Early therapeutic monitoring of β-lactams and associated therapy outcomes in critically ill patients

Background: In the ICU, early and appropriate antimicrobial therapy is important to lower infection-related mortality.

Objectives: Assess whether achieving early β-lactam free concentration above the MIC 100% of the time (fT>MIC) is associated with positive outcomes in the ICU.

Methods: This retrospective study was conducted in ICU patients admitted to UF Health Shands Hospital between 2016 and 2018. Adult patients who received β-lactam therapy and had drug concentration measured were included. Data collected included demographics, β-lactam regimens and concentrations, sources of infection, cultures and susceptibilities, mortality, length of stay, resistance acquisition for 30 days and clinical outcome at end of therapy. Multiple regression and time-to-event (TTE) analyses were performed.

Results: Two-hundred and six patients were included. Clinical cure occurred in 71%, microbial eradication occurred in 58% and new resistance to the β-lactam received developed in 8% of patients. Hospital and 30 day mortalities were 17% and 14%, respectively. fT>MIC and fT>4×MIC were associated with clinical cure (P = 0.0303), microbial eradication (P = 0.0476) and suppression of resistance (P = 0.0043). Delay in measuring β-lactam concentration was associated with clinical failure (P = 0.0072), longer ICU stay (P < 0.0001) and higher mortality (P = 0.0387). In the TTE analysis, patients with 100% fT>MIC had a significantly shorter ICU stay (P = 0.0297). Patients who had clinical cure and microbial eradication had drug concentrations measured earlier (P = 0.0025 and 0.0254, respectively).

Conclusions: This study highlights the importance of early measurement of β-lactam concentration and confirms the association between fT>MIC and clinical cure, microbial eradication and emergence of resistance.