Saturday, June 02, 2007
The Challenge of Treating Biofilm-associated Bacterial Infections
Clin Pharmacol Ther. 2007 May
Del Pozo JL, Patel R.
1Division of Infectious Diseases, Mayo Clinic, Rochester, Minnesota, USA.
Biofilm formation is a crucial step in the pathogenesis of many subacute and chronic bacterial infections, including foreign body-related infections. Biofilms are difficult to eradicate with conventional antimicrobial agents. Bacterial biofilms have several potential antimicrobial resistance mechanisms. Antimicrobial resistance mechanisms may act concurrently, and in some cases, synergistically. Persister cells play a major role in the tolerance of biofilm bacteria to antimicrobial agents. Understanding the mechanisms involved in biofilm-associated antimicrobial resistance is key to development of new therapeutic strategies.Clinical Pharmacology & Therapeutics advance online publication 30 May 2007. doi:10.1038/sj.clpt.6100247.
PMID: 17538551 [PubMed - as supplied by publisher]
Biofilms and antimicrobial resistance.
The pathogenesis of many orthopaedic infections is related to the presence of microorganisms in biofilms. I examine the emerging understanding of the mechanisms of biofilm-associated antimicrobial resistance. Biofilm-associated resistance to antimicrobial agents begins at the attachment phase and increases as the biofilm ages. A variety of reasons for the increased antimicrobial resistance of microorganisms in biofilms have been postulated and investigated. Although bacteria in biofilms are surrounded by an extracellular matrix that might physically restrict the diffusion of antimicrobial agents, this does not seem to be a predominant mechanism of biofilm-associated antimicrobial resistance.
Nutrient and oxygen depletion within the biofilm cause some bacteria to enter a nongrowing (ie, stationary) state, in which they are less susceptible to growth-dependent antimicrobial killing. A subpopulation of bacteria might differentiate into a phenotypically resistant state. Finally, some organisms in biofilms have been shown to express biofilm-specific antimicrobial resistance genes that are not required for biofilm formation.
Overall, the mechanism of biofilm-associated antimicrobial resistance seems to be multifactorial and may vary from organism to organism. Techniques that address biofilm susceptibility testing to antimicrobial agents may be necessary before antimicrobial regimens for orthopaedic prosthetic device-associated infections can be appropriately defined in research and clinical settings. Finally, a variety of approaches are being defined to overcome biofilm-associated antimicrobial resistance.