title: Antimicrobial dosing strategies in critically ill patients with acute kidney injury and high-dose continuous veno-venous hemofiltration.
abstract: OBJECTIVE
  Delivery of appropriate antimicrobial therapy is a great challenge during continuous veno-venous hemofiltration (CVVH), particularly if the recommended higher doses are applied. The present contribution discusses the principles of drug dosing during CVVH and compares the various proposed dosing strategies.
  
  
  RESULTS
  The basic principles underlying removal of antibiotics during CVVH and the published dosing strategies are reviewed. The key factor to consider is the fractional CVVH clearance (FrCVVH). Critical illness and acute kidney injury, however, may dramatically affect the pharmacokinetic properties of a drug and thus FrCVVH. Five dosing strategies have been proposed on the basis of either available references, total creatinine clearance, the reduction in total body clearance, the maintenance dose multiplication factor, or therapeutic drug monitoring. Dose predictions according to the various strategies show reasonable approximations for some but not all antibiotics.
  
  
  CONCLUSIONS
  The delivery of appropriate antimicrobial therapy during CVVH leaves us with uncertainty and presents a great challenge. To ensure efficacy and prevent toxicity, therapeutic drug monitoring is highly recommended. In the absence of therapeutic drug monitoring, adequate concentrations can only be inferred from clinical response. For nontoxic antibiotics overdosing is preferred to underdosing because the danger of underdosing is far greater than that of overdosing.
authors.affiliation: Department of Intensive Care, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. c.s.bouman@amc.uva.nl
authors.forename: Catherine S C
authors.initials: CS
authors.lastname: Bouman
mesh_terms: D058186:Acute Kidney Injury / Q000517:prevention & control / Q000628:therapy*; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D003401:Creatine / Q000378:metabolism / Q000502:physiology; D016638:Critical Illness; D016903:Drug Monitoring; D006440:Hemofiltration / Q000379:methods*; D006801:Humans
chemical_list: D000890:Anti-Infective Agents; D003401:Creatine