Dried plasma spots for therapeutic monitoring of amikacin: Validation of an UHPLC-MS/MS assay and pharmacokinetic application
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
Authors: Cezimbra da Silva, Anne Caroline; Feltraco Lizot, Lilian de Lima; Bastiani, Marcos Frank; Antunes, Marina Venzon; Brucker, Natalia; Linden, Rafael
Abstract
Amikacin (AMI) is an aminoglycoside antibiotic widely used in the treatment of severe infections caused by multi-resistant bacteria, with established exposition targets in therapeutic drug monitoring (TDM). The usual specimen for AMI concentration measurement is plasma or serum. The access to TDM of AMI in Developing Countries is constrained by the limited availability of laboratories performing the quantitation of this drug. In this context, the use of dried microsamples, such as dried plasma spots (DPS) could be an alternative to allow reduced specimen transportation and storage costs in resource-limited settings, increasing the access to TDM of AMI. This study aimed to develop and validate the first report of simultaneous determination of AMI and creatinine (CRE) in DPS, using UHPLC-MS/MS. Precision, accuracy and stability assays showed acceptable results. AMI was stable in DPS for 14 days at 6 degrees C, 2 days at 22 degrees C, and one day at 42 degrees C. CRE was stable during 14 days at all tested temperatures. AMI and CRE concentrations in DPS and plasma were compared by Passing-Bablok regression and Bland and Altmann plots and presented comparable results. Estimates of patient's clearance, volume of distribution and suggested doses of AMI were also similar using DPS or plasma concentrations. The assay provides a useful logistic alternative to allow more widespread access to dose individualization of AMI in limited resources settings. (C) 2020 Elsevier B.V. All rights reserved.
Evaluation of cinnamon extract effects on clbB gene expression and biofilm formation in Escherichia coli strains isolated from colon cancer patients
BMC CANCER
Authors: Kosari, Faezah; Taheri, Mohammad; Moradi, Abbas; Hakimi Alni, Reza; Alikhani, Mohammad Yousef
Abstract
BackgroundColon cancer is one of the most common malignancies and the fourth leading cause of cancer-related mortality in the world. Colibactin, which is synthesized by the pks genomic island of E. coli interfere with the eukaryotic cell cycle. Cinnamon has an antimicrobial effect and considered as a colon cancer-preventing agent. The aim of the study was to evaluate the effects of cinnamon extract and cinnamaldehyde on clbB gene expression and biofilm formation in clinical isolates of E. coli.MethodsThirty E. coli carrying pks gene were isolated from the colon cancer patients, inflammatory bowel disease and healthy subjects. Antibiotic susceptibility was evaluated by disk diffusion method and the minimum inhibitory concentration of cinnamon essential oil and cinnamaldehyde by microdilution broth method. In vitro biofilm formation of E.coli isolates was monitored using a microtiter plate method. The presence of clbB, clbA and clbQ genes in E.coli isolates were evaluated by PCR. The effect of cinnamaldehyde and cinnamon essential oil on clbB gene expression was evaluated by Real-Time PCR.ResultsThe highest antibiotic resistance was obtained with 94.4% for ticarcillin-clavulanic acid, azithromycin, amoxicillin, and amikacin. The MIC for all clinical isolates was 32 mu l/ml of cinnamon essential oil and the MIC of cinnamaldehyde was between 0.00002 to 0.03 mu l/ml. After exposure of isolates to cinnamon extract and cinnamaldehyde, 40 and 13.3% were weakly biofilm producers, respectively. The frequencies of clbB, clbA, and clbQ genes were 23.3, 23.3, and 26.7%, respectively. The expression of clbB gene in the presence of the Sub-MIC concentration of cinnamon essential oil and cinnamaldehyde was decreased in 8 isolates compared to untreated isolates (p-value <0.05).ConclusionsThe antibacterial activity of cinnamaldehyde and cinnamon essential oil allows the use of these herbal compounds for treatment or supplements in infections caused by E. coli and in patients with suspected colorectal cancer.