Effects of Renal Replacement Therapy on Antimicrobial Therapy

Matthias      G. Vossen; Florian      Thalhammer

Abstract

Antimicrobial therapy in patients receiving renal replacement therapy (RRT) is challenging due to the varying pharmacokinetic profile of each drug - membrane - technique combination. Renally excreted drugs are usually affected by RRT to a much higher extend than hepatically excreted drugs. However, highly protein bound drugs might be eliminated during RRTs regardless of their usual route of elimination through the formation of a protein membrane within the filter. Beta-lactames pose a good example: most beta-lactames are excreted renally as unchanged drug. However, some betalactames, e.g. flucloxacillin or ceftriaxone adhere to the filter membrane due to their strong protein-drug interaction.

Depending on the implemented RRT different administration regimens should be chosen. While beta-lactames may be administered three times daily as well as continuously during continuous RRT, they should be given only once after each hemodialysis session. Aminoglycosides on the other hand should best be given previous to HD to allow for high peak and low through concentrations due to their small therapeutic index and high toxicity. The current Recommendation for glycopeptides in hemodialysis is a post-HD administration. In both groups, aminoglycosides as well as glycopeptides drug monitoring is mandatory. For chinolones the standard dosing intervals should remain unchanged, however they require a significant reduction of the dose, with the exception of moxifloxacin which is excreted hepatically.

Until now there are few publications guiding the clinician to the correct dosing schemes in RRT. This review aims to give dosage recommendations for a broad collection of currently used antimicrobial agents and should be applicable for all types of presently employed membranes.

Keywords: Antimicrobial therapy, hemodialysis, hemodiafiltration, pharmacokinetics, renal replacement therapy, Beta-lactames, Chinolones, Vancomycin, Teicoplanin, Meropenem