Chronic infections and in vitro optimization of current antibiotics treatments: focus on Staphylococcus aureus

Biofilms are communities of bacteria which adhere to surfaces and are encapsulated in a self‐produced extracellular polysaccharide matrix. Bacteria embedded in biofilms are able to survive in harsh environmental conditions. In infected patients, they can protect themselves from components of the immune system and survive very high concentrations of antibiotics due to the expression of a persistent phenotype. In consequences, these bacteria are frequently responsible for chronic infections. Staphylococcus aureus is one of the main bacteria living as a biofilm and being responsible of chronic infections. Since it belongs to the normal skin microflora, it is considered as one of the most common opportunist pathogen of infected wounds or surgical sites both in human and animals. In veterinary medicine, S. aureus biofilms infections are also commonly found in chronic bovine mastitis which are known to be associated with impaired animal health and welfare and increased economic losses. The antibiotic therapies currently used against biofilm infections are often associated with poor clinical responses and frequent relapses. For several years, different solutions have been proposed to eradicate biofilm bacteria such as phages, quorum sensing inhibitors or physical methods. However, although highly innovative strategies still need to be developed to deal with severe infections by both tolerant and multi‐resistant bacteria, the method which can most rapidly and easily be implemented in patients at present to reduce treatment failures against biofilm‐associated infections is to combine existing drugs or to modify their therapeutic regimen (dose, frequency and mode of administration). Nevertheless, most assays of such combinations have been performed in vitro on standard inoculum of planktonic bacteria exposed to constant concentrations of antibiotics over only 24 hours and the synergistic effects obtained under these conditions do not necessarily predict the behavior of chronic clinical infections associated with biofilms. By taking the example of S. aureus, we will focus on improvement of in vitro optimization of current antibiotic treatment for chronic infections and will introduce the Hollow Fiber Infection model, which is a dynamic model allowing us to produce a biofilm and to expose bacteria to concentrations similar to free plasma concentrations obtained in patients after administrations of drugs over the complete duration of a treatment.