Sunday, July 24, 2011

Everything you thought you knew about cyst busters is wrong

Eva Sapi's recent research calls into question everything we thought we knew about Lyme "cysts." In fact it destroys the old thinking.

We have heard about cell wall antibiotics, intracellular antibiotics and cyst-busters. Think again.

She investigated the effect of various antibiotics on Lyme spirochetes and round body forms - also know as cystic forms.

Doxycycline worked according to plan. Doxy inhibits protein synthesis - it kills bacteria, including Lyme, by action within the cytoplasm, inhibiting the manufacture of proteins required for the bacteria's survival. Doxy and others are commonly referred to as intracellular antibiotics.

Spirochete loads decreased by about 90% while cyst levels increased by 200% - just as expected.

Then amoxicillin data was presented. Amoxicillin inhibits the formation of bacterial cell walls. Amox and similar drugs should then only be effective in killing spirochetes with an intact cell wall. This is where the results start deviating from the plotted course.

Amoxicillin killed 90% of spirochete forms - OK, but -- it also killed 68% of the cystic forms! Amoxicillin and other cell wall drugs are not cyst busters - only specific anti-parasite drugs kill cysts - or so we thought.

Well lets think again for a second: what are cysts? Are they balled up forms of spirochetes with a different kind of membrane - or blebs (also described) expressed through the spirochete membrane? Maybe the former retain much of the cell wall from the original spirochete - maybe that is why amoxicillin works here.

This would seem to clear up a nagging question raised by others. Are cysts and L-forms really the same thing? These results show that cysts cannot represent a version of L-forms or spheroplasts which result when gram negatives shed their cell walls. If this were the case a cell wall drug would be ineffective. Cysts and L-forms are distinct and different forms. (There may be a hole in this reasoning. I will explain later).

OK So we have learned something new: cell wall antibiotics can also kill some cyst forms which are not L-forms.

Let's look at some more data. Tigecyline is a not a cyst drug either. Wrong. Tigecycline kills 90% of spirochetes, good so far, but it also kills 90% of cysts! Tigecycline is an intracellular antibiotic similar to doxycycline! Another fly in the ointment.

OK. Cysts with their lower metabolic rate, still need ribosomal proteins to survive, just not at the levels of intact spirochetes. Tigecyline is a more powerful drug, higher levels are delivered into the cytoplasm of the cysts. This makes sense. Cyst forms are still essentially a pleomorphic version of Lyme bacteria with somewhat different features. In this scenario, cysts could be L-forms. But we have already shown that this is not true because amoxicillin can kill them. Right?

Amoxil is a cell wall drug. I thought so. Kersten, (antimicrobial agents and chemotherapy, May 1995, p. 1127-1133) states that Beta-lactam antibiotics, which include amox, penicillin and Rocephin, have been shown to cause a specific loss of total intracellular RNA in the absence of cell wall hydrolysis. In other words, amoxil could possibly work in part as an intracellular agent. If this is right cyst forms of Lyme could still be L-forms. So perhaps we have not shown that L-forms and cyst forms are different after all.

The question remains unanswered.

Let's get to the Cyst-busters. It takes antiparasitic drugs, so we thought, to kill the cysts. Cyst-busters, anti-parasite drugs, kill parasites (and Lyme cysts) not bacteria. The so called cyst-busters were heretofore used in combination or cycled with other antibiotics. Previous thinking was that typical antibiotics would kill spirochetes and/or L-forms and that cyst busters would disrupt only the cystic forms.

Cyst-busters do not kill intact spirochetes - so we are told. Very wrong this time.

I cannot cover the whole Sapi study. The most exciting finding is that Tindamax (tinidazole) - our premier Cyst-buster, is the most effective drug overall. This "cyst-buster" kills 90% of cysts and spirochetes: by far the best drug. We don't know it's effect on L-forms, but we can guess. Tindamax probably works by an intracellular mechanism. If this is true it should be equally effective against L-forms.

