A pharmacist-driven academic detailing program to increase adult pneumococcal vaccination.

OBJECTIVES: To describe our statewide, pharmacist-led education campaign to increase knowledge and awareness of pneumococcal immunization recommendations. SETTING: Immunization providers and residents in the state of Rhode Island. PRACTICE DESCRIPTION: A clinical pathway (i.e., decision-support tool) was developed to educate health professionals about appropriate indications, administration schedules, and frequently asked questions for the 2 different adult pneumococcal vaccines. Academic detailing and distribution of the clinical pathway to health professionals was conducted across Rhode Island. Community outreach activities included radio ads as well as distribution of patient handouts and wallet cards at community events. PRACTICE INNOVATION: To our knowledge, this was the first statewide, pharmacist-driven academic detailing and community outreach campaign to promote adult pneumococcal vaccination. EVALUATION: Academically detailed immunization providers received a 6-question survey. Pneumococcal disease rate differences between the study periods were evaluated with the use of Fisher exact tests, whereas changes in vaccination were assessed with the use of chi-square tests. RESULTS: From November 2013 through July 2015, our academic detailers visited and distributed our vaccination pathway materials to more than 400 practice sites across Rhode Island, including 68% of community pharmacies and all adult acute care hospitals. Of the 413 surveys completed, 92% of respondents agreed that their knowledge of the pneumococcal conjugate vaccine, 13-valent and pneumococcal polysaccharide vaccine, 23-valent had improved. Pneumococcal vaccination increased significantly (absolute difference 3.9%, percentage change in proportion 5.4%; P = 0.01), and pneumococcal disease decreased significantly between the preintervention and intervention periods (-2.74/10,000 discharges [95% CI -5.15 to -0.32], P = 0.02). Invasive pneumococcal disease decreased by 21 cases per 1,000,000 population per year between the preintervention and postintervention periods (-42.25 to 0.14, P = 0.05). CONCLUSION: Our statewide, pharmacist-driven pneumococcal vaccination educational outreach program resulted in favorable provider feedback relative to knowledge change and perceptions. Vaccination increased and pneumococcal disease decreased during the study period.

Risk stacking of pneumococcal vaccination indications increases mortality in unvaccinated adults with Streptococcus pneumoniae infections.

BACKGROUND: Several chronic disease states have been identified as pneumococcal vaccination indications due to their ability to increase pneumococcal disease development and subsequent mortality. However, the risk of mortality according to the number of these disease states present is unknown. We sought to determine the impact of concomitant, multiple risk factors (stacked risks) for pneumococcal disease on 30-day mortality in adults. METHODS: This was a national case-control study of unvaccinated older Veterans (≥50years of age) admitted to Veterans Affairs medical centers from 2002 to 2011 with serious pneumococcal infections (pneumonia, bacteremia, meningitis) based on positive S. pneumoniae blood, cerebrospinal fluid, or respiratory cultures, respectively. Cases were those not alive 30days following culture, while controls were alive. Using logistic regression, we quantified risk of 30-day mortality among patients with stacked risk factors, including age ≥65years, alcohol abuse, chronic heart disease, chronic liver disease, chronic respiratory disease, diabetes mellitus, immunodeficiency, and smoking. RESULTS: We identified 9730 serious pneumococcal infections, with an overall 30-day mortality rate of 18.6% (1764 cases, 7966 controls). Infection types included pneumonia (62%), bacteremia (26%), and bacteremic pneumonia (11%). Along with eight individual risk factors, we assessed 247 combinations of risk factors. Most cases (85%) and controls (74%) had at least two risk factors. Mortality increased as risks were stacked, up to six risk factors (one: OR 1.5, CI 1.08-2.07; two: OR 2.01, CI 1.47-2.75; three: OR 2.71, CI 1.99-3.69; four: OR 3.27, CI 2.39-4.47; five: OR 3.63, CI 2.60-5.07; six: OR 4.23, CI 2.69-6.65), with each additional risk factor increasing mortality an average of 55% (±13%). CONCLUSIONS: Among adults ≥50years with serious pneumococcal disease, mortality risk increased approximately 55% as vaccination indications present increased. Mortality with six stacked indications was double that of two indications.

Antimicrobial Resistance of Escherichia coli Urinary Isolates in the Veterans Affairs Health Care System.

