Tinidazole
Submitted by Jim K on Sat, 2006-06-24 18:11.
As we have more people on the CAPi protocolsi longer, our community is accruing clincal priceless experience with the different medications used and course of improvement and diffficulties on the CAP. One of these areas for observation and discussion has been use of Tinidazole versus Flagyli, and it's effect on treatment and course of recovery. There has been another thread discussing these, but I thought it was time to restart the discussion now that a number of people have experienced switching back and forth between these meds. So my own comments (posted on Rica's blog also) below.
Tini vs Flagyl-- interesting questions. I have to say, after doing Tini since pulse 3 and then trying Flagyl again for my last pulse (pulse 16) they do have different effects. Not just different side effects. It is possible, as our clinical experience accumulates, that there could even be good reason to do courses of both, or alternate them for pulses.
Post pulse reactions are a bit of a mystery. Please help us to gather some preliminary data about reactions CAPi users attribute to a pulse of metronidazolei or tinidazole by completing this survey. YOU MUST BE LOGGED IN AS A REGISTERED USER FIRST OR YOUR SURVEY DATA WON'T SUBMIT!
If you haven't done a pulse yet, await ye the results!
Submitted by Jim K on Mon, 2005-09-12 22:59.
What follows is an interview with a physician who has significant expertise in treating Cpni who has closely followed the Vanderbilt research over the years. He has garnered a lot of clinical experience, and his insights provide a lot of information both for patients and physicians who are looking to treat for Cpn. He prefers to remain anonymous. We’ll call him Dr. A for this interview.
Testing for Cpn
JimK- So what about serological testing for Cpn?
Dr. A-Testing for Cpn is only useful if you get a positive result. Because Cpn is an intracellulari pathogen, PCRi testing may be negative unless infected cells containing the DNA of the organism are directly tested. That is a problem for any PCR or antigen forms of testing. Serological testing has two problems. The first is that by middle age, most people have been exposed to Cpn and will have IgGi titers against this organism. If you are exposed and have a positive titer, then you most likely have a persistent infection somewhere, but this infection may not be causing symptoms. Thus, a positive serological test cannot distinguish asymptomatic persons from symptomatic persons. The second problem is that even persons with culture-proven Cpn in their coronary arteries only had a 35% positive rate by serological testing in a study done in Germany.
The most sensitive test appears to be reverse transcriptase PCR testing for messenger RNA produced by infected cells. This testing, for example, showed 18.5% of blood donors to have messenger RNA from Cpn in their peripheral blood mononuclear cells.
JIMK- So there’s no easy way to test for the intracellulari phase of Cpn?
Dr. A- It’s very difficult to test for the intracellular phase because the organism isn’t readily available to be tested unless you have infected cells to be tested. Testing for messenger RNA from infected cells appears to be the most sensitive method. However, this method is not commercially available.
JIMK- So PCR is just the most sensitive test for detecting DNA or RNA floating around in the serum or tissues.
Dr. A- If you test for antibodies you are testing for the response of the patient. If you test with PCR you are testing for DNA or RNA from the actual organism.
JIMK- You have said that they are useful if they are positive, but not particularly useful if they are negative.
Dr. A- Right
JIMK- That’s when you might decide to do an empirical course of treatment or something?
Dr. A- Exactly.
Empirical Diagnosis
JIMK- When you make a medical judgment on that, is it based on the disease? Are there also sets of symptoms you might be looking at? In David Wheldoni’s web site, he refers to history of respiratory illness. Are there other useful indicators?
Dr. A- The problem is that there are no symptoms that will hone in specifically on chronic Cpn infection. So if you have a suspicion, based on symptoms or the disease process, you begin with serologyi. And if you have positive serologyi then you may feel you have something to treat. If you don’t have positive serology and you are still convinced that Cpn is causing infection, then my approach would be to try a combination antibiotic protocol empirically, and if the patient has the side effects seen with the so-called “die-off” effect, such as those David Wheldon has described in his WebSite (Ed: these reactions typical of endotoxaemia include fever, chills, sweating, and muscle pains, coryza, widespread arthralgia and myalgia, and temporary worsening of neurological symptoms) then they may well have a Cpn infection. Once you treat for Cpn infection, all these side effects eventually go away!
JIMK- What about Borrellia that creates similar side affects when treated with metronidazolei? Any way to distinguish based on symptoms? I suggested to one person that porphyriai might be a distinguishing factor, any others?)
