OBJECTIVES:Skin and soft tissue infections (SSTI) caused by methicillin-resistant Staphylococcus aureus (MRSA) are prevalent in the emergency department (ED). We determined whether MRSA nasal carriage better identifies patients with MRSA wound infection than clinical risk factors or emergency medicine (EM) provider's choice of discharge prescriptions.METHODS:Adult patients presenting to a large academic medical centre ED in the USA with SSTI between May 2010 and November 2011 were screened. Research assistants administered a questionnaire regarding MRSA risk factors, and MRSA nares swab PCR testing, wound culture results and information on antibiotics prescribed at discharge were collected. Measures of classification accuracy for nares swab, individual risk factors and physician's prescription for MRSA coverage were compared with gold standard wound culture.RESULTS:During the study period, 116 patients with SSTI had both wound cultures and nares swabs for MRSA. S. aureus was isolated in 59.5%, most often MRSA (75.4%). Thirty patients (25.9%) had a positive MRSA nares swab and culture for a sensitivity of 57.7% and specificity of 92.2%. Positive predictive value (PPV) for MRSA nares swab was 85.7% and positive likelihood ratio was 7.4, while negative predictive value was 72.8% and negative likelihood ratio 0.5. None of the individual risk factors nor EM provider's prescription for MRSA coverage had a PPV or positive likelihood ratio higher than nares swabs.CONCLUSIONS:MRSA nares swab is a more accurate predictor of MRSA wound infection compared with clinical risk factors or EM provider's choice of antibiotics. MRSA nares swab may be a useful tool in the ED.

PURPOSEThe potential link between serious or life-threatening bleeding and the use of direct oral anticoagulants (DOACs) was evaluated.METHODSQualitative and quantitative reviews of case reports of bleeding events involving dabigatran, rivaroxaban, apixaban, edoxaban, and warfarin through March 31, 2017, were performed. A disproportionality analysis was conducted for each DOAC using an empirical Bayesian approach based on the relative reporting rate. Subanalyses were performed to assess (1) bleeding events (including mortality and life-threatening events) associated with DOACs among all adverse-event reports and (2) warfarin-related bleeding events. These analyses were conducted based on clinical definitions from the Medical Dictionary for Regulatory Activities.RESULTSDuring the Food and Drug Administration Adverse Event Reporting System (FAERS) review period, 35 adverse-event terms (in any system organ class) with a disproportionality score (EB05) of >7.5 for DOACs were identified; this accounted for 40,109 adverse-event reports. Adverse events with the highest disproportionality scores included atrial thrombosis, increased factor X level, dysfunctional uterine bleeding, high-frequency ablation, pericardial hemorrhage, and internal hemorrhage. Adverse events with the highest EB05 (>5) included internal hemorrhage, hemorrhage, and exsanguination; events with the greatest number of patient experiences included hemorrhage (6,881 events), internal hemorrhage (2,569 events), and hematoma (1,995 events). Warfarin-related events (including death or life-threatening events) were also assessed. A total of 8,729 adverse events were associated with warfarin use. The most common of these included hemorrhage (6,225 events), hematoma (2,199 events), and internal hemorrhage (270 events).CONCLUSIONThe disproportionality analysis of the FAERS database suggests a quantitative signal between DOAC use and life-threatening or serious bleeding.

Objective. To assess students' pre-pharmacy math experiences, confidence in math ability, and relationship between experiences, confidence, and grades in math-based pharmacy courses. Methods. A cross-sectional survey of first year to third year pharmacy students was conducted. Students reported type of pre-pharmacy math courses taken, when they were taken [high school (HS) vs. college] and year of HS and college graduation. Students rated their confidence in math ability using the previously validated 11-item Fogerty Math Confidence Scale (Cronbach alpha=0.92). Math grade point average (GPA), Pharmacy College Admission Test quantitative (PCAT quant) scores, and grades (calculations and kinetics) were obtained from transcripts and school records. Spearman correlation and multivariate linear regression were used to compare math experiences, confidence, and grades. Results. There were 198 students who reported taking math courses 7.1 years since HS graduation and 2.9 years since their last schooling prior to pharmacy school. Students who took math courses with more time since HS/last schooling had lower calculations and kinetics grades. Students reporting having taken more HS math courses had better calculations grades. Students with higher math GPA, and PCAT quant scores also had higher calculations and kinetics grades. Greater confidence in math ability was associated with higher calculations grades. In multivariate regressions, PCAT quant scores and years since HS independently predicted calculations grades, and PCAT quant scores independently predicted kinetics grades. Conclusion. The number of pre-pharmacy math courses and time elapsed since they were taken are important factors to consider when predicting a pharmacy student's success in math-based pharmacy school courses.

