Combination Antibiotic Treatment Protocol's (CAP's)

Combination Antibiotic Treatment Protocol's (CAP's)

This section covers the most current update of the Combination Antibiotic Protocol's (CAP's) for treating Chlamydia Pneumoniae. New material includes an updated protocol from Dr. Stratton, his most current observations on protecting the liver during treatment, as well as new charts to help users organize and understand suggested supplementation.

Jim K Tue, 2006-02-07 21:01

Initial and Following Blood Tests in CAP's Treatment

Initial and Following Blood Tests in CAP's Treatment

Initial and following blood work is not just a matter of Cpn related indicators, but also relevant to your particular history and case, as determined by your doctor. Suggestions drawn from experts treating Cpn in a variety of conditions include the following.Initial blood work can be obtained for the following tests:

  1. CBC & Differential
  2. Liver function tests
  3. Uric acid
  4. Serum iron studies (typically depleted by Cpn: low iron levels are more diagnostic, and are not necessariy indicators to supplement, which may actually increase Cpn infection-- see references below).
  5. Red blood cell ALA dehydratase
  6. Red blood cell PBG deaminase
  7. Vitamin B-12 level
  8. Homocysteine levels
  9. Serum methymalonate level.
  10. Vitamin D levels
  11. Thyroid panels (standard plus free T4, free T3, revers T3) [Endocrine disturbances common in Cpn and associated diseases]
  12. Creatinine
  13. AST
  14. ALT
  15. 24-hour urine and 24-hour stool specimens for porphyrins

Dr Stratton has noted relative to porphyrins:

Homocystine levels are elevated with B12 and folate deficiency, but can be reduced by folate alone. On the other hand, serum methyl malonate levels are elevated in B12 deficiency and are not changed by folate. Therefore, serum methyl malonate levels are the best indicator of B12 deficiency. Another indicator, according to Dr. Stratton, is high hemoglobin and high hematocrit.

Dr. Powell notes:

I also tst DHEA-S and free testosteron in perimenopausal females. Both increase nitric oxide levels, which kills Cpn.  No point heading into treatment with low androgens.

Regular Followup Tests

  1. CBC & Differential
  2. Liver function tests (especially important when using medications such as INH or Rifamcin which can have liver toxicity, and because die-off of liver cells infected with Cpn can affect liver function)
  3. Vitamin D levels (if supplementing deficiency)
  4. Thyroid panels (standard plus free T4, free T3, reverse T3) (if supplementing deficiency)
  5. AST
  6. ALT
  7. Others as determined by doctor relevant to your particular condition.

Some References-Iron and the Role of Chlamydia pneumoniae in Heart Disease, http://www.cdc.gov/ncidod/eid/vol5no5/letters.htmWeinberg ED. Patho-ecologic implications of microbial acquisition of host iron. Reviews in Medical Microbiology 1998;9:171-8.Freidank HM, Billing H. Influence of iron restriction on the growth of Chlamydia pneumoniae TWAR and Chlamydia trachomatis. Clinical Microbiology and Infection 1997;3 Suppl 2:193.Chapuy MC, Preziosi P, Maamer M, Arnaud S, Galan P, Hercberg S, Meunier PJ. Prevalence of vitamin D insufficiency in an adult normal population. Osteoporos Int. 1997;7(5):439-43.  http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&do… P, Chapuy MC, Dawson-Hughes B, Pols HA, Holick MF. An international comparison of serum 25-hydroxyvitamin D measurements.Osteoporos Int. 1999;9(5):394-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&do… MF. Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr. 2004 Mar; 79(3):362-71.Heaney RP. Functional indices of vitamin D status and ramifications of vitamin D deficiency. Am J Clin Nutr. 2004 Dec;80(6 Suppl):1706S-9S.May E, Asadullah K, Zugel U. Immunoregulation through 1,25-dihydroxyvitamin D3 and its analogs. Curr Drug Targets Inflamm Allergy. 2004 Dec;3(4):377-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&do…

Jim K Sun, 2006-02-12 09:43

Emerging Stratton Protocol 4/2008: a new approach to an old set of problems

Emerging Stratton Protocol 4/2008: a new approach to an old set of problems

Emerging Stratton Protocol 4/2008: a new approach to an old set of problems

Reported by Jim K

A number of dilemmas appear in treating Cpn. As we all know here at Cpnhelp, treating with protein-synthase inhibitors alone induces chlamydial persistence---conversion to the cryptic/persistent form of "aberrant" non-replicating RB's. Infectious EB's still remain in extracellular fluids and tissues to reinfect once antibiotics are withdrawn. The CAP which addresses all three phases has been the answer to this multi-phase nature of Cpn, but it has problems of its own. The biggest problem is the tendency to induce strong reactions to treatment which have been attributed to bacterial release of LPS endotoxin and inflammatory HSP60 endotoxin, and to secondary porphyria. This makes for the additional problem, which is the requirement of a gradual, slow, and long term process of treatment when addressing Cpn infections. There are more potent anti-chlamydials around, but using them kills the Cpn too fast for the body to tolerate resulting in mass apoptosis of infected cells and subsequent organ failure or neutropenia.

Existing CAP protocols have been focused on first halting replication, kill a lot of the RBs and force the rest into non-metabolizing and non-replicating cryptic/persistent form, with the notion that this will stop the progression of the disease. The cryptic Cpn can then be dealt with at one's leisure, gradually over time.

But emerging research has been suggesting that Cryptic Cpn is not benign even if it is not replicating. Cryptic Cpn is essentially a stressed form of Cpn, and stress causes it to generate of Heat Shock Protein (HSP60). HSP60 is many times more inflammatory than LPS endotoxin. LPS endotoxin is the one that causes the fever and chills and is released mostly when RB's are killed and lyse, or when EB's are killed. The inflammation of plaques in cardiovascular disease has been associated specifically with Cpn HSP60 and with the persistent (cryptic) form of Cpn. Inflammation by HSP60 when forcing Cpn into cryptic form may in fact, in Dr. Stratton's current view, be the major cause of so-called die-off reactions. "So-called" because HSP60 is induced not by the bacteria dying off, as the release of LPS is, but rather by the Cpn surviving in a stressed, cryptic form.

