Evaluation of adverse drug reaction formatting in drug information mobile phone applications.

OBJECTIVE: To evaluate the differences in presentation (formatting) of adverse drug reaction (ADR) information within drug monographs in commonly used drug information (DI) mobile device applications. METHODS: A cross-sectional analysis of ADR formatting of twenty commonly prescribed oral medications within seven DI mobile applications was performed. Databases were assessed for ADR information, including presence of placebo comparisons, severity of ADR, onset of ADR, formatting of ADRs in percentile (quantitative) format or qualitative format, whether references were used to cite information, and whether ADRs are grouped by organ system. Data was collected by two study investigators and discrepancies were resolved via consensus. RESULTS: The seven DI mobile applications varied significantly on every analyzed ADR variable with the exception of ADR onset, which was absent in all databases. Significant differences were found for variables known to impact clinical judgment such as placebo comparisons and qualitative versus quantitative formatting. Placebo comparisons were most common among monographs in Lexicomp (30%) but were absent among monographs within other applications. Quantitative information was commonly used in most databases but was absent in Epocrates. Qualitative formatting was present in all Epocrates and Micromedex applications but absent in the majority of other applications. Substantial variations were also found in severity and grouping information. CONCLUSION: Substantial variation in ADR formatting exists among the most common DI mobile applications. These differences may translate into alternative interpretations of medical information and thus impact clinical judgment. Health care librarians and clinicians should consider ADR formatting when choosing between DI applications.

Impact of Pharmacist Involvement in Heart Failure Transition of Care.

Background: Heart failure (HF) transition of care (TOC) programs may improve continuity of care and coordination and decrease hospital readmissions. Objective: This study evaluated the impact of pharmacy-led HF TOC on HF readmission rate. Methods: This was a single-center, pre-post quasi-experimental study. Pharmacy TOC comprised admission and discharge medication reconciliations and patient education. Patients were included if they had a primary HF diagnosis. Patients were excluded if they were admitted for a non-HF diagnosis, admitted for <24 hours, had a stage IV cancer or dementia diagnosis, or were transferred to hospice care. The primary outcome was HF 30-day readmission rate. Results: A total of 663 patients were included in the study: 330 in the control group and 333 in the intervention group. The average age for both groups was 67 ± 16 years; 48.1% were female; 56.9% were African American; and 51.4% of patients had an ejection fraction ≤40%. In the control group, 57 (17.3%) patients had a HF 30-day readmission compared with 35 (10.5%) patients in the intervention group. After adjusting for age, the intervention group continued to show a difference in readmission (odds ratio = 0.578; 95% CI = 0.367-0.911; P = 0.018). The most common interventions were medication addition (11%), dose titration (7.5%), medication discontinuation (6.6%), and duplication avoidance (2.7%). Conclusion and Relevance: Pharmacy-led HF TOC, as a component of a targeted hospital-based initiative, significantly decreased HF 30-day readmission rate. Results from this study warrant further research to explore which interventions in TOC are most effective.

Evaluation of adverse drug reaction formatting in drug information databases.

OBJECTIVE: The research evaluated the differences in formatting of adverse drug reaction (ADR) information in drug monographs in commonly used drug information (DI) databases. METHODS: A cross-sectional analysis of formatting of ADR information for twenty commonly prescribed oral medications in seven commonly used DI databases was performed. Databases were assessed for presentation of ADR information, including presence of placebo comparisons, severity of ADR, onset of ADR, formatting of ADRs in percentile (quantitative) format or qualitative format, whether references were used to cite information, whether ADRs are grouped by organ system, and word count of the ADR section. Data were collected by two study investigators and discrepancies were resolved via consensus. Chi-square analyses and one-way analysis of variance (ANOVA) were used to evaluate for mean group differences in categorical and continuous data, respectively. RESULTS: The seven DI databases varied significantly on each analyzed ADR variable, including variables known to impact interpretation such as placebo comparisons and qualitative versus quantitative formatting. Placebo comparisons were most common among monographs in Micromedex In-Depth Answers (70%) but were absent among monographs in Epocrates, Lexicomp, and Micromedex. Quantitative information was commonly used in most databases but was absent in Epocrates. Average word counts were higher in Clinical Pharmacology and Micromedex In-Depth answers compared to other databases. CONCLUSION: Substantial variation in ADR formatting exists between the most common DI databases. These differences may translate into alternative interpretations of medical information and, thus, impact clinical judgment. Further studies are needed to assess whether these differences impact clinical practice.