Background. The objective of this study was to characterize treatment of patients with acute bacterial skin and skin structure infections (ABSSSIs) and describe the association between hospital admission and emergency department (ED) visits or readmissions within 30 days after initial episode of care (IEC). Methods. Ihis was a retrospective, observational, cohort study of adults with ABSSSI who presented to an ED between July 1, 2012, and June 30, 2013. Patient, health care facility, and treatment characteristics, including unplanned ED visits or readmissions, were obtained through manual chart review and abstraction. Adjusted logistic regression analysis examined likelihood of all-cause unplanned ED visits or readmissions between admitted and nonadmitted patients. Results. Records from 1527 ED visits for ABSSSI from 40 centers were reviewed (admitted, n = 578 [38%]; nonadmitted, n = 949 [62%]). Admitted patients were typically older (mean age, 52.2 years vs 43.0 years), more likely to be morbidly obese (body mass index > 40 kg/m(2); 17.3% vs 9.1%), and had more comorbidities (Charlson Comorbidity Index <= 4; 24.4% vs 6.8%) compared with those not admitted. In the primary analysis, adjusted logistic regression, controlling for comorbidities and severity of illness, demonstrated that there was a similar likelihood of all-cause unplanned ED visits or readmissions between admitted and nonadmitted patients (odds ratio, 1.03; 95% confidence interval, 0.74-1.43; P = .87). Conclusions. ABSSSI treatment pathways leveraging outpatient treatment vs hospital admission support similar likelihood of unplanned 30-day ED visits or readmissions, an important clinical outcome and quality metric at US hospitals. Further research regarding the decision criteria around hospital admission to avoid potentially unnecessary hospitalizations is warranted.

BACKGROUND:Many factors contribute to medication nonadherence including psychological and memory disorders, aging, and pill burden. The Automated Home Medication Dispenser (AHMD) is a medication management system intended to help solve unintentional medication nonadherence.OBJECTIVE:The purpose of this study was to determine if use of the AHMD improved medication adherence.METHODS:We conducted a 6-month prospective, feasibility study assessing use of the AHMD in 21 patient-caregiver dyads. Patients were referred by their physician because of poor medication adherence and included if they resided in Rochester, NY and on at least two medications in pill form. Pill counts were performed at baseline to assess previous adherence. Prospective medication adherence was assessed using AHMD recorded dosing information. A paired t-test was used to compare previous and prospective adherence.RESULTS:The mean age of patients was 75.1 years. Fifteen patients (71.4%) and eight caregivers (38.1%) were women; half (47.6%) of caregivers lived with the patient. The most common patient comorbidities were hypertension (76.2%) and memory disorder (61.9%). Mean adherence increased from 49.0% at baseline to 96.8% after 6 months of AHMD use (p < .001).CONCLUSION:In a cohort of unintentionally nonadherent patients, use of the AHMD for 6 months significantly improved medication adherence.

PURPOSEThe financial and policy levers of population health and potential opportunities for pharmacists are described.SUMMARYThree long-standing problems drive the focus on population health: (1) the United States suffers far worse population health outcomes compared with those of other developed nations that spend significantly less on healthcare, (2) the U.S. healthcare system's focus on "sick care" fails to address upstream prevention and population health improvement, and (3) financial incentives for healthcare delivery are poorly aligned with improvements in population health outcomes. The Patient Protection and Affordable Care Act of 2010 (ACA) was arguably the first major healthcare legislation since 1965 and had 3 main strategies for improving population health: expand health insurance coverage, control healthcare costs, and improve the healthcare delivery system. Federal and state legislation as well as Medicare and Medicaid financing strategies have designated mechanisms to reward advances in population outcomes since the passage of the ACA. States are responsible for many of the factors that affect population health, and a bipartisan effort that builds upon state and federal collaboration will likely be needed to implement the necessary health policy initiative. Population health issues affect productivity in the United States; conversely, improvements in population health may increase productivity, helping to offset the rising federal debt. Employers are in a position to improve population health and consequently help reduce the federal debt by addressing lifestyle, chronic disease, poverty, and inequality. National pharmacy organizations, regulatory bodies, and journal editors need to collectively agree to a threshold of quality and rigor for publication and endorsement.CONCLUSIONKnowledge of the policy and financial drivers of population health may both support pharmacists' efforts to improve population outcomes and identify opportunities for professional advancement.