Additionally, ongoing disease and tissue damage may be occurring as much from the cryptic form, this is apparently so in heart and lung disease, as it is occurring from replication and sub-optimal cell functioning by infected cells. Autoimmune diseases, for example, also exhibit antibodies to HSP.

Some additional observations have collected together to add to this shift in viewpoint. A medical colleague who has treated Cpn through IV treatments using all the agents for all.

So this new approach is based on inducing existing persistent/cryptic Cpn to convert back to RB form and limit the conversion into persistent/cryptic form by the threat of antibiotic.

Paul Griffith, a non-medical friend researching this whole area, found that supplementing pyruvate might do the trick. Pyruvate may also have other beneficial effects. Basically, this approach uses 6 grams of calcium pyruvate one hour before taking the antibiotics, and an additional 6 grams if needed later for reactions when the antibiotics exert their effect. In theory the first dose of pyruvate encourages the cryptic/persistent form of Cpn to convert back into RB (replicating) form by supplying it with a ready source for generating cellular energy.

In RB form it is:

a) Susceptible to the regular antibiotics and,

b) Can be killed when it is not in "stress" so it is not stimulated into producing and releasing so much the highly inflammatory HSP60.

In essence, you are feeding it until it is comfy and sprawling in its chair at the dining table, and then whacking it upside the head before it can spew its hot sauce at you. I know, a terrible metaphor, but it's the best I could do. You get the point?

In theory this approach should limit turning Cpn into cryptic form by the treatment and make it more directly susceptible to the protein synthase inhibitors (like doxycycline and azithromycin).

In theory, it should also winnow down the cryptic load one has acquired, along with its inflammatory affects, without needing to kill it directly with flagyl. Flagyl would be used to "clean up" persistent/cryptic forms not gotten to by this approach.

Also in theory, the second dose of pyruvate for reactions to the antibiotics should supply the fundamental cellular energy needed to help lower the generation of porphyrins.

Dr. Stratton outlines below the experimental protocol that they have found, in a small subset of cases, to offer less difficult and faster treatment of Cpn. Please remember that this is experimental, and has not been clinically used with a wide array of Cpn related diseases yet, so should not be engaged in without a knowledgeable clinician to monitor treatment.

From Dr. Charles Stratton, 4/24/08

My thoughts on the current Stratton Protocol is that this is a work in

progress, but given what we know now, it would be the following:

NAC 600 mg one a day to test "Chlamydial Load."

If no reaction, go to 1,200 mg twice a day.

If a severe reaction ("Flu-Like" reaction), use low dose prednisone (5 mg per day) for the first few weeks of therapy.

The next step would be two weeks of a macrolide (clarithromycin preferred because of higher levels obtained, roxithromycin, or azithromycin) with 6 grams of pyruvate given 1 hour prior to the antibiotic dose. In addition, 400 mg of Ibuprofen should be taken twice a day along with 1,200 mg of NAC twice a day. For those with severe reaction, low dose prednisone 5 mg per day. For those who get a severe reaction with the pyruvate/macrolide, 3-4 days of low dose prednisone could be tried. Also, using additional pyruvate (3-6 grams) for reaction should be tried.

For those that have a major side effect on the pyruvate/macrolide alone, I'd continue to treat with the macrolide alone until the side effects are manageable. For those that don't, I'd add doxycycline 100 mg twice a day with 6 grams of pyruvate 1 hour before. Continue the NAC and Ibuprofen.

After two weeks of doxycycline if all went well, I'd add metronidazole 500mg twice a day with 6 grams of pyruvate before that. If a reaction is seen.

To the metronidazole, I'd then pulse it until the reactions were manageable.

If minimal reactions, I'd continue therapy for at least 1 year and then recheck titers. If titers were low, I'd add rifampin or rifabutin (preferably), using the rifamycin with pyruvate taken 1 hour before the rifamycin. If no reactions to this, I'd consider the therapy to be complete.

I would continue to monitor titers every several years. If the titers increased, I'd retreat with 6 months of clarithromycin or roxithromycin plus rifabutin plus pyruvate and ibuprofen. I'd continue the NAC for life.

For people on the existing CAP who are being switched:

For those on the current Doxycycline, Azithromycin, Metronidazole, and NAC protocol, my thoughts are that they should first switch from Azithromycin 250 MWF to Clarithromycin 500 mg twice a day (or Roxithromycin) and then add pyruvate

Dr. Stratton adds that Levaquin may be used instead of Clarithromycin for a short period (one month) as it has excellent activity for a short period of time. Clarithromycin = higher levels. Levoquin Both when combined with pyruvate theoretically will provide better killing.

Severe neutropenia among healthy volunteers given rifabutin in clinical trials

Glen Apseloff, MD, Clinical Pharmacology & Therapeutics, December 2003

This is probably why those "big" studies of 6 months of azithromycin showed no lowering of risk of heart disease---it's not caused by the replicating form of Cpn and the idiots never asked a microbiologist about what might kill cryptic Cpn!

Heat shock protein 60 from Chlamydia pneumoniae elicits an unusual set of inflammatory responses via Toll-like receptor 2 and 4 in vivo.

Da Costa CU, Wantia N, Kirschning CJ, Busch DH, Rodriguez N, Wagner H, Miethke T.

Institute of Medical Microbiology, Immunology and Hygiene, Technical University of Munich, Munich, Germany. Eur J Immunol. 2004 Oct;34(10):2874

Effects of Repeated Chlamydia pneumoniae Inoculations on Aortic Lipid Accumulation and Inflammatory Response in C57BL/6J Mice†

Liisa Tormakangas, et al

INFECTION AND IMMUNITY, Oct. 2005, p. 6458-6466 Vol. 73, No. 10

Worsened MRI Findings During the Early Period of Treatment with Penicillin in a Patient with General Paresis.

Zhang SQ, Wan B, Ma XL, Zheng HM.

