Early therapeutic monitoring of β-lactams and associated therapy outcomes in critically ill patients. (10th September 2020)

• Record Type: Journal Article
• Authors: Al-Shaer, Mohammad H; Rubido, Eric; Cherabuddi, Kartikeya; Venugopalan, Veena; Klinker, Kenneth; Peloquin, Charles
• Is Part Of: Journal of antimicrobial chemotherapy. Volume 75:Number 12(2020)
• Page Start: 3644
• Page End: 3651
• Publication Date: 2020-09-10
• Subjects: Anti-infective agents -- Periodicals; Chemotherapy -- Periodicals; 615.58
• DOI: 10.1093/jac/dkaa359
• Languages: English
• ISSNs: 0305-7453

Abstract

Abstract: 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.