The objective of this case case-control study was to identify risk factors for carbapenem-nonsusceptible Pseudomonas aeruginosa in adult acute care hospitalized patient at 2 large academic medical centers. Risk factors were evaluated using logistic regression within a generalized estimating equations framework to account for clustering of patients within study site. Of 1161 total isolates, 271 (23.3%) were carbapenem-nonsusceptible of which respiratory was the most common source (54.3%). In the multivariable model, intra-abdominal (P < 0.0001) and respiratory (P = 0.0014) sources were associated with a higher odds for carbapenem nonsusceptibility when compared to urine source. Prior positive culture (P < 0.0001), use of an antipseudomonal carbapenem in the prior 30 days (P < 0.0001) and culture collection in the intensive care unit (P < 0.0001) were also associated with increased odds for carbapenem-nonsusceptibility. Further studies to validate these findings are warranted.

BACKGROUND Methadone (ME) is commonly used in pain and palliative care (PPC) patients with refractory pain or intolerable opioid adverse effects (AEs). A unique ME AE is its corrected QT (QTc) interval prolongation risk, but most evidence exists in methadone maintenance therapy patients. OBJECTIVE Our goal was to identify QTc interval prolongation risk factors in PPC patients receiving ME and other medications known to prolong the QTc interval and develop a risk stratification tool. DESIGN We performed a case-control study of adult inpatients receiving ME for pain management. Settings/Subjects: Adult inpatients receiving ME with a QTc >470 msec (males) and >480 msec (females) were matched 1:2 according to age, history of QTc prolongation, and gender with ME patients who did not have a prolonged QTc interval. QTc prolongation risk factors were collected for both groups. Covariates were analyzed using conditional logistic regression. Classification and regression tree analysis was used to identify the ME dose associated with QTc prolongation. RESULTS Predictors of QTc prolongation included congestive heart failure (CHF) (OR: 11.9; 95% CI: 3.7-38.2; p < 0.00), peptic ulcer disease (PUD) (odds ratio [OR]: 8.3; 95% confidence interval [95% CI]: 2.4-28.9; p < 0.00), hypokalemia (OR: 6.5; 95% CI: 1.5-28.2; p < 0.01), rheumatologic diseases (OR: 4.7; 95% CI: 1.6-13.9; p < 0.00), taking medications with a known torsades de pointes (TdP) risk (OR: 4.4; 95% CI: 1.8-10.7; p < 0.01), malignancy (OR: 3.3; 95% CI: 1.2-9.3; p < 0.03), hypocalcemia (OR: 2.1; 95% CI: 0.9-4.8; p < 0.07), and ME doses >45 mg per day (OR: 1.9; 95% CI: 0.8-4.8; p < 0.16). Mild liver disease was protective against QTc prolongation (OR: 0.05; 95% CI: 0.0-0.46; p < 0.01). CONCLUSIONS Predictors of QTc prolongation in our multivariate conditional logistic regression model included CHF, PUD, hypokalemia, rheumatologic disorders, use of medications with a known TdP risk, malignancy, hypocalcemia, and ME doses >45 mg per day.