It gets even better. Tindamax is the only drug which does a great job on biofilm colonies as well!
(not to be discussed now). More on biofilms later.

Tindamax passes the blood brain barrier and penetrates well into most tissues. It has been effective in my patients with neurocognitive deficits - neuroborreliosis.

Recently I tried it on another sort of patient. This patient has had intractable Lyme arthritis of his knees. This young athlete had been extensively treated with IV Rocephin followed by a year of typical oral antibiotics. Knee effusions have persisted - until I prescribed Tindamax. Now, after two months, the fluid in his knees has evaporated. His knees are dry and painless for the first time in over one year.

This raises the question: should Tindamax be used as mono-therapy? Well, I cannot endorse blanket use at this time. Tindamax has a black box warning. It has been associated with cancer in some laboratory animals. Perhaps there are more compelling reasons to use Tindamax, but this will have to wait for another post.

My nagging question:

Why does penicillin kill Lyme? It shouldn't. Lyme is a gram negative bacteria. While certain Beta-lactam antibiotics can kill gram negative bacteria, penicillin cannot. Penicillin is only active against gram positive bacteria.

Maybe this other mechanism alluded to above, the alternative intracellular RNA mechanism is significant and explains why penicillin kills Lyme spirochetes. Maybe not.

We need to continually reevaluate things which we have assumed to be true, because many of them are not.

23 comments:

la quinta kid said...

Awesome post. Keep up the good work. Out of all the information out there on lyme, I find your blog to be the most level headed and logical.

Brittany Adams said...

I really love this post!!!

Speaking as one of your patients, I must say that when you switched me to Tindamax a few months ago it made all the difference in the world and i'm starting to feel better than I have in years. And I give you full credit for my progress with treating me for chronic lyme disease. Keep up the good work and awesome posts! :)

T9im said...

Hi Doc:

I went to Dr. Sapi's conference and she also presented combinations and Tindamax with Doxy worked the best.

It was great to see the presentations and while the bacteria load only went down to 10% the duration was not for a long period (I remember 72 hours).

Our daughter was on tindamax for 7 months and it helped tremendously with the neuro symptoms (she is 11 and has Lyme and Babesia) but we stopped due to some adverse reactions (alergic - itching which was triggered when we increased the dossage and anorexia - fortunately after appx. 6 weeks her appetite picked up but we have a ways to go to increase body weight).

One of Dr. Sapi's research students indicated it can take up to 6 weeks for a cyst to break and release spirochetes.

ShowMeMissouri said...

Thank you for the informative post. Son, 12, just started Tindamax and Bactrim. He is sleeping a lot at the moment, but I hope it is a healing sleep! Thank you again for all of your posts!

Susan said...

Great post, Tindamax gives me vertgo and headache, how do you rate Alinia as an alternative?

Camp Other said...

"Why does penicillin kill Lyme? It shouldn't. Lyme is a gram negative bacteria."

Actually, Lyme Borrelia is neither specifically gram negative bacteria or gram positive. It is in a category of its own.

Notes from my blog:

From the book, "Borrelia:Molecular Biology, Host Interaction and Pathogenesis":

""Although Borrelia spirochetes are often, but mistakenly described as Gram-negative bacteria due to their diderm, i.e. double-membrane envelopes, a closer examination reveals significant differences in composition and architecture. Probably most striking is the lack of LPS, the presence of major surface lipoproteins at the host-pathogen interface during transmission, persistence and ensuing pathogenic processes and the additional function of periplasmic flagella in defining cell shape."

and an additional source:

"Borrelia were thought to be Gram negative because of their double membrane structure, but genetic analysis places them - along with other spirochetes - into a separate eubacterial phylum. Ultrastructural molecular and biochemical studies have emphasized the wide taxonomic gap between spirochetes and Gram-negative bacteria. ( The Genus Borrelia. Melissa Caimano. Prokaryotes (2006) 7:235-293.)"

There is so much that has yet to be understood about this bacteria.

Lisa Winter said...

