SLR - May 2019 - Melissa M. Journot
Vitro Activity of Oritavancin Alone or in Combination Against
Vancomycin-Susceptible and –Resistant Enterococci
T. Wu, K. Meyer,
A.T. Harrington, L.H. Danzizger and E. Wenzler. In Vitro Activity of
Oritavancin Alone or in Combination Against Vancomycin-Susceptible and
–Resistant Enterococci. Journal of
2019 January 2.
Melissa M. Journot,
Medical Center Lakewood, Kansas City, MO
for susceptible and resistant enterococci can be difficult, and it is
recommended to perform combination therapy. This study uses oritavancin alone and
in combination to achieve optimal treatment in serious infections and reduction
in bacteria. This study looked at how oritavancin performs when it is combined
with ceftriaxone, daptomycin, gentamicin, linezolid and rifampicin versus alone
against enterococci strains.
Methods: Five different
enterococcal strains, three of the strains were resistant VanA-type
enterococcus faecium (VRE S38141, H19570, W21579), vancomycin resistant
VanA-type Enterococcus faecium (ATCC 7002210) and vancomycin-susceptible VanA-negative
Enterococcus faecalis (ATCC 29212). Analytical grade ceftriaxone, daptomycin,
gentamicin, linezolid and rifampicin were purchased commercially, and
oritavancin was provided by the Medicine Company. MICs determined in triplicate
via broth microdilution; detection of high-level aminoglycoside resistance was
performed via broth microdilution and disc diffusion according to CLSI
guidelines. Time kill experiments with individual drugs added to the suspension
so final concentration was 0.25, 0.5, 1, 2 and 4x the MIC. Time kill curves plotting
average (±SD)log10cfu/mL versus time to compare 24-hour killing
effects of single agents alone and in combination. Bacteriostatic defined as ≥0
to <3log10cfu/mL and bactericidal >3log10cfu/mL
reduction in bacterial density. Synergy ≥2log10 reduction in cfu/mL
between the combination and the most active single drug alone at 0.25x MIC.
five isolates were susceptible to linezolid and daptomycin.
VRE strains displayed high-level resistance to gentamicin.
faecalis was intermediate to rifampicin, and all VRE isolates were resistant.
kill study results:
- Ceftriaxone had no
- Daptomycin was
bactericidal in 5/5 strains.
- Gentamicin alone
was bactericidal against 2/4 VRE and Vancomycin sensitive e. faecium.
- Linezolid bacteriostatic
in 5/5 strains.
- Rifampicin bactericidal
VRE W21579, not bactericidal against others.
bactericidal against 3/4 VRE strains.
- Oritavancin was
synergistic with gentamicin against VRE H19570.
- Oritavancin and
daptomycin antagonistic against 2/4 VRE strains.
Oritavancin was bactericidal in 2/5 of the enterococcal strains, and daptomycin was shown to be the most active agent alone, bactericidal in 5/5 of the enterococcus. Oritavancin was synergistic with gentamicin and improved activity, but those strains did not have high aminoglycoside resistance. This study adds to the previously done work, which shows a lack of synergistic activity with oritavancin when it is in combination. This study added lipopeptides and oxazolidinones for further assessment in possible synergistic activity. This study could have gone further and done more strains and more antibiotics for a potential to find a more suitable antibiotic with which oritavancin is synergistic. Overall, this study showed that oritavancin should not be used in combination therapy when treating VRE. From this study specifically, oritavancin is a viable single option, but it may not potentially be available if combination therapy is required due to its antagonistic effects with other antibiotics. I believe additional studies are warranted to confirm this study's findings and to further assess if oritavancin can be synergistic with other antibiotics.