A narrative review of predictors for β-lactam antibiotic exposure during empirical treatment in critically ill patients

Abstract

Introduction: : Emerging studies suggest that antibiotic pharmacokinetics (PK) are difficult to predict in critically ill patients. The high intra-and inter-patient PK variability makes it challenging to accurately predict the appropriate dosage required for a given patient. Identifying patients at risk could help clinicians to consider more individualized dosing regimens and perform therapeutic drug monitoring. We provide an overview of relevant predictors associated with target (non-)attainment of β-lactam antibiotics in critically ill patients. Areas covered: : This narrative review summarizes patient and clinical characteristics that can help to predict the attainment of target serum concentrations and to provide guidance on antimicrobial dose optimization. Literature was searched using Embase and Medline database, focusing on β-lactam antibiotics in critically ill patients. Expert opinion: : Adequate concentration attainment can be anticipated in critically ill patients prior to initiating empiric β-lactam antibiotic therapy based on readily available demographic and clinical factors. Male gender, younger age, and augmented renal clearance were the most significant predictors for target non-attainment and should be considered in further investigations to develop dosing algorithms for optimal β-lactam therapy.

Barriers and Facilitators in the Clinical Implementation of Beta-Lactam Therapeutic Drug Monitoring in Critically Ill Patients: A Critical Review

“…Identifying patients at risk could help clinicians consider individualized dosing regimens and perform targeted use of TDM. 31 Relevant predictors related to target (non) achievement of beta-lactam antibiotics in critically ill patients have been well described, but their practical application has not yet been determined. Assessment tools (eg, MeroRisk Calculator 32 ) to identify patients at risk for target nonattainment could provide guidance and facilitate the implementation of beta-lactam TDM.…”

Quantification of Ceftaroline in Human Plasma Using High-Performance Liquid Chromatography with Ultraviolet Detection: Application to Pharmacokinetic Studies

“…It is well-known that the variability of PK of drugs in critically ill patients is very high [ 33 ], and clinical trials to estimate the PK parameters in this population must include a high number of patients; additionally, population models are recommended. In this regard, our study presents a limitation.…”

Therapeutic Drug Monitoring of Antibiotics in Critically Ill Patients: Current Practice and Future Perspectives With a Focus on Clinical Outcome

“…10 Currently, TDM of beta-lactams for efficacy in critically ill patients can be advised in individual cases with risk factors for target nonattainment. 67…”

“…3 In a recent review, male sex, younger age, and augmented clearance were shown to be significant predictors for target nonattainment of beta-lactams in critically ill patients. 67 Beta-lactams are time-dependent antibiotics and their PDT is commonly described as the percentage of a period in which free (f) concentrations exceed the MIC (% fT . MIC).…”