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Published on: September 9, 2015
In vitro activity of oritavancin alone or in combination against vancomycin-susceptible and -resistant enterococci
T Wu1, K Meyer1, A T Harrington2
1College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA.
Objectives:
The optimal treatment for serious infections due to Enterococcus spp. is unknown although combination antimicrobial therapy is often recommended for invasive infections to achieve bactericidal activity and improve clinical outcomes. Oritavancin is a novel lipoglycopeptide agent with in vitro activity against enterococci, including vancomycin-resistant VanA-type Enterococcus faecium. Data on its activity in combination with other antibacterials are limited. The objective of this study was to evaluate the activity of oritavancin alone and in combination with ceftriaxone, daptomycin, gentamicin, linezolid and rifampicin against vancomycin-susceptible and -resistant enterococci in in vitro time-kill analyses.
Methods:
Five enterococcal strains were used for all experiments: three vancomycin-resistant VanA-type E. faecium clinical bloodstream isolates, vancomycin-resistant VanA-type E. faecium ATCC 700221 and vancomycin-susceptible Enterococcus faecalis ATCC 29212. Individual drugs were tested at ¼, ½, 1, 2 and 4× MIC. Oritavancin combination experiments were performed with each agent at ¼× MIC.
Results:
Daptomycin was the most active single agent and was bactericidal against all strains at 4× MIC, followed by oritavancin, which was bactericidal against all three clinical VRE strains at ≥2× MIC. In combination experiments at ¼× MIC, oritavancin was synergistic with gentamicin against strains not displaying high-level aminoglycoside resistance. No other synergy against VRE strains was observed in any experiment. Strain- and drug-dependent antagonism was observed for many combinations.
Conclusions:
These in vitro data do not support the routine use of combination therapy with oritavancin in the treatment of infections due to VRE.
Insights
Oritavancin showed limited synergy with other antibiotics against vancomycin-resistant enterococci (VRE) in vitro. Combination therapy with oritavancin is not routinely supported for VRE infections based on these findings.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Optimal treatment for serious Enterococcus spp. infections remains unclear.
- Combination antimicrobial therapy is often recommended for invasive infections to improve outcomes.
- Oritavancin is a lipoglycopeptide with activity against enterococci, but combination data are limited.
Purpose of the Study:
- To evaluate the in vitro activity of oritavancin alone and in combination with other agents against vancomycin-susceptible and -resistant enterococci.
- To assess the bactericidal activity and potential synergy of oritavancin combinations.
- To inform treatment strategies for enterococcal infections.
Main Methods:
- Time-kill analyses were performed using five enterococcal strains (three VRE E. faecium, one VRE E. faecium ATCC, one VSE E. faecalis ATCC).
- Individual drugs were tested at various concentrations (¼, ½, 1, 2, 4× MIC).
- Oritavancin combination experiments used agents at ¼× MIC.
Main Results:
- Daptomycin was the most potent single agent, exhibiting bactericidal activity against all strains.
- Oritavancin was bactericidal against clinical VRE strains at ≥2× MIC.
- Oritavancin showed synergy with gentamicin against VRE strains lacking high-level aminoglycoside resistance; antagonism was noted in other combinations.
Conclusions:
- In vitro data do not support routine combination therapy with oritavancin for vancomycin-resistant enterococci (VRE) infections.
- Further research may be needed to identify specific scenarios where oritavancin combinations are beneficial.
- Oritavancin's role in combination therapy for enterococcal infections requires further investigation.
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