2391. Liposomal Vancomycin and Cefazolin Combinations for S. aureus Biofilms
Session: Poster Abstract Session: Treatment of AMR Infections
Saturday, October 6, 2018
Room: S Poster Hall
Posters
  • liposomal cfz-van 10-1-18-36-17.5.pdf (4.5 MB)
  • Background:

    Biofilms are sophisticated communities of matrix-encased and surface-attached bacteria that exhibit a distinct and specific resistant/tolerant phenotype to almost all antibacterial agents, with activity reduced 10-1000-fold. Interestingly, this augmented resistance rapidly reverts when bacteria detach from the biofilm and return to a planktonic state. However, in this in vitro pharmacokinetic and pharmacodynamic (PK/PD) model we are able to expose biofilms to shear rates that are consistent with human interface and mimic antibiotic penetration and diffusion pathways from serum antibiotic concentration in humans.

    Methods:

    Methicillin-susceptible ATCC 29213 and MRSA 494 strains were evaluated. Initial susceptibility tests were performed by broth microdilution method. Time kill studies were performed to identify synergy patterns for liposomal and commercial antibiotics. Biofilm eradication was investigated using antibiotics vancomycin (VAN) (commercial) vs. liposomal VAN (VAN-L) (Patent#17-1460) and also combination of VAN- cefazolin (commercial) vs. liposomal vancomycin and liposomal cefazolin (CFZ-L) (Patent# 17-1460) in biofilms for strain MRSA 494. Biofilms were generated overnight using the BioFlux Microfluidic system (Fluxion BioSciences) at constant and continuous shear rates to optimize biofilm attachment and creation. Perfusion of antibiotic solutions (free peak concentration) was applied over a 24h time period. Time lapse pictures were recorded to determine antibiotic biofilm eradication rates over 18h of incubation and pictures were analyzed using Bioflux Montage software.

    Results:

    MIC values demonstrated a 2-fold reduction for liposomal vancomycin vs. commercial vancomycin. Also, combination of liposomal VAN MIC in presence of CFZ-L showed a 15.87-fold reduction in comparison to commercial VAN for 494. Overall, our biofilm results demonstrated a 43.6% improved eradication using VAN-L and CFZ-L combination in comparison to commercial VAN-CFZ combination. We also observed 5.7% improved eradication using VAN-L vs. commercial VAN.

    Conclusion:

    Liposomal form of VAN and CFZ combinations are a promising approach to improved efficacy and reduced VAN resistance in S. aureus biofilms.

    Razieh Kebriaei, PhD1, Ketki Bhise, PhD candidate2, Samaresh Sau, PhD3, Seth Rice, BSc4, Kyle Stamper, BSc3, Arun Iyer, PhD3 and Michael J. Rybak, PharmD, MPH, PhD5,6, (1)Pharmacy Practice, Wayne State University, Grosse Pointe Park, MI, (2)Pharmacy, Wayne State University, Detroit, MI, (3)Wayne State University, Detroit, MI, (4)Pharmacy Practice, Wayne State University, Detroit, MI, (5)Anti-Infective Research Laboratory, Department of Pharmacy Practice, Wayne State University, Eugene Applebaum College of Pharmacy & Health Sciences, Detroit, MI, (6)Anti-Infective Research Laboratory, College of Pharmacy, School of Medicine, Division of Infectious Diseases, Wayne State University, Detroit, MI

    Disclosures:

    R. Kebriaei, None

    K. Bhise, None

    S. Sau, None

    S. Rice, None

    K. Stamper, None

    A. Iyer, None

    M. J. Rybak, Allergan: Consultant , Grant Investigator and Speaker's Bureau , Research grant and Research support . Achaogen: Consultant , Grant Investigator and Speaker's Bureau , Consulting fee , Research grant and Research support . Bayer: Consultant , Grant Investigator and Speaker's Bureau , Consulting fee , Research grant and Research support . Melinta: Consultant , Grant Investigator and Speaker's Bureau , Consulting fee , Research grant and Research support . Merck: Consultant , Grant Investigator and Speaker's Bureau , Consulting fee , Research grant and Research support . Theravance: Consultant , Grant Investigator and Speaker's Bureau , Consulting fee , Research grant and Research support . Sunovian: Consultant , Grant Investigator and Speaker's Bureau , Consulting fee , Research grant and Research support . Zavante: Consultant , Grant Investigator and Speaker's Bureau , Consulting fee , Research grant and Research support . NIAID: Consultant , Grant Investigator and Speaker's Bureau , Consulting fee , Research grant and Research support .

    Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 3rd with the exception of research findings presented at the IDWeek press conferences.