The clinical application of beta-lactam antibiotic therapeutic drug monitoring in the critical care setting

Abstract

Critically ill patients have increased variability in beta-lactam antibiotic (beta-lactam) exposure due to alterations in their volume of distribution and elimination. Therapeutic drug monitoring (TDM) of beta-lactams, as a dose optimization and individualization tool, has been recommended to overcome this variability in exposure. Despite its potential benefit, only a few centres worldwide perform beta-lactam TDM. An important reason for the low uptake is that the evidence for clinical benefits of beta-lactam TDM is not well established. TDM also requires the availability of specific infrastructure, knowledge and expertise. Observational studies and systematic reviews have demonstrated that TDM leads to an improvement in achieving target concentrations, a reduction in potentially toxic concentrations and improvement of clinical and microbiological outcomes. However, a small number of randomized controlled trials have not shown a mortality benefit. Opportunities for improved study design are apparent, as existing studies are limited by their inclusion of heterogeneous patient populations, including patients that may not even have infection, small sample size, variability in the types of beta-lactams included, infections caused by highly susceptible bacteria, and varied sampling, analytical and dosing algorithm methods. Here we review the fundamentals of beta-lactam TDM in critically ill patients, the existing clinical evidence and the practical aspects involved in beta-lactam TDM implementation.

Meropenem PK/PD Variability and Renal Function: “We Go Together”

“…However, a very limited number of studies have been conducted to properly analyze the impact of TDM activity, due to the low prevalence of hospitals with a routine TDM clinical service and the complexity of identifying an adequate performance outcome [ 11 , 36 ]. Nevertheless, the possibility of measuring drug concentration throughout the dosing interval helps physicians modify the labeled dose regimen in order to exploit the PK/PD properties of the active principle, promptly monitoring possible unexpected therapeutic underexposure or overexposure of patients, meanwhile evaluating the clinical evolution of the disease.…”

“…Therefore, an increasing amount of scientific evidence in the literature recommends performing the therapeutic drug monitoring (TDM) of beta-lactams, especially in critical care and in case of alterations of dysfunction of organs involved in the absorption, distribution, metabolism, and excretion of administered drugs [ 9 , 10 ]. Nevertheless, the TDM and the clinical pharmacologist advice is available only in a limited number of hospitals, mainly due to several organizational barriers to the implementation of this routine activity in terms of costs and dedicated staff [ 11 ].…”

Intra-abdominal infections survival guide: a position statement by the Global Alliance For Infections In Surgery

“…Tissue distribution is higher for lipophilic than hydrophilic agents, but disease-related factors (e.g., binding to plasma proteins, serum albumin concentration) may influence tissue distribution. In a 2020 prospective observational study of critically ill patients with cIAI who required surgery and received empiric beta-lactam antibiotic therapy [132] high doses of beta-lactams ensured 100% fT > 4×MIC for 78% of patients within the first 24 h. TDM of beta-lactams, as a dose optimization and individualization tool, has been recommended, but despite potential benefit, not all centers perform TDM for beta-lactams [133].…”