Activity of daptomycin, vancomycin and moxifloxacin alone or in combination with clarithromycin or rifampicin in a novel invitro model of Staphylococcus aureus biofilm
Abstract number: P1904
Parra-Ruiz J., Vidaillac C., Rose W., Rybak M.
Objectives: Biofilm is a common virulence factor that protects bacteria from host responses and antibacterial agents. The study aims were to assess the in vitro activity of several antimicrobials alone or in combination against 2 S. aureus isolates using a novel pharmacokinetic/pharmacodynamic (PK/PD) model of biofilm.
Methods: 1 methicillin-susceptible S. aureus (MSSA SH1000) and 1 methicillin-resistant S. aureus (MRSA NK315) were evaluated in a CDC biofilm reactor with polystyrene coupons (Biosurfaces Technology Corp., MT, USA). A 36 h biofilm conditioning phase was performed prior to antimicrobials administration. Regimens simulated free peak concentrations of daptomycin (DAP) 10 mg/Kg/24 h, vancomycin (VAN) 1g/12 h, and moxifloxacin (MOX) 400 mg/24 h alone or in combination with rifampicin (RIF) 600 mg/24 h or clarithromycin (CLA) 250 mg/12 h. Media and coupon samples were aseptically removed at 0, 4, 8, 24, 48 and 72 h to assess for the presence of viable planktonic (P) and embedded biofilm (EB) cells. Cidal activity and synergy were defined as 3 log10 decrease in the viable CFU/mL and 2 log10 reduction compared to the most efficient agent alone, respectively. Biofilm recovered on coupons was evaluated by scanning electron microscopy (SEM) at 0, 24 and 72 h.
Results: Starting planktonic and biofilm inocula were about 7.4 and 8.8 log10CFU/mL for SH1000, and about 7.3 and 6.8 log10CFU/mL for NK315, respectively. For SH1000, DAP and MOX were not cidal against P or EB cells. DAP+CLA and MOX+CLA were both cidal against P and EB cells at 24 h and 32 h, respectively. Only DAP+CLA was synergistic and reduced biofilm cells to the limit of detection at 72 h.
For NK315, DAP was bactericidal at 24 h against P cells but bacterial regrowth, uncorrelated to the emergence of resistance was observed after 48 h. In contrast, sustained cidal activity was observed with VAN+RIF from 32 h against P cells. Both regimens reduced biofilm cells only 1.82 log10 CFU/mL. The synergistic combination of DAP+RIF was cidal at 8 h against P and EB cells, and decreased the bacterial density to the limit of detection at 72 h. SEM studies confirmed changes observed in biofilm cells CFU/mL.
Conclusion: We developed a novel PK/PD model to assess the in vitro activity of antimicrobials against bacterial biofilm. DAP and MOX combinations were the most effective regimens and represent promising alternatives to treat persistent infections caused by staphylococci embedded in biofilm.
|Session name:||Abstracts 20th European Congress of Clinical Microbiology and Infectious Diseases|
|Location:||Vienna, Austria, 10 - 13 April 2010|
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