title: β-Lactam therapeutic drug monitoring in the critically ill: optimising drug exposure in patients with fluctuating renal function and hypoalbuminaemia.
abstract: β-Lactams are routinely prescribed in the treatment of serious infections. Empirical dosing schedules are typically derived from studies in healthy volunteers and largely fail to consider the significant changes in antibacterial pharmacokinetics often encountered in the critically ill. These changes are primarily driven by the underlying pathophysiology and the interventions provided, leading to altered protein binding, poor tissue penetration, and fluctuations in the volume of distribution and drug clearance. Each separately, and in combination, is likely to complicate successful β-lactam administration in this setting. Although antibacterial therapeutic drug monitoring (TDM) has traditionally been employed to minimise drug toxicity, the challenges to achieving 'optimal' drug concentrations in the critically ill suggest β-lactam TDM as an attractive means to optimise drug exposure. Whilst there is currently little evidence to support routine widespread application of such a service, β-lactam TDM may still have a role in select patients where difficulty in establishing therapeutic concentrations can be illustrated. This series utilises three representative cases from a β-lactam TDM service that highlight the utility of this intervention in optimising antibacterial dosing. These preliminary data support an expanding role for β-lactam TDM in select critically ill patients and provide insight into the subpopulations most at risk of suboptimal drug exposure. Future studies investigating the clinical outcome benefits of β-lactam TDM in these patient groups are now warranted.
authors.affiliation: The University of Queensland, UQ Centre for Clinical Research, Herston, QLD 4029, Australia. yoshi.icu@gmail.com
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lipman
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Udy
authors.forename: Mandy
authors.initials: M
authors.lastname: Ng
authors.forename: Brett
authors.initials: B
authors.lastname: McWhinney
authors.forename: Jacobus
authors.initials: J
authors.lastname: Ungerer
authors.forename: Karin
authors.initials: K
authors.lastname: Lust
authors.forename: Jason A
authors.initials: JA
authors.lastname: Roberts
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000188:drug therapy*; D003422:Critical Care / Q000379:methods*; D016638:Critical Illness; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006801:Humans; D034141:Hypoalbuminemia / Q000150:complications*; D007668:Kidney / Q000502:physiology*; D008297:Male; D047090:beta-Lactams / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D047090:beta-Lactams