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Tuesday, August 30, 2011

c diff

C diff - (clostridia difficile) infection is the bane of the existence for patients(and their doctors) who take long term antibiotics for Lyme disease. The infection occurs when normal gut flora are destroyed by antibiotics clearing the way for the opportunistic bacteria to take hold.

The biosphere of the GI tract is composed of trillions of micro-organisms including a wide variety of bacteria, fungi and parasites. Destruction of these "good bacteria" clears the way for c diff, previously contained within a narrow niche of the overall ecosystem of the gut flora, to disseminate and cause disease. The infection can be mild or severe, at times even life threatening.

Although c diff may be a naturally occurring part of the gut flora, infection may be introduced externally through spores or infected individuals. Even in these cases an intact gut flora helps to prevent the development of clinical disease.

So what are these good bacteria? Our bodies are colonized with massive quantities of micro-organisms. These bacteria/organisms may be parasitic or symbiotic. Parasites live off the land, offering nothing in return. Symbionts on the other hand can be either commensal (neutral) or mutualistic: something positive is provided to both the bacteria and the host.

One hears a lot about the beneficial effects of "good" bacteria. It turns out that some bacteria are good and beneficial to our immune systems

Good bacteria may: synthesize and excrete vitamins, prevent the colonization of pathogenic (disease causing) bacteria, provide natural antibiotic effects and aid in the production of natural antibodies (amongst others).

There are two take home points (yet to be made).

Some antibiotics are more commonly associated with c diff and some probiotics may help prevent the disease.

Quinolones such as Levaquin are highly associated with development of c diff. In addition, because of resistance, these agents appear to be associated with more virulent strains of c diff. Cephalosporins are more highly implicated. For example: Ceftin and Omnicef are more frequently associated with c diff then drugs from the penicillin family like amoxicillin. Clindamycin is also highly associated with c diff. This knowledge can help direct the prescription of the safest antibiotics.

In a published clinical study a proprietary mix(yogurt drink)of bacterial probiotics: L casei, L bulgaricus and S thermophilus has been shown to decrease the frequency of c diff. In addtion, the probiotic S boulardii, yeast based, may form a barrier which protects the gut.

Please take your probiotics. C diff can lead to sepsis, emergency surgery and even death. Treatments are available (Flagyl/Vancomycin), but they are not always effective. And, more virulent strains of c diff are starting to appear. More importantly, c diff tends to recur. This can make ongoing treatment very challenging to say the least.

Thursday, August 4, 2011

Biofilms

Biofilms are ubiquitous. Their role in chronic infections in mainstream. Biofims have been found in chronic sinusitis, chronic ear infections, chronic skin and bone infections, kidney stones and many other clinical scenarios.In these other diseases biofilms can be readily identified because the occur on surfaces. The existence of biofilms in Lyme disease is more difficut to establish because of infection within deeper, inaccessible tissues. It is commonly cited that biofilms may play a role in up to 80%of human infections.

Biofilms are indeed complex structures. Previously freely motile bacteria become frozen in a gel-like matrix due to the result of complex molecular and genetic swiching. The organisms within these films are able to communicate and establish a social network. Frequently these bacteria go into a starvation mode and exhibit a very low metabolic rate. Biofilms may release motile bacteria when enviromental factors become favorable. Biofilms may be polymicrobial or consist of a single organism. Biofilms have been cited as a mechanism by which opportunistic germs, eg Pseudomonas, can become pathogenic. Bacteria turn out to be very clever little fellows, after all, they have been on the earth for 3.5 billion years. Biofilm fossils have been uncovered evincing their antiquity.

Bacteria within these biofilms are difficult to kill. They exist in a highly protected niche. They frequently become extremely resistant to antibiotics and destruction through normal immune responses.

Antibiotics such as Beta-lactams (penicillins and cephalosporins) are generally ineffective because these cell wall inhibitors work only when bacteria are rapidly dividing or remodelling their cell walls. Biofilm bacteria are frequently in a state of suspended animation.

The biological characteristics of biofilm contained bacteria quickly begin to resemble those attributed to cystic forms of Borrelia burdorferi (Lyme). Both have a slow metabolic rate and are not typically killed by Beta-lactams, except for the amoxicillin paradox described in my last blog.

One could postulate that antibiotics which are effective against cyst forms of Lyme could also be effective against biofilm forms.

Some have been very critical of Dr. Sapi's work. She has developed "biofilm like" colonies which she does not define. These are not the same thing as actual biofilms which develop within infected tissues.

There are no published studies (in peer reviewed journals) documenting the existence of Lyme biofilms let alone which treatments might be effective.

When you Google the words Lyme and Biofilm it inevitably leads you to MacDonald and Sapi. MacDonald's work is fascinating but unpublsihed or vallidated by other investigators. It also is unhelpful from a clinical perspective.

In the meantime, my patients tell about earthworm extracts, mushroom extracts and a variety of other enzymes. I have found no compelling reasons to believe that any of these treatments would be effective.

At this point we are left at the same place we were two years ago. Lyme may persist because of many mechanisms. The contribution of biofilms remains unknown. Treatments (from the perspective of my allopathic mind) should be rational and based on what we do know from the the science at hand and what we have garnered from clinical experience.

It appears that Lyme infection within the brain is frequently manifested through biofilms and atypical cystic, granular/pleomorphic forms of the organism.

I only discus patient cases after I have recieved their consent. (Some have questioned this)

I have continued to treat patients with severe encephlopathic neuroborreliosis including some diagnosed with premature Alzheimer's disease.

My clinical experiences have been consistent. The addition of IV Flagyl has been very effective for such patients. Perhaps this relates to mechanisms alluded to above.