Optimal Duration for Continuation of Statin Therapy in Bacteremic Patients

Background: Evidence suggests statins may improve survival in patients with bloodstream infections. However, there is no consensus on optimal timing and duration of exposure. Objectives: To quantify statin therapy duration associated with decreased mortality in bacteremic statin users. Methods: We conducted a case-control study using OptumClinformatics™ with matched Premier hospital data (1 October 2009–31 March 2013). Cases who died during the hospitalization were matched 1:1 to survivors on disease risk scores (DRSs). Post-admission statin therapy duration was evaluated in patients with at least 90 days of pre-admission continuous statin use. Classification and regression tree (CART) analysis was conducted to identify the optimal duration of statin continuation which provided the lowest inpatient mortality. Logistic regression was used to calculate the odds of mortality. Results: We included 58 DRS matched pairs of cases and controls: 47 patients (41%) continued statin therapy during the hospital admission, 15 (32%) cases and 32 (68%) controls. The CART analysis partitioned the continuation of statin therapy at ⩾2 days, representing lower mortality for patients who continued statins for 2 days or more and higher mortality for patients who did not continue or remained on statins for only 1 day. Inpatient mortality was 76% lower among those with at least 2 days of continued statin use (odds ratio 0.24, 95% confidence interval 0.11–0.55)

Higher Daptomycin Dose Associated with Improved Survival in Methicillin-Resistant Staphylococcus aureus Bacteremia

Study Objective: Current guidelines recommend higher daptomycin doses than the daptomycin label dose of 6 mg/kg for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia; however, the evidence supporting this recommendation is from in vitro and case series studies. This study evaluated the comparative effectiveness of the daptomycin label dose versus higher daptomycin doses in patients with MRSA bacteremia. Design: Retrospective national cohort study. Setting: Veterans Affairs medical centers. Patients: A total of 371 adults with MRSA bacteremia who were admitted between 2002 and 2015 and treated initially with vancomycin within 24 hours of initial culture collection and then switched to daptomycin therapy within 7 days; 138 patients (37.2%) received daptomycin doses higher than the daptomycin label dose (7 mg/kg or greater), and 233 (62.8%) received the daptomycin label dose (6 mg/kg). Measurements and Main Results: Clinical outcomes were compared among those who received the daptomycin label dose and those who received the higher dose using propensity score–matched Cox proportional hazards regression models. To identify dose partitioning associated with optimal survival, classification and regression tree (CART) analysis was used among patients, controlling for confounding with a 30-day mortality disease risk score. Propensity score–matched 30-day mortality was 8.6% (6/70 patients) among the higher dose group versus 18.6% (13/70 patients) among the label dose group (hazard ratio 0.31, 95% confidence interval 0.10–0.94). No significant differences were observed in inpatient mortality, length of stay, 30-day readmission, or 30-day S. aureus reinfection between groups. CART analysis resulted in doses of 7 mg/kg or greater providing benefit only among patients with higher (more than 51%) predicted probabilities of 30-day mortality (p\u3c0.001). Conclusion: To our knowledge, this is the first comparative effectiveness study of daptomycin doses in patients with MRSA bacteremia. Survival benefits were observed with doses higher than the daptomycin label dose (7 mg/kg or greater) for the treatment of MRSA bacteremia. These data suggest that higher doses than the daptomycin label dose may be preferred over the label dose for improving clinical outcomes in patients with MRSA bacteremia

Heterogeneity in the treatment of bloodstream infections identified from antibiotic exposure mapping

