Background: Sepsis is a leading cause of morbidity and mortality among critically ill patients and is associated with intensive use of β-lactam antibiotics. These drugs show time-dependent pharmacodynamics and high pharmacokinetic variability in this population, making it difficult to achieve therapeutic levels. Therapeutic drug monitoring (TDM) may optimize dosing, but its routine clinical implementation remains limited.
Objective: To evaluate whether individualized β-lactam dosing guided by TDM reduces time to full clinical recovery compared with standard dosing in critically ill patients with sepsis.
Methods: OPTIBETA is a pragmatic, randomized, controlled, open-label clinical trial to be conducted at a tertiary hospital in Spain. Adult patients (≥18 years) admitted to the intensive care unit or infectious diseases ward with sepsis will be included. Participants will be randomized 1:1 to either a TDM-guided dosing arm (dose adjustments according to PK/PD targets) or a standard dosing arm. Clinical, microbiological, and pharmacological outcomes will be collected. The primary endpoint is time to complete clinical cure. Secondary outcomes include overall survival, microbiological cure, ICU and hospital length of stay, adverse events, and achievement of PK/PD targets. The estimated sample size is 198 patients.
Expected results: We hypothesize that TDM-guided dosing will reduce time to clinical cure, improve overall outcomes, and decrease adverse events compared with standard dosing.
Conclusions: OPTIBETA will provide high-quality evidence on the role of β-lactam TDM in critically ill septic patients and may support its inclusion in antimicrobial stewardship programs.