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Impact of Daptomycin Dose Exposure Alone or in Combination with β-Lactams or Rifampin against Vancomycin-Resistant

Seyedehameneh Jahanbakhsh1, Nivedita B Singh1, Juwon Yim1

  • 1Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA.

Antimicrobial Agents and Chemotherapy
|February 26, 2020
PubMed

Insights

Daptomycin combined with ertapenem or rifampin shows bactericidal activity against biofilm-producing vancomycin-resistant Enterococcus faecium (VREfm). These combinations are promising for treating difficult VREfm infections.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Pharmacology

Background:

  • Vancomycin-resistant Enterococcus faecium (VREfm) frequently causes challenging biofilm-associated infections.
  • VREfm exhibits resistance to multiple antibiotics, including β-lactams and vancomycin.
  • Daptomycin (DAP) is a key agent for VREfm, but its efficacy against biofilms requires optimization.

Purpose of the Study:

  • To evaluate the efficacy of daptomycin (DAP) monotherapy and combination regimens against biofilm-producing VREfm strains.
  • To investigate the impact of different dosing regimens of DAP alone and with ceftaroline (CPT), ampicillin (AMP), ertapenem (ERT), and rifampin (RIF).
  • To assess antibiotic activity in an in vitro biofilm model simulating human exposures.

Main Methods:

  • Utilized two clinical biofilm-producing VREfm strains (S447 and HOU503) in an in vitro biofilm reactor model.
  • Determined minimum inhibitory concentrations (MICs) for DAP, CPT, AMP, ERT, and RIF.
  • Employed 168-hour pharmacokinetic/pharmacodynamic (PK/PD) models with titanium and polyurethane coupons to simulate human antibiotic exposures.

Main Results:

  • Daptomycin (DAP) alone showed bactericidal activity against strain S447 at higher doses (12 and 14 mg/kg/day) but not against strain HOU503.
  • Combining DAP (8 and 10 mg/kg/day) with ertapenem (ERT) or rifampin (RIF) achieved bactericidal activity against both VREfm strains.
  • DAP combined with ampicillin (AMP), ceftaroline (CPT), or ertapenem (ERT) demonstrated enhanced and bactericidal activity against HOU503.

Conclusions:

  • Daptomycin (DAP) in combination with ertapenem (ERT) or rifampin (RIF) is effective against biofilm-producing vancomycin-resistant Enterococcus faecium (VREfm).
  • Combination therapy, particularly with ERT or RIF, offers a promising strategy for treating difficult VREfm biofilm infections.
  • Further research into DAP combinations against biofilm-forming enterococci is warranted.
Keywords:
Enterococcus faeciumbiofilmscombination therapydaptomycin

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