J Neuroimaging. 2007 Nov 6

Role of Heat Shock Proteins in Protection from and Pathogenesis of Infectious Diseases

Ulrich Zugel and Stefan H.E. Kaufmann

Microbiology Reviews, Jan. 1999, p. 19-39 Vol. 12, No. 1

Ethyl pyruvate: a novel anti-inflammatory agent

M. P. Fink

2007 Blackwell Publishing Ltd Journal of Internal Medicine 261; 349-362

Jim K Thu, 2008-05-08 22:51

Stratton Combination Antibiotic Protocol Update: February 2006

Stratton Combination Antibiotic Protocol Update: February 2006

Dr. Charles Stratton writes: As far as the ideal Cpn Antimicrobial Regimen is concerned, my thoughts (as of 2/06) are as follows: First, as a general rule, the sicker a patient is, the slower they should go. This is why our protocol started out with only one antibiotic and one dose, and then gradually adding the next dose/antibiotic as the reactions to each dose/antibiotic become apparent. These reactions, as you know, can be delayed by days to weeks. I still think that all patients should start with supplements/vitamins before they start any antibiotics. Baseline lab studies, including liver function studies, should be done and these parameters followed every 3-4 months, more frequently when INH is added. Our initial protocol, as you know, recommended this. I would add NAC to the supplements. We used amoxicillin in our regimen as an anti-elementary body agent, but NAC seems to work equally well and may offer additional benefits in boosting the immune system and protecting the liver. As far as supplements/vitamins are concerned, I think David's supplement/vitamin suggestions are very complete and should be the bench mark. Once antibiotics are ready to be started, I would start with a macrolide. We like azithromycin because it is easy to give and has become somewhat cheaper since it went off patent. I would still give just one 250 mg azithromycin tablet and then wait two weeks to see if there is any reaction to it. Then I would give two tablets, one on Monday and one on Wednesday. Once again I would wait two weeks. I'd continue in this way, adding each dose until the patient was taking 250 mg of azithromycin MWF. If the patient has severe reactions (meaning they can't work - most people are trying to work and take care of a family while they are on this therapy), I'd slow down the process. After the azithromycin, I'd add doxycycline - again doing this very slowly. Once the patient was taking both azithromycin and doxycycline, I'd start the metronidazole pulses - again, doing these slowly and working up to a once a month pulse. Once the patient could do the monthly pulse of metronidazole, I'd add rifampin, 150 mg BID. Once this was tolerated, I would add INH 300 mg QD to the metronidazole pulse, doing so slowly (i.e. pulsing both the metronidazole and INH together, Ed.). Once a patient could do this regimen without any reactions, I would continue it for at least a year and probably three for MS. It might take a year or two (or longer) to get to the point where there is no reaction to the metronidazole/INH pulse, depending on the chlamydia load, followed by 1-3 years of therapy. This might be a 5 year program, but should allow the patient to continue to work with minimal disruption. They, as you know, should also be gradually improving during this time. The sicker the patient is, the longer the therapy is going to be. There is no shortcut. With MS patients, due to the possible CNS damage that might occur by going slowly, I would move more quickly unless there were major reactions. This means compressing what might have taken a year into several months. (Ed note: David Wheldon has written his concurrence with this, "I think Chuck's update is excellent: it's clear in matters of detail. Where MS is rapidly progressive, and I know from experience that it can progress frighteningly fast, I too would speed things up with the protein-synthesis inhibitors, paying the price of reaction for stopping progression.") As you can see with Cpnhelp.org, the reactions patient have are varied - some are severe enough that they stop the antibiotics. That, of course, defeats the purpose of the therapy. It is very tricky and each patient needs to learn their own limitations. Cpn.help is very useful in providing support. When we started this, we were thinking of a hotline to answer questions that are now easily and better answered via the internet. Finally, I don't think this is the only regimen that will work nor do I think it will work better or faster. It is just what I would do in 2006 if I were treating a patient. Take care,-Chuck Stratton MD

Jim K Tue, 2006-02-07 21:08

B-12 Deficiency in Cpn Infection: Dr. Stratton's 2005 recommendations

B-12 Deficiency in Cpn Infection: Dr. Stratton's 2005 recommendations

As I could not find this in the current Handbook, I thought I'd create it's own page so it is more easy to locate! This is from a treatment handout created by Dr. Stratton in 2005, but the information is still relevant:II. THERAPEUTIC REGIMEN FOR VITAMIN B12 DEFICIENCY     Many patients with systemic/chronic chlamydial infection appear to have a subtle and unrecognized vitamin B12 deficiency at the cellular level. This functional B12 deficiency can be documented in an individual patient by obtaining both a vitamin B12 level (usually normal or low) and serum homocysteine and methylmalonate levels (one or both of these metabolites will be elevated). This vitamin B12 deficiency can corrected by high-dose vitamin B12 therapy as follows:1. Vitamin B12 Therapy Prior to Chlamydial Therapy     Adults normally have approximately 3,000 mcg of vitamin B12 in body stores, mostly in the liver. Initial vitamin B12 therapy before chlamydial therapy includes replacement therapy for any vitamin B12 deficit in these body stores. Therefore, over the first several days of antiporphyrin therapy, 6,000 mcg of parental (intramuscular or subcutaneous) vitamin B12 is given. For each of the next 3 weeks, 6,000 mcg of parental vitamin B12 is given once per week.2. Vitamin B12 Therapy During Chlamydial Therapy    Chlamydial antimicrobial therapy is associated with increased need for vitamin B12. Therefore, 6,000 mcg of parental vitamin B12 (3,000 mcg in each anterior thigh) is given once per week while the patient is receiving antimicrobial therapy for systemic/chronic chlamydial infection. This is in addition to the 5,000 mcg of sublingual vitamin B12 taken three times each day.3. Vitamin B12 Therapy Post Chlamydial Therapy    Following the completion of antimicrobial therapy of systemic/chronic chlamydial infection, the vitamin B12 and serum homocysteine/methylmalonate levels should be rechecked. If the methylmalonate level remains elevated, it suggests a continued vitamin B12 deficiency. Oral therapy with 5,000 mcg of sublingual cobalamin three times per day should be continued. After several months, 6,000 mcg of parental vitamin B12 may be given as a therapeutic trial. If the patient’s energy is not increased by the parental dose, continued therapy with sublingual vitamin B12 is probably adequate. Periodic trials of parental vitamin B12 can be used to assess the sublingual therapy.See the following note and web site for additional information on B12. Sublingual B12 can be obtained from <puritanspride.com>.Below is an introduction from the article: "Vitamin B12: Surprising New Findings" by Terri MitchellThe whole article can be found at: http://www.lef.org/magazine/mag2000/dec2000_report_b12_1.htmlFor years, vitamin B12 languished as the vitamin that cures anemia. Hardly any research was done into what this vitamin could do for non-anemic people. It turns out that it may do a lot. New studies show that the right amount of B12 can protect against dementia, boost immune function, maintain nerves, regenerate cells and more. B12 is in the news because it lowers homocysteine and protects against atherosclerosis. It's also vital for maintaining methylation reactions that repair DNA and prevent cancer. One of the crucial areas for B12 is the brain. It's not surprising that people with B12 deficiency develop mental disorders. The vitamin is crucial for the synthesis or utilization of important neuro-factors including monoamines, melatonin and serotonin. In addition, B12 is absolutely critical for the function and maintenance of nerves themselves. B12 is needed for methylation reactions that maintain these cells, and enable them to function. B12 contributes to brain function by lowering homocysteine. Homocysteine is a toxic by-product of methionine metabolism that can damage neurons. Importantly, homocysteine interferes with the methylation reactions critical for brain function. Studies show that people with elevated homocysteine can't think. 

