Susceptibility of monomicrobial or polymicrobial biofilms derived from infected diabetic foot ulcers to topical or systemic antibiotics in vitro: Topical antibiotics are effective in in vitro biofilms

Diabetic foot ulcers can become chronic and non-healing despite systemic antibiotic treatment. The penetration of systematically-administered antibiotics to the site of infection is uncertain, as is the effectiveness of such levels against polymicrobial biofilms. We have developed an in vitro model to study the effectiveness of different treatments for infected diabetic foot ulcers in a wound-like environment and compared the activity of systemic levels of antibiotics with that for topically applied antibiotics released from calcium sulfate beads. This is the first study that has harvested bacteria from diabetic foot infections and recreated similar polymicrobial biofilms to those present in vivo for individual subjects. After treatment with levels of gentamicin attained in serum after systemic administration (higher than corresponding tissues concentrations) we measured a 0-2 log reduction in bacterial viability of P. aeruginosa, S. aureus or a polymicrobial biofilm. Conversely, addition of gentamicin loaded calcium sulfate beads resulted in 5-9 log reductions in P. aeruginosa, S aureus and polymicrobial biofilms derived from three subjects. We conclude that systemically administered antibiotics are likely to be inadequate for successfully treating these infections, especially given the vastly increased concentrations required to inhibit cells in a biofilm, and that topical antibiotics provide a more effective alternative.