Dr. A- Metronidazole shouldn’t cause these effects, as it has no activity against Borrellia. It is probably killing Cpn. (Ed. Actually, this is not accurate. Dr. A does not treat Borrellia and was at this time unfamiliar with the way Flagyl is active against the cystic form of Borrellia- see Brorson & Brorson 2004, 1999. In I have been told that some Lyme doctors are using Wheldon's protocol as a primary Lyme Disease treatment. It is true that co-infection of Lyme and Cpn may be an unsuspected complication).
Length of Treatment
JIMK- I’ll tell you, it seems it can take quite a while…
Dr. A- It can take years, much as the initial treatment for tuberculosis did. It’s just like treating tuberculosis in that it takes many months to years of combination therapy.
JIMK- It Seems like people respond faster or slower.
Dr. A- People respond at different rates, which probably has to do with how much Cpn they have, what tissues are infected, and how good their immunei system is.
JIMK- Supposedly, you’re recovering your immune system function over time from disinfecting the monocytes and macrophages. It seems, just from being on it myself for 10-11 months that different tissues get reached at different times. Also, that different agents reach different tissues. When I added amoxicillini to the doxyi/zithi/tinadazole I got a big flare up in body areas I had not had pain in for a while. It surprised me how much additional effect I had, since I’d been on antibioticsi so long.
That’s one of the questions I had. The different protocolsi use different combinations of antibiotics. Do you find different effectiveness in different antibiotics, or is it more a practical matter of what’s available?
Dr. A- I think there are differences in tissue penetration, as well as a lot of other factors that aren’t yet clear.
Choice of antibiotics
JIMK Do you just tend to have a preference starting with certain antibiotic with a patient?
Dr. A- I’m pretty pragmatic and generally use the least expensive and safest antibiotics. I start them on: doxycyccline (Dr. A will attend to patient reaction and have them work up to 100mg twice a day over longer or shorter period, depending on tolerance with any of these medicines), and then I add azithromycin 250 mg working up to once per day Monday/Wednesday/Friday, I work up to 500 mg twice a day for metronidazole. I’ll finally add 300 mg twice a day of Rifamcini to that.
But I may start out working up to 500 mg twice a day of amoxicillin rather than doxycycline.
JIMK you start out with that because it’s the easiest on the patient?
Dr. A- It’s cheap, safe, and tolerated the best. Then after a month or two add the azithromycin Monday/Wednesday/Friday for a month, then the doxycycline, see how they do on all three. I’ve generally added the metronidazole into this and see how they do. I wouldn’t mind pulsing it as David Wheldon does in his protocol (Ed. This is a reference to the Wheldon protocol’s method of pulsing the metronidazole for 5 days every 3 weeks). By pulsing, you can give them time to recover from the side effects.
JIMK- But it sounds like you used to give the metronidazole as a constant, then?
Dr. A- Yes, that’s generally how I proceed.
JIMK- That’s one drug, the metronidazole, that I had the hardest time tolerating.
Dr. A- You think that one’s tough, wait until you get to the Rifamcin!
JIMK- That’s one my doctor isn’t real enthused about giving me (the Rifamcin). Not sure exactly why.
Dr. A- Well, most physicians aren’t familiar with it unless they’ve treated TB.
JIMK- Do you think the Rifamcin is a necessary one for this protocol?
Dr. A- Let me tell you what Rifamcin specifically does. When chlamydial EB’s germinate and transform into the RB’s, which is the replicating form, the first enzyme out of the EB’s is DNA-dependent-RNA-polymerase that Rifamcin specifically blocks.
EB’s are like spore-like infectious form of Cpn. The cryptic formi is also different to treat; it is metabolizing but is not replicating (Ed. The cryptic form is what the metronidazole is directed at, since it is metabolizing but in an anaerobic mode. Our expert is noting here that the EB’s are not metabolizing nor replicating, therefore are not affected by antibiotics that interfere either with bacterial metabolism or with bacterial replication. They are effected only by disulphide reducing agents, like amoxicillin, which breaks the disulphide latice bonds of the EB cell membrane). If you have a large EB load you’re going to keep getting cells reinfected. If you stop them before they start, that’s much better than letting them get started and then trying to kill them.
JIMK- So doxy/zith is inhibiting the replicating form?
Dr. A- Yes. Remember, you are trying to formulate a combination therapy that attacks all of the potential forms of Cpn. And so, N-formyl-penicillamine, which amoxicillin is metabolized to in the body, destroys the EB. It is these spore-like, non-replicating, EB’s, which invade your body’s cells and once inside transform into RB’s capable of replicating. In this transformation the first enzyme employed is DNA-dependent-RNA-polymerase, which allow this transformation. If they are in the RB replicating form, then azithromycin and doxycycline will interfere with that. If they are in cryptic form then metronidazole goes after that. If they are EB’s the amoxicillin takes care of that. If they are transforming from EB’s to RB’s, where they are particularly vulnerable, Rifamcin takes care of that. It takes a lot of different antibiotics because there are lots of different life forms. Otherwise it just goes from one life form to the next.
