title: Dosing of daptomycin in intensive care unit patients with acute kidney injury undergoing extended dialysis--a pharmacokinetic study.
abstract: BACKGROUND
  Daptomycin is a new intravenous cyclic lipopeptide antibiotic, licensed for the treatment of complicated skin and soft tissue infections caused by Gram-positive organisms including both susceptible and resistant strains of Staphylococcus aureus and for the treatment of various infections due to susceptible organisms, including serious and life-threatening Gram-positive infections, vancomycin-resistant enterococcal infections and right-sided endocarditis with associated bacteremia. Currently, no dosing recommendations exist for this drug for patients with acute kidney injury (AKI) undergoing renal replacement therapy. The aim of this study was to evaluate pharmacokinetics of daptomycin in critically ill patients with AKI undergoing extended dialysis (ED), a frequently used mean of renal replacement therapies in intensive care units (ICUs) around the world. Patients and methods. A prospective, single-dose pharmacokinetic study was performed in the medical and surgical ICUs of a tertiary care center. The aim was to investigate critically ill patients with anuric AKI being treated with ED and receiving daptomycin (n = 10). Daptomycin (6 mg/kg) was administered 8 h before ED was started.
  
  
  RESULTS
  Key pharmacokinetic parameters like half-life in critically ill patients treated with ED were comparable to healthy controls. The dialyser clearance for daptomycin was 63 +/- 9 ml/min. Based on the amount of the drug recovered from the collected spent dialysate, the mean fraction of the drug removed by one dialysis treatment was 23.3%.
  
  
  CONCLUSIONS
  Our data suggest that patients treated with ED using a high-flux dialyzer (polysulphone, 1.3 m(2); blood and dialysate flow, 160 ml/min; ED time, 480 min) and employing current dosing regimen, 6 mg/kg daptomycin every 48 h, run the risk of becoming significantly under dosed if one adheres to a twice daily dosing schedule that is recommended for patients on maintenance haemodialysis. Our data suggest that a daily dose of 6 mg/kg daptomycin is necessary in this special patient population to avoid under dosing, which may have detrimental effects in critically ill patients suffering from life-threatening infections.
authors.affiliation: Department of Nephrology and Hypertension, Medical School Hannover, Germany. Kielstein@yahoo.com
authors.forename: Jan T
authors.initials: JT
authors.lastname: Kielstein
authors.forename: Catrin
authors.initials: C
authors.lastname: Eugbers
authors.forename: Stefanie M
authors.initials: SM
authors.lastname: Bode-Boeger
authors.forename: Jens
authors.initials: J
authors.lastname: Martens-Lobenhoffer
authors.forename: Hermann
authors.initials: H
authors.lastname: Haller
authors.forename: Christian
authors.initials: C
authors.lastname: Joukhadar
authors.forename: Friederike
authors.initials: F
authors.lastname: Traunmüller
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Knitsch
authors.forename: Carsten
authors.initials: C
authors.lastname: Hafer
authors.forename: Olaf
authors.initials: O
authors.lastname: Burkhardt
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D017576:Daptomycin / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D006435:Renal Dialysis
chemical_list: D000900:Anti-Bacterial Agents; D017576:Daptomycin