Battling Bacterial Biofilm - antibiotic regimens targeting Grampositive pathogens in biofilm

Abstract: AbstractBacteria in most environments encase themselves in a hydrated matrix of polysaccharide and protein, forming organized communities called biofilms. In the biofilm bacteria are protected against hostile environments. Biofilms are important clinically because of their persistence despite host defence and their recalcitrance to antimicrobials. This thesis presents three main findings: (i) biofilm formation is an important virulence trait for opportunistic pathogens; (ii) combining different antibiotics may successfully cure device-related infections with biofilm-producing bacteria; (iii) mature biofilm is highly resistant to antibiotics. First, we observed that the opportunistic pathogen Propionibacterium acnes, when isolated from deep infections, produced more biofilm in a microtitre model of biofilm formation, than superficical P.acnes isolates. The serotype distribution of P.acnes, determined by sequencing of recA, was similar among isolates from skin and deep infections, demonstrating that P.acnes isolates with different genetic backgrounds have pathogenic potential. Furthermore, we observed that Enterococcus faecalis and Enterococcus faecium biofilms in vitro were susceptible to antibiotic combinations including rifampicin. Resistance to rifampicin was detected early if this agent was used as monotherapy, whereas combining it with some other specific antibiotics counteracted the development of rifampicin resistance. Finally, we demonstrated that mature biofilm of enterococci in vitro is much more tolerant to antibiotics compared to new biofilm of the same species. In conclusion, this thesis provides in vitro data stressing the importance of understanding the properties of bacterial biofilm in order to achieve successful antibiotic treatment of device related infections.