Purpose. The pharmacology, pharmacokinetics, pharmacodynamics, antimicrobial activity, clinical safety, and current regulatory status of solithromycin are reviewed.Summary. Solithromycin is a novel ketolide antibiotic developed for the treatment of community-acquired bacterial pneumonia (CABP). Its pharmacologic, pharmacokinetic, and pharmacodynamic properties provide activity against a broad range of intracellular organisms, including retained activity against pathogens displaying various mechanisms of macrolide resistance. Phase III clinical trials of solithromycin demonstrated noninferiority of both oral and i.v.-to-oral regimens of 5-7 days' duration compared with moxifloxacin for patients with moderately severe CABP. Nearly one third of patients receiving i.v. solithromycin experienced infusion-site reactions. Although no liver-related adverse events were reported in patients receiving oral solithromycin, more patients receiving i.v.-to-oral solithromycin experienced asymptomatic, transient transaminitis, with alanine transaminase levels of >3 to >5 times the upper limit, compared with those treated with moxifloxacin. These results led the Food and Drug Administration to conclude that the solithromycin new drug application was not approvable as filed, adding that the risk of hepatotoxicity had not yet been adequately characterized. The agency further recommended a comparative study of patients with CABP to include approximately 9,000 patients exposed to solithromycin in order to exclude drug-induced liver injury events occurring at a rate of 1 in 3,000 with 95% probability.Conclusion. Solithromycin is a novel ketolide antibiotic with activity against a broad spectrum of intracellular organisms, including those displaying macrolide resistance. While demonstrating noninferiority to a current first-line agent in the treatment of CABP, concerns for drug-induced liver injury and infusion-site reactions have placed its regulatory future in doubt.

Purpose. The implementation of a penicillin allergy screening tool to optimize the use of aztreonam is described.Methods. This study was conducted at a 528-bed tertiary referral community teaching facility and compared the use of aztreonam in patients before and after the implementation of a multipronged intervention consisting of a penicillin allergy screening tool (PAST), education, order set decision support, and prospective review of,aztreonam orders by the antimicrobial stewardship team and clinical pharmacists. Patients for whom aztreonam was prescribed at any time during their presentation to the hospital January 1-June 30, 2013 (preintervention period), and September 1, 2013-February 28, 2014 (postintervention period) were eligible for inclusion. Primary outcomes included total and inappropriate aztreonam usage. Secondary outcomes included cost avoidance and safety.Results. A total of 496 aztreonam orders were reviewed. The total number of days of therapy (DOT) with aztreonam significantly decreased from 9.5 per 1,000 patient-days in the preintervention group to 4.4 per 1,000 patient-days in the postintervention group (p < 0.0001). The number of inappropriate aztreonam DOT decreased from 4.0 per 1,000 patient days to 0.8 per 1,000 patient-days (p < 0.0001). The median number of inappropriate aztreonam doses decreased significantly in the postintervention period, as did inappropriate aztreonam DOT (p < 0.0001 for both comparisons). An estimated' cost avoidance of $60,0004100,000 was realized, depending on the alternative antibiotic selected.Conclusion. Implementation of the PAST and provider and pharmaciSt education reduced the use of aztreonam by promoting the first-line use of 3-lactam alternatives.

Antimicrobial stewardship programs (ASPs) focus on improving the utilization of broad spectrum antibiotics to decrease the incidence of multidrug-resistant Gram positive and Gram negative pathogens. Hospital admission for both medical and surgical intra-abdominal infections (IAIs) commonly results in the empiric use of broad spectrum antibiotics such as fluoroquinolones, beta-lactam beta-lactamase inhibitors, and carbapenems that can select for resistant organisms. This review will discuss the management of uncomplicated and complicated IAIs as well as highlight stewardship initiatives focusing on the proper use of broad spectrum antibiotics.

Antimicrobial stewardship is an activity that optimizes patient care through selection of the most appropriate antimicrobial therapy. Antimicrobial stewardship programs strive to enhance patient care and reduce preventable consequences of antimicrobial use. They are also vital in monitoring for the development of adverse events occurring as a result of antimicrobial therapy, although literature reviews of this activity are scarce. Although randomized controlled trials are considered the gold standard to study the efficacy of a medication, these trials are not designed to test safety end points and often are only able to identify the most commonly occurring and acute adverse events. In addition, prior to a drug going to market, it is difficult to detect rare adverse events because the associated costs are economically untenable given the limited pipeline of novel agents. These limitations in some ways may be resolved with the use of postmarketing surveillance and spontaneous reporting systems such as the United States Food and Drug Administration Adverse Event Reporting System. The focus of this commentary is to highlight the importance of adverse event reporting by antimicrobial stewardship programs to spontaneous reporting systems as a means to improve patient care.

