Investigation of pharmacokinetic and clinical outcomes of various meropenem regimens in patients with ventilator-associated pneumonia and augmented renal clearance.

INTRODUCTION: Augmented renal clearance (ARC) defined as creatinine clearance (Clcr) above 130 mL/min/1.73m2 may lead to suboptimal antibacterial treatment. The aim of this study was to determine a strategy for meropenem administration to achieve both pharmacodynamic-pharmacokinetic (PK-PD) target (50%fT > MIC) and better clinical outcomes in patients with VAP and ARC. MATERIALS AND METHODS: In this randomized clinical trial, patients with VAP and high risk for ARC were recruited. An 8-h urine collection was performed on the 1st, 3rd, and 5th days of study to measure Clcr. Included patients were divided into three groups: (1) 1 g meropenem, 3-h infusion, (2) 2 g meropenem, 3-h infusion, (3) 1 g meropenem, 6-h infusion. On the 2nd, 3rd, and 5th days of treatment, peak and trough blood samples were collected to undergo HPLC assay. MICs were assessed using microdilution method. Patients were also clinically monitored for 14 days. RESULTS: Forty-five patients were included. Group 3 showed significanty higher rate of patients achieving fT > MIC > 50% (100% for group 3 versus 40% for group 2 and 13% for group 1; p = 0.0001). Mean fT > MIC% was significantly higher in group 3 (78.77 ± 5.87 for group 3 versus 49.6 ± 7.38 for group 2 and 43.2 ± 7.98 for group 1; p = 0.0001). Statistical analysis showed no significant differences among groups regarding clinical improvement. CONCLUSION: According to the findings of this trial, prolonged meropenem infusion is an appropriate strategy compared to dose elevation among ARC patients.

Blood Glucose Control and Opportunities for Clinical Pharmacists in Infectious Diseases Ward.

OBJECTIVE: Increased risk of infection following hyperglycemia has been reported in hospitalized patients. Sliding-scale insulin protocol is an out-of-date method; therefore, it is necessary to examine new approaches in this regard. This study aimed to evaluate the efficacy of sliding-scale protocol versus basal-bolus insulin protocol, which supervised by clinical pharmacists in an infectious disease ward. METHODS: In this prospective randomized clinical trial, 90 hyperglycemic patients who hospitalized in Loghman Hakim Hospital Infectious Disease Ward (Tehran, Iran) were randomized into two groups: sliding-scale insulin protocol (the control group) and the basal-bolus protocol groups that were under supervision clinical pharmacists. Some demographic, laboratory, and clinical variables, as well as patient's blood glucose were measured four times daily. FINDINGS: The results indicated significant improvement among the patients in the intervention group. General indicators including fever, blood glucose level, the duration of hospitalization, incidence of hypoglycemia, days to achieve normal blood glucose, and leukocyte count improved in intervention group. CONCLUSION: According to this study, basal-bolus insulin protocol, which supervised by clinical pharmacy service, showed better blood glucose control and infection remission compared to the sliding-scale protocol.

Gamma-tocopherol enhances apoptotic effects of lovastatin in human colorectal carcinoma cell line (HT29).

Recently, we found that lovastatin, a HMG-CoA reductase inhibitor, and gamma-tocopherol, one of the significant types of vitamin E in diet, additively induced apoptosis in a colorectal carcinoma cell line. In this study we mechanistically monitored the loss of mitochondrial membrane potential, amount of cytosolic cytochrome c and caspase 3 activity after treatment by lovastatin and gamma-tocopherol. HT29 cells were treated with different doses of lovastatin and gamma-tocopherol for 48 and 72 h. Lovastatin and gamma-tocopherol in combination induced the release of cytochrome c, caspase 3 activation, and loss of mitochondrial membrane potential more significantly compared to their controls. Our data showed that lovastatin plus gamma tocopherol potently induced mitochondrial membrane potential collapse, cytochrome c release along with caspase 3 activation that reveals the importance of targeting programmed cell death signaling at different points of its signaling pathway for cancer therapy.