Adverse drug reactions in drug information databases: does presentation affect interpretation?

OBJECTIVE: Formatting of adverse drug reaction (ADR) information differs among drug information (DI) resources and may impact clinical decision-making. The objective of this study was to determine whether ADR formatting impacts adverse event interpretation by pharmacy practitioners and students. METHODS: Participants were randomized to receive ADR information in a comparative quantitative (CQUANT), noncomparative quantitative (NQUANT), or noncomparative qualitative (NQUAL) format to interpret 3 clinical vignettes. Vignettes involved patients presenting with adverse events that varied in the extent to which they were associated with a medication. The primary outcome was interpretation of the likelihood of medication-induced adverse events on a 10-point Likert scale. Lower scoring on likelihood (i.e., ADR deemed unlikely) reflected more appropriate interpretation. Linear regression was performed to analyze the effects of ADR information format on the primary outcome. RESULTS: A total of 108 participants completed the study (39 students and 69 pharmacists). Overall, the CQUANT group had the lowest average likelihood compared to NQUAL (4.0 versus 5.4; p<0.01) and NQUANT (4.0 versus 4.9; p=0.016) groups. There was no difference between NQUAL and NQUANT groups (5.4 versus 4.9; p=0.14). In the final model, at least 2 years of postgraduate training (-1.1; 95% CI: -1.8 to -0.3; p<0.01) and CQUANT formatting (-1.3; 95% CI: -0.9 to -1.7; p<0.01) were associated with reduced likelihood. CONCLUSIONS: Formatting impacts pharmacists' and pharmacy students' interpretation of ADR information. CQUANT formatting and at least two years of postgraduate training improved interpretation of adverse events.

Insulin Detemir Versus Insulin Glargine in the Hospital: Do Hypoglycemia Rates Differ?

IN BRIEF Several studies have compared the safety and efficacy of insulin detemir and insulin glargine; however, most have been conducted in the ambulatory care setting. This retrospective cohort study compared hypoglycemia rates between the two basal insulin analogs in hospitalized patients with diabetes. No difference was found between the two insulin cohorts in the proportion of patients who experienced hypoglycemic events.

"I Never Would Have Caught That Before": Pharmacist Perceptions of Using Clinical Decision Support for Antimicrobial Stewardship in the United States.

To systematically improve the appropriateness of antibiotic prescribing, antimicrobial stewardship programs have been developed. There is a paucity of literature examining how pharmacists perform antimicrobial stewardship using a clinical decision support system in a hospital setting. The purpose of this qualitative study was to develop a model exploring how pharmacists perform antimicrobial stewardship to identify areas for programmatic improvement. Semistructured interviews were conducted across a health care system until saturation of themes was reached. Pharmacists identified that self-efficacy and time were vital for antimicrobial stewardship to be performed, while culture of the hospital and attitude facilitated the process of stewardship. Antimicrobial stewardship programs using clinical decision support tools should ensure pharmacists have adequate time to address rules, provide easy-to-use resources and training to support self-efficacy, and engage influential physicians to support a culture of collaboration.

Safety and Efficacy of a Pharmacist-Managed Patient-Controlled Analgesia Service in Postsurgical Patients.

