Personalised beta-lactam therapy: basic principles and practical approach

Bacterial infections are potentially life-threatening diseases requiring effective antibiotic treatment right from the outset to achieve a favourable prognosis. Therapeutic success depends on the susceptibility of the bacterial pathogen, determined by the minimum inhibitory concentration (MIC), and the concentration of the antibiotic at the focus of infection, which is influenced by drug metabolism and pharmacokinetic (PK) factors. Beta-lactams are time-dependent antibiotics. Bacterial killing correlates with the duration of the drug concentration above the MIC of the pathogen. Critical illness is associated with major PK changes. This may lead to unexpected drug concentrations and unpredictable dose requirements differing significantly from standard dosages. Emerging dosing strategies are therefore based on PK/pharmacodynamic (PD) principles. Therapeutic drug monitoring (TDM) is increasingly playing a key role in antibiotic treatment optimisation in general and in beta-lactam therapy, in particular, notably in severely ill patients. Furthermore, evidence of the superiority of continuous beta-lactam infusions over shorter administration regimens is growing. Target drug concentrations have to be defined, considering MIC values especially in pathogens with limited susceptibility. For reliable TDM results, correct pre-analytical sample handling is indispensable. Personalised, TDM-guided therapy currently offers the most promising approach to assuring that beta-lactam treatment is effective, especially in critically ill patients.