Antibiotic Optimization in the Intensive Care Unit

Semin Respir Crit Care Med 2022; 43: 125-130
DOI: 10.1055/s-0041-1740972

Effective antimicrobial therapy remains paramount to the successful treatment of patients with critical illness, such as pneumonia and sepsis. Particularly in sepsis, alterations in volume of distribution (Vd) and protein binding lead to unpredictable effects on serum levels of various antimicrobials. These factors may increase the likelihood of deleterious effects such as treatment failure or toxicity. Vancomycin and β-lactam antimicrobials are frequently utilized and have been the focus of dose optimization strategies including extended infusion (EI) or continuous infusion (CI). Available data suggests that administration of vancomycin by CI may reduce the risk of nephrotoxicity without increasing the risk of treatment failure. The use of β-lactams in patients with sepsis is similarly problematic due to observational data demonstrating fluctuations in serum levels in the setting of critical illness. Implementing TDM of agents such as piperacillin-tazobactam, cefepime, and meropenem has been suggested as a method of improving time above MIC (T >MIC). This practice is limited by the lack of access to commercial assays and the failure of rigorous studies to demonstrate improved treatment success. Clinicians should be aware of these challenges and should refine their dosing strategies based on individualized patient factors to reduce treatment failure.