The impact of continuous renal replacement therapy on antibiotic pharmacokinetics in critically ill patients

ABSTRACT

Introduction: Mortality due to severe infections in critically ill patients undergoing continuous renal replacement therapy (CRRT) remains high. Nevertheless, rapid administration of adequate antibiotic therapy can improve survival. Delivering optimized antibiotic therapy can be a challenge, as standard drug regimens often result in insufficient or excessive serum concentrations due to significant changes in the volume of distribution and/or drug clearance in these patients. Insufficient drug concentrations can be responsible for therapeutic failure and death, while excessive concentrations can cause toxic adverse events.

Areas covered: We performed a narrative review of the impact of CRRT on the pharmacokinetics of the most frequently used antibiotics in critically ill patients. We have provided explanations for the changes in the PKs of antibiotics observed and suggestions to optimize dosage regimens in these patients.

Expert opinion: Despite considerable efforts to identify optimal antibiotic dosage regimens for critically ill patients receiving CRRT, adequate target achievement remains too low for hydrophilic antibiotics in many patients. Whenever possible, individualized therapy based on results from therapeutic drug monitoring must be given to avoid undertreatment or toxicity.

KEYWORDS:

• Aminoglycosides
• antibiotics
• acute kidney injury
• beta-lactams
• critically ill patients
• renal replacement therapy
• glycopeptides
• lipopeptides
• pharmacokinetics
• sepsis

Article highlights

• Rapid, appropriate and adequate antibiotic therapy is necessary to increase survival in critically ill patients with severe bacterial infections on continuous renal replacement therapy (CRRT)

• There is significant inter and/or intra-individual antibiotic pharmacokinetic (PK) variability in critically ill patients on CRRT, due to unpredictable changes in volume of distribution and drug clearance, very heterogeneous CRRT prescription (i.e. modality, intensity and the use of pre- or post-dilution fluid replacement) and to variability in drug regimens.

• Many critically ill patients on CRRT fail to reach antibiotic therapeutic target concentrations, at least for less susceptible strains.

• Individualized antibiotic therapy, guided by therapeutic drug monitoring and minimal inhibitory concentration (MIC) determination, should be given, whenever possible, to all critically ill patients on CRRT to increase chances of attaining therapeutic concentrations and avoid potentially toxic levels.

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Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

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

Additional information

Funding

This paper was not funded.