Importantly, pharmacokinetic studies to define drug dosages for regulatory purposes are usually carried out in healthy volunteers, who by definition are not patients. The issue of dosing is of particular relevance in patients with severe sepsis or septic shock, in whom various pathophysiological conditions may significantly alter the pharmacokinetic behaviour of drugs. In contrast, less attention – if any – was given to the fact that failures of anti-infective therapy in the intensive care unit (ICU) setting might occur not only as a consequence of inappropriate choice but also with inappropriate dosing, potentially leading to suboptimal exposure to the broad-spectrum antimicrobial agent at the infection site, even if it is administered in a timely manner. It is of note that both in these earlier studies and in subsequent confirmatory ones, the appropriateness of treatment was typically assessed in terms of antimicrobial coverage, defined as the use of an agent to which a pathogen is susceptible.

During the last half decade of the 20th century, several major studies conducted in critically ill patients in both Europe and the USA demonstrated unequivocally that initial inappropriate antimicrobial treatment for pneumonia was associated with increased mortality.

Betsid review