Effects of Tigecycline, Linezolid and Vancomycin on Biofilms of Viridans Streptococci Isolates from Patients with Endocarditis

BACKGROUND: Endocarditis, and prosthetic valve endocarditis in particular, is a serious disease with high morbidity and mortality. We investigate the effects of tigecycline, linezolid and vancomycin on biofilms of viridans group streptococci (VGS) isolated from patients with definite native or prosthetic valve endocarditis. METHODS AND RESULTS: Ten of 20 VGS blood stream isolates from patients with endocarditis formed biofilms in the microtiter plate biofilm model. The minimal inhibitory concentrations (MIC) for tigecycline, linezolid and vancomycin were determined using the microdilution broth method. Biofilms were grown for 24 hours and were incubated with tigecycline, linezolid and vancomycin at increasing concentrations from 1-128x MIC of the isolate being tested. Biofilm thickness was quantified by measuring the optical density (OD) after dyeing it with crystal violet. The incubation of the biofilms with tigecycline, linezolid or vancomycin resulted in a significant reduction of OD compared to the control biofilm without antibiotic (p<0.05). The optical density ratio (Odr) decreased significantly at 2x MIC for tigecycline, and at 8x MIC for linezolid and vancomycin (p<0.05). Although biofilms persisted even at the highest antibiotic concentrations of 128x MIC, bacterial growth was eradicated starting at concentrations of 16x MIC for vancomycin and of 32x MIC for linezolid, but not for tigecycline, up to a concentration of 128x MIC. CONCLUSIONS: In the present study on viridans streptococci isolated from patients with endocarditis, tigecycline and linezolid reduced the density of the biofilms as effectively as vancomycin. However, linezolid and vancomycin were bactericidal at higher concentrations. Linezolid and vancomycin at very high doses may be useful in the treatment of biofilm-associated diseases caused by VGS infections.