An evaluation on the association of vancomycin trough concentration with mortality in critically ill patients: A multicenter retrospective study

To determine the impact of initial vancomycin trough concentration (VTC) on mortality in adult patients in the intensive care unit (ICU) undergoing vancomycin therapy. During their first ICU stay, patients with initial VTC records after vancomycin treatment were recruited from the eICU Collaborative Research Database to this multicenter retrospective cohort study, and classified into four groups according to VTC: less than 10, 10–15, 15–20, and greater than 20 mg/L. Multivariable logistic regression and sensitivity analyses were performed to explore the association of VTC, as a continuous and categorical variable, with mortality. This study enrolled 7220 patients from 335 different ICUs at 208 hospitals. Multivariable logistic regression models indicated that VTC was positively correlated with ICU (odds ratio [OR], 1.028, 95% confidence interval [CI], 1.019–1.037) and hospital (OR 1.028, 95% CI, 1.020–1.036) mortalities. Moreover, compared with VTC less than 10 mg/L, VTCs of 10–15, 15–20, and greater than 20 mg/L were associated with a higher risk of ICU mortality (OR, 1.330, 95% CI, 1.070–1.653; OR, 1.596, 95% CI, 1.265–2.015; abd OR, 1.875, 95% CI, 1.491–2.357, respectively), and VTCs of 15–20 and greater than 20 mg/L were also correlated with increased hospital mortality (OR, 1.482, 95% CI, 1.225–1.793; and OR, 1.831, 95% CI, 1.517–2.210, respectively). Similar results persisted in patients with different Acute Physiology and Chronic Health Evaluation Ⅳ scores, creatinine clearance levels, ages, and body mass indexes. Our findings indicated a potential relationship of initial VTC with ICU and hospital mortalities in patients in the ICU. However, due to the retrospective nature of this study, future prospective studies or randomized controlled trials are needed to validate those results.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Although monitoring vancomycin trough concentration as a feasible pharmacokinetic method was recommended for personalized vancomycin dosing by the Infectious Diseases Society of America in 2009, it remains controversial regarding the association of trough concentration with treatment outcomes in patients with gram‐positive bacterial infection.

• WHAT QUESTION DID THIS STUDY ADDRESS?

A large‐scale multicenter cohort was performed to identify the association between initial trough concentration and prognosis in 7220 patients in the intensive care unit (ICU), aiming to evaluate the clinical value of trough concentration for ensuring vancomycin efficacy.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

Our study demonstrated that trough concentration was positively related with ICU and hospital mortalities. Trough concentration greater than or equal to 10 mg/L was associated with increased ICU mortality. Moreover, hospital mortality failed to decrease at trough concentration 10–15 mg/L, even raised at trough concentration greater than 15 mg/L, compared with trough concentration less than 10 mg/L. The present study revealed that increased initial vancomycin trough concentration might not guarantee treatment success for critically ill patients.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

We found that high initial VTC might be associated with incremental ICU and hospital mortalities. However, due to the retrospective nature of this study, those findings are worth further investigation with prospective studies or randomized controlled trials.