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Friday, January 9, 2009

Flagyl: On the fence

Why do you need Flagyl or Tindamax? The conventional wisdom is that treatment needs to address all three forms of the bacteria. After all, the spirochete morphs into L-forms and cyst forms; if these different morphologies are not targeted the disease cannot be "cured." Otherwise, the bacteria cannot be eradicated. The cysts after all, become be a reservoir of disease waiting for the right conditions, to become active spirochetes. The science, the bacteriology, the immunology tells us something different. The body cannot be sterilized of Lyme or Bb bacteria. The intracellular niche is too protected. The immune response to intracellular bacteria is not far reaching enough. Despite clinical remission, Bb will forever persist within our cells and tissues. Many patients who are in a clinically remission relapse significantly when "cyts busting" drugs are added. The immune system becomes activated; inflammatory cytokines are produced and the symptoms return. The patient "Herxes" all over again. Frequently cognitive dysfunction worsens, joint pain and fatigue return as well as other symptoms. And to what end?

Yes- Cystic and granular forms of Bb have been demonstrated in the brain. In some cases the addition of Flagyl can lead to cognitive improvement. I don't think this is usually the case. Many cyst and granular forms have found under biofilms. My suspicion is that biofilms are not a cause for alarm. At any rate, there is no way to reach or kill such germs. By far, the biggest source of foreign bacteria is found in our oral cavities. These bacteria contained within biofilms generally cause us no adverse health consequences. It is only when the biolfims become broken down by active infection that these previously walled of colonies of bacteria become problematic. Sometimes- anti-cyst therapy seems to improve mental clarity. If cognitive issues persist, then the drugs can be tried. The mechanism by which this occurs in unclear to me. For the most part treating Bb cysts may be a lot like swatting a stick at an otherwise quiet hornet's nest.

The goal of successful Lyme therapy is to eliminate symptoms and restore health.

These would be parasites(Lyme Bb) have the nasty habit of stimulating our immune responses in ways which are deleterious. The infection- but perhaps to a greater extent, our immune responses makes us sick. If we lower the spirochete load, minimize the ability of the germs to replicate and reduce or eliminate the harmful immune responses, then hopefully a clinical remission can be established.

In order to achieve this balance it may be necessary to keep most patients on persistent low dose antibiotic therapy. This maintains a perpetually hostile environment for cystic forms. No- Minocin for example won't kill the cysts, but if any cysts convert into spirochetes, antimicrobial will be on board and nip the conversion in the bud. Disease reactivation will not occur.

16 comments:

Michele said...

I wonder if you have read Dr.Burrascano's October 08 "Advanced Topics in Lyme Disease" and what you thought of it.

cehansen said...

What about pulsing to allow the cysts to open and spirochetes to emerge? That makes it easier on the body to tolerate, plus the added benefit of teasing the cysts into converting. It makes sense to me that this would be a tactic to try, once the bacterial load is way down, etc.

Unknown said...

Very interesting...

Our LLMD, Dr. Liegner, doesn't use Flagyl or so-called "cyst busters", he doesn't believe they are necessary.

Dr. Sam Donta in MA doesn't believe in using Flagyl either. He said it has no effect on lyme disease.

Michele said...

Yes that is interesting and is logical. Is there another function for flagyl in Lyme treatment? I usually feel better with it.

dogdoc said...

Makes sense to me. Our evidence for cysts and flagyl/tindamax is all in-vitro as well. There is no work that I know of other than that. The in vitro work does not show any "chasing" out of cysts- only degradation and non- vitality by the way. That seems to be theory from some.
We have good evidence from sepsis that the way different antibiotics work can greatly effect LPS and cytokine release and outcome with bacterial killing. It may be a similar thing that we see with Borrelial killing and lipoprotein release/ subsequent cytokine release. In vivo/ in the patient, we really do not know what forms do what or what kills them. It may be that mino and flagyl kill the same form (ie L or cyst may be variations of the same thing) and the mino does it more slowly without excessive lipoprotein release and the flagyl does not. Just a possibility.

Michele said...

It seems Flagyl used to be a "have to" medicine. Its amazing what is being found out. Someday we will have the answer. Having had a lot of memory and cognitive problems I, like many, I have missed quite a bit of work. Even though I won a WC case and got Lyme on the job I found out yesterday that they are trying to fire me. I wonder how this can be done. Hopefully patients a year or so from now will not have to go through what we have. No more Flagyl.

EyeBob said...

LymeMD

You know, I think that this blog entry should be required reading for anyone who gets Bb.

The idea that we're on ABX treatment to help kill AND keep the bugs in their cubbies (so-to-speak) is a very simplistic, yet understandable way to look at treatment.

Thanks for writing. You're pretty good at it, and certainly informative.

BT

sukey said...
This comment has been removed by the author.
sukey said...

N-Acetyl-Cysteine breaks biofilms. I had a tough time starting due to increase in symptoms.

