Therapeutic drug monitoring of β-lactam antibiotics in the ICU

ABSTRACT

Introduction

Individualizing antibiotic therapy is paramount to improve clinical outcomes while minimizing the risk of toxicity and antimicrobial therapy. β-lactam antibiotics are amongst the drugs most commonly prescribed in the Intensive Care Unit (ICU). The pharmacokinetics of β-lactam antibiotics are profoundly altered in critically ill patients, leading to the failure of standard drug dosing regimens to result in adequate drug concentrations. Therapeutic Drug Monitoring (TDM) of β-lactam antibiotics is a promising tool to help optimize β-lactam antibiotic therapy.

Areas covered

The rationale behind TDM for β-lactam antibiotics is explained, as well as some more practical aspects such as when to sample, what concentrations to strive for and how to use it in clinical practice. We also discuss microbiological and analytical considerations, knowledge gaps, and future perspectives of β-lactam antibiotics TDM in ICU patients.

Expert opinion

TDM of β-lactam antibiotics has been studied intensively in recent years. While TDM may not yet be widely available, and targets need to be further refined, TDM of β-lactam antibiotics will help to optimize antibiotic therapy in the critically ill patient, as an integrated part of an antimicrobial stewardship program.

KEYWORDS:

• Β-lactam antibiotics
• intensive care
• critical care
• sepsis
• antimicrobial
• critically ill
• pharmacokinetics
• therapeutic drug monitoring

Article highlights

• TDM is an invaluable tool to optimise antibiotic therapy

• TDM bypasses the pharmacokinetic variability of β-lactam antibiotics in ICU patients

• TDM does not alleviate the need to invest in a sound strategy to adapt dosing based on TDM results

• There is a lack of consensus regarding the optimal level of drug exposure (PK/PD target)

Declaration of interest

J De Waele discloses grants from the Flanders Research Foundation (Senior Clinical Investigator Grant); and has consulted for Accelerate, Bayer Healthcare, Cubist, Grifols, MSD, Pfizer (honoraria were paid to his institution). 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. All other authors have no conflict of interest to report.

Reviewer disclosures

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

Additional information

Funding

This paper was not funded.