PURPOSE: To compare the safety and efficacy of a pharmacist-managed patient-controlled analgesia (PCA) service with physician/midlevel provider-managed (standard) PCA services in postsurgical patients. METHODS: This was a multicenter, retrospective cohort study performed at 3 major hospitals in the Detroit, Michigan, metropolitan area. Postsurgical patients from October 2012 to December 2013 were included. The primary outcome compared the pain area under the curve adjusted for time on PCA (AUC/T) of patients receiving pharmacist-managed PCA services vs. standard care, up to 72 hours after initiation of PCA. Secondary outcomes included initial opioid selection, programmed PCA settings, duration of PCA use, frequency of adjunct analgesia utilization, and frequency of breakthrough analgesia utilization. Safety outcomes were assessed as a composite safety endpoint and individually. RESULTS: Total pain AUC/T scores did not differ between the pharmacist-managed and standard-managed groups (3.25 vs. 3.25, respectively; P = 0.98). Adjunct pain medications were given with similar frequency in the 2 groups; however, significantly fewer patients required breakthrough pain medication in the pharmacist-managed group (11% vs. 36%, respectively; P < 0.0001). A composite endpoint of any adverse event occurring was found to be greater in the pharmacist-managed group. This was driven by a higher proportion of patients requiring antiemetic use (46% vs. 32%; P = 0.04). CONCLUSION: A pharmacist-managed PCA service provided no difference in pain control compared to standard management. The requirement for breakthrough analgesia was decreased in the pharmacist group, while the need for antiemetic use was increased. Further research should be conducted to evaluate different PCA management strategies.

Evaluation of High-dose versus Standard-dose of Dexamethasone on Mortality among the Mechanically Ventilated COVID-19 Patients.

INTRODUCTION: Anti-inflammatory agents like dexamethasone (DEX) are a mainstay of treatment for COVID-19. Despite randomized trials demonstrating that a 6 mg daily dose of DEX improved patient outcomes in hospitalized COVID-19 patients receiving oxygen, clinicians often prescribe higher doses of corticosteroids without evidence to support this practice. The purpose of this study was to compare outcomes of ventilated COVID-19 patients who received standard dose (SD) versus high dose (HD) DEX. METHOD: This was a multi-site, retrospective, observational study on ventilated COVID-19-positive patients who received DEX for at least three days between June 1, 2020, and January 31, 2022. The primary outcome of this study was the association between mortality and SD (<6mg daily) versus HD (>10mg daily) DEX in ventilated COVID-19 patients. Secondary outcomes included average blood glucose (BG), number of BG readings above 200, incidence of bacterial nosocomial infection, ventilator-free days, length of stay (LOS), and ICU LOS. RESULTS: Of the 212 included patients, 53 (25%) received SD DEX, and 159 (75%) received HD DEX. There was no significant effect of DEX dose on mortality, number of BG readings >200, incidence of nosocomial infections, LOS, or ventilator-free days (p >0.05). After controlling for confounding factors, no difference in mortality persisted (OR 1.34 95% CI 0.62- 2.90). Average daily BG and ICU LOS were significantly greater in the HD group compared to the SD group (p = 0.003, p = 0.019, respectively). CONCLUSION: There was no association between HD DEX and mortality among ventilated COVID-19 patients compared to SD DEX. Moreover, HD DEX is associated with detrimental effects such as prolonged ICU LOS and higher average daily BG. This study supports the use of SD DEX in ventilated COVID-19 patients.

Empiric guideline-recommended weight-based vancomycin dosing and mortality in methicillin-resistant Staphylococcus aureus bacteremia: a retrospective cohort study.

