quote: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.
Posted by shadesofpurple (Member # 23923) on :
Very interesting, Thank you for posting this.
Posted by nhlymeguy (Member # 30783) on :
So this is saying that tindimax is the best option?...has anyone been on this drug?...nice to see actual research.
Posted by Abxnomore (Member # 18936) on :
Took compounded Tinidazole over Ten years ago before Tindamax was even on the market. It's much easier to tolerate than Flagyl and there have been prior studies. It's good stuff!
An in vitro study of the susceptibility of mobile and cystic forms of Borrelia burgdorferi to tinidazole. Brorson O, Brorson SH. Source
Department of Microbiology, Vestfold Sentralsykehus, T�nsberg, Norway. Abstract
The susceptibility of mobile and cystic forms of Borrelia burgdorferi to tinidazole (TZ) was examined. The minimal bactericidal concentration (MBC) of TZ against the mobile spirochetes was >128 microg/ml at 37 degrees C in micro-oxic atmosphere when incubated for 14 days. TZ significantly reduced the conversion of mobile spirochetes to cystic forms during incubation. The MBC for older (10-months-old) cysts at 37 degrees C in a micro-oxic atmosphere was >0.5 microg/ml, but >0.125 microg/ml for young (1-day-old) cysts. Acridine orange staining, dark-field microscopy and transmission electron microscopy revealed that, when the concentration of TZ was > or = MBC, the contents of the cysts were partly degraded, core structures did not develop inside the young cysts, and the amount of RNA in these cysts decreased significantly. When cysts were exposed to TZ, both the spirochetal structures and core structures inside the cysts dissolved, and the production of blebs was significantly reduced. These observations may be valuable in the treatment of resistant infections caused by B. burgdorferi, and suggest that a combination of TZ and a macrolide antibiotic could eradicate both cystic and mobile forms of B. burgdorferi.
PMID: 15248163 [PubMed - indexed for MEDLINE]
Free full text
Posted by lou (Member # 81) on :
Tinidazole has a black box warning and tygacil makes people so nauseous that they cannot continue to take it. But these results were in vitro. Erythromycin was found to be effective in vitro with lyme, but not in vivo. In other words, what works in the test tube may not work the same way in the body.
However, the study was certainly a step in the right direction.
Posted by seibertneurolyme (Member # 6416) on :
My question is what about flagyl? Does it really kill cysts or does it just go after babesia and other blood borne parasites?
Hubby crashed and ended up in the ER and hospital the first 2 times he tried tindamax -- about a year apart. But then he was able to take it once he added in IV Rocephin.
Then he tried IV flagyl and the fevers started. Every time he tries IV flagyl it raises his fevers -- and they stay elevated for weeks. The flagyl seems to cause hemolysis when it goes after babesia and whatever else (Rocky mountain spotted fever or rickettsia) is hiding out intracellularly is released out into the open.
As Lou stated -- what happens in the body and a test tube are 2 different things. Wish I really knew what was going on with hubby.
Bea Seibert
Posted by Jason21 (Member # 16393) on :
Tindamax worked great for me, especially when combined with cipro, which helps to shuttle the tindamax into your cells where it can get to all forms of LD or bart.
Additionally, a forum member gave me some good info about taking NAC (cysteine)with cipro. If you google cipro and NAC, you will find several studies indicating that taking NAC with cipro helps to break up biofilms.
Posted by sickmate (Member # 31502) on :
Nice theory. Unfortunately I have much more symptoms since taking Tindamax.
Posted by Abxnomore (Member # 18936) on :
That probably means it's working.
Posted by scorpiogirl (Member # 31907) on :
I have been on Tinidazole for 15 months. While I tolerated them fine... I can't tell if they have helped. So we're switching things up a bit now by taking me off that and starting IV Flagyl. I don't even herx on Tinidazole anymore.
Posted by Haley (Member # 22008) on :
Tindamax has also given me new symptoms. Stuff that I never had before. Not sure I can handle having more symptoms. Flagyl did not do that.
Wow - that would be great if I could do mono therapy for a while with just Tindamax...... So tired of taking all of these meds.
Posted by Tincup (Member # 5829) on :
Be REAL careful here before you jump on a tindi wagon or anything else.
As lou pointed out, the study and continuing work by Eva is ONLY in a dish, not in humans or even animals.
It's a great start, but it is dangerous (ESPECIALLY for a doctor) to jump to conclusions and use her work to try to convince patients or anyone else they may need a certain (or different) drug.
And Eva does NOT intend for her work to be used in relationship to patient care. Everyone should know, especially a doctor, it is way too early for that.
And this is ONE person's opinion. A person who is guessing and making assumptions and basically calling everyone else "wrong", with no documentation to prove anything.
It appears he is basing his comments or observations on a handful of patients he has seen, at best? And who, like everyone else, is NOT able to test patients for a cure or to see if there has been an elimination of any or all bacteria or other organisms.
