Optimizing Meropenem in Highly Resistant Klebsiella pneumoniae Environments: Population Pharmacokinetics and Dosing Simulations in Critically Ill Patients.

Critically ill patients are characterized by substantial pathophysiological changes that alter the pharmacokinetics (PK) of hydrophilic antibiotics, including carbapenems. Meropenem is a key antibiotic for multidrug-resistant Gram-negative bacilli, and such pathophysiological alterations can worsen treatment outcomes. This study aimed to determine the population PK of meropenem and to propose optimized dosing regimens for the treatment of multidrug-resistant Klebsiella pneumoniae in critically ill patients. Two plasma samples were collected from eligible patients over a dosing interval. Nonparametric population PK modeling was performed using Pmetrics. Monte Carlo simulations were applied to different dosing regimens to determine the probability of target attainment and the cumulative fraction of response, taking into account the local MIC distribution for K. pneumoniae. The targets of 40% and 100% for the fraction of time that free drug concentrations remained above the MIC (ƒT>MIC) were tested, as suggested for critically ill patients. A one-compartment PK model using data from 27 patients showed high interindividual variability. Significant PK covariates were the 8-h creatinine clearance for meropenem and the presence of an indwelling catheter for pleural, abdominal, or cerebrospinal fluid drainage for the meropenem volume of distribution. The target 100% ƒT>MIC for K. pneumoniae, with a MIC of ≤2 mg/liter, could be attained by the use of a continuous infusion of 2.0 g/day. Meropenem therapy in critically ill patients could be optimized for K. pneumoniae isolates with an MIC of ≤2 mg/liter by using a continuous infusion in settings with more than 50% isolates have a MIC of ≥32mg/L.

Contribution to the study on process of lipid peroxydation in cellular membran and modifications of some anti-oxydant enzymes during the storage process of erythrocytes

Study on the peroxidation of membrane lipid and the change of some anti-oxidant enzymes during the storage of erythrocytes by additive system. The invitro study was conducted with two additive systems: one is the AS-T which is the first preparation in VN and the other is the preparation of Terumo, a leading company of the world on the blood preparations. The results demonstrate that the two systems are equally in the anti-peroxidation activation of membrance lipid. The ability to maintain enzyme activation of Superoxyd dismutase (SOD) and Gluathion peroxidase (GCH-Px) of erythrocytes during of storage process (from ) to 35 days), the erythrocyte mass which is preserved by AST solution abilize activity of SOD and GSH-Px better than by Terumo solution, with this result os signficant slower increasing of MDA concentration at the end of storage

Study on effect of pH to 2,3-Diphospho glycerat level, pyruvat kinase and glucose-6-photphat dehydrogenase activity in erythrocytes preserved long-time storage

To compare the influence of the Bach Mai prepared AS-T preserving solution and Japanese Turumo firm prepared preserving solution in a same condition on the blood of 5 healthy persons of B group blood, who did not donate the blood. AS-T solution had stabilized and maintained the red blood cells, pH higher than 7 through a storage duration of 42 days. AS-T solution had maintained 2.3-DPG concentration in a level higher significantly in comparing with Terumo solution at the terminal points of the storage time PK and G6PD activities of the red blood cells mass preserved by AS-T solution as well as Terumo solution had decreased progressively in the duration of storage.

Study of adenin influence on erythrocyte number, pH and osmotic pression of erythrocytes volume during the process of conservation

Adenin made a comfortable impact on erythrocytes during preservation, both on the ability to maintain the number of red blood cell (RBC), to stabilize the pH and osmotic pressure of erythrocytes. The presence of adenin in the component of the solution that preserved erythrocytes with the most suitable concentration was 0.04/100ml. At the 28th of preservation, RBC of all studied formulas suddenly decreased. Adenin didn't maintain over 98% RBC, stabilized the pH of erythrocytes on the level 7 at the 42nd days during preservation