Jim K Mon, 2007-12-24 21:44

Dr. Stratton Answers Some Questions:

Dr. Stratton Answers Some Questions:

In some recent correspondance with Dr. Stratton at Vanderbilt University, he kindly answered some of the questions which had formed as I've understood more about the combination antibiotic protocol and about Cpn. From the patient's perspective I wanted to correlate some observations about treatment reactions with his deeper understanding about the biology of the Cpn. I'll list the questions I put to him, and then his generous response below.1.  In an earlier correspondance you had mentioned pulsing the INH band metronidazole together.         * Why do that rather than take it continuously?        * My understanding is that INH is one of the anti-replicatives, and the point is to use these continuously to drive the bug into the cryptic phase where it will be obliterated by the flagyl/tini. Does INH act differently than the other antireplicatives?        * I also understood that we use a dual abx to prevent developing resistance. Why can we use INH alone without developing resistance? 2. Although doxy/azith/mino and the other antireplicatives are not supposed to kill Cpn, only inhibit it's replication, clearly everyone with any kind of bacterial load reports a die-off reaction as they start these agents. People commonly note some agents as causing more die-off than others, azith for example seems to create more die-off than doxy. This could, of course, be an inexact measure of immunomodulatory action or it's lack, but azith is definitely immunomodulatory. My experience and others on the site say that it generates more die-off. What do you think this die-off is from? Do the antireplicatives also kill Cpn? 3. About flagyl and energy increase: Although often this agent creates a more challenging die-off reaction, it can also result in a burst of energy and reduction in brain fog. The liberation of energy and brain fog after (sometimes during) pulses suggests to me that the so called "non-metabolizing" or "dormant" image of the cryptic phase is incorrect. If cryptic Cpn wasn't stealing host energy or gumming up the machinery in some way, it should not have such an energizing effect to kill it. After all, flagyl isn't killing the RB's which we know are actively using host ATP.JimK 

 Dr. Stratton responds:

Here are some of my thoughts on your questions. First of all, remember that Cpn is able to shift to different phases in its life cycle. In order to eradicate the organism, you have to deal with all three phases and, I believe, you have to deal with them simultaneously. For example, INH alone does not eradicate Cpn from a cell culture, INH plus metronidazole does not eradicate Cpn from a cell culture, but INH plus metronidazole plus penicillamine does eradicate Cpn from a cell culture. (NAC does the same as penicillamine.) So, Stratton Rule Number One is that the best effect is going to be when all the antibiotics are present. It doesn’t mean that you have no effect if all are not present, just that the best effect is when all are present. One combination that we tried years ago was INH, Bactrim, and Amoxicillin (i.e., penicillamine). People got better while on the drugs, but relapsed when they were stopped, even after years of therapy. Therefore, Cpn was not eradicated. My educated guess would be that INH is more potent, but physicians are not happy prescribing INH. By the way, the most potent combination (in the original studies described in the patent materials) was metronidazole, INH, and penicillamine (NAC does the same thing.). My thoughts would be to pulse INH along with the metronidazole, starting slowly (1 pill at a time) so as to reduce the side effects. As long as you are also taking NAC, the metronidazole/INH pulse should root out Cpn very effectively. Again, the average physician is probably unwilling to do this. Because INH is known to have hepatotoxicity and physicians feel uncomfortable using it and thus must obtain monthly liver function tests when using it. This suggests to me that a pulse would be better (less risk of liver toxicity unmonitored), and if the best effect is when the metronidazole is present, that is when the pulse should be done. Now, on the resistance issue: INH is a prodrug and is converted to the active drug, a free-radical,  by catalases/peroxidases – which may be supplied by the pathogen or perhaps by the cell, if the cell is a monocyte/macrophage. Metronidazole is also a prodrug and is converted by electrons to the active drug, a free-radical. Free-radicals damage DNA/RNA and can destroy the pathogen and in some cases the host cell. Although it does happen, resistance to free-radicals is much less likely to occur. Why the antireplicatives create die-off-Moreover, Cpn can prevent apoptosis (natural cell death), a cell mechanism to deal with intracellular pathogens. When Cpn is shut down by macrolides or tetracyclines and can’t make the proteins that prevent apoptosis, apoptosis can happen and the cell dies. The more cell death, the more side effects. Finally, Cpn-infected cells are protected from additional Cpn entering the cell and causing more infection in the same cell. When infected cells are cleared, they can then be re-infected if elementary bodies are nearby. This is why a reducing agent such as NAC is so important as they eliminate the elementary bodies. Re-infection is why we like rifampin, which prevents the re-infection as it targets the DNA-dependant RNA polymerase – elementary bodies need this enzyme to transform to a reticulate or cryptic body.Also, both the replicating phase and the cryptic phase may be stealing ATP – but the cryptic phase may also have anaerobic metabolism at work and thus be generating ATP as well. It’s all very complicated and much is theoretical. Hope this helps. Take care.-Chuck Stratton, M.D. 