JIMK- So, adding the Rifamcin is to be as complete as possible?
Dr. A- It is hard to say if you can get by without the amoxicillan, or the Rifamcin. I suspect that you can in younger healthy persons. I tend to think that they are especially important for those who have been sick for a long time, and likely have a lot of EB’s looking for homes. I want to destroy these EB’s (amoxicillin) or if they are finding homes I want to short-circuit them (Rifamcin). The transformation from EB to RB is where they are particularly vulnerable.
JIMK- That is really important information to get out there. Especially for those of us who have, indeed, been sick with this for a long time. I knew when I added the amoxicillin to the Wheldon protocol that I was killing something additional. And it was so clearly, highly inflammatory too; by the amount of pain and inflammationi I had in reaction to it.
Dr. A- You probably have a high EB load. Those were probably Elementary Bodies that you were destroying. By the way, you can use penicilamine directly, but that’s a very scary drug.
JIMK- And that tends to dump a big load of the endotoxini when they get popped?
Dr. A- That and a lot of other antigens. The response to the antigens is somewhat dependent on your body’s immune system.
JIMK- So you’re getting a cytokinei reaction.
Dr. A- Yes.
JIMK- Do you find tinidazole as effective as metronidazole?
Dr. A- I don’t see why it wouldn’t be. It’s just been recently approved in the US, so I have no experience with it, or what they are charging for it!
JIMK- I find I tolerate it much better than metronidazole. I got so sick on that, which I believe is more a drug side effect than a kill effect.
Dr. A- Well, I wouldn’t necessarily see it that way. My experience is that people who don’t have any Cpn organisms can tolerate metronidazole without any side effects. You’re talking to someone who has had patients taking metronidazole as a post treatment preventative for a number of years without side effects.
JIMK- So your bet then would be that I got sick from the metronidazole because it was killing cryptic Cpn, not because of drug side effects (Ed. which would suggest that tinidazole is not as potent in this as metronidazole).
Dr. A- There are two explanations as to why you are tolerating tinidazole better. One is that you just knocked down enough of your Cpn load with the earlier metronidazole pulses. And people have done that; they say they can’t tolerate the metronidazole and then after a time they can. The other is that you were getting better penetration with the metronidazole than with the tinidazole.
JIMK- So it may be that the tinidazole is not quite as strong, so it may be a good way to gear up over time to the metronidazole.
Dr. A- Yes, but if you were to try metronidazole for a couple weeks and you didn’t get any side effects, then you probably don’t have much Cpn.
Brain Fog
JIMK- You see brain fog a lot in Cpn patients; do you see this as CNSi involvement or more as an effect of endotoxin?
Dr. A- It is most likely a combination of endotoxinsi, porphyrins, and cytokinesi. It may largely be porphyrins for the simple reason that reactions from porphyrins last longer than those from cytokines and there’s no fever.
And you know you are better when…?
JIMK- So that’s the kind of “gold standard” test: that you can take metronidazole and not get hammered?
Dr. A- And Rifamcin. Rifamcin has deep tissue penetration too. So if you can tolerate the metronidazole and then I challenge you with Rifamcin and you tolerate that as well, you have very few Cpn left. I periodically challenge patients with a short course containing metronidazole and Rifamcin to see if they continue to be cleared of Cpn.
JIMK- The complete challenge.
The more I understand, the more I appreciate how tough a bug this is, and long it takes to get it, how complex it is, and all the tissues you need to penetrate to get there.
Dr. A- Not only the tissue penetration, but also both the organism and your cells have active efflux pumping mechanisms to pump out the antibiotic. You have to work against these natural mechanisms to keep adequate concentrations in the cells. Rifamcin tends to inhibit these efflux pumps. I also use another drug, Quercetin, a bioflavonoid that also acts as a cell efflux inhibiter. It works on a different efflux pump than Rifamcin. It’s, also active against Chlamydia on it’s own.
JIMK- Plus Quercetin is also an anti-inflammatory and free radical quencher.
Dr. A- But the antichlamydial effect may be more important than it’s anti-inflammatory effect.
JIMK- How much Quercetin do you use a day—I tend to take three caps with the bromelain.
Dr. A- I tend to use 2 caps a day containing 500 mg of Quercetin along with vitamin C.
