11/17/2009

Pharmax Limited

Eradication of Biofilms...Why is this Important in Endoscopy?

Conventional methods of killing bacteria that cause nosocomial biofilms are almost always ineffective. Since all registered disinfectants have not been tested against biofilms, and since most nosocomial infections can be traced to biofilms, they present new challenges in the healthcare industry.

Collaborative research at the University of Calgary has enabled Pharmax Limited to identify some of the significant differences between microorganisms in their planktonic state as compared to their biofilm state. Apart from the slimy matrix they extrude, bacteria (attached to a surface) trigger a whole different set of genes, creating a change in phenotype, even though their genotype is consistent. Most researchers study cells only in a suspension state, which is odd given that this change in phenotype can result in resistance to biocides that are 40 to 1000 times greater than the resistance of bacterial cells in suspension. All disinfectants/sterilants continue to be evaluated and registered using only their ability to kill microorganisms in planktonic forms (ie. individual, free-swimming cells). This is true for Health Canada, the FDA/EPA, and the European Union.

The Centre for Disease Control in Atlanta estimates that up to 70% of human bacterial infections in the Western world are caused by biofilms. Our colleagues at the University of Calgary set that number at 80% or higher. We (and other investigators) have learned that part of the extraordinary resilience of bacteria arises from their remarkable heterogeneity inside these biofilms. Microbes closest to the fluid that surrounds the biofilm have greater access to nutrients and oxygen than those in the centre of the matrix or near the substratum. The bacteria in the outer layers of the community grow more quickly than those inside. As a result, the bacteria in the outer layers are more susceptible to antimicrobials, which target fast-growing cells. The slower growing cells in the interior of the matrix tend to be sheltered and exhibit greater resistance.

Heterogeneity also contributes to antimicrobial tolerance due to the existence of “survivor cells” (called persisters) in a biofilm. These are slow-growing variants that exist in bacterial populations, and are genetically programmed to survive any environmental stress, including antimicrobials. Persisters are not mutants. Even in a uniform colonization, a small portion of cells undergo a spontaneous switch to the persistent form. In this form, they generate a toxin that drives the cells into a dormant state. Once antimicrobial treatment has ceased, the persisters give rise to a new bacterial population, resulting in a new, potential cross-contaminant in, what is otherwise, a disinfected or sterile instrument or device.
How can we meet these challenges posed by biofilms?
Pharmax understands the significance of testing its chemistry against the most resistant forms of biofilms – Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. In 2005, both Glutacide® and Polycide® we evaluated for their ability to destroy these resistant strains in a biofilm state. (These results are available.)
In 2007, Pharmax Limited participated in testing at SMP Labs (in Germany) to determine the efficacy of enzyme chemistry in breaking down the polysaccharide matrix associated with biofilms. (This study was funded by Fujinon – the Japanese endoscope manufacturer.) The objective was to test a very wide selection of endoscope cleaning products to determine their ability to breakdown biofilms. A further study was also conducted to determine the effectiveness of various makes of brushes used to clean endoscope channels. The results were quite startling. Fujinon discovered that tap water worked equally as well as many of the leading enzyme cleaning products currently in use in Europe.
Although Fujinon would not publish the total results, due to confidentiality, they did confirm that Pharmax’ enzyme chemistry, coupled with the proprietary EndoBrush®, accomplish the best cleaning results of any combination of products and brushes tested, and their overall rating was 9.6 out of 10.
Subsequent to the Fujinon testing, Pharmax undertook evaluations in 2007 with EndoTechnik GMBH (in Germany) to compare its enzyme chemistry with many leading brands in Europe that unitize TOSI Test Strips (HealthMark Industries) in the EndoTechnik Washmaster Series Washer/Disinfector machine. The Pharmax enzymatic cleaner removed more than 85% of the polysaccharide plated on the TOSI strip, as compared to 62% obtained by the next best result.
Summary views for endoscopy:
The science of biofilms is extremely complex. Their implications in endoscopy are profound. For example, researchers are convinced that a residue of bacteria on an endoscope could reform a biofilm in around 12 to 14 hours.
The protocol that Pharmax Limited has developed to reprocess flexible endoscopes dictates initially cleaning with KwikKleen® products, since no other protocol has been proven effective against early stage biofilms. Once cleaning has been concluded, the disinfection with Glutacide® will destroy any residual microorganisms, whether a biofilm persists or not. It is clear that proper reprocessing before each procedure and at the end of each patient list, utilizing the KwikKleen protocol and Glutacide as a terminal disinfectant/sterilant, will mitigate against the potential of cross-contamination, since these products are tested and proven effective against bacterial biofilms.
Pharmax continues to collaborate globally with its peers to develop new and better technologies for these and other emerging risks to human health.
Pharmax Limited is the only company currently offering cleaning and disinfecting chemistry in North America that has been tested against biofilms.