Jim K Mon, 2006-01-30 22:13

Dr. Stratton Cautions on Protecting the Liver

Dr. Stratton Cautions on Protecting the Liver

In recent correspondence, Dr. Stratton has been discussing reports in the medical literature that certain antibiotic agents can cause liver damage or failure. Noting that these agents are typically the most potent anti-chlamydials, he has drawn some important hypotheses from this that anyone on an antibiotic protocol should know about.His cautionary note is that use of some of the new, powerful agents against Cpn must be carefully monitored, and that a more gradual treatment for many is advisable. His observations also affirm the importance of supplements in their liver-protective role.Dr. Stratton notes:"A recent report of Ketek causing liver failure has crystallized some thoughts that I have had for some time. Cpn can infect the liver and the kidney, but in particular the liver is a target due to the Kupfer cells. Any drug that acts against Cpn (including statins) will therefore in some patients cause hepatic damage or even hepatic failure. The better the activity against Cpn of the agent (or combination of agents), the more likely the liver damage. Even penicillamine can cause liver damage, as does Augmentin. "Surprisingly, the only anti-chlamydial agent that did not cause hepatitis in some patients was NAC. In fact, NAC is recognized as being protective. See attached references. My conclusion is that NAC should be the first agent in an anti-chlamydial regimen and should be a constant part of the therapy for this protective effect, not to mention it’s effect against elementary bodies. This, of course, is another reason to go slowly, but liver damage has been seen with only a few days of Ketek, for example. Notice the NAC in the Clarithromycin-induced hepatic injury in the end seemed protective in that transplantation was not needed. I think this caveat needs to be in the therapy Website. Although we have not seen hepatitis in any of our patients at Vanderbilt, soon or later this could happen."Dr. David Wheldon concurs that this is a very important observation by Dr. Stratton, noting that it takes someone of Dr. Stratton’s depth of understanding about Cpn’s affect on body systems to recognize these reports as possibly Cpn related (ie not necessarily toxicity originating from the drug itself). Dr. Wheldon notes that, in addition to NAC, supplements such as Alpha-Lipoic Acid, acetyl-L-carnitine, selenium and zinc, are also important liver protectors. These all have been recommended supplements for people taking a combination antibiotic protocol for Cpn.Dr. Wheldon also noted that in his protocol, recommendations for using agents such as doxycycline, azithromycin and NAC were considered both because of their antichlamydial affect, but are less known for liver toxic. Dr. Wheldon also patterned his protocolo after Dr. Stratton’s early recommendations to start gradually and add to the combination only as patients tolerate die-off. References:Isoniazid- and rifampicin induced oxidative hepatic injury– protection by N-acetylcysteineAttri, S. et alHuman & Experimental Toxicology (2000) 19, 517-522Long-term ethanol administration enhances age-dependent modulation of redox state in different brain regions in the rat: protection by acetyl carnitine.Calabrese V, Scapagnini G, Latteri S, Colombrita C, Ravagna A, Catalano C, Pennisi G, Calvani M, Butterfield DA.Int J Tissue React. 2002;24(3):97-104.Brief Communication: Severe Hepatotoxicity of Telithromycin: Three Case Reports and Literature ReviewKimberly D. Clay, MD, MPH; John S. Hanson, MD; Scott D. Pope, PharmD; Richard W. Rissmiller, MD; Preston P. Purdum III, MD; and Peter M. Banks, MD21 March 2006 | Volume 144 Issue 6 | Carolinas Medical Center, Charlotte Gastroenterology and Hepatology, Carolinas HealthCare System, and Carolinas Pathology Group, Charlotte, North Carolina.Fulminant Liver Failure Associated with Clarithromycin Andreas Tietz, Markus H Heim, Urs Eriksson, Stephan Marsch, Luigi Terracciano, and Stephan Krähenbühl The Annals of Pharmacotherapy_2003 January, Volume 37,  57-60Role of nutritional fatty acid and L-carnitine in the final outcome of thioacetamide hepatotoxicity Sanjay Chanda and Harihara M. Mehendale Vol. 8 October 1994 The FASEB Journal 1061-1068Mitigation of oxidative stress in cyclophosphamide-challenged hepatic tissue by DL-alpha-lipoic acid.Selvakumar E, Prahalathan C, Mythili Y, Varalakshmi P. Mol Cell Biochem. 2005 Apr;272(1-2):179-85.Feeding acetyl-L-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress Tory M. Hagen, Jiankang Liu, Jens Lykkesfeldt, Carol M. Wehr, Russell T. Ingersoll, Vladimir Vinarsky, James C. Bartholomew, and Bruce N. Ames1870 –1875  PNAS  February 19, 2002  vol. 99  no. 4 www.pnas.orgAbrogation of Nuclear Factor-Involved in Zinc Inhibition of Lipopolysaccharide-Induced Tumor Necrosis Factor- Production and Liver Injury Zhanxiang Zhou, Lipeng Wang, Zhenyuan Song, Jack T. Saari, Craig J. McClain, and Y. James Kang*American Journal of Pathology, Vol. 164, No. 5, May 2004

Jim K Tue, 2006-02-07 21:35

Case Reports from the Mitchell, Stratton et al patent

Case Reports from the Mitchell, Stratton et al patent

patent 6,838,552 TABLE 11 Serological and PCRi Responses to Combination Antibiotic Therapy Months of Combination Pa- Titer Antibiotic tient Diagnosisa IgMi IgGi Therapy PCR Status PH FM 800 800 6 months + Asymptomatic 3200 1600 + 800 200 wk+ BL MSi 2000 500 9 months + Dramatic 400 3200 9 months wk+ Improvement: MM CFSi/AND 3200 800 1 month.sup. + Improvement; 400 1600 + Relapse (non- compliant) PM CFS 2000 25 6 months + Asymptomatic 400 800 wk+ AM IBD 800 0 6 months wk+ 90% 3200 400 + Improvement FO MS 800 3200 10 months st+ Improvement 800 800 + in speeds and 400 600 wk+ bowl contin- 400 800 + ence WM CF 25 25 Pre-illness wk+ Asymptomatic 1000 25 serum <-- st+ 50 800 Antibioticsi + 50 1600 start wk+ 50 400 - HM CF 2000 100 6 months + Asymptomatic 3200 3200 + 200 800 wk+ CN CFS 3200 800 8 months + 75% 800 800 wk+ Improvement AN MS/CFS 400 400 wk+ Strength .uparw. 200 3200 st+ Fatigue .dwnarw. JS CFS 2000 2000 5 months st+ Asymptomatic (severe) 2000 2000 + 200 800 - AG IBD 3200 400 9 months + Improvement 800 400 + in joint Sx 800 800 + 800 400 - AT CF 3200 3200 9 months + Asymptomatic 1600 1600 + 1600 1600 + 800 800 + 400 400 + LH RAi 3200 1600 6 months wk+ Improvement 600 400 wk+ 200 50 + HS MS 2000 400 5 months + Improvement 3200 800 + 50 200 - ST CFS/FM >1000 100 7 months wk+ Asymptomatic 1000 100 wk+ 400 100 + 800 3200 + 100 100 + RV CF 1000 100 10 months + Asymptomatic 400 1600 + 400 400 - a CF = Chronic Fatigue < 6 months CFS = Chronic Fatigue Syndromei FM = Fibromyalgiai IBD = Inflammatory Bowel Diseasei MS = Multiple Sclerosisi AND = Autonomic nervous dysfunction (neural-mediated hypotension) RA = Rheumatoid Arthritis IgM >> IgG .fwdarw. immunei tolerance to the antigeni IgG >> IgM .fwdarw. successful immune control of the antigenCAP for Chlamydia pneumonia since 11/04. 25yrs CFS & FMSi- Currently: 300mg INHi, 200 Doxycyclinei, 500mg MWF Azithromycini, 1000mg Tinii daily (Taking a break from continuous protocol) » delete | edit | reply | prune | email this page | write to author | mark as spam - mark as not spam | report as spam

