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Background: To analyse the effect of haemodiafiltration (CVVHDF) flow rate on amikacin pharmacokinetics and blood concentrations. Methods: Prospective observational study. Patients receiving CVVHDF and amikacin treatment were included. Pharmacokinetic parameters were calculated using Bayesian analysis. Spearman correlation test was used in order to assess the influence of CVVHDF flux on amikacin minimum concentration (Cmin) and plasma clearance. Results: Thirty patients undergoing CVVHDF procedures were included. The treatment with amikacin started at an initial mean dose of 12.4 (4.1) mg/kg/day. An association between the flow rate and Cmin value (r = 0.261; p = 0.161) and plasma clearance was found (r = 0.268; p = 0.152). Four patients (13.3%) were not able to achieve peak concentration over MIC value higher than 8. In 4 patients, amikacin had to be discontinued due to a high Cmin value. Conclusions: Amikacin clearance in patients with CVVHDF is affected by the flow rate used. Therefore, CVVHDF dose should be taken into account when dosing amikacin. [ABSTRACT FROM AUTHOR]

Objectives: To assess the probability of reaching adequate pharmacokinetic/pharmacodynamics values for ceftolozane/tazobactam at different doses and degrees of renal functions in patients with Pseudomonas aeruginosa bacteremia. Methods: Six dosing regimens were evaluated: 0.5/0.25 g, 1/0.5 g, and 2/1 g every 8 hours given as 1 hour or 3 hours infusions. Pharmacokinetic data were obtained from the literature. Susceptibility data to ceftolozane were collected from patients with P aeruginosa infection treated with ceftolozane-tazobactam. Probability of reaching a fraction of time (fT) >40% minimum inhibitory concentration (MIC) and fT >100%MIC value for ceftolozane at 3 different renal clearance values was evaluated. For tazobactam, the probability of reaching an fT >40% and >70% for 3 limit values was calculated. Results: Thirty-seven strains were included. For ceftolozane, the probability of reaching a fT >40%MIC was greater than 90% for any degree of renal function. The probability of reaching a fT >100%MIC for 1 g dose infused over 1 hour and 3 hours was 82.2% and 86.4% for a creatinine clearance (ClCr) >90 mL/min. Using a 2 g dose, the probability was greater than 90% for both infusions rates. For tazobactam, the probability of reaching a value of fT >50% of the limit concentrations was greater than 90% for a ClCr of 70 mL/min. In the case of a ClCr >90 mL/min and limit concentration values ≥ 0.25 mg/mL, only extended infusions showed a probability >90%. Conclusions and Relevance: The standard doses of ceftolozane/tazobactam achieve an adequate fT >40%MIC value. However, doses of 2 g in extended infusion is necessary to reach a value of fT >100%MIC, especially in patients with an increased renal clearance and high levels of beta-lactamases expression. [ABSTRACT FROM AUTHOR]