Dose Optimization of Vancomycin for Critically Ill Patients Undergoing CVVH: A Prospective Population PK/PD Analysis

The optimal dose of vancomycin in critically ill patients receiving continuous venovenous hemofiltration (CVVH) remains unclear. The objective of this study was to identify factors that significantly affect pharmacokinetic profiles and to further investigate the optimal dosage regimens for critically ill patients undergoing CVVH based on population pharmacokinetics and pharmacodynamic analysis. A prospective population pharmacokinetic analysis was performed at the surgical intensive care unit in a level A tertiary hospital. We included 11 critically ill patients undergoing CVVH and receiving intravenous vancomycin. Serial blood samples were collected from each patient, with a total of 131 vancomycin concentrations analyzed. Nonlinear mixed effects models were developed using NONMEM software. Monte Carlo Simulation was used to optimize vancomycin dosage regimens. A two-compartment model with first-order elimination was sufficient to characterize vancomycin pharmacokinetics for CVVH patients. The population typical vancomycin clearance (CL) was 1.15 L/h and the central volume of distribution was 16.9 L. CL was significantly correlated with ultrafiltration rate (UFR) and albumin level. For patients with normal albumin and UFR between 20 and 35 mL/kg/h, the recommended dosage regimen was 10 mg/kg qd. When UFR was between 35 and 40 mL/kg/h, the recommended dosage regimen was 5 mg/kg q8h. For patients with hypoalbuminemia and UFR between 20 and 25 mL/kg/h, the recommended dosage regimen was 5 mg/kg q8h. When UFR was between 25 and 40 mL/kg/h, the recommended dosage regimen was 10 mg/kg q12h. We recommend clinicians choosing the optimal initial vancomycin dosage regimens for critically ill patients undergoing CVVH based on these two covariates.

A New and Ecological Method to Quantify Vancomycin in Pharmaceutical Product by Infrared Spectrometry

Vancomycin, an antimicrobial, does not present quantitative method by infrared spectrometry in the literature for the evaluation of a pharmaceutical product. This technique is considered a clean alternative because in the main, there is no solvent involved and the generation of waste is reduced. So, the aim of this study was to develop and validate a new, ecological, low cost and fast method by infrared spectrometry using KBr and band between 1450–1375 cm–1. It was linear in the range of 1.0–2.0 mg/150 mg, with a correlation coefficient of 0.9994. Selective when the spectra of vancomycin reference and sample were compared. Precise by repeatability (2.29%) and intermediate precision (3.12%). Accurate with average recovery of 99.37% and robust when strength and compression time of the pellets and KBr brand were varied. Considering all the methods found in literature, there is not one using infrared spectrometry for quantitative purpose, so the method developed and validated could be considered an innovation and clean alternative. This is due to the fact that it is fast, easy to handle, low cost, and non-toxic as well as generating minimal waste. The method can be applied in the routine analysis of vancomycin dosage form and is an important option for the current and sustainable pharmaceutical analysis.

Skin necrosis and calcifications after extravasation of vancomycin: a localised form of calciphylaxis?

Vancomycin is a tricyclic glycopeptide antibiotic produced from Streptococcus orientalis. There is much variation in the literature with regard to the recommended dose, dilution rate and type of infusion. Given the vesicant properties of vancomycin at supratherapeutic doses (>10mg/ml), tissue damage including blistering and necrosis have been reported. We report a rare case of bilateral cutaneous necrosis induced by accidental extravasation of vancomycin when being intravenously administered. The skin surrounding the injection site was marked by the appearance of subcutaneous calcifications. The development of iatrogenic skin calcinosis has not yet been described for the extravasation of vancomycin. The mechanism underlying the calcinosis observed in our case remains unclear, but we hypothesised a form of localised calciphylaxis induced by a local triggering factor. The ulcers progressed to re-epithelialisation following necrosis debridement and local conservative treatments. Given the increased prevalence of meticillin-resistant Staphylococcus aureus, which has prompted clinicians to gradually increase vancomycin dosage, clinicians should be aware of the high risk of skin toxicity in cases of vancomycin high-dose extravasation.

A New Ecological HPLC Method for Determination of Vancomycin Dosage form

Aims: To develop and validate a new ecological HPLC method for the determination of vancomycin dosage form. Background: Vancomycin is an important antimicrobial. According to the literature, there are many methods that use HPLC, but none of these methods follow the green analytical chemistry principles. Objective: Therefore, a green analytical method to quantify vancomycin in lyophilized powder for injectable solution by HPLC was developed. Materials and Methods: It uses less quantity of toxic solvents, minimizing the costs and optimizing the time of analysis. Water + 0.1% acetic acid and ethanol (85:15, v/v), 0.5 mL min-1, and C18 column (15 cm) at 280 nm were used. Results and Discussion: The method was linear in the range of 40 to 140 μg mL-1, with a correlation coefficient of 0.9998. It was selective when subjected to acid 0.1M, basic 0.01M, oxidative 0.3%, UV light and neutral degradation in a bath of 60 ºC for 8 hours. The precision of the method was proved at intraday (RSD 1.08%), interday (RSD 0.47%) and intermediate levels (RSD 2.35%). It was accurate with a mean recovery of 100.19% and robust when changes were performed in seven parameters of the method and analyzed by the Youden and Steiner test. Conclusion: The method can be applied to routine quality control of vancomycin lyophilized powder for injectable solution as an ecological and sustainable alternative that contemplates the green analytical chemistry and the current pharmaceutical analyses.

The Effect of Hypoalbuminemia on the Therapeutic Concentration and Dosage of Vancomycin in Critically Ill Septic Patients in Low-Resource Countries

Purpose: To determine whether severe hypoalbuminemia (<25 mg/L) has a significant effect on serum levels of vancomycin and whether it can effect vancomycin dosage regimen and the loading dose administration. Material and Methods: Prospective, cohort, and a single-center study included 61 patients whose vancomycin serum levels were measured in steady state. Vancomycin trough levels ( C min) that were in the range 15 to 20 µg/mL were considered therapeutic and trough levels higher than 15 µg/mL were considered potentially nephrotoxic. Results: In the group of patients with severe hypoalbuminemia, C min was significantly higher compared to the those with nonsevere hypoalbuminemia (>25 mg/L; 23.04 [19.14] vs 13.28 [11.28], P = .01). In the group of patients who received the vancomycin loading dose of 2 g, C min was significantly higher in patients with severe hypoalbuminemia compared to the patients with nonsevere hypoalbuminemia (34.52 [25.93] vs 15.37 [10.48], P = .04). Conclusion: In critically ill septic patients with severe hypoalbuminemia, there is a high probability that the loading dose of vancomycin is not necessary since it is associated with potentially toxic vancomycin C min, while in the patients with nonsevere hypoalbuminemia the loading dose may be necessary to achieving therapeutic C min.