Differences in treating different diseasesi?
JIMK- Do you see differences in treatment based on disease entity, or more on the person.
Dr. A- That’s hard to say. My generalization is that: the longer the person’s been sick and the sicker the person has been, the more problematic the therapy is going to be. In addition, the older the person is, the more likely that they’ve had a Cpn load building for a long time without knowing it. Their ability to tolerate treatment can be low, both from the high Cpn load, and from an aging immune system. On the other hand, I know of a young patient who had a very strong family history of cardiac disease. For this reason, his doctor placed him on the regimen. He had very few reactions. He was in his early 30’s.
JIMK- He had some reactions, which let you know that he had some Cpn building.
Dr. A- Yes.
JIMK- I know in my family there’s both cardiac disease and Alzheimer’s, and another sibling has fibromyalgiai. So there may be a common link genetically that is more about the susceptibility to Cpn.
Dr. A- AOE4 probably has a place in Cardiac disease, Alzheimer’s and MS.
I’ve observed that the recent memory problems that come with brain fog for patients can really lift once the Chlamydia is gone, even in those 50 or more.
Porphyria
JIMK- On the porphyrin stuff- do you think the porphyrin testing is worthwhile, or do you just assume it and treat for it anyway when you are treating for Cpn?
Dr. A- The trouble is that you really have to test for the fat soluble porphyrins to get the best data, and that involves a 24-hour stool test, and you have to freeze that sample and so on. You need a 24-hour urine to look for water-soluble porphyrins.
There is a poor man’s way to check for porphyrins. It seems that if you have porphyrins, you will have an increased hemoglobin level, on the high end of normal on most CBC’s.
JIMK- when I was first treated I was very low on iron, which I understand is heavily used by chlamydial metabolism. Would that make a problem for using hemoglobin’s as an indicator of porphyrins?
Dr. A- Initially, low iron would mask the increased hemoglobin you would expect with porphyrins. Once your iron levels are normal, it would no longer mask the elevated hemoglobin. But in general, a high-normal hemoglobin and high-normal hematocrit are both good indicators of porphyrins.
JIMK- I can’t tell you how unusual it is to speak to a physician who sees it his or her job to actually investigate and reason out what’s going on in a patient, rather than look to see which already-known-box to put them in. I spoke to David Wheldon about that and he said, “Yes, I know, if I’d listened to those doctors I would be a widower now.” Kind of put home the point.
Submitted by notasperfectasyou on Thu, 2009-12-03 10:42.
Kim's just starting her December 2009 pulse and she's "Out the Gate Early". Meaning, Flagyl "fun" started up on day-1 of the pulse. I've read that folks on Tinii have less of this and I came here today to think about it. First here's a couple links to RxList: Flagyl (Metronidazole) and Tindamax (Tinidazole) I thought it was interesting that both of them had peripheral neuropathy listed as side effects. Being a good cpnhelp'er I did a search and here are links I found:
Submitted by raven on Thu, 2009-11-26 01:40.
The day before Thanksgiving and I was rushing around gathering food to take to my Mom's house. I made too tight a turn in the parking lot, ran over the curb and blew out one of my tires. Looking back, I was probably a little dingy from the 4th day of Tinii. Later in the day I was making pie shells and put them in the oven to bake a bit before I poured in the pumpkin filling. I was looking for some dry beans to weight the crust but only found some rice. I poured the rice in the shell and put them in the oven. When I took them out I found the rice had sunk into the pie crust and I had to dig all of it out. Well, I got most of the rice out but some is still stuck in the crust. The pies were very good in spite of this--just have to pick a few hard kernels out.
Submitted by Sunnivara on Sat, 2009-11-14 02:44.
After reading this website... http://onthepharm.net/2007/08/flagyl-alcohol-reaction.html/ ...I decided to take a chance and have a glass of wine on my second day of a tinii pulse. I had no negative reaction whatsoever, other than the anxiety of worrying about what might happen! Next morning I was still fine. On the third night of taking tini I had 2 glasses of wine. Still no bad reaction. In fact, in stark contrast to flagyl, which causes me severe depression, I've actually been in a particularly good mood these last 2 days. Is it possible that tini+alcohol could actually have a positive effect on those who don't get violently ill from it?
Submitted by adamt on Fri, 2009-10-09 04:17.