 Even more detailed case

Submitted by Jim K on Tue, 2007-08-21 19:10.  Even more detailed case descriptions in the latter part of Patent: 6,884,784 Response to Antibiotic Therapy Table 13(a) illustrates typical responses to combination antibiotic therapy in a variety of patients with diagnostic evidence of an active infection by C. pneumoniae. Unlike typical immunei responses to infection with infectious agents, most of the included patients have not only detectable IgMi titers against the chlamydial genus but in many cases very high IgM titers. With specific therapy over time the IgM titers generally fall, with a rise in IgGi titer (as expected). Current methods of detecting antibodies against C. pneumoniae (Indirect immunofluoresence, MIF) are incapable of accurately identifying high IgM titers against C. pneumoniae. Moreover, current procedures are genus specific and not species specific as are peptide-based ELISAs. With clearing of the pathogen, the IgG titers fall. Concomitant with combination antibiotic therapy, there is generally an improvement of patient symptoms associated with the specific diagnosis indicative of evidence of an active chlamydial infection. Table 13(b) describes the course of therapy for a number of individuals treated with a combination of agents and their clinical outcomes. Table 13(c) describes the detailed case histories of the patients undergoing combination therapy, as reported in Table 13(b). Table 13(d) provides a listing of drugs and standard dosages for those used herein. TABLE 13a Serological and PCRi Responses to Combination Antibiotic Therapy Pa- Diag- Titer Time on tient nosisa IgM IgG Therapy PCR Status PH FM 800 800 6 months + Asymptomatic 3200 1600 + 800 200 wk+ BL MSi 2000 500 9 months + Dramatic 400 3200 wk+ Improvement MM CFSi/ 3200 800 1 month + Improvement; AND 400 1600 + Relapse (non-compliant) PM CFS 2000 25 6 months + Asymptomatic 400 800 wk+ AM IBD 800 0 6 months wk+ 90% Improvement 3200 400 + FO MS 800 3200 10 months st+ Improvement in 800 800 + speech and bowel 400 800 wk+ continence 400 800 + WM CF 25 25 Pre-illness wk+ Asymptomatic 1000 25 serum st+ 50 800 <--Anti- + 50 1600 biotics wk+ 50 400 start - HM CF 2000 100 6 months + Asymptomatic 3200 3200 + 200 800 wk+ CN CFS 3200 800 8 months + 75% 800 800 wk+ Improvement AN MS/ 400 400 wk+ Improved Strength CFS 200 3200 st+ Fatigue decrease JS CFS 2000 2000 5 months st+ Asymptomatic (severe) 2000 2000 + 200 800 - AG IBD 3200 400 9 months + Improvement 800 400 + in joint Sx 800 800 + 800 400 - AT CF 3200 3200 9 months + Asymptomatic 1600 1600 + 1600 1600 + 800 800 + 400 400 + LH RAi 3200 1600 6 months wk+ Improvement 800 400 wk+ 200 50 + HS MS 2000 400 5 months + Improvement 3200 800 + 50 200 - ST CFS/ >1000 100 7 months wk+ Asymptomatic FM 1000 100 wk+ 400 100 + 800 3200 + 100 100 + RV CF 1000 100 10 months + Asymptomatic 400 1600 + 400 400 - a CF = Chronic Fatigue < 6 months, CFS = Chronic Fatigue Syndromei, FM = Fibromyalgiai, IBD = Inflammatory Bowel Diseasei, MS = Multiple Sclerosis, AND = Automatic nervous dysfunction (neural-mediated hypotension), RA = Rheumatoid Arthritis IgM >> IgG: immune tolerance to the antigeni; IgG >> IgM: successful immune control of the antigen TABLE 13b Treatment Regimens Treatment Regimen Phase of Chlamydial Life Cycle EBi (Extra- or EB->RB Stationary Replicating RB->EB Duration Patient Sex Diag Intracellulari) Transition Phase RB RB Transition Enhancer (months) Comments BL M MS Rifampin Flagyli Floxin 2 Flagyl Bactrim, 5 Levaquin -- -- -- -- -- 3 Took a break, had relapse Flagyl Bactrim, 2 Levaquin Penicillimine Flagyl Bactrim, Penicillimine 7 Levaquin Penicillimine Rifampin INHi INH Penicillimine Probenicid 3 MC M MS Rifampin INH INH 9 Flagyl Levaquin 6 Probably not compliant Minocyclinei -- -- -- -- -- -- Discontinued JM M MS Flagyl Floxin 7 Bactrim Minocycline Amoxicillini Levaquin Amoxicillin 4 Bactrim Amoxicillin Levaquin Amoxicillin Probenicid 3 Bactrim LL F MS Flagyl Levaquin 15 Minocycline Penicillimine Levaquin Penicillimine Probenicid 1 Minocycline AN F MS Tenitizole Floxin 7 She was given a copy of the protocol, but ran her own therapy FO M MS Prednizone 0.25 Phased in over several days to mitigate effect of therapy Flagyl Biaxin 2 Biaxin 1 Stopped flagyl due to persistance of side effects Kemet Biaxin Kemet 0.5 Kemet Flagyl Biaxin Kemet 6 Began phasing Flagyl back in over a month Kemet Flagyl Biaxin Kemet 1 Began 2 week switchover to Amoxicillin Amoxicillin Amoxicillin Amoxicillin Flagyl Biaxin Amoxicillin 2 Amoxicillin Flagyl Biaxin Amoxicillin Probenicid 6 Began 6 week phase in of probenicid JC F MS Amoxicillin Amoxicillin 1 Phased in over 7 months. Amoxicillin Amoxicillin Probenicid 1 Amoxicillin Bactrim Amoxicillin Probenicid 1 Amoxicillin INH Bactrim Amoxicillin Probenicid 7 FW M MS Penicillimine Flagyl Doxicycline Penicillimine 7 Penicillimine INH INH Penicillimine Probenicid 5 Bactrim -- -- -- -- -- -- Stopped treatment LH F RA Penicillimine Flagyl Minocycline Penicillimine 11 Penicillimine Flagyl Minocycline Penicillimine Probenicid 3 -- -- -- -- -- -- 3 PCR negative, symptom free, but titer @ 1:800. Decided to stop. Penicillimine Flagyl Minocycline Penicillimine Probenicid 2 After symptoms flared, PCR went positive, and titer to 1:1600, restarted therapy XX F IC Amoxicillin INH INH Amixicillan Probenicid 4 Symptoms gone after 4 Bactrim months of treatment NC F PG Amox INH INH Amoxicillin 7 Continued improvement Bactrim CH M PG Amoxicillin INH INH Amoxicillin 3 Levaquin Amoxicillin INH INH Amoxicillin 2 Bactrim -- -- -- -- -- -- Discontinued after all ulcers cleared up except for those in poorly blood-supplied leg RI M PG Missing patient chart PL M PG Amoxicillin INH INH Amoxicillin 2 Non-compliant because Bactrim could not afford