Then what about therapeutic doses of any antibiotics? Could that be a difference in play here? Bactericidal vs. Bacterial-static?
Blogger said.. "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.
[IN THE DISH ONLY!]
This "cyst-buster" kills 90% of cysts and spirochetes: by far the best drug.
[IN THE DISH ONLY!]
We don't know it's effect on L-forms, >> but we can guess.<< ????
GUESS?
Tindamax >> probably<< works by an intracellular mechanism.
PROBABLY?
>>If this is true<<< it should be equally effective against L-forms."
Posted by Tincup (Member # 5829) on :
OK, now I am upset.
It truly concerns me that a doctor would continue to put this kind of stuff out there, especially knowing patients are reading and commenting on it and the "other side" is watching it. It is, foremost, irresponsible.
And in MY opinion it is like waving a big red flag in front of the "other side" and asking for trouble.
As he very well knows, NOW, in Maryland, after YEARS of not having one and keeping our docs "safe", there IS a standard of care set, and in the guidelines it states... thanks to his buds who fiddled with the medical board and tried to play politics...
"5. Because of a lack of biologic plausibility, lack of efficacy, absence of supporting data, or the potential for harm to the patient, the following are not recommended for treatment of patients with any manifestation of Lyme disease:
first-generation cephalosporins, fluoroquinolones, carbapenems, vancomycin, metronidazole,tinidazole, amantadine, ketolides, isoniazid, trimethoprim-sulfamethoxazole, fluconazole, benzathine penicillin G, combinations of antimicrobials, pulsed-dosing (i.e., dosing on some days but not others), long-term antibiotic therapy, anti-Bartonella therapies, hyperbaric oxygen, ozone, fever therapy, intravenous immunoglobulin, cholestyramine, intravenous hydrogen peroxide, specific nutritional supplements, and others (see ) (E-III)."
For him to admit on a blog (not a controlled and approved study) going against the standard of care is just plain old stupid and puts sick patients at risk of losing their doctor, not to mention the hard times, loss of license and big expense the doctor could face.
Can he not find someone else to talk to- maybe other doctors perhaps, in private? Something besides this?
I'm sorry for "blowing", but we have worked too hard for too many years to do all we can to protect our Lyme-treating doctors, so it irks me to see a doctor out there asking for trouble.
Ugggggggggggg!!!!!!!!!
Posted by philly78 (Member # 31069) on :
Well now I feel bad for posting this! I did post the study as well but with so much going on here, I haven't had time to read it.
Posted by Tincup (Member # 5829) on :
Philly!
This is not your fault. Not at all. This doctor KNOWS better.
Actually I am glad you pointed it out because I now know what waves are being made here, and the trouble it can bring with it, now that he is blogging again.
So thank you!
Posted by IckyTicky (Member # 21466) on :
I disagree. I think it's GOOD to post things like this for us to see! It gives us HOPE to know someone is studying this and getting results...IN A DISH!
Posted by IckyTicky (Member # 21466) on :
Oh..but I guess I do see your point Tincup, seeing your last post
Posted by Abxnomore (Member # 18936) on :
Tinidazole has been used for lyme and other parasitic treatment for years. It's nothing new.
It was originally marketed by Pfizer all over the world but was never marketed or available in the U.S. You can buy it every where around the world under the name fasigyn or have it compounded as I did.
I had it compounded in 2000 and took it instead of flagyl and the Brorsens of Norway were doing research on in then, as well as flagyl and the cyst form.
Tindamax has been on the market in the U.S. for a good while and many Lyme doctors use it. It was marketed in response to Tinidazole not being available in the states.
Not sure what the fuss is about. It's a known cyst buster and I took a ton of it for years with no adverse affects. It is not new in Lyme treatment. Flagyl and Tinidazole have been used inter-changeably since at least 1999.
Posted by Lymetoo (Member # 743) on :
I also took the tinidazole .. before Tindamax was developed. Very standard treatment. What's with the black box?
This thread can always be deleted by the one who began it. Not that I'm advocating it. Jus sayin' ..
Posted by willbeatthis (Member # 31111) on :
I am thankful for this post. The more I know... the better off I am. I believe with everything in me that a chronic lyme patient has to work to get well... we all know the paths we have had to embark on.. Thank you again.
Posted by lou (Member # 81) on :
Research on drugs always starts in the "test tube." Sometimes it proceeds on to much more expensive animal and human studies. This was a study specific to lyme, which is rare since the govt is not interested in helping us, and done with private money. Knowing the drug profiles against non-lyme germs is not as useful as specific to lyme. So, we must thank the funders and Dr. Sapi and associates for doing the work, while recognizing that the results from in vivo, if that ever happened, might not be exactly the same.
Posted by Bluemoon (Member # 25255) on :
The Lyme MD blog is one of the few good blogs on Lyme out there. I'm glad he is posting again.
Posted by dyna3495 (Member # 24126) on :
Knowledge is power.
