Peritoneal dialysis fluid concentrations of linezolid in the treatment of vancomycin-resistant Enterococcus faecium peritonitis.
OBJECTIVE
To determine linezolid concentrations in peritoneal dialysis fluid after multiple oral doses of the drug in a 46-year-old man with vancomycin-resistant Enterococcus faecium peritonitis who was undergoing peritoneal dialysis.


METHODS
After administration of oral linezolid 600 mg twice/day was started, peritoneal dialysis fluid was collected at the end of several 4- and 8-hour dwell times and submitted for analysis of linezolid concentration. Before linezolid therapy was begun, and immediately after several peritoneal dialysis exchanges, 30 ml of expended peritoneal dialysis fluid was collected in a sterile container and immediately frozen at -70 degrees C until analysis by high-performance liquid chromatography.


RESULTS
Peritoneal dialysis concentrations of linezolid greater than 4 microg/ml were achieved after the first dose of linezolid and maintained after repeated doses. During the course of therapy, mean linezolid concentrations in peritoneal dialysis fluid tended to increase (mean 7.60 pg/ml, range 3.54-16.2 microg/ml). All assayed peritoneal dialysis samples demonstrated linezolid concentrations greater than 4 microg/ml at the end of 4- or 8-hour dwell times, except for one level after a missed dose on linezolid treatment day 3. Duration of dwell times did not appear to correlate with linezolid concentrations.


CONCLUSIONS
In this patient, linezolid 600 mg twice/day penetrated into peritoneal dialysis fluid at or above the concentrations necessary to treat common gram-positive bacteria. Linezolid therapy is likely to have a role in peritoneal dialysis-associated peritonitis based on its antimicrobial activity, pharmacokinetic properties, ease of administration, and tolerability.
DePestel
Daryl D
DD
Department of Clinical Sciences, College of Pharmacy, University of Michigan, UHB2D301 University Hospital, 1500 East Medical Center Drive, Ann Arbor, MI 48109-0008, USA. daryldd@umich.edu
Peloquin
Charles A
CA
Carver
Peggy L
PL
D000081:Acetamides / Q000032:analysis* / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000032:analysis* / Q000627:therapeutic use; D015314:Dialysis Solutions / Q000737:chemistry; D013293:Enterococcus faecalis; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D007676:Kidney Failure, Chronic / Q000628:therapy; D000069349:Linezolid; D008297:Male; D008875:Middle Aged; D023303:Oxazolidinones / Q000032:analysis* / Q000627:therapeutic use; D010530:Peritoneal Dialysis; D010538:Peritonitis / Q000188:drug therapy* / Q000382:microbiology; D020713:Vancomycin Resistance
D000081:Acetamides; D000900:Anti-Bacterial Agents; D015314:Dialysis Solutions; D023303:Oxazolidinones; D000069349:Linezolid