medicines -- -- -- -- -- -- 1 Amoxicillin INH INH Amoxicillin 0.5 Would often only take what Bactrim he had left. -- -- -- -- -- -- 2 Off for 2 months, then flared Amoxicillin INH INH Amoxicillin 1 No subsequent follow-up Zithromaxi TW M PG Flagyl Minocycline 4 Amoxicillin INH INH Amoxicillin 2 Levaquin -- -- -- -- -- 1 Amoxicillin Levquin 4 No improvement -- -- -- -- -- Moved to topical antibioticsi AM M UC Flagyl Biaxin 11 Amoxicillin Flagyl Biaxin Amoxicillin 2 INH INH Amoxicillin Flagyl Bactrim Amoxicillin Probenicid 5 Now doing very well INH INH AG F UC Flagyl Doxycyclinei 6 -- -- -- -- -- -- Discontinued after symptoms resolved. DM F IBD Flagyl 7 Cupramine1 Flagyl Doxycycline Cupramine Probenicid 5 -- -- -- -- -- -- Discontinued after doing well clinically; wanted to start a family. RP F UC Flagyl Biaxin 5 -- -- -- -- -- -- Discontinued after impvt AB F CD Flagyl Doxycycline 7 -- -- -- -- -- -- Non-compliant EU F UC Flagyl Doxycycline 9 -- -- -- -- -- -- 1 Stopped Amoxicillin Flagyl Doxycycline Amoxicillin Probenicid 2 Restarted after symptoms flared. Now doing well again RR CD Flagyl Doxycycline 2 Colectomy 2 months prior Amoxicillin Flagyl Doxycycline Amoxicillin Probenicid 6 Now doing well; no evidence of active disease 1 125 mg BID TABLE 13c Detailed Case Histories Patient Diag Test data1 Case History BL MS Row 2 First symptoms began with numbness of the left arm and leg which rapidly progressed to a partial Brown-Sequard syndrome (i.e.-cord myelitis) with an associated urinary retention. Despite therapy with corticosteroids, and Beta interferon he rapidly progressed over the next three months with an EDSS - 8.0 (triplegic plus speech and swallowing impairments). A positive CSF PCR and culture for C. pneumoniae led to treatment with combination antibiotics. The patient improved on all spheres of neurologic function over the following six months. HIS EDSS score 9 months later was 3.0 with return to work and routine athletic activities (e.g.-jogging). His neurological status remains stable and he continues on an anti-chlamydial combination regimen. MC MS This patient had a ten year history of MS with evidence of progressive ataxia and weakness in the legs. Over 5 months his EDSS score worsened from 7.0 to 8.0. His CSF was positive by PCR for C. pneumoniae and he was placed on combination antibiotics. Over the next six months he gradually improved in his balance, coordination and lower extremity strength. His most recent EDSS score was 6.5. JM MS Initially seen with rapidly progressive paraparesis secondary to MS. He failed to response to corticosteroids on two successive occasions. Five months later, his EDSS score was 7.5. Following a positive C. pneumoniae PCR he was placed on combination antibiotics. He has gradually gained strength in his lower extremities and five months later was able to walk with a walker (EDSS = 6.5) while being maintained on combination antibiotics. LL MS Patient with a long history (14 years) of secondary progressive MS with recent progressive bulbar symptoms, axtaxia, and paraplegia (EDSS = 8.5). PCR for the MOMP gene of C. pneumoniae in the CSF was positive. She was placed on combination antibiotics with no further progression of symptoms for the last six months. AN MS Row 10 Long history of MS and wheel chair bound for approximately ten years. She has received continuous physical therapy to retain leg muscle tone. Following approximately 6 months of combination antibiotics, she was able to stand unaided and take several unaided steps. She reports a significant decrease in fatigue and cognitive dysfunction. She remains on combination antibiotics and other supportive medications. FO MS Row 6 Wheel chair bound with a long history of MS with a 2-3 year progression of severe dysarthriae and incontinence. On combination antibiotics (14 months) he has had improvement of speech and incontinence. Speech, ability to open mouth for dentist, stamina all improved. Can stand better on his own mid- transfer. He remains wheel chair bound. JC MS Diagnosis of MS with development of a foot drop approximately one year prior to therapy requiring the use of a cane in walking. Approximately four months after initiation of combination antibiotic therapy, patient reports reversal of foot drop and no longer requires a cane. She continues on antibiotic therapy. FW MS Male executive in late 50s with a year history of MS. Used a cane for a rolling, unstable gait. Easily fatigued: After 12 months of combination antibiotics, was able to walk without cane or excessive fatigue, although his gait can still wander. Can easily make it across the parking lot, which had previously been a challenge. Stopped antibiotics even though was still PCR positive; plans to restart therapy if he has another flare-up. LH PA Row 14 Patient LH had an active case of RA which was moderately debilitating. Following two months of combination antibiotic therapy, her RA is in complete remission. XX IC She responded to combination antibiotics with complete remission of symptoms after one month. Cessation of antibiotics resulted in a return of IC symptoms. NC PG PCR + 61 year old man who had had lesions for several years. Large ulcerated lesions on feet that resolved on combination antibiotic therapy. Only residual hypertrophic scars remain. CH PG PCP + 75-year-old male diabetic with multiple, large, severe lesions on both legs, abdomen, and arms. Lesions first formed in 1993. Severity of process required chronic nursing home care at an estimated cost of $300-400 per day. All lesions above the knee have resolved on combination antibiotic therapy: lesions only remain on right lower leg, where inadequate blood supply offers poor prognosis. The patient no longer requires nursing home care. RI PG PCR + Original severe