Principles of antibacterial dosing in continuous renal replacement therapy.

Abstract:

OBJECTIVES:To outline the concepts involved in optimizing antibacterial dosing in critically ill patients with acute renal failure undergoing continuous renal replacement therapy (CRRT), provide a strategy for optimizing dosing, and summarize the data required to implement the strategy. DATA SOURCES:MEDLINE search from February 1986 to 2008. DATA EXTRACTION AND SYNTHESIS:Optimal dosing of antibacterials is dependent on achieving pharmacokinetic targets associated with maximal killing of bacteria and improved outcomes. The initial dose is dependent on the volume of distribution. Maintenance doses are dependent on clearance. Both should be adjusted according to the pharmacokinetic target associated with optimal bacterial killing, when known. The volume of distribution of some antibacterials is altered by critical illness or acute renal failure or both. Clearance by CRRT is dependent on the dose and mode of CRRT and the sieving or saturation coefficient of the drug. Both sieving and saturation coefficient are related to the plasma protein binding and thus may be altered in renal failure. CONCLUSIONS:Appropriate dose calculation requires knowledge of the pharmacokinetic target and the usual minimum inhibitory concentration of the suspected organism in the patient's locality (or if unavailable, the break point for the organism), published pharmacokinetic data (volume of distribution, non-CRRT clearance) on critically ill patients receiving CRRT (which may differ substantially from noncritically ill patients or those without renal failure), the sieving or saturation coefficient of the relevant drug in critically ill patients, the dose and mode of CRRT being used, and the actual dose of CRRT that is delivered. This large number of variables results in considerable inter- and intrapatient heterogeneity in dose requirements. This article provides basic principles and relevant data to guide the clinician in prescribing individualized dosing regimes.

journal_name

Crit Care Med

journal_title

Critical care medicine

authors

Choi G,Gomersall CD,Tian Q,Joynt GM,Freebairn R,Lipman J

doi

10.1097/CCM.0b013e3181aab3d0

subject

Has Abstract

pub_date

2009-07-01 00:00:00

pages

2268-82

issue

7

eissn

0090-3493

issn

1530-0293

journal_volume

37

pub_type

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