Efficacy of oritavancin alone and in combination against vancomycin-susceptible and -resistant enterococci in an in-vivo Galleria mellonella survival model

Kevin A Meyer; Matthew F Deraedt; Amanda T Harrington; Larry H Danziger; Eric Wenzler

doi:10.1016/j.ijantimicag.2019.04.010

Efficacy of oritavancin alone and in combination against vancomycin-susceptible and -resistant enterococci in an in-vivo Galleria mellonella survival model

Int J Antimicrob Agents. 2019 Aug;54(2):197-201. doi: 10.1016/j.ijantimicag.2019.04.010. Epub 2019 Apr 26.

Authors

Kevin A Meyer¹, Matthew F Deraedt², Amanda T Harrington³, Larry H Danziger⁴, Eric Wenzler⁵

Affiliations

¹ College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA.
² Alaska Native Medical Center, Anchorage, AK, USA.
³ Loyola University Medical Center, Maywood, IL, USA.
⁴ College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA; College of Medicine, University of Illinois at Chicago, Chicago, IL, USA.
⁵ College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA. Electronic address: wenzler@uic.edu.

PMID: 31034937
DOI: 10.1016/j.ijantimicag.2019.04.010

Abstract

Objective: The optimal therapy for serious enterococcal infections, especially vancomycin-resistant enterococci (VRE), remains unclear, although combination therapy is often recommended. Oritavancin has demonstrated in-vitro activity against VRE, but data evaluating oritavancin in combination with other agents and in in-vivo systems are lacking. The objective of this study was to evaluate the efficacy of oritavancin alone and in combination with ceftriaxone, daptomycin, gentamicin, linezolid and rifampin against vancomycin-susceptible enterococci and VRE in an in-vivo Galleria mellonella survival model.

Methods: Five enterococcal strains were used: three clinical isolates (VRE S38141, VRE H19570, VRE W21579), Enterococcus faecium ATCC 700221 and Enterococcus faecalis ATCC 29212. G. mellonella larvae were inoculated with the test strain followed by the test drug at humanized weight-based dose alone or in combination within 1 h of inoculation. After injection, larvae were incubated at 37°C and survival was measured daily for 7 days. Survival was plotted using the Kaplan-Meier method, and differences between groups were determined via the log-rank test. Mean survival times were also determined.

Results: Each single agent improved survival significantly compared with the untreated control strain. Oritavancin was the most efficacious single agent, and led to a significant increase in survival compared with ceftriaxone, gentamicin and daptomycin. Compared with oritavancin alone, none of the oritavancin combinations tested were significantly better, and mean survival times were comparable.

Conclusions: Oritavancin monotherapy had the highest survival rate at 7 days, and none of the combinations tested showed improved survival over oritavancin alone. These data add to the body of literature rebutting the routine use of combination therapy with oritavancin for the treatment of infections due to VRE.

Keywords: Enterococci; Galleria mellonella; Oritavancin; Survival model; VRE.

MeSH terms

Animals
Anti-Bacterial Agents / administration & dosage*
Disease Models, Animal
Drug Therapy, Combination / methods
Enterococcus faecalis / drug effects*
Enterococcus faecium / drug effects*
Gram-Positive Bacterial Infections / drug therapy*
Lepidoptera
Lipoglycopeptides / administration & dosage*
Survival Analysis
Treatment Outcome
Vancomycin-Resistant Enterococci / drug effects

Substances

Anti-Bacterial Agents
Lipoglycopeptides
oritavancin