title: Linezolid levels in a patient with biliary tract sepsis, severe hepatic failure and acute kidney injury on sustained low-efficiency dialysis (SLED).
abstract: We report on a patient with biliary sepsis due to Vancomycin-resistant Enterococcus faecium (VRE) treated with linezolid (LNZ), who had both hepatic failure and acute kidney injury requiring daily sustained low-efficiency dialysis (SLED), a new intermittent, prolonged diffusive modality of renal replacement therapy for ICU patients. Following cholecystostomy and peritoneal drain insertion, serum, bile and peritoneal fluid serial samples were simultaneously collected for LNZ concentration measurement (chromatography/mass spectrometry). Unusually high serum antibiotic levels (20 mg/L or more) were achieved as early as 36 hours since the start of LNZ administration, owing to relatively low hepatic clearance. Serum LNZ leveled off after commencing SLED, apparently reaching steady state levels. The lowest values of Cmin in bile was 5.86 mg/L; the average serum and bile AUC0-12 over the observation period were 204 mg/L*h and 276 mg/L*h, with a AUC0-24/MIC ratio of 227 h and 307 h, respectively. The excellent biliary pharmacodynamic exposure suggests that standard-dose LNZ might represent a valuable choice in severe biliary infection, even in the presence of hepatic failure, when the patients receive highly efficient modalities of renal replacement therapy.
authors.affiliation: Department of Medical Clinic, Nephrology and Prevention, University of Parma, Parma, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Cremaschi
authors.forename: U
authors.initials: U
authors.lastname: Maggiore
authors.forename: C
authors.initials: C
authors.lastname: Maccari
authors.forename: C
authors.initials: C
authors.lastname: Cademartiri
authors.forename: R
authors.initials: R
authors.lastname: Andreoli
authors.forename: E
authors.initials: E
authors.lastname: Fiaccadori
mesh_terms: D018806:APACHE; D000081:Acetamides / Q000097:blood* / Q000627:therapeutic use*; D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000378:metabolism; D000368:Aged; D000900:Anti-Bacterial Agents / Q000097:blood* / Q000627:therapeutic use*; D001660:Biliary Tract Diseases / Q000188:drug therapy* / Q000378:metabolism; D002763:Cholecystectomy; D016984:Enterococcus faecium; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D006801:Humans; D000069349:Linezolid; D017093:Liver Failure / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D023303:Oxazolidinones / Q000097:blood* / Q000627:therapeutic use*; D006435:Renal Dialysis; D018805:Sepsis / Q000188:drug therapy* / Q000378:metabolism*; D020713:Vancomycin Resistance
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D000069349:Linezolid