BACKGROUND: No studies have evaluated the effect of guideline-recommended weight-based dosing on in-hospital mortality of patients with methicillin-resistant Staphylococcus aureus bacteremia. METHODS: This was a multicenter, retrospective, cohort study of patients with methicillin-resistant Staphylococcus aureus bacteremia receiving at least 48 hours of empiric vancomycin therapy between 01/07/2002 and 30/06/2008. We compared in-hospital mortality for patients treated empirically with weight-based, guideline-recommended vancomycin doses (at least 15 mg/kg/dose) to those treated with less than 15 mg/kg/dose. We used a general linear mixed multivariable model analysis with variables identified a priori through a conceptual framework based on the literature. RESULTS: A total of 337 patients who were admitted to the three hospitals were included in the cohort. One-third of patients received vancomycin empirically at the guideline-recommended dose. Guideline-recommended dosing was not associated with in-hospital mortality in the univariable (16% vs. 13%, OR 1.26 [95%CI 0.67-2.39]) or multivariable (OR 0.71, 95%CI 0.33-1.55) analysis. Independent predictors of in-hospital mortality were ICU admission, Pitt bacteremia score of 4 or greater, age 53 years or greater, and nephrotoxicity. CONCLUSIONS: Empiric use of weight-based, guideline-recommended empiric vancomycin dosing was not associated with reduced mortality in this multicenter study.

A scaffolded problem-based learning course for first-year pharmacy students.

BACKGROUND AND PURPOSE: There has been an increased use of active learning pedagogies in pharmacy curricula. Structured, complex pedagogies such as problem-based learning (PBL) may require rigorous training for students to be successful. We aim to describe the development and implementation of an introductory PBL course for first-year pharmacy students. We describe the theoretical framework for course development, including the educational philosophies informing the course design. Development of PBL skills and professional behavior were evaluated using student self-assessment throughout the course. EDUCATIONAL ACTIVITY AND SETTING: This introductory PBL course was developed using educational philosophies to scaffold student learning of the pedagogy and development of PBL skills. A student self-assessment was administered at two time points throughout the course. The self-assessment contained items related to PBL skills and professional behaviors. Self-assessment scores were compared with facilitator evaluations of student performance to determine reliability of self-assessment results. FINDINGS: Eighty-eight students completed both self-assessments (93.6% response rate). Self-assessment of PBL skills increased significantly. There was no improvement in self-assessed professional behaviors. Self-assessment scores did not correlate with facilitator assessment of student performance in a small group. SUMMARY: Integrating a scaffolded, theoretically sound educational approach to introduce students to the PBL pedagogy improves students' self-assessed PBL skills but not professional behavior.

Clinical Outcomes of Zinc Supplementation Among COVID-19 Patients.

BACKGROUND: Zinc supplementation is frequently prescribed during the treatment of COVID-19. However, the evidence supporting the efficacy of this intervention is mixed. OBJECTIVE: Establish the clinical utility of zinc supplementation to alter disease severity in COVID- 19 illness. METHODS: We performed a multicenter, retrospective, observational chart review of patients admitted to Ascension St. John Hospital or Detroit Medical Center from January 1st, 2020 to May 31st, 2020. All included patients received concomitant hydroxychloroquine due to its zinc ionophore activity. Our primary outcome was a change in Sequential Organ Failure Assessment (SOFA) score with secondary outcomes including all-cause mortality, need for intubation, and QTc prolongation as a safety outcome. RESULTS: We identified 489 patients who received zinc and 587 patients who did not. The primary outcome showed a small difference in the change in SOFA score in patients receiving zinc in univariate analysis (1.08 vs. 1.43, p=0.02), but this difference was not significant after adjustment for confounding factors such as receipt of corticosteroids and ICU admission. Mortality was not different between those that received zinc compared to those that did not (32.7% vs. 35.9%, p=0.268). CONCLUSION: Our retrospective study, including 1064 patients hospitalized in Detroit, demonstrated no differences in mortality or disease severity with zinc combination. Furthermore, prospective studies are needed to establish the utility of zinc in the treatment of COVID-19.

Pancreatic enzyme products: digesting the changes.

