebo-controlled trial of sertraline for major depression with congestive heart failure.

BACKGROUND: Sertraline, a selective serotonin-reuptake inhibitor, has demonstrated substantial mood improvement in patients with post myocardial infarction or with unstable angina. The impact of sertraline on the prognosis and depression of patients with chronic heart failure (HF) and comorbid major depressive disorder (MDD) is unknown. METHOD: This is a prospective, randomized, double-blind, placebo-controlled study designed to assess the safety and efficacy of sertraline in the treatment of MDD in patients with HF. The study is designed also to examine the effects of treating depression on cardiac events and morbidity/mortality in patients with HF. Approximately 500 men and women who are >or=45 years of age with current MDD and chronic systolic HF, characterized by left ventricular ejection fraction or=II, comprise the study population. Eligible participants are randomized to either sertraline or placebo for a 12-week acute treatment phase. All patients, regardless of acute treatment phase completion, are followed routinely until the last subject completes 6-month follow-up. Quality of life and certain physiologic parameters, as well as pro-inflammatory and HF biomarkers, that may reflect the impact of sertraline in this particular population are measured at baseline and at the end of the acute treatment phase. CONCLUSION: Because of the high prevalence of depression and its significant adverse impact on prognosis of patients with ischemic heart disease (IHD) and HF, the Safety and Efficacy of Sertraline for Depression in Patients with Chronic Heart Failure (SADHART-CHF) trial aims to assess the effects of sertraline on response of depression as well as on the cardiac prognosis of patients with HF.