This is so exciting to me as I'm a mother to a 13year daughter who has been on Biaxin & Plaquenil. She has been plagued with nero symptoms.I would love for her to see you and try Tindamax. She is so desperate to get her life back as eveyday is a struggle for her. If we are able to make a appt please email @ ccmom13@aol.com Our family would be forever greatful

Lisa Winter

txbutterfly said...

What is the latest research on IV Flagyl? Will it work as well as the others mentioned to kill cysts? Thanks!

Lynn said...

I'm very excited about Tindamax but afraid to use it because of the black box warning. My doctor is very sensitive to those so I figure it's for good reason. But people here are using this drug with success. Can you elaborate on the cancer warning?

bumblebee said...

Did your patient who had the lyme arthritis take Tindamax for the entire two months?

LYMEMJ said...

Tindamax is the newest anthelmintic but if you see the studies in vitro showed it as the best cyst buster while the in vivo showed the Flagyl because the doses used in vitro were lower i=of Flagyl equivalence. i just mean to mention this to show there are other anthelmintics that could serve as well, in my particular case Tindamaz didn't do much while Flagyl and ivermectin did much. The point is there are medicines to treat if the concept changes from just treating with antibacterials or antibiotics to anthelmintics or call them antiparasitics, my opinion!

kim goodwin said...

Tindamax has been the first drug in a year to change my life. I am so greatful for it and i think it saved me many years of other antibiotics.

victoria said...

hi i've been on tindemax for several months now and not doing anything but keeping me where i was I am and stagnant in my treatments - at 1st thought it was helping, nope. my llmd switching me to doxy start of new yr bacuse of herx after chritmas - should i indeed stay on the tindemax? been on it 4+ months no improvement? hummmmm. thanks for the article - & i'm surprised i could scan it and get some helpful info. :-) lyme brain

Greg said...

Hi,

Have you noticed that in her published study in may 2011


http://www.canlyme.com/Sapi_et_al_2011.pdf

Eva Sapi doesnt mention anymore her conclusions about Plaquenil.
Do you think she has moved backward?

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

hello. All tried, IV ceftriaxone, doxy, metronidazole. Whas the dosis of tinidazole for 60 kg weight? 2*500 kg a day?

Lesley Banks said...

Have you tried GcMAF on your patients? This appears to work by rebooting the immune system. I've googled it and there are lots of positive comments out there, but wondered if you could comment and give your point of view? Thanks

Sylvia said...

Is Alinia as good as tindamax? I wasn't able to use tindamax due to side effects.
Thanks for your help.../

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brookek said...

in your judgment, does tindamax penetrate cancellous and cortical bone very well? I have late stage Lyme and probably bart and babesia and have had nothing but decline and infection now to most bones of head and face. Am nearly convinced this illness is incurable because of pleomorphism and symbiosis with bone and nerve cells. Have you heard good things about ivermectin and lYME? Any ideas if it penetrates into bones?

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Voice of Reason said...

there's only one way to avoid chronic lyme disease, and that is get a regimen of antibiotics immediately after the bite, same day, and no later than a week or 2 later. after about 19 days it gets into your spinal and cerebral fluid and is very hard if not impossible to eradicate. it would pay to take along a stash of doxycycline when hiking or camping, in case one gets bit. there's no other way around it. most of the nightmare horror stories about lyme are because it went months or years before being diagnosed. by then the horse has already left the barn. the government doesn't want to admit how bad this is, because they don't want to create "public anxiety"- but in reality they don't want to admit just how f-ing BAD it is. and the medical industry is working along with the insurance companies to not treat people, to save money on meds and treatment. it's as plain as a nose on a face- the longer they can keep telling the big lie, the longer they can save money. this would cost them billions $$ to treat correctly. and many lyme patients would have major lawsuits against their MD's and insurance co's for lack of treatment over the years. if you have an MD who is dragging his feet treating you, tell them you will sue if you get sicker. you'll see how fast they treat you then. take grape seed extract, apple seeds, and oil of oregano to try to kill the cyst forms of lyme.