OBJECTIVE: To review the pharmacology, dosage regimens, efficacy, and safety of currently marketed pancreatic enzyme products (PEPs). DATA SOURCES: Studies were identified by PubMed (1966-January 2011), clinicaltrials.gov, fda.gov, and International Pharmaceutical Abstracts. Search terms included pancreatic enzyme, lipase, Creon, Zenpep, Pancreaze, and exocrine pancreatic insufficiency (EPI). STUDY SELECTION AND DATA EXTRACTION: All human studies evaluating the efficacy of currently approved or potential PEPs were reviewed. DATA SYNTHESIS: PEPs are composed of porcine lipase, amylase, and protease and are used in patients with EPI secondary to cystic fibrosis, chronic pancreatitis, and pancreatectomy. In 1938, PEPs were exempted from the Food, Drug, and Cosmetic Act of 1938 and never underwent a formal Food and Drug Administration (FDA) review process. In response to reports of treatment failures during product interchange, the FDA conducted a review of available PEP products. This review found a large variability of response between the unapproved PEP products, which resulted in the FDA requiring approval of all PEP products by April 2010. The 3 delayed-release, enteric-coated PEPs currently approved by the FDA (Creon, Zenpep, and Pancreaze) have demonstrated efficacy and safety in EPI secondary to cystic fibrosis. Creon has also demonstrated safety and efficacy in EPI secondary to chronic pancreatitis and pancreatectomy. Cost difference between the 3 products is minimal. Treatment-related adverse events in clinical studies for all PEPs were less than or similar to those with placebo. CONCLUSIONS: At this time, Creon is an appropriate first-line agent, as it has been approved for chronic pancreatitis, pancreatectomy, and cystic fibrosis.

Glycemic Variability With Insulin Glargine Versus Detemir in Hospitalized Patients With Diabetes.

BACKGROUND: Prior research has demonstrated increased mortality with increasing glycemic variability (GV) in hospitalized patients with diabetes. OBJECTIVE: We aimed to compare glycemic variability (GV) of insulin glargine to detemir in the inpatient setting. METHODS: This single-center, retrospective, cohort study evaluated noncritically ill patients with diabetes on long-acting insulin at a large academic medical institution between 2010 and 2017. This study was reviewed and approved by the Institutional Review Board. The formulary transitioned from insulin glargine to detemir in December 2013; therefore, patients were compared before and after transition. The primary endpoint was to compare coefficient of variation (CV), a measure of GV, between detemir and glargine. Secondary endpoints included GV measured by standard deviation (SD), CV within 72 hours of long-acting insulin initiation, length-of-stay (LOS), in-hospital mortality, and comparison between subgroups. RESULTS: 2334 patients were included in the study, and there were 1167 in each group. CV was significantly less variable with detemir compared to glargine (33.7% versus 34.8%, difference = 1.09, p = 0.02) and remained significant after controlling for confounders. Similarly, SD was significantly less with detemir (p = 0.048). CV within 72 hours, LOS, and in-hospital mortality were not statistically different. Lastly, GV was higher in medical patients compared to surgical. CONCLUSION: Insulin detemir exhibited less GV than insulin glargine, although the small difference is unlikely to be clinically significant. Application of this data will aid in formulary decisions and support the use of either agent within the hospital setting.

Enoxaparin versus unfractionated heparin for venous thromboembolism prophylaxis in renally impaired ICU patients.

