Harmonizing antibiotic regimens with renal replacement therapy

ABSTRACT

Introduction: Critically ill patients with acute kidney injury often require renal replacement therapy and antibiotic therapy. Mortality rates are high in these patients, possibly due to ineffective dosing due to altered pharmacokinetic profiles and drug removal by renal replacement therapy.

Areas covered: The main types of renal replacement therapies are intermittent hemodialysis, prolonged intermittent renal replacement therapy and continuous renal replacement therapy. Each of these renal replacement therapies may have drastic, yet different, effects on antibiotic serum concentration profiles. Moreover, three antibiotic administration strategies are often used: (1) standard infusion; (2) extended infusion; and (3) continuous infusion. A literature review was conducted on Medline in December 2019 to identify pertinent research.

Expert opinion: Renal replacement therapies used in the treatment of acute kidney injury in critically ill patients usually complicates antibiotic use. Although antibiotic toxicity can be seen, most studies find that these patients do not receive sufficient antibiotic doses to achieve desired pharmacodynamic targets. Clinicians should dose antibiotics to match renal replacement therapy drug clearance characteristics to antibiotic pharmacodynamic profiles.

KEYWORDS:

• Renal replacement therapy
• acute kidney injury
• antibiotics
• pharmacokinetics
• pharmacodynamics

Article highlights

• Mortality rates of critically ill patients receiving renal replacement therapies remain high, and infection is a prominent cause of death.

• Pharmacokinetic studies suggest that optimal antibiotic exposure is not achieved in these patients, likely because of patient-specific pharmacokinetic changes, drug clearance by renal replacement therapies, and insufficient antibiotic dose prescription.

• Different types of renal replacement therapies (intermittent hemodialysis vs. prolonged intermittent renal replacement therapy vs. continuous renal replacement therapy) have unique effects on drug serum concentrations.

• Each class of antibiotic (time-dependent vs. concentration-dependent vs. time-and-concentration-dependent) has a different pharmacodynamic profile that yields optimal anti-bacterial activity.

• Adjusting drug infusion techniques depending on antibiotic class can help attain pharmacodynamic goals.

• Regardless of renal replacement therapy and anti-bactericidal activity of antibiotics, a loading dose needs to be administered as a standard infusion (0.5–1 hour) to reach pharmacodynamic targets as soon as possible.

• Harmonization of antibiotic infusions with the clearance profile of a given renal replacement therapy can help meet pharmacodynamic and toxicodynamic targets.

Declaration of interest

BA Mueller has received grant funding from Merck and NxStage. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.