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Nanomechanics of Drug-target Interactions and Antibacterial Resistance Detection
Published on: October 25, 2013
Long-Acting Lipoglycopeptides Can Interfere With Vancomycin Therapeutic Drug Monitoring
Dan F Smelter1, Michael J Trisler2, Erin K McCreary3
1School of Pharmacy, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Abstract:
Oritavancin and dalbavancin are long-acting lipoglycopeptides with activity against susceptible gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. Though similar in structure to traditional glycopeptide antibiotics like vancomycin, these antibiotics have terminal half-lives >10 days, and, as a result, there is potential for administration of vancomycin to a patient while oritavancin or dalbavancin are still appreciably present in serum. Given the structural similarities, this creates an opportunity for lab assay interference when performing therapeutic drug monitoring for vancomycin. Following higher-than-expected serum vancomycin concentrations in a patient who received both oritavancin and vancomycin within a short time frame, we evaluated the potential for lipoglycopeptide interference with clinical vancomycin assays. Five platforms covering 3 immunoassay technologies were used to quantify vancomycin concentrations in serum spiked with oritavancin or dalbavancin. Oritavancin generated spurious vancomycin concentrations (20%-84% increase) in both enzyme-multiplied immunoassay technique and a particle-enhanced turbidimetric inhibition immunoassay. However, the improper detection of oritavancin was not consistent across all particle-enhanced turbidimetric inhibition immunoassay platforms. Dalbavancin interference was not detected on any of the platforms tested. The interference from oritavancin may result in falsely elevated vancomycin concentrations and, subsequently, inappropriately adjusted vancomycin doses.
Insights
Oritavancin can interfere with vancomycin lab assays, causing falsely high readings. This lipoglycopeptide interference may lead to incorrect vancomycin dosing adjustments in patients.
Area of Science:
- Pharmacology
- Clinical Chemistry
- Infectious Diseases
Background:
- Oritavancin and dalbavancin are long-acting lipoglycopeptides effective against Gram-positive bacteria.
- Their long half-lives can lead to co-administration with vancomycin.
- Structural similarities to vancomycin raise concerns for assay interference.
Purpose of the Study:
- To investigate the potential for oritavancin and dalbavancin interference with clinical vancomycin assays.
- To evaluate the impact of lipoglycopeptides on therapeutic drug monitoring of vancomycin.
Main Methods:
- Serum samples were spiked with oritavancin or dalbavancin.
- Vancomycin concentrations were measured using five platforms across three immunoassay technologies.
- Assay interference was quantified by the percentage increase in vancomycin levels.
Main Results:
- Oritavancin caused spurious vancomycin elevations (20%-84%) on specific immunoassay platforms.
- Dalbavancin did not interfere with vancomycin assays on any tested platform.
- Interference varied between different particle-enhanced turbidimetric inhibition immunoassay platforms.
Conclusions:
- Oritavancin can interfere with vancomycin assays, leading to falsely elevated concentrations.
- This interference may result in inappropriate vancomycin dose adjustments.
- Careful consideration of concurrent lipoglycopeptide therapy is needed for vancomycin therapeutic drug monitoring.
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