The treatment of infections in critically ill obese and morbidly obese patients is challenging because of the combined physiological changes that result from obesity and critical illness. The aim of this study was to describe the population pharmacokinetics of piperacillin in a cohort of critically ill patients, including obese and morbidly obese patients. Critically ill patients who received piperacillin-tazobactam were classified according to their body mass index (BMI) as nonobese, obese, and morbidly obese. Plasma samples were collected, and piperacillin concentrations were determined by a validated chromatographic method. Population pharmacokinetic analysis and Monte Carlo dosing simulations were performed using Pmetrics software. Thirty-seven critically ill patients (including 12 obese patients and 12 morbidly obese patients) were enrolled. The patients' mean Ϯ standard deviation age, weight, and BMI were 50 Ϯ 15 years, 104 Ϯ 35 kg, and 38.0 Ϯ 15.0 kg/m 2 , respectively. The concentration-time data were best described by a two-compartment linear model. The mean Ϯ SD parameter estimates for the final covariate model were a clearance of 14.0 Ϯ 7.1 liters/h, a volume of distribution of the central compartment of 49.0 Ϯ 19.0 liters, an intercompartmental clearance from the central compartment to the peripheral compartment of 0.9 Ϯ 0.6 liters · h Ϫ1 , and an intercompartmental clearance from the peripheral compartment to the central compartment of 2.3 Ϯ 2.8 liters · h Ϫ1 . A higher measured creatinine clearance and shorter-duration infusions were associated with a lower likelihood of achieving therapeutic piperacillin exposures in patients in all BMI categories. Piperacillin pharmacokinetics are altered in the presence of obesity and critical illness. As with nonobese patients, prolonged infusions increase the likelihood of achieving therapeutic concentrations.

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e Severe pathophysiological changes in critical illness can lead to dramatically altered antimicrobial pharmacokinetics (PK). The additional effect of obesity on PK potentially increases the challenge for effective dosing. The aim of this prospective study was to describe the population PK of meropenem for a cohort of critically ill patients, including obese and morbidly obese patients. Critically ill patients prescribed meropenem were recruited into the following three body mass index ( ؊1 . Higher creatinine clearance (CL CR ) was associated with a lower probability of target attainment, with BMI having little effect. Although obesity was found to be associated with an increased V 1 , dose adjustment based on CL CR appears to be more important than patient BMI.

A method for the analysis of vancomycin in plasma (total, unbound), urine and renal replacement therapy effluent, suitable for use in any patient pharmacokinetic study, has been developed and validated.

In-vitro adsorption and sieving coefficient of ticarcillin-clavulanate during continuous haemofiltration.Wan, Winnie a ,