Pre-dialytic administration of aminoglycosides – case report and review of literature

Abstract

Objectives: Aminoglycoside (AG) antimicrobial agents are potent therapeutics against a wide variety of gram positive and negative bacteria including . Until now AGs are usually administered post-hemodialysis (HD) in patients receiving chronic HD. This regimen has been doubted with increasing knowledge of their PK/PD characteristics. Due to the concentration dependent mechanism of these drugs, high peak and low trough levels seem desirable, leading to the conclusion that a pre-dialytic administration would probably yield increased killing and reduced toxicity. This has already been proposed by O’Shea et al. Unfortunately until now there is little clinical data to support this claim. This report aims to provide an overview of the available literature as well as clinical expertise to the discussion.Methods: We present a case of a 55-year-old double lung transplant patient with chronic renal failure and recurring episodes of sepsis. The patient had received multiple antimicrobial agents without a significant reduction in inflammation parameters (CRP, WBC) or a marked improvement of her general status. Due to the lacking effect of piperacillin/tazobactam as well as carbapenems in this patient, she received 7.1 mg amikacin per kg bodyweight two hours previous to dialysis. To ensure patient safety as well as treatment efficacy amikacin peak as well as trough levels were assessed by the treating physicians.Results: The reported peak concentration was 53.3 µmol/l after the first administration, and 43.6 µmol/l 30 minutes post-infusion. During the subsequent HD the amikacin serum concentration dropped to . In the following days HD was performed daily with a trough-level adapted dose of amikacin two hours pre-HD, each time resulting in high peak and low trough levels. During this treatment the CRP level dropped from 30 mg/dl to 5.73 mg/dl within six days, and the patient recovered clinically within the first 24 hours. No difference between pre-treatment and post-treatment audiograms was observed.Discussion: Predialytic administration of AGs is a compelling regimen from a pharmacokinetic point of view. In the presented case very high peak and low trough concentrations were reached, showing that the previously proposed regimen is easily employable in daily patient care. The often expressed concern this treatment might lead to treatment failures may be countered with the good clinical result in our patient. We feel that a comparative trial is warranted and might provide better insight into the matter.

Keywords

• aminoglycosides
• dialysis
• pharmacokinetics
• pharmacodynamics