Purpose: As changes in antibiotic therapy are common, intent‐to‐treat and definitive therapy exposure definitions in infectious disease clinical trials and observational studies may not accurately reflect all antibiotics received over the course of the infection. Therefore, we sought to describe changes in antibiotic therapy and unique treatment patterns among patients with bacteremia. Methods: We conducted a retrospective cohort study of hospitalizations from Veterans Affairs (VA) Medical Centers (January 2002‐September 2015) and community hospitals (de‐identified Optum Clinformatics DataMart with matched Premier Hospital data; October 2009‐March 2013). In the VA population, antibiotic exposures were mapped from the culture collection date among those with positive Staphylococcus aureus cultures. In the Optum‐Premier population, exposures were mapped from the admission date among those with a primary diagnosis of bacteremia. Results: Our study included 50 467 bacteremia admissions, with only 14% of admissions having the same treatment pattern as another admission. For every 100 bacteremia admissions, 89 had changes in antibiotic therapy. For every 100 bacteremia admissions with changes in therapy, 95 had unique antibiotic treatment patterns. These findings were consistent in both populations, over time, and among different facilities within study populations. The median time to first therapy change was 2 days after initial therapy, with a median of three changes. Conclusions: Changes in antibiotic therapy for bloodstream infections were nearly universal regardless of hospital setting. Based on our findings, common antibiotic exposure definitions of intent‐to‐treat and definitive therapy would misclassify exposure in 86% of admissions, which highlights the need for better operational definitions of exposure in infectious diseases research

The Effect of Molecular Rapid Diagnostic Testing on Clinical Outcomes in Bloodstream Infections: A Systematic Review & Meta-analysis

Background. Previous reports on molecular rapid diagnostic testing (mRDT) do not consistently demonstrate improved clinical outcomes in bloodstream infections (BSIs). This meta-analysis seeks to evaluate the impact of mRDT in improving clinical outcomes in BSIs. Methods. We searched PubMed, CINAHL, Web of science, and EMBASE through May 2016 for BSI studies comparing clinical outcomes by mRDT and conventional microbiology methods. Results. Thirty-one studies were included with 5,920 patients. Risk of morality was significantly lower with mRDT as compared to conventional microbiology methods (OR 0.66, 95% CI 0.54-0.80) yielding a NNT of 20. The risk of mortality was slightly lower with mRDT in studies with antimicrobial stewardship programs (ASPs) (OR 0.64, 95% CI 0.51-0.79) and non-ASP studies failed to demonstrate a significant decrease in risk of mortality (OR 0.72, 95% CI 0.46-1.12). Significant decreases in mortality risk were observed with both Gram-positive (OR 0.73, 95% CI 0.55-0.97) and Gram-negative organisms (OR 0.51, 95% CI 0.33-0.78) but not yeast (OR 0.90, 95% CI 0.49-1.67). Time to effective therapy decreased by a weighted mean difference of -5.03 hours (95% CI -8.60 to -1.45) and length of stay decreased by -2.48 days (95% CI -3.90 to -1.06). Conclusions. For BSIs, mRDT was associated with significant decreases in risk of mortality in the presence of a ASP, but not in its absence. Additionally, mRDT decreased time to effective therapy and length of stay. mRDT should be considered as part of the standard of care in patients with BSIs

Assessments of Opportunities to Improve Antibiotic Prescribing in an Emergency Department: A Period Prevalence Survey

Introduction Approximately 30% of all outpatient antimicrobials are inappropriately prescribed. Currently, antimicrobial prescribing patterns in emergency departments (ED) are not well described. Determining inappropriate antimicrobial prescribing patterns and opportunities for interventions by antimicrobial stewardship programs (ASP) are needed. Methods A retrospective chart review was performed among a random sample of non-admitted, adult patients who received an antimicrobial prescription in the ED from January 1 to December 31, 2015. Appropriateness was measured using the Medication Appropriateness Index, and was based on provider adherence to local guidelines. Additional information collected included patient characteristics, initial diagnoses, and other chronic medication use. Results Of 1579 ED antibiotic prescriptions in 2015, we reviewed a total of 159 (10.1%) prescription records. The most frequently prescribed antimicrobial classes included penicillins (22.6%), macrolides (20.8%), cephalosporins (17.6%), and fluoroquinolones (17.0%). The most common indications for antibiotics were bronchitis or upper respiratory tract infection (URTI) (35.1%), followed by skin and soft tissue infection (SSTI) (25.0%), both of which were the most common reason for unnecessary prescribing (28.9% of bronchitis/URTIs, 25.6% of SSTIs). Of the antimicrobial prescriptions reviewed, 39% met criteria for inappropriateness. Among 78 prescriptions with a consensus on appropriate indications, 13.8% had inappropriate dosing, duration, or expense. Conclusion Consistent with national outpatient prescribing, inappropriate antibiotic prescribing in the ED occurred in 39% of cases with the highest rates observed among patients with bronchitis, URTI, and SSTI. Antimicrobial stewardship programs may benefit by focusing on initiatives for these conditions among ED patients. Moreover, creation of local guideline pocketbooks for these and other conditions may serve to improve prescribing practices and meet the Core Elements of Outpatient Stewardship recommended by the Centers for Disease Control and Prevention

