Therapeutic drug monitoring of antibiotics in critically ill patients

The basic principle of therapeutic drug monitoring (TDM) is the quantification of drug concentrations in body fluids, mostly from venous blood samples, for optimizing drug dosage, improving clinical outcome, and minimizing toxicity. TDM was traditionally applied to a small number of drugs only, which possess a narrow therapeutic index. This means that for these drugs the window for either safety or toxicity is exceptionally small, and therapeutic ranges of drug concentrations have been defined. Hence, TDM was hitherto mainly offered for early-generation antiepileptics, mood stabilizers and antipsychotics, immunosuppressants, specific anticancer agents, and other, often older drugs like digoxin and theophylline. For antibiotic therapy, TDM was mainly used in clinical routine to monitor vancomycin and aminoglycosides, substances known to have a narrow therapeutic range. However, as antimicrobial multidrug-resistant pathogens, such as carbapenemase-producing enterobacteria or Acinetibacter spp., are globally emerging limiting the availability of effective antibiotics, there is an urgent need to optimize dosing of anti-infectives. Especially in the early phase of antibiotic therapy, it is essential to optimize antibiotic dosages to reduce the bacterial inoculum at the infection site and also minimize the risk for promoting resistance. In today's context, TDM of antibiotics in critically ill patients is not only used for limiting toxicity but in particular to guard against clinically inadequate concentrations and minimizing the risk of the development of resistance.