**3.1 Antibiotic penetration of biofilms**

Biofilms are typically characterized by dense, highly hydrated clusters of bacterial cells enclosed in a self-produced polymeric matrix that is primarily composed of exopolysaccharides such as polysaccharide intercellular adhesin (PIA) in staphylococci and adherent to a surface. This matrix, also termed slime or extracellular polymeric substance (EPS), impairs the access of antimicrobial agents to the bacterial cells [21]. Additionally, either a reaction of EPS with or its adsorption to the components of the biofilm matrix can delay penetration of the antibiotics through the biofilm matrix. The effective diffusion coefficients of solutes in biofilms average about 40% of the respective diffusion coefficient in pure water [20]. *S. epidermidis* slime has been found to remarkably decrease the activity of the glycopeptides vancomycin and teicoplanin. The efficacy of cloxacillin, amoxicillin/clavulanic acid, imipenem, cefpirome, erythromycin, roxithromycin, clindamycin, fusidic acid, trimethoprim/sulfamethoxazole, doxycycline, gentamicin, tobramycin, netilmicin, amikacin, isepamicin, ofloxacin, ciprofloxacin, and daptomycin is also moderately affected by the exopolysaccharide matrix of *S. epidermidis*. Other studies have suggested that *S. epidermidis* glycocalyx reduces susceptibility to pefloxacin and moderately affects the activity of daptomycin, linezolid, and quinupristin/dalfopristin [22, 23]. The role of biofilm matrix in retarding the penetration of antibiotics is thereby contributed to the drug resistance of *S. epidermidis* biofilms.