Hello ,im new to the site :) My story: I was diagnosed with MSi in 2002, and i recently read how lyme disease can mimic MS, and after getting alot worse on LDNi (which makes MS patients stop progressing) made me realise i could have been misdiagnosed. So earlier this year had a Lyme disease blood test - Lymphocyte Transformation test, which came back positive, showing two different strains of Borrelia - Garinii and Sensu stricto. Ive been using a rife ,achine - 'Doug Coil machine' for the past 5 months, but haven't had a herx reaction, which shows NO spirochetes are being killed, and as the rife machine can only kill spirochetes, i now need to attack the hidden/dormant cyst forms of the infection.
Submitted by PattiR on Sat, 2009-08-22 14:05.
Hello to all on CAP i, It has been a while since I have posted. I have been on the CAP since late Dec. 08 and I have to say it has not been easy,but when faced with the fear of Alzheimers I find that I am highly motivated to stick with it. I took my first Tindamax today and it was really scary,especially after reading everything about the bad reactions, but I figure I really want to break thru to the other side! Lately I have had much pain in my head, especially in the front and very bad eye sensitivity. I am hoping the addition of Tindamax will help me. I also have been having what I think is reflux and post nasal drip. I have increased my yogurt and vitamin c intake. I will let you know of my progress and will try to do as many days as I can of the pulse.
Submitted by Sunnivara on Fri, 2009-08-14 19:45.
I'm overdue for a pulse because my last couple flagyl i pulses were so bad I needed a break. My doc and I decided we should give Tindamax a try. Now I'm trying to get up the nerve to try it but am hesitant. Anyone want to share their tini i experiences or offer advice on any of tini's quirky effects I should watch out for (such as flagyl's alcohol issue)?
Submitted by Finch on Sat, 2009-08-01 17:03.
Well, I finally completed another full Flagyli pulse on July 10, and I'm ready to pulse again in two days. The last Flagyl pulse was very difficult on my digestive system no matter what I tried to do to help. I had lots of pain, bloating, gas, all that fun stuff. It also didn't go away very quickly after I finished the pulse, although I'm pretty much back to normal now. I used charcoal, extra probiotics, glucose, Emergen-C with no relief.
Submitted by macorn on Tue, 2009-07-21 10:39.
My body is so sore??? It seems (to me) that it has been such a long time of 'poping pills' without results. However, maybe I have had some; I seriously do not know. I have been a little sore in my shoulder/neck area for about a year; I would only notice it when my big brother would give me a big hug (which he doesn't do anymore since I yelped at his big squeeze). I changed from Flagyl i to Tinidazole at my last pulse, which concluded three days ago. The last few days I have been EXCEEDINGLY sore in this area. I never thought this could be a reaction until this mornng, thus this blog. Oh, I occasionlly get sore-to-the-touch on my skull; this has been going on a long time, I don't remember how long. Would like input on this.
Submitted by Miying Meng on Sun, 2009-04-05 15:47.
Tinidazole Pulses. (Note: Latest entry at the bottom of page) 3.2.09 - 1 - 500 mg tablet 3.16.09 - 1 - 500 mg tablet The reason I took one 500 mg tablet 14 days after the first tablet is that most of the reactions from it seemed to be gone so I thought, why not? I am in the process of ramping up to a full pulse so I am taking liberty to change things a bit for my benefit. Speed things up when I can as I am such a slow poke.
Submitted by liz n on Fri, 2009-04-03 05:40.
Just completed my 4th pulse. Switched to Tiniazole instead of Flagyli. This time managed to get through the whole 5 days with no major hiccups! The only side effects I noticed were; - slightly swollen glands (which always seem to appear when I start a new antibiotic - hopefully a die off reaction) - minor nausea and headache on day 2-4 - feeling a bit down - I read that depression can be a side effect of taking Tini. Has anyone else experienced this? (although it could also just be the week of miserable, wet weather Sydneys been through!)
Submitted by Louise on Wed, 2009-03-18 09:33.
Treatment Overview on March 11, 2009; Diagnostic Evaluation May 24, 2007. Chronic Fatigue Sydrome - Progressive onset - 20 to 30 years to overwhelming fatigue, Fibromyalgiai, Mild Form. C.Pn. positive by Lab test result > 1:512, Bb positive by Lab test Western Blot after doxycycline taken for 3 -4 weeks for CPni, Borrelia Burgdorferi (Lyme Disease) was revealed as positve on Western Blot late July 2007. Started CAProtocol 6-21-07 with Doxycycline, N-A-C and all supplementsi, CAP Progressed on 10-31-07 Macrolide-added, progressed 11-22-07 Tinidazole-added and also Cholestyramine HS PRN x 7d starting day 3 - 4 of pulse and continuing for +/- 7 days.
Submitted by Miying Meng on Wed, 2009-03-11 12:37.
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