Bacterial antibiotics have been designed to target unique and essential prokaryotic targets including cell wall synthesis, DNA replication and protein synthesis. In addition, recent data has demonstrated that multiple classes of bactericidal antibiotics stimulate the production of hydroxyl radicals through Fenton chemistry thus accelerating bacterial cell death [1
]. The efficacy of bacterial antibiotics has classically been tested using bacteria in the exponential phase of growth employing an in vitro
broth system that is meant to simulate the planktonic growth of bacteria in blood or other sterile body fluids. Furthermore, clinical microbiology laboratories typically test the antibiotic susceptibility of bacterial pathogens with a microbroth dilution test utilizing planktonic bacteria. However, many different types of bacterial infections are known or presumed to be due bacteria growing in a biofilm state including biomaterial-related infections, chronic wounds (e.g. diabetic foot wounds), cystic fibrosis-related lung infections, endocarditis and otitis media. The National Institutes of Health (United States) estimates that 80% of all infections are biofilm-related [2
]. It is well accepted that bacteria growing in a biofilm are more recalcitrant to the action of antibiotics than cells growing in a planktonic state and are associated with chronic inflammation and resistance to the innate immune system [3
]. In many cases, it is unclear how clinical microbiology laboratories should test the antibiotic susceptibility of bacteria isolated from a biofilm-mediated infection. Several groups have proposed diagnostic criteria for the identification of biofilm-mediated infections that include (among others) association with a surface, recalcitrance to antibiotics, and ineffective clearance by host inflammatory cells [4
]. The development of biofilm is thought to consist of four separate stages: 1) binding of planktonic bacteria to a foreign body or tissue; 2) liberation of extracellular material consisting of protein, polysaccharide and extracellular DNA (eDNA; originating from the bacteria due to autolysis) allowing for intercellular aggregation; 3) biofilm maturation which includes the development of towers and water filled channels and 4) biofilm dispersal. This review will focus on the available literature describing the physiological and metabolic differences between cells growing in a planktonic state in comparison to those growing in a biofilm; several promising aspects of treatment of biofilms will be discussed. Although several models of bacterial biofilm formation have been developed for Pseudomonas aeruginosa, Vibrio cholerae, Escherichia coli and Bacillus subtilis
], this review will focus primarily on staphylococcal biofilm models.