Evidence to support continuation of statin therapy in patients with Staphylococcus aureus bacteremia

In addition to cholesterol-lowering capabilities, statins possess anti-inflammatory and immunomodulatory effects. We sought to quantify the real-world impact of different statin exposure patterns on clinical outcomes in Staphylococcus aureus bacteremia. We conducted a retrospective cohort study among hospitalized patients with positive S. aureus blood cultures receiving appropriate antibiotics within 48 h of culture collection (Veterans Affairs hospitals, 2002 to 2013). Three statin exposure groups were compared to nonusers: pretreated statin users initiating therapy in the 30 days prior to culture and either (i) continuing statin therapy after culture or (ii) not continuing after culture, and (iii) de novo users initiating at culture. Nonusers included patients without statins in the year prior to culture through discharge. Propensity score-matched Cox proportional hazards regression models were developed. We were able to balance significantly different baseline characteristics using propensity score matching for pretreated without continuation (n = 331), pretreated with continuation (n = 141), and de novo (n = 177) statin users compared to nonusers. We observed a significantly lower 30-day mortality rate (hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.25 to 0.84; number needed to treat [NNT], 10) among pretreated and continued statin users, while protective effects were not observed in de novo (HR, 1.04; 95% CI, 0.60 to 1.82; NNT, undefined) or pretreated but not continued (HR, 0.92; 95% CI, 0.64 to 1.32; NNT, 47) users. In our national cohort study among patients with S. aureus bacteremia, continuation of statin therapy among incident statin users was associated with significant beneficial effects on mortality, including a 54% lower 30-day mortality rate

Predicting Extended-Spectrum Beta-Lactamase and Carbapenem Resistance in Enterobacteriaceae Bacteremia: A Diagnostic Model Systematic Review and Meta-Analysis

Enterobacteriaceae bacteremia, particularly when associated with antimicrobial resistance, can result in increased mortality, emphasizing the need for timely effective therapy. Clinical risk prediction models are promising tools, stratifying patients based on their risk of resistance due to ESBL and carbapenemase-producing Enterobacteriaceae in bloodstream infections (BSIs) and, thereby, improving therapeutic decisions. This systematic review and meta-analysis synthesized the literature on the performance of these models. Searches of PubMed and EMBASE led to the identification of 10 relevant studies with 6106 unique patient encounters. Nine studies concerned ESBL prediction, and one focused on the prediction of carbapenemases. For the two ESBL model derivation studies, the discrimination performance showed sensitivities of 53–85% and specificities of 93–95%. Among the four ESBL model derivation and validation studies, the sensitivities were 43–88%, and the specificities were 77–99%. The sensitivity and specificity for the subsequent external validation studies were 7–37% and 88–96%, respectively. For the three external validation studies, only two models were evaluated across multiple studies, with a pooled AUROC of 65–71%, with one study omitting the sensitivity/specificity. Only two studies measured clinical utility through hypothetical therapy assessments. Given the limited evidence on their interventional application, it would be beneficial to further assess these or future models, to better understand their clinical utility and ensure their safe and impactful implementation

Diagnostic Stewardship as a Team Sport: Interdisciplinary Perspectives on Improved Implementation of Interventions and Effect Measurement

Diagnostic stewardship aims to deliver the right test to the right patient at the right time and is optimally combined with antimicrobial stewardship to allow for the right interpretation to translate into the right antimicrobial at the right time. Laboratorians, physicians, pharmacists, and other healthcare providers have an opportunity to improve the effectiveness of diagnostics through collaborative activities around pre-analytical and post-analytical periods of diagnostic testing. Additionally, special considerations should be given to measuring the effectiveness of diagnostics over time. Herein, we perform a narrative review of the literature on these potential optimization opportunities and the temporal factors that can yield changes in diagnostic effectiveness. Our objective is to inform on these considerations to ensure enhanced value through improved implementation and measurement of effectiveness for local stakeholder metrics and/or clinical outcomes research