Affiliation:
1. Faculties of Pharmacy
2. Medicine, University of Manitoba
3. Microbiology Laboratory, St. Boniface General Hospital, Winnipeg, Manitoba, Canada
4. Department of Pharmacy
Abstract
ABSTRACT
Standard microbiological tests (i.e., MIC) do not account for the unique factors of peritoneal dialysis (PD)-related peritonitis which can significantly influence treatment response. Our goals were to develop a peritoneal fluid titer (PFT) test and to conduct a pilot study of its association with clinical outcome. The methodology was developed by using spent dialysate collected from patients with bacterial PD-related peritonitis prior to the initiation of antibiotics. Dialysate was processed and spiked with antibiotic to simulate two standard intraperitoneal regimens: cefazolin plus tobramycin and cefazolin alone. Thirty-six clinical isolates, including
Staphylococcus epidermidis
,
Staphylococcus aureus
,
Escherichia coli
,
Klebsiella pneumoniae
,
Enterobacter cloacae
, and
Pseudomonas aeruginosa
, were tested. In the pilot study, dialysate was collected from 14 patients with bacterial PD-related peritonitis. Titers were determined by using each patient's dialysate and infecting pathogen. Titers were highly reproducible, with discrepancies in only 1% of cases. Overall, PFTs were notably higher against gram-positive bacteria (
P
< 0.0001). The addition of tobramycin increased titers significantly from zero to values of 1/16 to 1/64 against
E. cloacae
and
P. aeruginosa
(
P
< 0.0001). In the pilot study, peritoneal fluid inhibitory titers were significantly associated with clinical outcome, with a median value of 1/96 for patients who were cured compared to 1/32 for those who failed treatment (
P
= 0.036). In conclusion, this study provides preliminary support for the PFT as a pharmacodynamic index specific to the treatment of PD-related peritonitis. With further characterization and validation in patients, the PFT test may advance the study of antibiotic therapies for PD-related peritonitis.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
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