BACKGROUND: Little information is available on the disposition of vancomycin during chronic peritoneal dialysis (PD) in children. The primary objective of this study was to investigate the disposition of vancomycin following intraperitoneal (IP) administration in children receiving short-dwell [e.g., automated PD (APD)] and long-dwell [e.g., continuous ambulatory PD (CAPD)] PD. METHODS: A 6-hour exchange containing vancomycin 500 mg/L, using an exchange volume of 1100 mL/m2 body surface area (BSA), was followed by 4-, 6-, and 8-hour antibiotic-free exchanges. The 8-hour exchange was followed by three to four 90-minute antibiotic-free exchanges. Serial blood and dialysis effluent samples were obtained and analyzed for vancomycin concentration by high-pressure liquid chromatography. Pharmacokinetic parameters were computed using noncompartmental methods. RESULTS: The bioavailability of vancomycin during a 6-hour IP exchange was 70% +/- 5%, resulting in a delivered dose of 12.0 +/- 1.8 mg/kg, and a 6-hour serum vancomycin concentration of 23.3 +/- 7.2 microg/mL. Total body vancomycin clearance measured 10.72 +/- 4.52 mL/minute/1.73 m2 BSA, while clearance attributable to PD measured 2.78 +/- 1.08 mL/min/1.73 m2 BSA and accounted for 29% +/- 11% of total vancomycin clearance. Dialysis clearance during long-dwell (CAPD) and short-dwell (APD) regimens was similar, measuring 2.46 +/- 1.04 and 3.09 +/- 1.28 mL/min/1.73 m2 BSA, accounting for 25% +/- 13% and 32% +/- 12% of total body clearance respectively. CONCLUSIONS: Intraperitoneal absorption and dialysis clearance of vancomycin in children receiving PD are similar to those reported in adult dialysis patients. In contrast, total body clearance of vancomycin appears to be increased and the elimination half-life decreased in children, due to increased elimination by non-renal nondialysis routes. For intermittent IP vancomycin therapy in children with peritonitis, an IP load containing vancomycin 1000 mg/L (or 30 mg/kg), followed a single full-fill (1100 mL/m2 BSA) daily exchange, containing vancomycin 250 mg/L (or 7.5 mg/kg), from day 2 until the end of treatment will maintain a vancomycin dialysate concentration of >4 microg/mL.
BACKGROUND: Little information is available on the disposition of vancomycin during chronic peritoneal dialysis (PD) in children. The primary objective of this study was to investigate the disposition of vancomycin following intraperitoneal (IP) administration in children receiving short-dwell [e.g., automated PD (APD)] and long-dwell [e.g., continuous ambulatory PD (CAPD)] PD. METHODS: A 6-hour exchange containing vancomycin 500 mg/L, using an exchange volume of 1100 mL/m2 body surface area (BSA), was followed by 4-, 6-, and 8-hour antibiotic-free exchanges. The 8-hour exchange was followed by three to four 90-minute antibiotic-free exchanges. Serial blood and dialysis effluent samples were obtained and analyzed for vancomycin concentration by high-pressure liquid chromatography. Pharmacokinetic parameters were computed using noncompartmental methods. RESULTS: The bioavailability of vancomycin during a 6-hour IP exchange was 70% +/- 5%, resulting in a delivered dose of 12.0 +/- 1.8 mg/kg, and a 6-hour serum vancomycin concentration of 23.3 +/- 7.2 microg/mL. Total body vancomycin clearance measured 10.72 +/- 4.52 mL/minute/1.73 m2 BSA, while clearance attributable to PD measured 2.78 +/- 1.08 mL/min/1.73 m2 BSA and accounted for 29% +/- 11% of total vancomycin clearance. Dialysis clearance during long-dwell (CAPD) and short-dwell (APD) regimens was similar, measuring 2.46 +/- 1.04 and 3.09 +/- 1.28 mL/min/1.73 m2 BSA, accounting for 25% +/- 13% and 32% +/- 12% of total body clearance respectively. CONCLUSIONS: Intraperitoneal absorption and dialysis clearance of vancomycin in children receiving PD are similar to those reported in adult dialysis patients. In contrast, total body clearance of vancomycin appears to be increased and the elimination half-life decreased in children, due to increased elimination by non-renal nondialysis routes. For intermittent IP vancomycin therapy in children with peritonitis, an IP load containing vancomycin 1000 mg/L (or 30 mg/kg), followed a single full-fill (1100 mL/m2 BSA) daily exchange, containing vancomycin 250 mg/L (or 7.5 mg/kg), from day 2 until the end of treatment will maintain a vancomycin dialysate concentration of >4 microg/mL.
Authors: Martin Wiesholzer; Petra Pichler; Gottfried Reznicek; Michaela Wimmer; Manuel Kussmann; Peter Balcke; Heinz Burgmann; Markus Zeitlinger; Wolfgang Poeppl Journal: Antimicrob Agents Chemother Date: 2016-04-22 Impact factor: 5.191