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 Apr 26;:
Authors: Meyer KA, Deraedt MF, Harrington AT, Danziger LH, Wenzler E
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, although data evaluating it 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 and VRE in in vivo G. mellonella survival models.
METHODS: Five enterococcal strains were used: 3 clinical isolates (VRE S38141, VRE H19570, VRE W21579), E. faecium ATCC 700221, and E. 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 one hour of inoculation. After injection, larvae were incubated at 37°C and survival was measured daily for 7 days. Survival was plotted via Kaplan-Meier method and differences between groups was determined via the log-rank test. Mean survival times were also determined.
RESULTS: Each single agent significantly improved survival compared to the untreated control strain. Oritavancin was the most efficacious single agent and produced statistically significantly increased survival compared to ceftriaxone, gentamicin, and daptomycin. Compared to oritavancin alone, none of the oritavancin combinations tested were significantly better and mean survival times were comparable.
CONCLUSIONS: Oritavancin monotherapy provided the highest rate of larvae 7-day survival, and none of the combinations tested 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.
PMID: 31034937 [PubMed - as supplied by publisher]