INTRODUCTION: Intensive care unit (ICU) patients with renal insufficiency are more likely to develop venous thromboembolism and are at an increased risk for bleeding. There is conflicting data on whether enoxaparin or unfractionated heparin (UFH) is preferred for preventing thromboembolism in this population. Therefore, the purpose of this study was to evaluate the safety of prophylactic enoxaparin versus UFH in ICU patients with renal impairment. METHODS: We conducted a single-center, retrospective cohort study of ICU patients with renal impairment who received venous thromboembolism prophylaxis with either enoxaparin or UFH. Patients were included if they were at least 18 years of age, had renal impairment (acute kidney injury, severely decreased renal function, or end-stage renal disease), and an ICU length of stay ≥72 h. The primary outcome was the proportion of patients experiencing a major bleeding event, including fatal bleed, symptomatic bleed in a critical area, or bleeding causing a ≥2 g/dl decrease in hemoglobin leading to a transfusion of ≥2 units of packed red blood cells. RESULTS: A total of 460 patients were included in the study. Of these, 231 received enoxaparin and 229 received UFH. In the unadjusted analysis, there was no difference in major bleeding events observed with enoxaparin compared to UFH (29.4% vs. 22.3%; p = 0.08) or rates of venous thromboembolism (4.3% vs. 3.5%; p = 0.64), respectively. After adjusting for confounding factors, enoxaparin showed a significant increase in major bleeding (OR: 1.84; 95% CI: 1.11 - 3.04; p = 0.02). CONCLUSION: Thromboprophylaxis with enoxaparin in critically ill patients with renal impairment was associated with an increased risk of major bleeding compared to UFH.

Open-Label Randomized Trial of Early Clinical Outcomes of Ceftaroline Fosamil Versus Vancomycin for the Treatment of Acute Bacterial Skin and Skin Structure Infections at Risk of Methicillin-Resistant Staphylococcus aureus.

INTRODUCTION: Acute bacterial skin and skin structure infections (ABSSSIs) remain among the most common infectious processes seen in the clinical setting. For patients with complicated ABSSSIs deemed to require intravenous antibiotics, vancomycin remains the mainstay therapy. Ceftaroline has been shown to be non-inferior to vancomycin and may result in faster resolution of signs of infection. METHODS: Multicenter, prospective, open-label, randomized trial of ceftaroline versus vancomycin for the treatment of adult patients admitted for management of ABSSSIs from April 2012 to May 2016; 166 patients in the clinically evaluable (CE) group were needed to determine a 20% difference in primary outcome of clinical response at day 2 or 3 of antibiotics. Clinical response was defined as cessation of spread of lesion and improvement in systemic signs/symptoms of infection. A secondary outcome was a ≥ 20% reduction in lesion size at day 2 or 3 of antibiotics. RESULTS: One hundred seventy-four patients were enrolled in the intention-to-treat (ITT) group and 108 were CE. Among CE patients, 54 were randomized to ceftaroline and 54 to vancomycin. Baseline characteristics were similar except patients in the ceftaroline arm were older and had a non-significantly higher degree of comorbidities (median Charlson score 2 vs. 4, respectively). Cellulitis was the most common type of ABSSSI (85.2% vs. 79.6%, respectively). Rapid diagnostic testing of available cultures (n = 55) demonstrated high agreement with clinical microbiology for identification of Staphylococcus aureus (100%) and MRSA (100%). There was no significant difference in primary outcome of day 2 or 3 clinical response (50.0% vs. 51.9%). CONCLUSION: Early clinical response between vancomycin- and ceftaroline-treated ABSSSIs was similar. Patients with ABSSSIs rarely remained hospitalized for > 2-3 days, thus limiting our ability to critically assess clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02582203. FUNDING: Allergan plc.

Patient controlled analgesia: The impact of an 8 versus 10 minute lockout interval in postoperative patients.

The purpose of this study was to compare the level of pain control achieved with 8 versus 10 minute lockout intervals in adult patients who received patient controlled analgesia (PCA) within 24 hours of surgery. There was no difference in pain in the first 72 hours between the 8 minute and 10 minutes group. Additionally, there was no difference in time to first PCA regimen change or a composite outcome of adverse events.

Is the Combination of Piperacillin-Tazobactam and Vancomycin Associated with Development of Acute Kidney Injury? A Meta-analysis.

