2026. Efficacy of oritavancin and comparator agents against vancomycin-resistant Enterococcus faecium in an in vivo Galleria mellonella survival model
Session: Poster Abstract Session: Antimicrobial Resistant Infections: Treatment
Saturday, October 29, 2016
Room: Poster Hall
Posters
  • 2026 IDWeek Wenzler G mellonella v02b.pdf (570.8 kB)
  • Background:

    The optimal antimicrobial therapy for serious vancomycin-resistant enterococcal (VRE) infections remains unclear. Oritavancin has demonstrated potent bactericidal activity against VanA type VRE in vitro. Galleria mellonella is well-established model of both microbial virulence and therapeutic response. 

    Methods:

    5 isolates were used: E. faecalis ATCC 29212, E. faecium VanA ATCC 700221 (VRE), and 3 E. faecium VanA VRE clinical bloodstream isolates. Bacterial inocula were adjusted in an initial pilot study until approximately 90% of larvae died within 72 hours of inoculation. Antibiotic regimens tested were oritavancin (O) 15 mg/kg, daptomycin (D) 10 mg/kg, linezolid (L) 7.5 mg/kg, gentamicin (G) 1.3 mg/kg, ceftriaxone (C) 25 mg/kg, and rifampin (R) 3.75 mg/kg, representing humanized weight-based doses. Groups of 10 larvae were injected with each isolate followed by each antimicrobial agent after approximately 1 hour, with one group of 10 receiving no antimicrobial treatment (untreated group). Uninfected PBS-injected and untouched control groups were included with each experiment. After injection, larvae were incubated at 37°C and survival was measured daily for 7 days. Survival was plotted via Kaplan-Meier curves and groups were compared using the log rank test with Bonferroni correction for multiple comparisons (SPSS version 22, Inc., Chicago, IL).

    Results:

    Aggregate log-rank pairwise comparisons of each antibiotic compared the untreated group are shown in Table 1, adjusted for the pathogen being tested. Each antimicrobial agent significantly improved survival over the untreated group. O provided the largest magnitude of survival across all isolates (χ2=76.9) although strain-to-strain variability in efficacy was observed. D and C afforded the least survival. Compared to the other agents, O increased survival over C, G, and D but not compared to L or R. Mean survival time ranged from 3.2 days for C to 3.9 days for O vs. 2.4 days for the untreated group.

    Table 1. Log Rank Pairwise Comparisons

    Untreated group

    Antibiotic

    χ2

    p-value

    C

    26.3

    .00

    L

    58.3

    .00

    G

    36.8

    .00

    D

    18.3

    .00

    R

    60.3

    .00

    O

    76.9

    .00

    Conclusion:

    Compared to the untreated, infected group O was the most efficacious agent in this in vivo G. mellonella survival model, although efficacy was strain-dependent. O provided significantly improved survival over C, G, and D but not over L or R.

    Eric Wenzler, PharmD1, Matthew Deraedt, BS2, Kevin Meyer, BS2, Amanda Harrington, PhD, D(ABMM)3 and Larry H. Danziger, Pharm.D., FIDSA1, (1)Pharmacy Practice, University of Illinois at Chicago, Chicago, IL, (2)University of Illinois at Chicago, Chicago, IL, (3)Clinical Microbiology Service, University of Illinois at Chicago, Chicago, IL

    Disclosures:

    E. Wenzler, None

    M. Deraedt, None

    K. Meyer, None

    A. Harrington, None

    L. H. Danziger, None

    Findings in the abstracts are embargoed until 12:01 a.m. CDT, Wednesday Oct. 26th with the exception of research findings presented at the IDWeek press conferences.