December 17, 2010 at 7:02 pm #2948HarrisonKeymaster2 pts
Dr. Rodney Donlan is team leader for the Division of Healthcare Quality Promotion Biofilm Laboratory, National Center for Infectious Diseases, CDC. His research interests focus on biofilms on indwelling medical devices, the role of biofilms in antimicrobial-drug resistance, and survival and treatment of pathogenic organisms in potable water system biofilms.
Most of his work focuses on medical procedures, but we discussed a wide range of bacterial biofilm issues, as we tried to better understand the standard of care as it relates to diagnosing and treating chronic bacterial (biofilm-based) infections.
See a video excerpt from our interview here.
Interesting points covered in our interview (questions, pauses deleted for clarity & brevity):
I am a research microbiologist. I work in the division of healthcare quality promotion in a laboratory called a biofilm laboratory. A laboratory we started about 12 years ago. I am actually trained in microbiology and more on the environmental side. I consider myself an environmental microbiologist and a microbial ecologist really working in the arena of public health and in clinical microbiology
I have seen our work focus in three areas; broad areas to do with biofilms in public health. One has to do with biofilms in potable water systems; the role of biofilms in those systems in terms of the survival of pathogenic organisms, for example in biofilms. Other areas have to do with antimicrobial resistance; understanding the role of biofilms in the horizontal transfer of resistance genes in biofilms and the dissemination of resistant organisms. And the third area, of course, has to do with biofilms on indwelling medical devices
One of the big changes for me has been a better understanding of biofilms as microbial communities. we need to understand that it is more than strictly just an organism attached to a surface; the organisms in biofilms interact with one another. And that is important in terms of their ability to attach to a surface, to grow and develop a biofilm structure, and to be dispersed into the environment or into the patients blood stream, for example, and how different organisms interact in terms of things like quorum sensing
I think we have seen the development of new methods for actually examining biofilms directly on surfaces. So we can look, for example, using molecular probes, fluorescent in situ hybridization probes, or various kinds of fluorescent dyes and methods that will allow us to examine the interaction of cells in a biofilm or examine the effect of a disinfectant or a, an antimicrobial agent on the biofilm cells
we have seen a real development of the use of non-culture based methods for determining the extent and the diversity of microbial communities and also, of course, the role of biofilms in things like chronic wounds and understanding that a little bit better
I might use for an example a chronic infection would be something that is ongoing, that is sort of recalcitrant to antimicrobial agents; for example: biofilms in osteomyelitis or biofilms on a prosthetic joint or an intravascular catheter. An acute infection might be something thats, thats more easily treated, something that is more easily detected
I think that we understand Kochs postulates. I think at the time and in infectious disease microbiology, I think that Kochs postulate approach is very valuable to our understanding of the disease process. The ability that we can take an organism, isolate it, put it back into an animal, and produce symptoms of a disease. But, I think probably it is quite true. I think it is well supported that there are certain diseases that have a biofilm component that may not adhere exactly to that process. In the sense that we might have multiple organisms involved in a disease process. And there could be other nonpathogenic organisms that could play a role in the disease process.
The whole concept of opportunistic pathogens. Organisms like Pseudomonas aeruginosa, which may not be frank pathogens but could be very important under certain conditions in the disease process. So I think that is an important consideration. One of the things that is really interesting to me is not so much that we find an organism in a biofilm, and even that that organism for example on a medical device, is related using molecular methods to the blood stream isolate. But what is really interesting to me is virulence
in terms of treatment, we know that organisms in a biofilm are very recalcitrant of antimicrobial agents. They are very tolerant. And so that tells us that the standard protocol that we use for treating biofilm associated infections is not going to work very well. The literature bears that out. Systemic drug treatments, for example, are not very effective against device associated infections. So, that is one of the areas that is important. We need to know of course, biofilms are very tolerant to the immune system. Immune system is not very effective at eradicating biofilms. Organisms in a biofilm tend to become more tolerant and more difficult to treat as they age, as the biofilm ages. And, so we need to have a different approach in terms of treatment for biofilms than we would for normally, processes that occur, under more where the organisms are planktonic, which means suspended and not associated with a biofilm
One of the things that happens to cells in a biofilm is that their growth rates tend to change. We have observed this. We have observed that a certain bacteria, for example, they grow much more slowly in a biofilm. And that is very important for certain kinds of drugs. For example, the glycopeptides, or the Penicillin type drugs, which are based upon the growth of the organisms. If the organisms are growing much more slowly; therefore, the drugs are not going to be nearly as effective at treating them. So that is one of the proposed mechanisms: growth rate
biofilms, as they become established, develop different chemical and physical gradients. For example, gradients of oxygen that might tend to protect the cells from the antimicrobial challenge. Another has to do with the structure, the structural matrix, the extracellular matrix, the slime (if you will) that is formed in a biofilm structure that will, in fact, protect organisms from diffusion of the drugs. And then there even some work, is even some work pertaining to the, the survival of certain persister type cells. Cells that are just naturally more resistant to the agent and being selected for. So there could be a number of mechanisms generous of their tolerance. I will state that I am using the word tolerance because I think tolerance is different from resistance. I think, when I think of resistance, I think of a genetically based mechanism for the ability of the organisms to resist the drug. And biofilms can be important there as well because through genetic exchange, through conjugation for example, cells can, in a biofilm, have been shown to have an enhanced ability to exchange resistance factors one to another
I think that I speak, for example, of a resistance with a specific drug. In that case there could be genetic exchange. So that, in that case, we could see either through conjugation or transformation with the cells to take up the, the DNA containing and coding the resistance factors in a biofilm. And that has been demonstrated in the laboratory. That is one mechanism. Another is the fact that the cells are just naturally tolerant to the various antimicrobial agents in the biofilm community. There is some literature suggesting too that organisms can have a protective effect one to another. So, for example, in the laboratory with polymicrobic biofilms, we have seen evidence that one organism might provide a protective effect for another organism in the biofilm. So that can be sort of a third mechanism for, resistance
I think that we do need new approaches. I think the old approaches arent very effective. One of the things we can do right now, I think,is have a recognition in the healthcare community that biofilms happen, that they are important, that they dont respond the same way that other, that what we call planktonic or non biofilm cells will respond…
…So therefore, the first thing might be in the way that we test and evaluate different treatments against organisms. I think it would be helpful to provide new testing protocols that can be standardized, that could be accepted, and can be utilized by healthcare practitioners for treating organisms in a biofilm. That could be a first step.
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