Background: To date, there is limited literature regarding the association between dipeptidyl peptidase-4 (DPP-4) inhibitors and pancreatic carcinoma. Objective: To describe the comparative incidence of DPP-4 inhibitors and pancreatic carcinoma as reportedly available in the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. The goal was to provide health care practitioners a general understanding of the drug-disease occurrence. Methods: This is a case/noncase study utilizing Empirica Signal software to query FAERS from November 1968 to December 31, 2013. The software was used to calculate a disproportionality statistic-namely, the empirical Bayesian geometric mean (EBGM)-for reports of DPP-4 inhibitors associated pancreatic carcinoma. The FDA considers an EBGM significant if the fifth percentile of the distribution is at least 2, defined as an EB05 >= 2. With use of a disproportionality analysis, DPP-4 inhibitors were compared with all agents listed in FAERS. Results: A total of 156 patients experienced pancreatic carcinoma while receiving DPP-4 inhibitor therapy. An EB05 of 10.3 was determined for sitagliptin, 7.1 for saxagliptin, 4.9 for linagliptin, and 1.4 for alogliptin, compared with all other agents included in FAERS. Although an EB05 > 2 was achieved in 2 other antihyperglycemic agents, the findings were not consistent within their medication classes. Conclusion: There appears to be a statistical association between DPP-4 inhibitor use and pancreatic carcinoma. Causality cannot be inferred from the data provided. Additional clinical studies are needed to further explore this statistical association.

STUDY OBJECTIVE:To review quantitatively and qualitatively the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) database to provide clinicians with a general understanding of the comparative occurrence of clinically meaningful adverse events associated with 15 antimicrobial new molecular entities approved by the FDA since 2006: anidulafungin, darunavir, maraviroc, raltegravir, doripenem, telavancin, ceftaroline, boceprevir, telaprevir, fidaxomicin, bedaquiline, dolutegravir, simeprevir, sofosbuvir, and dalbavancin. DESIGN:Retrospective analysis. DATA SOURCE:FDA AERS database. MEASUREMENTS AND MAIN RESULTS:Empirica Signal software was used to query the AERS database from November 1968 to December 2012. Using disproportionality analyses, we calculated a relative reporting ratio (RRR) estimate for reports of antimicrobial adverse events. The RRR estimate compares the occurrence of a specific adverse event with an index drug of interest to the occurrence of the same adverse event with similar agents or with all other FDA-approved prescription drugs. Common industry practice considers an RRR meaningful if the 5th percentile of the distribution is at least 2 (RRR05 of 2.0 or higher). Antimicrobials were compared with agents within their respective antimicrobial therapeutic class as well as with all agents in the AERS database. Seventeen adverse signals with an RRR05 of 2.0 or higher were identified from the database for six agents. Ten of the 17 signals were not included in the most up-to-date manufacturers' package inserts for four of the six agents: doripenem-associated hepatic dysfunction (RRR05 3.7) and hyperchloremia (RRR05 2.6); boceprevir-associated weight loss (RRR05 2.2); darunavir-associated premature labor (RRR05 3.1), sudden infant death syndrome (RRR05 2.9), ventricular hypertrophy (RRR05 2.7), acute coronary syndrome (RRR05 2.4), and congenital anomaly in offspring (RRR05 2.4); and raltegravir-associated congenital heart valve disorders (RRR05 2.5) and SIDS (RRR05 2.3). CONCLUSION:Clinically meaningful adverse event signals appeared to be associated with antimicrobial new molecular entities approved since 2006 including many not yet identified in package inserts. Although a disproportionality analysis suggests a quantitative signal for these associations, causality cannot be inferred from the data. Due to several key limitations in this type of analysis, investigative studies are needed to further explore these adverse event signals and the potential mechanisms by which they occur.

The authors aimed to determine if first-professional-year pharmacy students retain library literature search skills throughout the school year. Students (n = 61 consented) were given an identical seven-item quiz on basic library search skills prior to library instruction in the fall semester and at the end of the spring semester. There was no significant difference between median scores on the two quizzes, nor were any significant differences noted in subgroup analyses. Search competency may be retained to a higher degree if library instruction is moved later in the pharmacy curriculum when literature search skills are used more often.

