Inhibition of biofilm maturation by linezolid in meticillin-resistant Staphylococcus epidermidis clinical isolates: comparison with other drugs

Biofilm resistance mechanisms are multifactorial and vary from one organism to another. The purpose of this study was to investigate the efficacy of linezolid against indwelling device-related meticillin-resistant Staphylococcus epidermidis (MRSE) biofilm, and compare this with other antimicrobials. MICs, minimum biofilm inhibitory concentrations (MBICs) and minimum biofilm eradication concentrations (MBECs) were determined by the microtitre plate method. Fourteen and thirteen isolates from patients with indwelling device-related bacteraemia (IDB) and indwelling device colonization not associated with bacteraemia, respectively, were assessed. High MBIC was associated with a high intensity of biofilm formation (gentamicin r=0.796; linezolid r=0.477; rifampicin r=0.634; tigecycline r=0.410; and vancomycin r=0.771), but this correlation was not observed with MBEC. Linezolid demonstrated better in vitro antimicrobial activity than other antimicrobials (MBIC - gentamicin P<0.001, rifampicin P=0.019, vancomycin P=0.008; MBEC - gentamicin P<0.001, rifampicin P=0.002, vancomycin P<0.001). Biofilm growth inhibition was strongly associated with biofilm formation intensity; however, biofilm eradication was not cell number dependent. MRSE biofilm eradication would represent a huge advance for IDB, although high concentrations of gentamicin, linezolid, rifampicin, tigecycline and vancomycin were required for that. In general, linezolid reached better in vitro concentrations and was demonstrated to be highly active against MRSE biofilms by inhibiting their growth during biofilm formation.