STUDY OBJECTIVE: To evaluate the association of the development of acute kidney injury (AKI) when piperacillin-tazobactam is used in combination with vancomycin compared with vancomycin with or without a ß-lactam. DESIGN: Meta-analysis of 15 observational cohort studies. PATIENTS: A total of 3258 adult inpatients who received vancomycin + piperacillin-tazobactam versus vancomycin alone (10 studies); vancomycin + piperacillin-tazobactam versus vancomycin + ß-lactam (four studies); or vancomycin + piperacillin-tazobactam versus vancomycin alone or vancomycin + other antibiotics (one study). MEASUREMENTS AND MAIN RESULTS: The PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, and Cochrane databases, as well as meeting proceedings, were searched (1966-June 1, 2016). Quality of studies was assessed by using the Newcastle-Ottawa Quality Assessment Scale (NOQAS). The primary outcome of this meta-analysis was to evaluate the association of development of AKI with the combined use of piperacillin-tazobactam and vancomycin. A subgroup analysis was also performed that examined the outcome by comparison groups (vancomycin alone or vancomycin + ß-lactam). Sensitivity analysis was performed to explore if the results differed based on removal of abstracts and removal of low-quality studies (NOQAS scores of 6 or lower). All analyses were performed using the random effects model. NOQAS scores for the 15 studies ranged from 3-7 points (of a total of 9). Overall, there was an association with the development of AKI with vancomycin + piperacillin-tazobactam compared with vancomycin ± ß-lactam (odds ratio [OR] 3.649, 95% confidence interval [CI] 2.157-6.174; I2 = 83.5%, p<0.001). The association remained significant when abstracts were removed (OR 3.498, 95% CI 1.747-7.003, I2 = 82.3%, p<0.001) and when low-quality studies were removed (OR 4.596, 95% CI 2.929-7.212, I2 = 0%, p<0.001). The association for the development of AKI with vancomycin + piperacillin-tazobactam compared with vancomycin alone was significant (OR 3.980, 95% CI 2.749-5.763, I2 = 31.4%, p<0.001), although the association did not remain significant for the vancomycin + ß-lactam subgroup (OR 3.029, 95% CI 0.942-9.738, I2 = 82.3%, p=0.063). CONCLUSION: Vancomycin + piperacillin-tazobactam was associated with an increased risk of AKI compared with vancomycin ± ß-lactam. Practitioners need to be vigilant about this association when prescribing this combination of antibiotics.

Efficacy of triclosan as an antimicrobial hand soap and its potential impact on antimicrobial resistance: a focused review.

Triclosan is a synthetic biocide found in many household products, including antimicrobial hand soap. Levels of triclosan have been found throughout the environment and in human urine, blood, and even breast milk. Increasing levels of exposure to triclosan have led to concerns over the development of resistance to triclosan and cross-resistance to other antimicrobials. We performed a literature search to assess whether the widespread use of triclosan displays a favorable benefit: risk ratio, defined by evaluation of triclosan's efficacy as an antimicrobial hand soap and its potential effect on the development of antimicrobial resistance. Data from laboratory-based studies regarding the efficacy of triclosan are conflicting, although well-designed studies suggest no significant difference in efficacy over nonantimicrobial soap. In addition, when triclosan was introduced in a community setting, no beneficial effects were observed on the reduction of infections over nonantimicrobial soap. Resistance to triclosan and cross-resistance to antimicrobials have been consistently demonstrated in laboratory settings, although overall resistance rates and cross-resistance rates in the community setting are low. Based on the available evidence, the risk of potential antimicrobial resistance outweighs the benefit of widespread triclosan use in antimicrobial soaps.

Empiric weight-based vancomycin in intensive care unit patients with methicillin-resistant Staphylococcus aureus bacteremia.