The purpose of our article was to outline the currently available rapid methicillin-resistant Staphylococcus aureus (MRSA) platforms and how they might be of value to a particular institution’s antimicrobial stewardship team (AST). Dr. Cunha describes “real world” medicine and is concerned that a misunderstanding of site-related clinical significance will result in unforeseen problems. The fundamental basis of his concern is that the reporting of irrelevant clinical isolates will result in the prescribing of unneeded antibiotics. The fact is that ASTs are run not by rookies but by physicians trained and certified in infectious diseases and pharmacists and other professionals who have specific expertise in infectious diseases. Dr. Cunha also states that the use of narrow- rather than broad-spectrum antibiotic therapy does not influence resistance. This is not completely accurate. Dr. Cunha supports his premise with literature that is over 15 years old and reflects an era when MRSA rates were a fraction of what they are now.1 Literature supports the current belief that deescalation of antibiotic therapy stabilizes or possibly reduces rates of resistance, reduces costs, and has the potential to improve outcomes.2–5 This belief is a tenet of ASTs and is supported by guidelines of the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America.6 Furthermore, rapid MRSA testing as described in our article focuses on the deescalation of therapy from empirical vancomycin to semisynthetic penicillins in patients with methicillin-susceptible S. aureus, not on the change that Dr. Cunha refers to (changing from cefazolin to a semisynthetic penicillin).

PURPOSE:The results of a case-control study of the potential role of caffeine citrate therapy in the development of necrotizing enterocolitis (NEC) are presented.METHODS:Patient records for a 10-year period were reviewed to collect sufficient data to test the hypothesis that newborns treated in a hospital's perinatal intensive care unit for NEC might have had a higher cumulative exposure to caffeine citrate relative to that of neonates of similar postconceptional and postnatal age who did not develop NEC. Ninety-five cases of NEC were identified; each case was matched to a control case by gestational age and birth weight. To enable comparative analyses, each control was assigned an index date according to the number of days from birth to NEC diagnosis in the paired case. Data collected for analysis included patient demographics, information on caffeine citrate and concomitant medication use, and potential confounding factors.RESULTS:Analysis of aggregated data for the entire seven-day NEC event timeframe indicated no significant differences between cases and controls with regard to average caffeine citrate loading doses (p = 0.5), cumulative exposure (p = 0.2), and trough serum concentrations (p = 0.5); mean cumulative exposure values differed significantly at one time point (four days prior to NEC diagnosis (p = 0.04).CONCLUSION:Cumulative exposure to caffeine citrate among infants who developed NEC and infants who did not develop NEC differed significantly at only one of six evaluated time points during the seven days before NEC development or the index date. There was no significant difference between groups in the proportions of patients who received caffeine citrate or in mean serum caffeine concentrations.

Study Objective To provide clinicians with an understanding of the comparative occurrence of tigecycline and pancreatitis, and to provide any clinically relevant characteristics that may be useful in identifying the patients at risk. Design Retrospective cohort study. Data Source Spontaneous reports in the United States Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) database generated between January 1997 and December 2010. Patients Sixty-two patients who experienced pancreatitis while receiving tigecycline therapy. Measurements and Main Results Disproportionality analysis with Bayesian correction methodology was used to compare tigecycline with all other agents listed in the AERS. Disproportionality analysis uses an adverse event relative reporting ratio (RRR) to compare the occurrence of a specific adverse event with an index drug of interest to the occurrence of the same adverse event with similar agents or with all other FDA-approved prescription drugs. The value was considered meaningful if the 5th percentile of the distribution of the RRR (RRR05) was 2 or greater. Our review identified 62 potential cases of tigecyline-related pancreatitis. An RRR05 score of 10.4, 10.38, and 2.87 was determined for tigecycline-related pancreatitis compared with all other agents, systemic antibiotics, and select tetracyclines listed in the AERS, respectively. In addition, a sex-based RRR05 score was higher in women versus men (14.432 vs 3.125) when tigecycline was compared with all agents in the AERS. Conclusion Our analysis suggests a quantitative signal between tigecycline use and pancreatitis; however, given the limitations of our study, a cause-and-effect relationship cannot be inferred. Thus, additional rigorous scientific analyses are warranted to explore these findings.