Background: Vancomycin is usually administered after the dialysis sessions to patients undergoing hemodialysis. Administration of vancomycin during (as opposed to after) sessions would save time, and would be more acceptable to patients and staff, but may lead to vancomycin underexposure. The aim of this study was to propose a new dosing regimen of vancomycin taking into account the dialysis-related losses of vancomycin when administered during dialysis. Methods: In this monocentric prospective study, vancomycin was infused to dialyzed patients during the last hour of the dialysis session at increased doses. Monitoring of vancomycin was performed using repeated blood samples by pharmacokinetics modeling. Patients were treated according to our protocol and guidelines. Results: Twenty patients were included. Vancomycin protocol was efficient: 17 of 20 (85%) patients were cured, 1 needed additional vancomycin treatment, and 2 died (sepsis n = 1, multiple organ failure n = 1). Median pre-dialysis concentration was adequate (16.2 [10.2-24.4] µg/mL), and there was no emergence of resistant bacteria. Infusion of vancomycin during dialysis therefore decreased the exposure to vancomycin by 25% compared to infusion of vancomycin after dialysis. For a typical patient, the dose of vancomycin to be administered during dialysis would be 1.4 g. Conclusion: Administration of vancomycin during the last hour of dialysis session is safe, efficacious with regards to infection control, achieved recommended vancomycin concentrations despite the use of high-flux membranes, and improved patients' quality of life.
SummaryAn increased basiliximab dose may saturate T-cell CD25 receptors in kidney transplant patients receiving calcineurin inhibitor (CNI)-free immunosuppression. In a 12-week study, 16 de novo kidney transplant patients were randomized to (i) 40 mg basiliximab with cyclosporine [n = 3] (controls), (ii) 80 mg basiliximab with cyclosporine [n = 6], or (iii) 80 mg basiliximab with everolimus (CNI-free) [n = 7], all with mycophenolic acid and steroids. Recruitment was stopped prematurely due to increased biopsy-proven acute rejection (BPAR) in the basiliximab 80 mg CNI-free group. BPAR occurred in 1/3, 1/6, and 4/7 patients in the three treatment groups, respectively. The primary endpoint, area under the effect curve of CD25 saturation to week 12, was 8.4(1.6) % 9 weeks in the control group, 11.1(1.1) % 9 weeks with basiliximab 80 mg + cyclosporine, and 9.7(0.7) % 9 weeks in the basiliximab 80 mg CNI-free group (P = 0.020 for basiliximab 80 mg + cyclosporine versus controls; P = 0.119 for basiliximab 80 mg CNI-free versus controls). Although small patient numbers prohibit robust conclusions, these results suggest that doubling the cumulative basiliximab dose to 80 mg does not provide adequate immunosuppression during the first 3 months after kidney transplantation in the absence of CNI therapy (ClinicalTrials.gov number: NCT01596062). 184
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