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Ceftaroline restores daptomycin activity against daptomycin-nonsusceptible vancomycin-resistant Enterococcus faecium
George Sakoulas1, Warren Rose, Poochit Nonejuie
1University of California San Diego School of Medicine, La Jolla, California, USA.
Antimicrobial Agents and Chemotherapy
|December 25, 2013
Summary
Daptomycin-nonsusceptible vancomycin-resistant Enterococcus faecium (VRE) poses a significant threat. Ceftaroline shows potential as an adjunctive therapy, enhancing daptomycin and LL37 activity against VRE by altering bacterial cell surface properties.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Daptomycin-nonsusceptible vancomycin-resistant Enterococcus faecium (VRE) presents a critical challenge in treating severe infections.
- Limited therapeutic options exist for VRE infections, especially in immunocompromised patients.
Purpose of the Study:
- To investigate the effects of ceftaroline, ceftriaxone, and ampicillin on VRE membrane properties and susceptibility.
- To evaluate the synergistic potential of these antibiotics with daptomycin and LL37 against VRE.
Main Methods:
- Utilized isogenic VRE strains with differing daptomycin susceptibilities.
- Assessed changes in membrane fluidity, surface charge, and bacterial susceptibility to daptomycin and LL37.
- Investigated synergistic effects of ceftaroline, ceftriaxone, and ampicillin in vitro.
Main Results:
- Ceftaroline demonstrated synergy against daptomycin-nonsusceptible VRE, reducing bacterial load.
- Ceftaroline increased daptomycin surface binding, membrane fluidity, and net negative surface charge.
- Ceftaroline enhanced the binding and killing activity of LL37 against daptomycin-nonsusceptible VRE.
Conclusions:
- Ceftaroline, despite VRE resistance, significantly impacts VRE growth and cell surface biophysics.
- Ceftaroline potentiates the activity of daptomycin and host defense peptides like cathelicidin against VRE.
- Further in vitro and in vivo studies are warranted to explore ceftaroline's adjunctive role in VRE therapy.
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