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Antimicrobial Synergy Testing by the Inkjet Printer-assisted Automated Checkerboard Array and the Manual Time-kill Method
Published on: April 18, 2019
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β-Lactam combinations with daptomycin provide synergy against vancomycin-resistant Enterococcus faecalis and
Jordan R Smith1, Katie E Barber1, Animesh Raut1
1Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Detroit, MI, USA.
The Journal of Antimicrobial Chemotherapy
|February 4, 2015
Summary
Beta-lactams (BLs) combined with daptomycin show promise against vancomycin-resistant enterococci (VRE). Ceftaroline demonstrated the most potent synergy, enhancing daptomycin
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Enterococcus faecalis (Efc) and Enterococcus faecium (Efm) are significant causes of hospital-acquired infections.
- These enterococci frequently exhibit resistance to vancomycin and beta-lactams (BLs), complicating treatment options.
- Previous in vitro studies suggest potential synergy between BLs and other antibiotics against resistant pathogens.
Purpose of the Study:
- To evaluate the in vitro synergy of beta-lactams (BLs) in combination with daptomycin against vancomycin-resistant enterococci (VRE).
- To determine the impact of specific BLs on daptomycin's efficacy through checkerboard and time-kill assays.
- To investigate the mechanism of synergy, including daptomycin binding enhancement.
Main Methods:
- Combination checkerboard microdilution assays were performed on 15 Efc and 20 Efm strains to determine daptomycin MICs in the presence of various BLs (ceftaroline, ertapenem, cefepime, ceftriaxone, cefotaxime, cefazolin, ampicillin).
- Time-kill experiments were conducted using selected strains, including daptomycin-susceptible/non-susceptible pairs, with daptomycin at 0.5x MIC combined with BLs at biological free concentrations.
- Fluorescently labeled daptomycin (BoDipy) was used to assess daptomycin binding enhancement by ceftaroline.
Main Results:
- Ceftaroline demonstrated the greatest reduction in daptomycin MIC values across all tested strains.
- Synergistic activity in time-kill assays was observed with daptomycin combined with ceftaroline, ertapenem, cefepime, ceftriaxone, and ampicillin against all strains.
- Ceftaroline significantly enhanced daptomycin binding compared to other agents, suggesting a mechanistic basis for the observed synergy.
Conclusions:
- Daptomycin and beta-lactam combination therapy shows potential for treating vancomycin-resistant enterococci (VRE) infections.
- Combinations including ceftaroline, ertapenem, cefepime, ceftriaxone, or ampicillin offer superior bacterial kill compared to daptomycin monotherapy.
- Further clinical investigation into daptomycin-beta-lactam combinations is warranted to establish their therapeutic value.
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