Retrospective review of intermittent and continuous infusion vancomycin for methicillin-resistant Staphylococcus aureus bacteremia.

PURPOSE: Vancomycin is commonly administered as an intermittent infusion (IIV), although vancomycin's stability at room temperature permits administration continuously over 24 h (CIV). At our institution, CIV has been the preferred infusion method for over 20 years due to ease of administration and simplicity of therapeutic drug monitoring. The purpose of this study was to examine the outcomes associated with IIV compared to CIV. METHODS: This was a retrospective study of patients who received vancomycin for MRSA bacteremia. The primary outcomes were the time to therapeutic goal and frequency of adverse drug reactions on IIV compared to CIV. Secondary outcomes evaluated all-cause readmission, relapse, and mortality 30 days after completion of therapy. RESULTS: Sixty-three patients were included. Significantly fewer patients were able to achieve a therapeutic goal on IIV compared to CIV (52.4% vs. 82.5%, p < 0.01). Patients on IIV took 3.6 days, on average, to reach the target goal, compared to 1.9 days when patients were switched to CIV (95% confidence interval, 0.48-3.04, p < 0.01). Six patients experienced adverse events on IIV, and 15 patients experienced adverse events on CIV (IIV 9.5%, CIV 23.8%, p = 0.035). One patient experienced relapse of infection, and six patients (9.5%) were readmitted 30 days after completion of therapy. There were no deaths in the cohort. CONCLUSION: For MRSA bacteremia, CIV enabled patients to achieve the AUC/MIC goal significantly faster than when patients received IIV. Furthermore, patients who were unable to achieve a therapeutic trough on IIV became therapeutic once switched to CIV.

A Retrospective Case Series on Valproic Acid for Early Post-Traumatic Seizure Prophylaxis After Traumatic Brain Injury in Patients With Concomitant Agitation.

Purpose: Early post-traumatic seizures occur within 7 days following a traumatic brain injury and may lead to additional brain damage and poor outcomes. Levetiracetam or phenytoin is often used for seizure prophylaxis in this patient population, but valproic acid may be an appropriate therapeutic alternative in patients with concomitant agitation. Evidence for the use of valproic acid for both early post-traumatic seizure prophylaxis and agitation is limited. The purpose of this study is to examine the safety and efficacy of valproic acid for both early post-traumatic seizure prophylaxis and agitation. Methods: This single-center, retrospective case series includes 18 patients who received valproic acid for both early post-traumatic seizure prophylaxis and agitation. Efficacy for early post-traumatic seizure prophylaxis is assessed by the incidence of seizures within 7 days of injury. Efficacy for agitation is assessed by changes in Riker Sedation-Agitation Scale scores during valproic acid therapy. The safety of valproic acid is defined by the incidence of selected adverse events. Results: Among 18 patients with traumatic brain injuries receiving valproic acid for both early post-traumatic seizures and agitation, one patient experienced a seizure during the period of prophylaxis and thrombocytopenia was the most common adverse event. Conclusion: In this small cohort of patients, valproic acid appears be a potential option to prevent early post-traumatic seizures in patients with traumatic brain injuries and concomitant agitation with minimal adverse effects. Randomized, controlled studies are needed to further investigate the role of valproic acid for this indication, including standards for dosing regimens, serum drug monitoring, and the relationship between valproic acid treatment and mortality.

Suppression of triple-negative breast cancer metastasis by pan-DAC inhibitor panobinostat via inhibition of ZEB family of EMT master regulators.

Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer subtype that lacks effective targeted therapies. The epithelial-to-mesenchymal transition (EMT) is a key contributor in the metastatic process. We previously showed the pan-deacetylase inhibitor LBH589 induces CDH1 expression in TNBC cells, suggesting regulation of EMT. The purpose of this study was to examine the effects of LBH589 on the metastatic qualities of TNBC cells and the role of EMT in this process. A panel of breast cancer cell lines (MCF-7, MDA-MB-231, and BT-549), drugged with LBH589, was examined for changes in cell morphology, migration, and invasion in vitro. The effect on in vivo metastasis was examined using immunofluorescent staining of lung sections. EMT gene expression profiling was used to determine LBH589-induced changes in TNBC cells. ZEB overexpression studies were conducted to validate requirement of ZEB in LBH589-mediated proliferation and tumorigenesis. Our results indicate a reversal of EMT by LBH589 as demonstrated by altered morphology and altered gene expression in TNBC. LBH589 was shown to be a more potent inhibitor of EMT than other HDAC inhibitors, SAHA and TMP269. Additionally, we found that LBH589 inhibits metastasis of MDA-MB-231 cells in vivo. These effects of LBH589 were mediated in part by inhibition of ZEB, as overexpression of ZEB1 or ZEB2 mitigated the effects of LBH589 on MDA-MB-231 EMT-associated gene expression, migration, invasion, CDH1 expression, and tumorigenesis. These data indicate therapeutic potential of LBH589 in targeting EMT and metastasis of TNBC.