The Impact of Early Achievement of Therapeutic Levels of Vancomycin in Critically ill Patients with Confirmed Gram-positive Infection: A Retrospective Cohort Study

Abstract Background: Vancomycin is a commonly used antibiotic in critically ill patients for various indications. Critical illness imposes pharmacokinetic-pharmacodynamics challenges which makes optimizing vancomycin in this population cumbersome. Data are scarce on the clinical impact of time to therapeutic trough levels of vancomycin in critically ill patients. The aim of this study to evaluate the timing to achieve therapeutic trough level vancomycin on 30-day mortality in critically ill patients.Method: A retrospective cohort study for all adult critically ill patients aged 18 years or older with confirmed Gram-positive infection and received vancomycin between January 1st, 2017 and December 31st, 2018 at a tertiary teaching hospital. We compared early (<48 hours) versus late (≥ 48 hours) attainment of vancomycin therapeutic trough levels. Primary outcome was the 30-day mortality in critically ill patients. Secondary outcomes were development of resistant organisms, eradicating microorganisms within 4-5 days of vancomycin initiation, vancomycin-induced acute kidney injury (AKI), and ICU length of stay (LOS). Results: Two hundred and nine patients were included. No significant differences between comparative groups in baseline characteristics. Achieving therapeutic levels were associated with better survival at 30 days (OR: 0.48; 95% CI [0.26-0.87]; p<0.01). Additionally, patients who achieved therapeutic levels of vancomycin early were less likely to develop resistant organisms (OR=0.08; 95% CI [0.01-0.59]; p=0.01). The AKI and ICU LOS were not significant between the two groups.Conclusion: Early attainment of vancomycin therapeutic levels was associated with possible survival benefit.