Antibiotic Administration in an Animal Model of Chronic Peritoneal Dialysate Exposure

Abstract

♦ Objectives The high incidence of intraperitoneal infection remains an important problem in animal models of chronic dialysate exposure. Prophylactic antibiotic administration can be used to resolve this problem, but the isolated effects of antibiotics on peritoneal membrane function and structure are unknown. The present study examined the effects of prophylactic antibiotics on infection rate and peritoneal membrane function and structure in a rat model of chronic dialysate exposure. ♦ Design A first group of rats (A; n = 12) received 10 mL 3.86% glucose dialysate twice daily through a heparin-coated catheter. In a second group of animals (B; n = 12), oxacillin 2.5 mg/day and gentamicin 0.04 mg/day were added to the dialysate. Group C ( n= 12) was injected twice daily with an identical dose of antibiotics dissolved in 1 mL of buffer solution. Group D ( n = 12) was left untreated. Dialysate cultures were obtained regularly. After 8 weeks of exposure, peritoneal transport studies were performed and samples for histology were obtained. ♦ Results Technique survival was 92% in group A and 100% in the remaining groups. Five rats in group A but none of the animals in the other groups developed peritonitis. The transport rates of small solutes were elevated and net ultrafiltration was decreased in group A compared to the controls. Fibrosis, as evaluated by quantifying Picro Sirius Red staining with image analysis, was significantly elevated in group A (3.48% ± 1.06% vs 0.72% ± 0.51% in group D, p < 0.05) but not in group B (0.29% ± 0.07%) or in group C (0.52% ± 0.28%). Vascular density, measured by counting the number of blood vessels that stained positive for endothelial NO synthase, was increased in both groups that were exposed to dialysate: 153.0 ± 12.9/μm2 in group A and 131.6 ± 14.3/μm2 in group B, versus 76.76 ± 12.37/μm2 in group C and 73.2 ± 10.4/μm2 in group D ( p < 0.01). ♦ Conclusions Prophylactic administration of oxacillin and gentamicin adequately prevented intraperitoneal infection in an animal model of chronic dialysate exposure. In addition, fibrosis was absent, suggesting intra-peritoneal infection rather than dialysate exposure is a causative factor.