Ensuring target concentrations of antibiotics in critically ill patients through dose adjustment

ABSTRACT

Introduction

Antibiotics are commonly prescribed in critical care, and given the large variability of pharmacokinetic (PK) parameters in these patients, drug PK frequently varies during therapy with the risk of either treatment failure or toxicity. Therefore, adequate antibiotic dosing in critically ill patients is very important.

Areas covered

This review provides an overview of the basic principles of PK and pharmacodynamics of antibiotics and the main patient and pathogen characteristics that may affect the dosage of antibiotics and different approaches to adjust doses.

Expert opinion

Dose adjustment should be done for aminoglycosides and glycopeptides based on daily drug concentration monitoring. For glycopeptides, in particular vancomycin, the residual concentration (Cres) should be assessed daily. For beta-lactam antibiotics, a loading dose should be administered, followed by three different possible approaches, as TDM is rarely available in most centers: 1) antibiotic regimens should be adapted according to renal function and other risk factors; 2) nomograms or software can be used to calculate daily dosing; 3) TDM should be performed 24–48 h after the initiation of treatment; however, the results are required within 24 hours to appropriately adjust dosage regimens. Drug dosing should be reduced or increased according to the TDM results.

KEYWORDS:

• Antibiotics
• dosing adjustment
• pharmacodynamics
• pharmacokinetics
• therapeutic drug monitoring
• software

Article highlights

• Organ dysfunctions, weight, patients’ clinical presentation, therapeutics used (in particular continuous renal replacement therapy, mechanical ventilation, and/or extracorporeal membrane oxygenation), and the patient’s inflammatory state are factors leading to pathophysiological changes influencing the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of antibiotics in intensive care.

• The minimum inhibitory concentration value serves as the basis for assessing whether the pathogen is susceptible or resistant to a given antibiotic.

• Dosage adjustment is not only important to attain PK/PD targets but also to avoid overexposure in some patients and thus an increased risk of adverse effects.

• As most hydrophilic antimicrobials are cleared by the kidneys, renal function is one of the most important clinical factors that contributes to target non-attainment at the time of antibiotic initiation and therefore to individualized antibiotic dosing.

• Therapeutic drug monitoring (TDM), initially used to avoid drug toxicity, is now increasingly being used in critical care patients to attempt to improve PK/PD target attainment.

• TDM results can be integrated with other tools, such as dosing nomograms and/or software to help improve PK/PD target attainment by guiding dosage adjustment.

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.