Does the journey toward efficacy and safety of high dose beta-lactams pass through therapeutic drug monitoring?

The recommended fixed timing of antibiotic administration is one of the reasons why the Infectious Disease Society of America did not endorse the Surviving Sepsis Campaign guidelines. Conflating suspected sepsis with suspected septic shock has resulted in a one-size-fits-all recommendation to administer wide spectrum antibiotics within one hour from the clinical suspicion of both conditions, but this aggressive timeliness could increase the likelihood that broad-spectrum antibiotics are given to uninfected patients, since up to 40% of patients admitted to the ICU with a diagnosis of sepsis do not actually have an infection. Personalized diagnostic workflows by means of patient stratification criteria, such as severity of illness and/or risk of rapid clinical progression, should be adopted in order to rationalize the use of these new technologies. Recently, the implementation of an Antimicrobial stewardship strategy (AMS) and mRDTs intervention bundle allowed significant reductions in median time to de-escalation from combination antimicrobial therapy, antipseudomonal beta-lactams, and carbapenems. The recent finding of the safety of a short-course therapy in postoperative peritonitis with early source control and appropriate antimicrobial therapy further corroborates this strategy. In conclusion, implementing in-ICU AMS requires a prescribing physician who is confident with the evidence-based measures of good antibiotic practice, taking advantage of expertise from other specialties, as well as from new technologies, which should become routinely available once their cost-effectiveness will be definitively established.