We reviewed data for almost 300,000 clinical Escherichia coli urinary isolates (collected in 2009 through 2013) from 127 inpatient and outpatient facilities, to assess antibiotic resistance among Veterans Affairs health care system patients using Clinical and Laboratory Standards Institute and Centers for Disease Control and Prevention National Healthcare Safety Network definitions or guidance. Rates of resistance to amoxicillin or ampicillin/ß-lactamase inhibitors were approximately 40% and rates of resistance to fluoroquinolones and trimethoprim-sulfamethoxazole approached 30%. Rates of resistance to nitrofurantoin, antipseudomonal penicillin/ß-lactamase inhibitors, and carbapenems remained less than 10%. The percentage of isolates that were considered multidrug resistant varied (4% to 37%), depending on the definitions used.

Predictors of Mortality Among U.S. Veterans With Streptococcus Pneumoniae Infections.

INTRODUCTION: Serious Streptococcus pneumoniae infections, encompassing pneumonia, bacteremia, and meningitis, are a major cause of mortality. However, literature regarding mortality is often limited to invasive pneumococcal disease, excluding pneumonia. This study sought to identify predictors of mortality among adults with serious pneumococcal disease, including pneumonia and invasive pneumococcal disease. METHODS: This was a nested case-control study of unvaccinated older Veterans with positive S. pneumoniae cultures (blood, cerebrospinal fluid, respiratory) admitted to Veterans Affairs medical centers nationally between 2002 and 2011. Patients vaccinated against pneumococcal disease were excluded. Using multivariable logistic regression, predictors of 30-day mortality were identified, including patient demographics, comorbidities during admission, and medical history within the previous year. RESULTS: Among 9,468 patients, there were 9,730 serious pneumococcal infections; 1,764 (18.6%) resulted in death within 30 days (cases), whereas 7,966 did not (controls). Pneumonia accounted for half (49.4%, n=871) of all deaths. Mortality predictors consistent with vaccine recommendations included dialysis (during hospitalization, OR=3.35, 95% CI=2.37, 4.72), moderate to severe liver disease (during hospitalization, OR=2.47, 95% CI=1.53, 3.99; within 1 year, OR=1.49, 95% CI=1.01, 2.20), and neutropenia (during hospitalization, OR=2.67, 95% CI=1.32, 5.42). Predictors not included in current recommendations included dementia (during hospitalization, OR=1.8, 95% CI=1.23, 2.61) and neurologic disorders (during hospitalization, OR=1.86, 95% CI=1.42, 2.45; within 1 year, OR=1.28, 95% CI=1.02, 1.59). CONCLUSIONS: Several mortality predictors among unvaccinated Veterans with serious pneumococcal disease were consistent with pneumococcal vaccine recommendations, including organ or immune system dysfunction-related conditions. Other predictors, including neurologic disorders or dementia, may warrant expanded vaccination recommendations.

Are non-allergic drug reactions commonly documented as medication "allergies"? A national cohort of Veterans' admissions from 2000 to 2014.

PURPOSE: Adverse drug reactions (ADRs) including medication allergies are not well-described among large national cohorts. This study described the most common documented medication allergies and their reactions among a national cohort of Veterans Affairs (VA) inpatients. METHODS: We evaluated inpatient admissions in any VA Medical Center from 1 January 2000 to 31 December 2014. Each admission was linked with allergy history preceding or upon admission. Individual drugs were aggregated into drug class category including: penicillins, sulfonamides, angiotensin converting enzyme (ACE) inhibitors, opiates, HMG-CoA reductase inhibitors ("statins") and non-steroidal anti-inflammatory inhibitors (NSAID). Results were reported in aggregate and over time. RESULTS: Approximately ~10.8 million inpatient admissions occurred from 2000 to 2014. We found the most commonly reported allergy drug classes were penicillins (13%, n = 1 410 080), opiates (9.1%, n = 984 978), ACE inhibitors (5.7%, n = 618 075) sulfonamides (5.1%, n = 558 653), NSAIDs (5.1%, n = 551 216) and statins (3.6%, n = 391 983). Several allergy histories increased over time including opiates (6.2 to 11.2%), ACE inhibitors (1.3 to 10.2%), statins (0.3 to 7.3%) and NSAIDs (3.9 to 6.0%). Rash was the most commonly documented reaction on reports for penicillins (25.5%, n = 371 825), sulfonamides (25.6%, n = 165 954) and NSAIDs (10.3%, n = 65 741). The most common reaction for opiates was nausea/vomiting (17.9%, n = 211 864), cough/coughing for ACE inhibitors (41.0%, n = 270 537) and muscle pain/myalgia for statins (34.1%, n = 186 565). CONCLUSIONS: We report that penicillins and opiates are the most commonly documented drug allergies among VA inpatients, but other drug classes such as ACE inhibitors, statins and NSAIDs are becoming increasingly common. Clinicians also commonly document non-allergic ADRs in the allergy section such as cough or myalgia. Copyright © 2016 John Wiley & Sons, Ltd.