Posted by nefferdun (Member # 20157) on :
Thanks for posting this study. It was given to me as a cyst buster because I could not tolerate Flagyl. If it works much better than originally suspected, that is good news. It is good that it also kills spirochetes so taking another drug is not necessary.
When I take it, I get burning and aching in my shins so I felt it was hitting bart/ehrlichia. I herx almost immediately and it seems to bring out what is buried. That is the reason I have never continued using it - just too much.
Posted by RC1 (Member # 31923) on :
I love the LymeMd blogger, and I'm so glad he's back at it because I missed him!
Posted by Abxnomore (Member # 18936) on :
Tinidazole is not new to lyme treatment. It has been used as a better alternative to flagyl for at least twelve years, that I am aware of, and a much easier medication for the patient to handle. It has also been used to treat parasites and amoebas in many countries for years:
Metronidazole has been shown to be carcinogenic in mice and rats. (See PRECAUTIONS.) Unnecessary use of the drug should be avoided. Its use should be reserved for the conditions described in the INDICATIONS section below."
Carcinogenicity has been seen in mice and rats treated chronically with metronidazole, another nitroimidazole agent. Although such data have not been reported for tinidazole, the two drugs are structurally related and have similar biologic effects. Its use should be reserved for the conditions described in INDICATIONS AND USAGE."
An in vitro study of the susceptibility of mobile and cystic forms of Borrelia burgdorferi to tinidazole. Brorson O, Brorson SH. Source
Department of Microbiology, Vestfold Sentralsykehus, T�nsberg, Norway. Abstract
The susceptibility of mobile and cystic forms of Borrelia burgdorferi to tinidazole (TZ) was examined. The minimal bactericidal concentration (MBC) of TZ against the mobile spirochetes was >128 microg/ml at 37 degrees C in micro-oxic atmosphere when incubated for 14 days. TZ significantly reduced the conversion of mobile spirochetes to cystic forms during incubation. The MBC for older (10-months-old) cysts at 37 degrees C in a micro-oxic atmosphere was >0.5 microg/ml, but >0.125 microg/ml for young (1-day-old) cysts. Acridine orange staining, dark-field microscopy and transmission electron microscopy revealed that, when the concentration of TZ was > or = MBC, the contents of the cysts were partly degraded, core structures did not develop inside the young cysts, and the amount of RNA in these cysts decreased significantly. When cysts were exposed to TZ, both the spirochetal structures and core structures inside the cysts dissolved, and the production of blebs was significantly reduced. These observations may be valuable in the treatment of resistant infections caused by B. burgdorferi, and suggest that a combination of TZ and a macrolide antibiotic could eradicate both cystic and mobile forms of B. burgdorferi.
PMID: 15248163 [PubMed - indexed for MEDLINE]
Free full text
[ 08-05-2011, 02:58 PM: Message edited by: Abxnomore ]
Posted by t9im (Member # 25489) on :
I have learned a lot from reading his blog and am thankful he is posting again.
He is helping a lot of people out here.
I can see why his posts dropped off if some people attack him as it ends up not worth his time.
It will be all our loss.
Posted by nefferdun (Member # 20157) on :
I agree. He has been very helpful answering questions as well as posting information. Most LLMDs would not do this - at least not for no charge - except Burrascano , who is a God send.
Posted by nomoremuscles (Member # 9560) on :
I also agree.
I think more LLMD's should have the courage to do this -- thinking out loud, weighing ideas on disease and trx, illustrating specific case histories with outcomes; just putting it out there. If they did, Perhaps more ordinary docs, those sitting on the fence, would be encouraged to move out of lock step and help their Lyme patients. Or at least not be so quick to dismiss them.
We need more daylight, not less.
I don't care who sees it.
Posted by Katrina (Member # 15236) on :
Thank you so much for posting this article. It is very encouraging that research is being done. It is very helpful to see how different drugs are working intracellularly.
As a health care professional myself. I found it very interesting.
More studies need to be done to show support but at least this is a start. It gives all of us hope!!
Kathleen
Posted by LAXlover (Member # 25518) on :
Tindamax helped me very much as part of a combo (can't remember what else I was taking with it). In fact, I'm looking forward to going back to it again in the future. I herxed and then started feeling better and better. But that's me.
I feel thankful every day for Lymenet and for all of those who share information they come across. It is up to the reader to sift through it all and decide what path to choose, either alone or with their doctor.
I believe that freedom of speech and "out of the box" doctors are all we really have to help us at this time. Most "mainstream" doctors....um, well, you know!
Take care everyone,
Posted by Abxnomore (Member # 18936) on :
I was happy to read this study, too. I took a ton of Tinidazole and Amoxi long before any of this was studied. I suppose it did me some good. Posted by nomoremuscles (Member # 9560) on :
Wow.
Big surprise.
Posted by My2B (Member # 31975) on :
My doctor agrees with this article. He believes that Tindamax will take longer but will eventually destroy all forms of the lyme bacteria.
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