title: Antimicrobial dosing in acute renal replacement.
abstract: Acute kidney injury (AKI) is a common problem in hospitalized patients and is associated with significant morbidity and mortality. Two large trials showed no benefit from increased doses of renal replacement therapy (RRT) despite previous clinical data suggesting that increased clearance from RRT has beneficial effects. Since infection is the leading cause of death in AKI, my group and others hypothesized that increased RRT antibiotic clearance might create a competing morbidity. The data from my group, as well as those of other groups, show that many patients are underdosed when routine "1 size fits all" antibiotic dosing is used in patients with AKI receiving continuous RRT (CRRT). Here, concepts of drug distribution and clearance in AKI are briefly discussed and then 1 antibiotic (piperacillin) is discussed in depth to illustrate the challenges in applying the medical literature to clinical practice. The fact that published data on drug dosing in AKI and dialysis reflect the evolution of practice patterns and often do not apply to present prescribing habits is also discussed. A more general approach to drug dosing facilitates situation-specific prescribing by the nephrologist and critical care specialist.
authors.affiliation: Department of Nephrology and Hypertension, Vanderbilt University, Nashville, TN 37232, USA. william.fissell@vanderbilt.edu
authors.forename: William H
authors.initials: WH
authors.lastname: Fissell
mesh_terms: D058186:Acute Kidney Injury / Q000628:therapy*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001682:Biological Availability; D003422:Critical Care / Q000379:methods*; D016638:Critical Illness; D004334:Drug Administration Schedule; D054796:Drug Dosage Calculations; D006801:Humans; D008658:Inactivation, Metabolic; D008657:Metabolic Clearance Rate; D010878:Piperacillin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D017410:Practice Guidelines as Topic; D017582:Renal Replacement Therapy / Q000379:methods; D014018:Tissue Distribution
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D010878:Piperacillin