Antimicrobial Stewardship in Rhode Island Long-Term Care Facilities: Current Standings and Future Opportunities.

Our survey of antimicrobial stewardship practices among Rhode Island long-term care facilities demonstrated opportunities to develop formal programs. Results suggest infection preventionists are largely responsible for ensuring appropriate antibiotic use in long-term care facilities and there is a need for increased interdisciplinary access to individuals with antimicrobial stewardship expertise. Infect Control Hosp Epidemiol 2016;37:979-982.

Impact of a Prospective Audit and Feedback Antimicrobial Stewardship Program at a Veterans Affairs Medical Center: A Six-Point Assessment.

BACKGROUND: Prospective audit and feedback is a core antimicrobial stewardship program (ASP) strategy; however its impact is difficult to measure. METHODS: Our quasi-experimental study measured the effect of an ASP on clinical outcomes, antimicrobial use, resistance, costs, patient safety (adverse drug events [ADE] and Clostridium difficile infection [CDI]), and process metrics pre- (9/10-10/11) and post-ASP (9/12-10/13) using propensity adjusted and matched Cox proportional-hazards regression models and interrupted time series (ITS) methods. RESULTS: Among our 2,696 patients, median length of stay was 1 day shorter post-ASP (5, interquartile range [IQR] 3-8 vs. 4, IQR 2-7 days, p<0.001). Mortality was similar in both periods. Mean broad-spectrum (-11.3%), fluoroquinolone (-27.0%), and anti-pseudomonal (-15.6%) use decreased significantly (p<0.05). ITS analyses demonstrated a significant increase in monthly carbapenem use post-ASP (trend: +1.5 days of therapy/1,000 patient days [1000PD] per month; 95% CI 0.1-3.0). Total antimicrobial costs decreased 14%. Resistance rates did not change in the one-year post-ASP period. Mean CDI rates/10,000PD were low pre- and post-ASP (14.2 ± 10.4 vs. 13.8 ± 10.0, p = 0.94). Fewer patients experienced ADEs post-ASP (6.0% vs. 4.4%, p = 0.06). CONCLUSIONS: Prospective audit and feedback has the potential to improve antimicrobial use and outcomes, and contain bacterial resistance. Our program demonstrated a trend towards decreased length of stay, broad-spectrum antimicrobial use, antimicrobial costs, and adverse events.

Antimicrobial Stewardship in Long-Term Care Facilities: A Call to Action.

Antimicrobial resistance is a global public health crisis and a national security threat to the United States, as stated in an executive order signed by the president in September 2014. This crisis is a result of indiscriminant antimicrobial use, which promotes selection for resistant organisms, increases the risk of adverse drug events, and renders patients vulnerable to drug-resistant infections. Antimicrobial stewardship is a key measure to combat antimicrobial resistance and specifically seeks to do this by improving antimicrobial use. Antimicrobial stewardship compliments infection control practices and it is important to note that these 2 disciplines are distinct and cannot be discussed interchangeably. Antimicrobial stewardship promotes the appropriate diagnosis, drug, dose, and duration of treatment. The appropriate diagnosis falls into the hands of the prescriber and clinical staff. Optimal antimicrobial drug selection, dosing strategy, and duration of treatment, however, often require expertise in antimicrobial therapy, such as an infectious disease-trained physician or pharmacist. Therefore, successful antimicrobial stewardship programs must be comprehensive and interdisciplinary. Most antimicrobial stewardship programs focus on hospitals; yet, in long-term care, up to 75% of antimicrobial use is inappropriate or unnecessary. Thus, one of the most pressing areas in need for antimicrobial stewardship is in long-term care facilities. Unfortunately, there is little evidence that describes effective antimicrobial stewardship interventions in this setting. This review discusses the need for and barriers to antimicrobial stewardship in long-term care facilities. Additionally, this review describes prior interventions that have been implemented and tested to improve antimicrobial use in long-term care facilities.

