Impact of Daptomycin Dose Exposure Alone or in Combination with β- lactams or Rifampin against Vancomycin-Resistant Enterococci (VRE) in an In vitro Biofilm Model.

Impact of Daptomycin Dose Exposure Alone or in Combination with β- lactams or Rifampin against Vancomycin-Resistant Enterococci (VRE) in an In vitro Biofilm Model. Antimicrob Agents Chemother. 2020 Feb 24;: Authors: Jahanbakhsh S, Singh NB, Yim J, Kebriaei R, Smith JR, Lev K, Tran TT, Rose WE, Arias CA, Rybak MJ Abstract Enterococcus faecium (Efm) strains are commonly resistant to vancomycin and β-lactams. In addition, Efm often causes biofilm-associated infections and these infections are difficult to treat. In this context, we investigated the activity of DAP dosing regimens (8, 10, 12 and 14 mg/kg/d) alone and in combination with ceftaroline (CPT), ampicillin (AMP), ertapenem (ERT) and rifampin (RIF) against 2 clinical strains of biofilm-producing vancomycin-resistant Enterococcus faecium (VREfm) S447 and HOU503 in an in vitro biofilm model. HOU503 harbors common LiaS and LiaR substitutions whereas S447 lacks mutations associated with the LiaFSR pathway. Minimum inhibitory concentrations (MIC) results demonstrated that both strains were susceptible to DAP and resistant to CPT, AMP, ERT and RIF. The 168-h pharmacokinetic/pharmacodynamic (PK/PD) CDC biofilm reactor models (simulating human antibiotic exposures) with titanium and polyurethane coupons were used to evaluate the efficacy of antibiotic combinations. DAP 12 and 14 achieved bactericidal activity against S447 but lacked such effect against HOU503. Addition of ERT and RIF ...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research