Friday, November 4, 2016

Biofilms and prosthetic joint infections - the news is mostly bad

What's New in Musculoskeletal Infection: Update on Biofilms.

Here we try to summarize this interesting article for those of us in the shoulder world. 

A biofilm is a complex structure formed by bacteria adherent to our favorite materials:  cobalt-chromium, titanium, polyethylene, and polymethylmethacrylate cement. These bacteria (one or several different species) surround themselves with an extracellular polymeric matrix consisting of proteins, polysaccharides, lipids and nucleic acids.  The bacteria in a biofilm communicate via quorum sensing leading them to team up in the establishment of virulence, antibiotic resistance, and the formation of an enhanced extracellular matrix that only anchors the bugs to the implant surface, but also provides a physical barrier against host defenses and antibiotics. This barrier also slows the flow of nutrients to the bacteria, causing them to enter a 'dormant' stage reminiscent of Rip Van Winkle or Sleeping Beauty (take your choice).

In this dormant state the bacteria can resist antimicrobials that are effective against actively growing bugs. Cells in a biofilm can also develop inherent resistance to antibiotics and hang around as 'persister' cells in spite of vigorous therapy. The term 'minimum biofilm eradicate concentration (MBEC)' has been used to refer to the concentration of an antimicrobial necessary to kill all the persister cells - n.b. the battle against infection is not won if the number of bacteria is reduced, only if they're all dead. If persisters persist, the infection is still present.

Several factors make it difficult to recover and grow bacteria in biofilm infections. (1) there may be no free floating (planktonic) bacteria, so that culturing fluid or surfaces is unproductive, (2) without vortexing or sonicating implants, biofilm bacteria may not be recoverable, and (3) bacteria from biofilms may have become genetically altered so that they may not grow well in the laboratory setting. 

Comment: While our understanding of biofilms is increasing, the foundation was presented by our late friend Tony Gristina over 25 years ago, in his largely forgotten article "Infections from biomaterials and implants: a race for the surface" (see this link). 

From the abstract to that article, we can see that he got it right, "Microorganisms in nature and disease are dependent on substratum attachment for optimal growth and development. Similarly, implanted biomaterials tend to potentiate bacteria on their surfaces so that normally friendly special or opportunistic organisms become virulent pathogens. Virulence is also enhanced because both bacteria and biomaterials interfere with host defense mechanisms. Infections centered on biomaterials are most difficult to eliminate and usually require removal of the device. The consequences of device failure are catastrophic and costly. It is the specific nature of the biomaterial surface, which is indirectly a reflection of bulk features, that causes and directs the changes in bacterial behavior which result in virulence. "

The recognition that biofilms are the problem in shoulder prothetic infections, causes us to move from the conventional presentation of infections (which we refer to as 'obvious') to the current recognition of 'stealth' infections. Both can contribute to prosthetic failure, just as both fire and carpenter ants can lead to failure of a house, but the presentation is different.