Vancomycin Dosing Considerations in a Real-World Cohort of Obese and Extremely Obese Patients.

STUDY OBJECTIVE: To compare the effects of empiric vancomycin dosing regimens on attainment of optimal target trough concentrations in obese (body mass index [BMI] 30-40 kg/m(2) ) and extremely obese (BMI ≥ 40 kg/m(2) ) patients. DESIGN: Retrospective cohort study. DATA SOURCE: National Veterans Affairs standardized databases. PATIENTS: A total of 263 obese and 71 extremely obese (actual body weight range 72-244 kg in both groups) inpatients from all Veterans Affairs facilities nationally who had suspected methicillin-resistant Staphylococcus aureus pneumonia and were treated with vancomycin between 2002 and 2012. MEASUREMENTS AND MAIN RESULTS: Patients with steady-state trough concentrations (measured ≤ 2 hours before the next vancomycin dose) and no evidence of acute kidney injury before vancomycin initiation were included. Logistic regression models were used to measure the effect of various vancomycin dosing regimens on attainment of optimal target trough concentrations (15-20 mg/L). The mean total daily vancomycin dose was lower in obese versus extremely obese patients (2005 ± 736 vs 2306 ± 934 mg, p<0.05). The mean weight-based daily dose was higher in obese patients (20 ± 7 vs 17 ± 7 mg/kg/day, p<0.05). In each group, ~ 20% of patients achieved optimal target trough concentrations. In obese patients, the standard dose of ~ 30 mg/kg/day was appropriate for target trough concentration attainment (odds ratio 5.15, 95% confidence interval 1.69-15.64). In extremely obese patients, a lower dosage of 20 to 25 mg/kg/day was appropriate for target trough concentration attainment (odds ratio 6.07, 95% confidence interval 1.01-36.51). CONCLUSION: In this real-world study, we offer additional consideration of vancomycin dosing in obese and extremely obese patients. Extremely obese patients may require a lower weight-based daily dose than obese patients to reach target vancomycin trough concentrations.

Treatment Options for Carbapenem-Resistant Enterobacteriaceae Infections.

This article provides a comprehensive review of currently available treatment options for infections due to carbapenem-resistant Enterobacteriaceae (CRE). Antimicrobial resistance in Gram-negative bacteria is an emerging and serious global public health threat. Carbapenems have been used as the "last-line" treatment for infections caused by resistant Enterobacteriaceae, including those producing extended spectrum ß-lactamases. However, Enterobacteriaceae that produce carbapenemases, which are enzymes that deactivate carbapenems and most other ß-lactam antibiotics, have emerged and are increasingly being reported worldwide. Despite this increasing burden, the most optimal treatment for CRE infections is largely unknown. For the few remaining available treatment options, there are limited efficacy data to support their role in therapy. Nevertheless, current treatment options include the use of older agents, such as polymyxins, fosfomycin, and aminoglycosides, which have been rarely used due to efficacy and/or toxicity concerns. Optimization of dosing regimens and combination therapy are additional treatment strategies being explored. Carbapenem-resistant Enterobacteriaceae infections are associated with poor outcomes and high mortality. Continued research is critically needed to determine the most appropriate treatment.

Epidemiology of pneumococcal disease in a national cohort of older adults.

