1. Field of Invention
Not Applicable
2. Description of Related Art
Bacteria and fungi form biofilms under certain conditions. When a group of bacteria or fungi accumulate on a surface and reach a particular cell density, they begin to secrete a polymeric substance that consists of polysaccharides, proteins and DNA and form a matrix in which the bacterial or fungal cells are entrenched. The multi-cellular aggregates or biofilms allow for individual bacterial or fungal cells or colonies of bacterial or fungal cells to exhibit coordinated behavior and confer upon the microorganism advantages including, for example, resistance to antibiotics and host immune systems. More specifically, biofilms are structured to allow respiration and fluid and nutrient exchange while preventing access of host immune cells such as phagocytes and preventing inhibitory or lytic concentrations of antimicrobials from reaching the microorganisms. As a result of these properties, infections that result from biofilm formation are notoriously difficult to eradicate and require the use of high concentrations of antimicrobial agents, removal of tissue, debridement of affected tissues and combination of these treatments.
Biofilm formation appears to be governed by secretion and detection of autoinducer molecules in a process referred to as “quorum sensing.” By this process, as quorum sensing autoinducer molecules begin to accumulate in the area surrounding the microorganisms, the microorganisms begin to undergo a number of physiological changes which allow for formation of the extracellular biofilm. For example, as a result of quorum sensing autoinducer accumulation, the microorganisms may begin surface attachment, extracellular polymer production, biosurfactant production, sporulation, bioluminescence and secretion of nutrient sequesteration molecules and virulence factors among other effects resulting in biofilm formation.
Because of the properties provided by the polymeric matrix and the physiological changes exhibited by microorganisms in a biofilm, microorganisms in a biofilm are typically less susceptible to antibiotics, antimicrobials and biocides. In some cases, bacteria in a biofilm can be up to 4,000 times more resistant (i.e., less susceptible) than the same organism in a free-floating (planktonic) state. Comparisons of minimum inhibitory concentration (MIC) which describes the amount of an active agent delivered to planktonic microorganisms necessary to inhibit biofilm formation and minimum biofilm eradication concentration (MBEC) which describes the minimum concentration of an active agent delivered to a biofilm necessary to inhibit or eradicate biofilm growth illustrate the differences in susceptibility from the planktonic bacteria to those in a biofilm and show that biofilm forming bacteria are much less susceptible to antimicrobial agents at standard therapeutic concentrations. Moreover, using an MIC concentration of antibiotic in a biofilm infection can inadvertently expose the biofilm to a sub-lethal dose of antibiotics which may increase the likelihood of the exposed biofilm forming microorganisms developing resistance to the antimicrobial agent which can have grave consequences for effective treatment of the biofilm.