Factors increasing the risk of inappropriate vancomycin therapy in ICU patients: A prospective observational study

Background Vancomycin trough levels are frequently subtherapeutic in intensive care unit (ICU) patients. The aim of this study was to identify patients at risk of therapeutic failure defined as vancomycin area-under-the-curve(0-24)/minimum inhibitory concentration (AUC(0-24)/MIC) <400, and to examine possible effects of different MICs, the variability in renal clearance and continuous renal replacement therapy (CRRT), and the relevance of vancomycin therapy. Methods A prospective observational study of ICU patients >= 18 years at initiation of vancomycin therapy was conducted from May 2013 to October 2015. The patients were divided into four groups according to renal function and CRRT-mode as follows: normal- or augmented renal clearance and continuous venovenous hemodialysis or -hemofiltration. Vancomycin peak and trough levels were measured at 24, 48, and 72 hours after therapy initiation. Relevance of vancomycin therapy was retrospectively evaluated based on microbiological results. Results Eighty-three patients were included, median age 54.5 years, 74.5% male, SAPS II score 46, and 90 day mortality 28%. Vancomycin therapy was initiated on ICU-day 8 (IQR, 5-12), with a median treatment time of 7.5 (IQR, 5-12) days. AUC(0-24)/MIC > 400 was reached in 81% and 8% with MIC = 1 and 2 mg/L respectively. The CRRT groups had higher AUC(0-24)/MIC-ratios than the non-CRRT groups (P < .001). Augmented renal clearance increased the risk of AUC(0-24)/MIC < 400, independent of MIC-value. Initiation of vancomycin therapy was retrospectively considered relevant in 28 patients (34%). Conclusion A MIC-value >1 mg/L and augmented renal clearance, were factors increasing the risk of therapeutic failure. Vancomycin treatments could have been omitted or shortened in most of these patients.