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Published on: August 30, 2018
Factors increasing the risk of inappropriate vancomycin therapy in ICU patients: A prospective observational study
Elin Helset1, Ingvild Nordøy2,3, Hilde Sporsem4
1Division of Critical care and Emergency Medicine, Oslo University Hospital, Oslo, Norway.
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-curve0-24 /minimum inhibitory concentration (AUC0-24 /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. AUC0-24 /MIC > 400 was reached in 81% and 8% with MIC = 1 and 2 mg/L respectively. The CRRT groups had higher AUC0-24 /MIC-ratios than the non-CRRT groups (P < .001). Augmented renal clearance increased the risk of AUC0-24 /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.
Insights
Vancomycin therapy often fails in ICU patients. High MIC values and augmented renal clearance increase this risk, suggesting vancomycin use could be reduced.
Area of Science:
- Pharmacokinetics and Pharmacodynamics
- Critical Care Medicine
- Infectious Diseases
Background:
- Subtherapeutic vancomycin trough levels are common in intensive care unit (ICU) patients.
- Therapeutic failure is defined as vancomycin area-under-the-curve (AUC) to minimum inhibitory concentration (MIC) ratio <400.
- Factors influencing vancomycin efficacy, including MIC, renal clearance, and continuous renal replacement therapy (CRRT), require investigation.
Purpose of the Study:
- Identify ICU patients at risk for vancomycin therapeutic failure.
- Examine the impact of varying MICs, renal clearance, and CRRT on vancomycin efficacy.
- Evaluate the relevance of vancomycin therapy in critically ill patients.
Main Methods:
- Prospective observational study of ICU patients aged 18 years or older receiving vancomycin.
- Patients categorized into four groups based on renal function (normal or augmented clearance) and CRRT mode (hemodialysis or hemofiltration).
- Vancomycin levels measured at 24, 48, and 72 hours; therapy relevance assessed retrospectively via microbiological data.
Main Results:
- Eighty-three patients included; 90-day mortality was 28%.
- Achieved target AUC/MIC >400 in 81% of patients with MIC=1 mg/L and 8% with MIC=2 mg/L.
- Continuous renal replacement therapy (CRRT) groups showed higher AUC/MIC ratios (P < .001). Augmented renal clearance independently increased the risk of subtherapeutic AUC/MIC (<400).
Conclusions:
- Higher MIC values (>1 mg/L) and augmented renal clearance are significant risk factors for vancomycin therapeutic failure.
- Vancomycin therapy could have been omitted or shortened in a majority of studied patients.
- Optimizing vancomycin dosing and de-escalation strategies are crucial in critically ill patients.
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