INTRODUCTION: Streptococcus pneumoniae is a major cause of morbidity and mortality. We sought to describe the epidemiology of non-invasive and invasive pneumococcal disease in a national Veterans Affairs population within the United States. METHODS: We conducted a retrospective study in older patients (aged ≥50 years) with positive pneumococcal cultures from any site between 2002 and 2011. We described outpatient and inpatient pneumococcal disease incidence per 100,000 clinic visits/hospitalizations. Repeat cultures within a 30-day period were considered to represent the same episode. To describe the epidemiology of serious pneumococcal infections (bacteremia, meningitis, pneumonia), we assessed demographics, clinical characteristics, and risk factors for S. pneumoniae. Pneumonia was defined as a positive respiratory culture with a pneumonia diagnosis code. Bacteremia and meningitis were identified from positive cultures. Generalized linear mixed models were used to quantify changes over time. RESULTS: Over the study period, we identified 45,983 unique episodes of pneumococcal disease (defined by positive cultures). Incidence decreased significantly by 3.5% per year in outpatients and increased non-significantly by 0.2% per year in inpatients. In 2011, the outpatient and inpatient incidence was 2.6 and 328.1 infections per 100,000 clinic visits/hospitalizations, respectively. Among inpatients with serious infections, chronic disease risk factors for pneumococcal disease increased significantly each year, including respiratory disease (1.9% annually), diabetes (1.3%), and renal failure (1.0%). Overall, 30.2% of inpatients with serious infections had a pneumococcal immunization in the previous 5 years. Invasive disease (37.4% versus 34.9%, P = 0.004) and mortality (14.0% versus 12.7%, P = 0.045) were higher in non-vaccinated patients compared to vaccinated patients. CONCLUSIONS: In our national study of older adults, the baseline health status of those with serious pneumococcal infections worsened over the study period. As the population ages and the chronic disease epidemic grows, the burden of pneumococcal disease is likely to increase thus highlighting the importance of pneumococcal vaccination.

Antimicrobial stewardship program prompts increased and earlier infectious diseases consultation.

A recent analysis demonstrated that infectious diseases (ID) specialty intervention was associated with decreased mortality and hospital readmission. These benefits were greatest if involvement occurred within two days of hospital admission. Antimicrobial stewardship programs should augment the services of an ID specialist team and promote formal consultation. Implementation of an antimicrobial stewardship program at the Providence Veterans Affairs Medical Center was associated with an increased number of consults (increase of 72.2%) and decreased time to consult (3.5 days sooner), which might also dramatically improve patient outcomes, including mortality and readmission rates.

Predictors of clinical success among a national Veterans Affairs cohort with methicillin-resistant Staphylococcus aureus pneumonia.

BACKGROUND: The treatment of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia is exceedingly complicated, which is concerning because of the high mortality rate associated with the infection. Identification of independent predictors of clinical success can optimize patient care by assisting clinicians in treatment decisions. OBJECTIVES: Our goal was to identify independent predictors of clinical success in a national Veterans Affairs (VA) cohort of patients with MRSA pneumonia. METHODS: A nested case-control study was conducted among a cohort of VA patients with MRSA pneumonia receiving linezolid or vancomycin between January 2002 and September 2010. Cases included those demonstrating clinical success, defined as discharge from the hospital or intensive care unit by day 14 after treatment initiation, in the absence of death, therapy change, or intubation by day 14. Control subjects represented nonsuccess, defined as therapy change, intubation, intensive care unit admission, readmission, or death between treatment initiation and day 14. The potential predictors assessed included treatment, patient demographic and admission characteristics, previous health care and medication exposures, comorbidities, and medical history. Odds ratios (ORs) and 95% CIs were calculated from logistic regression. RESULTS: Our study included 2442 cases of clinical success and 1290 control subjects. Demographic characteristics varied between the clinical success and nonsuccess groups, including age, race, and region of facility. A current diagnosis of chronic respiratory disease (46% vs 42%) and diagnosis of pneumonia in the year before the MRSA pneumonia admission (37% vs 32%) were both more common in the clinical success group. Despite these significant differences, only 2 predictors of clinical success were identified in our study: previous complication of an implant or graft, including mechanical complications and infections, in the year before the MRSA pneumonia admission (adjusted OR, 1.55 [95% CI, 1.17-2.06]) and treatment with linezolid (adjusted OR, 1.53 [95% CI, 1.12-2.10]). Predictors of nonsuccess (adjusted OR [95% CI) included diagnosis of concomitant urinary tract infection (0.82 [0.70-0.96]), intravenous line (0.76 [0.66-0.89]), previous coagulopathy (0.74 [0.56-0.96]), previous amputation procedure (0.72 [0.53-0.98]), current coagulopathy diagnosis (0.71 [0.53-0.96]), dialysis (0.54 [0.38-0.76]), multiple inpatient procedures (0.53 [0.45-0.62]), inpatient surgery (0.48 [0.41-0.57]), and previous endocarditis (0.24 [0.07-0.81]). CONCLUSIONS: MRSA pneumonia tends to affect patients with complex care, and identification of the predictors of clinical success is useful when considering different therapeutic approaches. In this national cohort of VA patients with MRSA pneumonia, treatment was the only modifiable variable predicting clinical success.

