A Monte Carlo Analysis of Peritoneal Antimicrobial Pharmacokinetics

The microbial cause of peritoneal dialysis-related peritonitis is an important determinant of clinical outcome and the basis of widely used treatment guidelines. Five hundred forty-six cases of peritonitis in 374 patients from 1991 to 1998 were analyzed. The rate of peritonitis declined significantly from 1.37 episodes/patient-year in 1991 to 0.55 episode/patient-year in 1998 (P = 0.02). The rate of Gram-positive peritonitis decreased significantly from 0.75 to 0.28 episode/patient-year during the same period (P = 0.02). Conversely, the occurrence of Gram-negative peritonitis remained constant at approximately 0.16 episode/patient-year (P = 0.28). Staphylococcus epidermidis and Staphylococcus aureus were the most common causes of peritonitis, isolated in 27.8% and 19.3% of the culture-positive cases, respectively. A distinct decrease in peritonitis caused by S epidermidis was observed, with 0.40 episode/patient-year in 1991 compared with 0.11 to 0.20 episode/patient-year during subsequent years. The rate of infections caused by S aureus decreased significantly over time from a high of 0.21 episode/patient-year in 1992 to a low of 0.04 episode/patient-year in 1998 (P = 0.01). Pseudomonas aeruginosa, Escherichia coli, and KLEBSIELLA: species were the most common causes of Gram-negative peritonitis, identified in 7.1%, 6.8%, and 5.2% of culture-positive cases, respectively. The most dramatic increase in antibiotic resistance was seen among S epidermidis. From 1991 and 1992 to 1997 and 1998, resistance to ciprofloxacin increased from 5.4% to 47.8% (P = 0.003), and resistance to methicillin increased from 18.9% to 73.9% (P = 0.03). Our study showed significant trends in the causative pathogens of peritoneal dialysis-related peritonitis and dramatic increases in antibiotic resistance. These data support further study and warrant reevaluation of current treatment practices.

Mupirocin (Mup) has been used extensively to prevent Staphylococcus aureus (SAu) infections in patients undergoing peritoneal dialysis (PD). Resistance to Mup has been reported, but its relevance after long-term use of this drug in PD is unknown. Colonization by SAu was treated with topic Mup in our unit between September 1990 and December 2000. Sensitivity to Mup was tested in 437 strains of SAu isolated from 155 PD patients and 62 dialysis partners. Resistance to Mup was classified as low (minimal inhibitory concentration [MIC] > or = 8 microg/mL) or high (MIC > or = 512 microg/mL) degree. MIC90 was 0.125 microg/mL in 1990 to 1996 (5% low, 0% high-degree resistance), 64 microg/mL in 1997 to 1998 (6.6% low, 8.3% high-degree resistance), and 1,024 microg/mL in 1999 to 2000 (2.3% low, 12.4% high-degree resistance). Mup-resistant SAu were isolated from 25 patients and 13 partners a median of 15 months after starting PD. Resistance was associated frequently with repeated treatments of SAu recolonization, but was detected in 3 cases at the start of PD therapy. The accumulated incidence of SAu exit-site infection in the period 1997 to 2000 was 32.3% in patients colonized by Mup-resistant SAu as compared with 14.5% in those colonized by Mup-sensitive SAu (P = 0.03). Mup-resistant SAu have emerged in a significant proportion of our PD patients and dialysis partners. This emergence has resulted in a moderate, but significant, increase in the risk of SAu exit-site infection and raises concerns about the future of Mup as the therapy of choice for SAu colonization in patients undergoing chronic PD. Copyright 2002 by the National Kidney Foundation, Inc.

To determine the prevalence and rate of acquisition of vancomycin-resistant enterococci (VRE) among patients undergoing chronic (i.e., long-term) hemodialysis who were admitted to a tertiary care center, serial rectal cultures for VRE were performed at hospital admission and every 5 days until hospital discharge. A total of 7 (6%) of the 119 patients were colonized with VRE at admission. Six (19%) of the 32 patients who remained in the hospital > or =4 days acquired VRE. A nonambulatory status was significantly associated with colonization at admission (OR, 9.7; 95% CI, 1.8-53; P=.01), and vancomycin exposure was significantly associated with VRE acquisition (relative risk, 1.8; 95% CI, 1.1-2.9; P=.02). All patients acquired VRE from epidemiologically linked dialysis patients colonized with similar VRE genotypes. Hospital acquisition of VRE contributes substantially to the increasing prevalence of VRE in the chronic hemodialysis patient population.