Pharmacologic Approach to Management of Clostridium difficile Infection.

Clostridium difficile is a gram-positive, anaerobic, spore-forming bacterium that is the leading cause of nosocomial infections in hospitals in the United States. Critically ill patients are at high risk for C. difficile infection (CDI) and face potentially detrimental effects, including prolonged hospitalization, risk of recurrent disease, complicated surgery, and death. CDI requires a multidisciplinary approach to decrease hospital transmission and improve treatment outcomes. This article briefly reviews the current literature and guideline recommendations for treatment and prevention of CDI, with a focus on antibiotic treatment considerations including dosing, routes of administration, efficacy data, adverse effects, and monitoring parameters.

Assessing the Impact of a Pharmacist-Managed Discharge Medication Reconciliation Pilot at a Community Hospital System.

INTRODUCTION: With unintended medication discrepancy rates ranging from 30% to 70%, a formal discharge medication reconciliation process must be developed. One strategy shown to reduce medication errors is a pharmacist medication review at discharge. The purpose of this study is to determine the impact of a pharmacist-driven discharge medication reconciliation program. METHODS: The intervention group included pharmacist-reviewed patients with a high risk of unplanned readmission score and had a discharge order signed during a 2-month period. The control group included eligible patients who were not reviewed by a pharmacist. The after-visit summaries for both groups were then reviewed for additional medication discrepancies. RESULTS: This study included 140 patients, with 70 patients in each group. A total of 176 discrepancies were identified in the intervention group and 235 were found in the control group. The median number of discrepancies per patient was not statistically different between groups (2 vs. 2, p-value = .196). There were 22 and 24 30-day hospital readmissions in the intervention and control groups, respectively (p-value = .857). CONCLUSIONS: More medication discrepancies were identified in the control group compared to pharmacist-reviewed patients. More robust studies including a pharmacist dedicated to discharge medication reconciliation should be conducted to identify the potential benefit.

Impact of time-dependent inactivation on the estimation of enzyme kinetic parameters for midazolam.

Enzyme kinetic parameters for midazolam were time-dependent in human liver microsomes, under initial velocity conditions. V(max) and K(m) decreased up to 3.7 and 3.1-fold, respectively, for 10 min compared to 1 min incubations. Mathematical models describing the relationship between inactivation and the time-dependency of enzyme kinetic parameter estimates were derived and discussed.

Comparison of HIV-1 and EIAV-based lentiviral vectors in corneal transduction.

In this study we compare the ability of self-inactivating Human Immunodeficiency Virus 1 (HIV-1) and Equine Infectious Anaemia Virus (EIAV)-based vectors to mediate gene transfer to rabbit and human corneas and to a murine corneal endothelial cell line. Both vectors were pseudotyped with vesicular stomatitis virus-G (VSV-G) envelope and contained marker transgenes under the control of an internal CMV promoter. For specificity of action, the heterologous promoter in the EIAV-vector was exchanged for an inducible E-Selectin promoter, previously shown to regulate gene-expression in a plasmid system. We show that EIAV is more efficient than HIV in transducing human and rabbit corneal endothelial cells. Rabbit corneal endothelial cells are transduced in higher quantity than human corneal endothelial cells. In the inducible system, however, we detected impairment between the vector and its internal E-Selectin promoter. Instead of controlled transgene expression or silencing of promoter activity, the U3-modified long-terminal-repeats (LTR) impaired the conditional activity of the E-Selectin promoter. Significant transgene expression was seen without stimulation of the inducible promoter. We show efficient transduction by lentiviruses of a corneal endothelial cell line and of full thickness corneas from different species, confirming that those vectors would be appropriate tools for gene therapy of selected corneal diseases. However, the modification within the U3-LTR did not adequately allow regulated transgene expression. These findings have important implications for vector design for diagnostic or therapeutic opportunities.