Anthony Murawski said...

Following up on docdog's remark that the L and cyst form may be varations of the same thing - I noticed that Burrascano notes that there is controversy whether the cyst is different from the L form.

A recent article by Miklossy et al. in the Journal of Neuroinflammation, titled "Persisting atypical and cystic forms of Borrelia burgdorferi and local
inflammation in Lyme neuroborreliosis," includes some fascinating microsopy images of morphological changes in B.b. spirochetes subjected to adverse conditions. Atypical forms induced from spirochetes included knob, ring-shaped and loop formations,
uni- or multi-spirochetal cysts, bleb formation,
granular disintegration, and colony-like masses enclosing
numerous cystic forms. Following 1 week exposure to adverse conditions, free
minute granules and re-growing of slender motile L forms
of young spirochetes along injured spirochetal cells were
observed.

The article is availabe for free access at http://www.jneuroinflammation.com/content/pdf/1742-2094-5-40.pdf

My preference in my own treatment regimen is to try to target all the forms of the infection, in their intra and extra-cellular locations, aggressively and simultaneously. I'd like to at least give this a try. Whether I can tolerate the treatment remains to be seen.

Miklossy notes at p. 13 of this article that "atypical, cystic and granular forms were observed in primary neuronal and astrocytic cell cultures exposed for 1 week to the Borrelia burgdorferi strains B31 and
ADB1. Nuclear fragmentation of a subset of infected cells
as revealed by TUNEL suggests that Borrelia burgdorferi can
cause functional damage and cell death." Of course, this isn't definitive proof, but it suggests that non-spirochetal forms may be harmful.

Anthony Murawski said...

I forgot to mention that Dr. Harris in San Francisco is now prescribing Alinia (nitazoxanide) as his first choice of cyst buster. He says he's getting better results with Alinia than with Flagyl, with fewer side effects. I'm don't know whether he's tried using tinidazole.

This is a fantastic blog. It's very good to know that knowledgeable LLMDs such as LymeMD who runs this blog and Dr. Liegner question the usefulness of cyst busters.

Claire - you mentioned that Dr. Donta doesn't use Flagyl. Does he use any other cyst busters, or does he take the same approach as Dr. Liegner?

pugilist said...

I think that the difficulties of the disease have lowered your expectations.

I believe you have to try to eradicate the illness completely.

What about adding NAC, or DMSA to destroy biofilms?

Anonymous said...

I began a new lyme dr. who started me pulsing 1 week a month on tindamax while using my regular antibiotics the rest of the month. THIS STUFF WORKS! the herx was severe ..sore throat eye twitching shooting burning..but the comfort level in my legs after taking it 3 months was worth it. unfortunatly i cant take it anymore because of the side effects so i'm hoping my dr. will try a new one that i tolerate better. I hope anyone who can tolerate pulsing on this drug will try it as i think it would help...and to Starlings Preschool...i also wonder about that but since the bb split in half every 12 hours i wonder if it's worth the risk of missing doses to "get" the cysts that open up...i can be wrong thou because on the flip side i guess all the new bacteria would also be effected and die...or roll up into more cysts?

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Requisite Software said...

Dr. Stricker coauthored a paper on antibiotics effective in eradicating round-body, spirochetes, and biofilms. The title is "Evaluation of in-vitro antibiotic susceptibility of different morphological forms of Borrelia burgdorferi" (http://www.lymebook.com/eva-sapi-tinidazole-study.pdf). Granted the info is all in-vitro but I think it's worth noting. According to the data metronidazole is not nearly as potent at destroying cysts, granular forms, and biofilms as tinidazole and tigecycline. Metronidazole is also worse at killing spirochetes and has poor penetration of the blood-brain barrier when compared with tinidazole (http://jac.oxfordjournals.org/content/3/3/239.short), tigecycline has worse penetration of the barrier than metronidazole. Another benefit of tinidazole was it's impressive destruction of biofilms. It looks like it destroys the actual biofilm structure. I don't know if this is just because of the specific strain they used but it looks promising.

Another important point, doxycycline didn't kill much of anything. Spirochetal forms completely decreased but cystic. forms grew by ~200%. This means they were growing despite hostile conditions to motility. I believe it furthers Murawski's point on maintained virulence in so-called dormant states.

In fact I was reading a paper on the granular state of spirochetes and it seems a primary feature, if not the primary feature is its ability to continue reproducing. I imagine that, along with other lifestyle issues, is the reason why many people do not get better on long term antibiotics. The paper is spirochaetes in their granule phase, from 1905 (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2347289/pdf/brmedj07040-0011.pdf).

Unknown said...

Treated with Flagyl for 10 days, 250mg 3x daily, for intestinal problems; suspected cause, bad well water. Had very bad Herx on day 4-10. Have suspected Lyme for 5 years; Western blot test negative twice, but said test did not test for band 24-25, nor 31, 34. Will follow up with 60 days, 200mg, 2x daily.