Comparative effectiveness of linezolid and vancomycin among a national veterans affairs cohort with methicillin-resistant Staphylococcus aureus pneumonia.

STUDY OBJECTIVE: As variability in vancomycin dosing, susceptibility, and tolerability has driven the need to compare newer agents with vancomycin in real-world clinical settings, we sought to quantify the effectiveness of linezolid compared with vancomycin on clinical outcomes for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. DESIGN: Retrospective cohort study. DATA SOURCE: Veterans Health Administration national databases. PATIENTS: Adults admitted to Veterans Affairs hospitals between January 2002 and September 2010 with diagnosis codes for MRSA and pneumonia, plus initiation and receipt of at least 3 days of continuous intravenous vancomycin therapy (4943 patients) or intravenous or oral linezolid therapy (328 patients) while in the hospital. MEASUREMENTS AND MAIN RESULTS: Propensity score-adjusted Cox proportional hazards regression models quantified the effect of linezolid compared with vancomycin on time to 30-day mortality (primary outcome), therapy change, hospital discharge, discharge from intensive care, intubation, 30-day readmission, and 30-day MRSA reinfection. In addition, a composite outcome of clinical success was defined as discharge from the hospital or intensive care unit by day 14 after treatment initiation, in the absence of death, therapy change, or intubation by day 14. Subgroup analyses were performed in a validated microbiology-confirmed MRSA subgroup and clinical subgroup meeting clinical criteria for infection. Although a number of baseline variables differed significantly between the vancomycin and linezolid treatment groups, balance was achieved within propensity score quintiles. A significantly lower rate of therapy change was observed in the linezolid group (adjusted hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.48-0.96). The clinical success rate was significantly higher among patients treated with linezolid (adjusted HR 1.25, 95% CI 1.07-1.47). Comparable findings were observed in the subgroup analyses. CONCLUSION: Individual clinical outcomes were similar among patients treated for MRSA pneumonia with linezolid compared with vancomycin. A significantly higher rate of the composite outcome of clinical success was observed, however, among patients treated with linezolid compared with vancomycin.

Risk of hepatotoxicity associated with fluoroquinolones: a national case-control safety study.

PURPOSE: Results of a pharmacoepidemiologic evaluation of fluoroquinolone-associated hepatotoxicity using national hospital admissions data on Veterans Affairs (VA) patients are reported. METHODS: In a retrospective case-control study, all adults with a primary diagnosis of hepatotoxicity on admission to a VA facility during a 6.5-year period (January 2002-June 2008) were identified. After the exclusion of patients whose records indicated known causes of hepatotoxicity or a history of liver disease, a subgroup of 7,862 patients with exposure to fluoroquinolone antibiotics in the six months prior to hospital admission were matched with nonexposed controls (n = 45,512). Conditional logistic regression was used to assess the overall and drug-specific risks of hepatotoxicity in the case group, controlling for comorbidities, concomitant use of known hepatotoxic medications, and other variables. RESULTS: After adjusting for confounders, logistic regression analysis indicated a significantly higher overall risk of hepatotoxicity development among fluoroquinolone users relative to controls (odds ratio [OR], 1.20; 95% confidence interval [CI], 1.04-1.38). Drug-specific risk analyses focused on three fluoroquinolone agents (ciprofloxacin, levofloxacin, and moxifloxacin) indicated a significant association between ciprofloxacin use and an increased risk of hepatotoxicity (OR, 1.29; 95% CI, 1.05-1.58); when considered as independent variables, levofloxacin use and moxifloxacin use were not significantly associated with hepatotoxicity risk. CONCLUSION: The findings of a national VA safety study suggested an increased hepatotoxicity risk asssociated with fluoroquinolone exposure in the study population.