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Antibiotic dosing in critically ill patients with acute kidney injury

Nature Reviews Nephrology volume 7, pages 226–235 (2011)Cite this article

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Abstract

A common cause of acute kidney injury (AKI) is sepsis, which makes appropriate dosing of antibiotics in these patients essential. Drug dosing in critically ill patients with AKI, however, can be complicated. Critical illness and AKI can both substantially alter pharmacokinetic parameters as compared with healthy individuals or patients with end-stage renal disease. Furthermore, drug pharmacokinetic parameters are highly variable within the critically ill population. The volume of distribution of hydrophilic agents can increase as a result of fluid overload and decreased binding of the drug to serum proteins, and antibiotic loading doses must be adjusted upwards to account for these changes. Although renal elimination of drugs is decreased in patients with AKI, residual renal function in conjunction with renal replacement therapies (RRTs) result in enhanced drug clearance, and maintenance doses must reflect this situation. Antibiotic dosing decisions should be individualized to take into account patient-related, RRT-related, and drug-related factors. Efforts must also be made to optimize the attainment of antibiotic pharmacodynamic goals in this population.

Key Points

  • Altered drug pharmacokinetics in critically ill patients with acute kidney injury (AKI) and heterogeneous renal replacement therapy (RRT) techniques in intensive care units preclude standardized antibiotic dosing

  • Most critically ill patients with AKI exhibit altered antibiotic pharmacokinetics that necessitate increased doses in spite of decreased renal clearance, particularly when serious infections are implicated

  • Drug dosing decisions must take into account pharmacodynamic as well as pharmacokinetic considerations

  • Clinicians should compare their RRT protocols to those in published guidelines and ensure that their recommendations are applicable to the individual patient's clinical situation

  • Hybrid RRTs require the same antibiotic dosing alterations as do continuous RRTs, but for hybrid therapies the dose timing must also be considered

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C. P. Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape, LLC-accredited continuing medical education activity associated with this article.

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  1. Department of Clinical, Social, and Administrative Sciences, College of Pharmacy, University of Michigan, 428 Church Street, Ann Arbor, 48109-1065, MI, USA

    Rachel F. Eyler & Bruce A. Mueller

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R. F. Eyler and B. A. Mueller contributed equally to all aspects of the manuscript.

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R. F. Eyler has received research funding from Merck and Roche. B. A. Mueller has received research funding from Cubist Pharmaceuticals, Merck, and Roche, and is a member of the speaker's bureaus for Amgen, Gambro, and Cubist Pharmaceuticals.

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Eyler, R., Mueller, B. Antibiotic dosing in critically ill patients with acute kidney injury. Nat Rev Nephrol 7, 226–235 (2011). https://doi.org/10.1038/nrneph.2011.12

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