Once weekly intraperitoneal therapy for gram-positive peritonitis.

The pharmacokinetics and clinical outcome following a 30 mg/kg/2 L intraperitoneal (IP) dose of vancomycin, which was administered once a week for 3 weeks, was studied in ten continuous ambulatory peritoneal dialysis patients with peritonitis. Vancomycin was 91% absorbed following the first dose and rapidly achieved therapeutic serum concentrations, 19 +/- 8 mcg/mL at 1 hour and a peak of 37 +/- 8 mcg/mL at 6 hours. Vancomycin was eliminated slowly with a mean total clearance of 7 +/- 3 mL/min/70 kg and a distribution volume of 1.2 +/- 0.3 L/kg. The resultant mean serum t1/2 over the first week was 184 hours and the mean serum concentration at 168 hours was 10 +/- 4 mcg/mL. Based on the positive clinical outcome (100% cure) among patients with uncomplicated gram-positive peritonitis, the potential use of this alternative vancomycin dosing regimen is proposed.

Overestimation of vancomycin concentrations utilizing fluorescence polarization immunoassay in patients on peritoneal dialysis.

During a study of vancomycin pharmacokinetics in patients undergoing continuous ambulatory peritoneal dialysis (CAPD), a discrepancy was noted when serum concentrations were determined by high performance liquid chromatography (HPLC) in comparison to a fluorescence polarization immunoassay (FPI) technique. Following three weekly intraperitoneal doses (30 mg/kg/2 L), peak serum concentrations (at the end of the 6-h dwell) by FPI were 42.1 +/- 9.1, 43.1 +/- 8.7, and 45.6 +/- 7.4 micrograms/ml. In comparison, the same samples when analyzed by HPLC yielded 36.3 +/- 9.4, 32.2 +/- 8.9, and 31.6 +/- 9.1 micrograms/ml, respectively. A subsequent in vitro study of vancomycin (40 micrograms/ml) in serum indicated a degradation half-life of 693 (FPI) compared with 210 (HPLC) h. These data suggest that vancomycin degradation products accumulate in CAPD patients and lead to an overestimation of vancomycin serum concentrations when measured by FPI.

Peritoneal transport of cefonicid.

The pharmacokinetic characteristics of cefonicid, a highly protein-bound expanded-spectrum cephalosporin, were examined in six noninfected, clinically stable patients undergoing continuous ambulatory peritoneal dialysis. After a 1.0-g intravenous dose of cefonicid, the mean concentrations in serum were 105 +/- 25 and 35.6 +/- 14.4 micrograms/ml at 3 and 72 h, respectively. Despite a prolonged half-life in serum of 49.7 +/- 18 h, the penetration into peritoneal fluid was low. The average concentration in dialysate over the 72-h study period was 2.7 micrograms/ml. The serum clearance was 2.6 +/- 1.0 ml/min, and the distribution volume was 0.14 +/- 0.02 liter/kg. Dosage recommendations and clinical considerations for cefonicid use in continuous ambulatory peritoneal dialysis patients are discussed.