BACKGROUND: Previous studies were conducted in all hospitalized patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia to determine safety and effectiveness of guideline-recommended, weight-based dosing of vancomycin. In these studies, it was observed that severely ill patients (Pitt bacteremia score ≥4 or intensive care unit [ICU] patients) were at an increased risk of mortality and/or nephrotoxicity. Therefore, a subanalysis of the effect of guideline-recommended vancomycin dosing on in-hospital mortality and nephrotoxicity in ICU patients with MRSA bacteremia was conducted. METHODS: This multicenter, retrospective, cohort study was conducted in a subset of ICU patients from a previous MRSA bacteremia study. Patients were ≥18 years old and received ≥48 hours of empiric vancomycin from July 1, 2002, to June 30, 2008. The incidence of nephrotoxicity and in-hospital mortality was compared in patients who received guideline-recommended dosing (at least 15 mg/kg per dose) to patients who received non-guideline-recommended dosing of vancomycin. Multivariable generalized linear mixed-effects models were constructed to determine independent risk factors for in-hospital mortality and nephrotoxicity. RESULTS: Guideline-recommended dosing was received by 34% of patients (n = 137). Nephrotoxicity occurred in 35% of patients receiving guideline-recommended dosing and 39% receiving non-guideline-recommended dosing (P = 0.67). In-hospital mortality rate was 24% among patients who received guideline-recommended dosing compared with 31% for non-guideline-recommended dosing (P = 0.40). Guideline-recommended dosing was not associated with nephrotoxicity (odds ratio: 1.10; 95% confidence interval: 0.43-2.79) or in-hospital mortality (odds ratio: 0.54; 95% confidence interval: 0.22-1.36) in the multivariable analysis. CONCLUSIONS: Guideline-recommended dosing of vancomycin in ICU patients with MRSA bacteremia is not significantly associated with nephrotoxicity or in-hospital mortality. However, the 7% absolute difference for in-hospital mortality suggests that larger studies are needed.

Empiric guideline-recommended weight-based vancomycin dosing and nephrotoxicity rates in patients with methicillin-resistant Staphylococcus aureus bacteremia: a retrospective cohort study.

BACKGROUND: Previous studies have established a correlation between vancomycin troughs and nephrotoxicity. However, data are currently lacking regarding the effect of guideline-recommended weight-based dosing on nephrotoxicity in methicillin-resistant Staphylococcus aureus bacteremia (MRSAB). METHODS: Adults who were at least 18 years of age with methicillin-resistant Staphylococcus aureus bacteremia and received of empiric vancomycin therapy for at least 48 hours (01/07/2002 and 30/06/2008) were included in this multicenter, retrospective cohort study. The association between guideline-recommended, weight-based vancomycin dosing (at least 15 mg/kg/dose) and nephrotoxicity (increase in serum creatinine (SCr) by more than 0.5 mg/dl or at least a 50% increase from baseline on at least two consecutive laboratory tests) was evaluated. Potential independent associations were evaluated using a multivariable general linear mixed-effect model. RESULTS: Overall, 23% of patients developed nephrotoxicity. Thirty-four percent of the 337 patients who met study criteria received weight-based dosing. The cohort was composed of 69% males with a median age of 55 years. The most common sources of MRSAB included skin/soft tissue (32%), catheter-related bloodstream bacteremia (20%), pulmonary (18%). Eighty-six percent of patients received twice daily dosing. Similar rates of nephrotoxicity were observed regardless of the receipt of guideline-recommended dosing (22% vs. 24%, OR 0.91 [95% CI 0.53-1.56]). This finding was confirmed in the multivariable analysis (OR 1.52 [95% CI 0.75-3.08]). Independent predictors of nephrotoxicity were (OR, 95% CI) vancomycin duration of greater than 15 days (3.36, 1.79-6.34), weight over 100 kg (2.74, 1.27-5.91), Pitt bacteremia score of 4 or greater (2.73, 1.29-5.79), vancomycin trough higher than 20 mcg/ml (2.36, 1.07-5.20), and age over 52 years (2.10, 1.08-4.08). CONCLUSIONS: Over one out of five patients in this study developed nephrotoxicity while receiving vancomycin for MRSAB. The receipt of guideline-recommended, weight-based vancomycin was not an independent risk factor for the development of nephrotoxicity.