PG lesions on legs required bilateral amputation. Lesions now occurring on arms. Treatment with combination antibiotics has resulted in resolution of lesions although not complete to date. [No update - chart missing] PL PG PCR + 18 year old female with history of leg ulcers. Multiple PG lesions completely healed on combination antibiotic therapy. Patient then lost his job and could not afford to maintain drug regimen. Upon re-flaring of ulcers, re-started therapy and ulcers improved again. TW PG Severe PG, initiated after a chemical burn in 1991, but with PCR negative serologyii for C. pneumoniae. Patient did not initially respond to combination antibiotic therapy. A positive biopsy culture for C. pneumoniae resulted in the recent re-institution of combination antibiotics. However, after no improvement, patient went off therapy. AM IBD Row 5 This is a 35 year old male who first presented as a prostititisi ten years ago at the age of 25. This progressed to acute ulcerative colitis, involving the entire colon, which was associated with severe arthritis, iritis, and weight loss. Diagnosis was biopsy confirmed. Control required high doses of corticosteroids and azacol. Attempts to reduce steroids resulted in partial control of symptoms. Six months prior to initiation of combination antibiotic therapy, patient was experiencing frequency (20-25 times per day), frank bleeding, and mucus in the stool. Patient on combination antibiotics for one year. Following significant stress, patient had significant increase in symptoms. Alteration of antibiotic combination has resulted in normal bowel habits with no mucus and minimal blood. Associated neuropsychiatric manifestations of cognitive dysfunction and depression have resolved. Steroids have been discontinued. AG IBD Row 12 This is a 27 year old white female with two month history of fulminate, progressive ulcerative colitis which had not responded to the usual medical therapy. A total abdominal colectomy with ileostomy and rectal pouch was done. The microscopic appearance confirmed ulcerative colitis. Following the colectomy, the patient experienced neurologic symptoms, fatigue, myalgias, arthralgias, and a acneoform skin rash. Serology was performed for C. pneumoniae and was positive with an IgM of 1:3200, IgG 1:400, and PCR positive. Therapy with combination antibiotics was initiated. After six months of antimicrobial therapy, her serology was IgM 1:800, IgG 1:400, and PCR positive. The neurologic symptoms, fatigue, myalgias, arthralgias, and acneoform rash resolved completely. There was no further evidence of inflammatory bowel disease, and the ileostomy was successfully anastomised to the rectal stump. The patient has felt more energetic. Serology after 1 year was PCR negative. DM IBD This 37 year old female had a six year history of inflammatory bowel disease (uncertain CD or UC) associated with painless rectal bleeding, arthritis, myalgias, skin ulceration, abdominal cramping/diarrhea, and rectal fistulas. She had increasing fatigue which caused her to frequently miss work as a minor executive. On combination antibiotic therapy, all symptoms resolved but recurred with cessation of antibiotics while on vacation. Reinstitution of combination antibiotics resulted in a second remission of symptoms. Prior to combination antibiotic therapy, she had not gone longer than 3 months without an anal manifestation of IBD. She has been symptom free of IBD for over a year. RP IBD Patient presented with proctocolectomy and ileostomy due to UC. Following a flu-like illness in 1993, she became fatigued and anemic with blood-tinged diarrhea. Examination of her ileostomy pouch revealed inflammationi and ulcerations. Upper GI series/small bowel series revealed no abnormalities and no cause of her anemia was diagnosed. On combination antibiotics her ileostomy activity was more regular and less spastic. She claimed to feel better with higher energy levels and ceased antibiotic therapy. Six months post- antibiotic therapy she remained asymptomatic other than a moderate anemia. AB IBD Patient with long history of CD involving small bowel, large bowel, and anus. She had been treated with a small bowel resection and fissurectomy. She continued to suffer from numerous rectal fistulas. On combination antibiotics she experience some symptomatic improvement but failed to completely resolve her IBD symptoms. She discontinued antibiotics due to a probable chronic Herxheimer reaction. Currently she is lost to follow-up. EU IBD Colitis with inflamed distal sigmoid colon and proctitis associated with frequent loose stools with significant mucus. Following six weeks of combination antibiotic therapy with a significant reduction in symptoms. Shortly after cessation of antibiotics her symptoms return. Reinstitution of antibiotics resulted in a second remission of the majority of her symptoms with resolution of her proctitis on visual exam. NM CFS Vanderbilt University initial patient that resulted in our first association of C. pneumoniae, initially complained of the insidious onset of debilitating fatigue. This was associated with a severe cognitive dysfunction that disrupted his ability to function as the supervisor of a clinical diagnostic laboratory. Despite six months of intensive diagnostic efforts by the Infectious Disease Clinic at Vanderbilt no definitive or presumptive diagnosis could be made. A subsequent high antibody titer against C. pneumoniae led to standard anti-chlamydial antibiotic therapy over a three month period with gradual disappearance of fatigue and cognition symptoms. On cessation of a fluroquinolone antibiotic, symptoms returned within two weeks. He was placed on combination antibiotics with complete reversal of symptoms after six months. He remains asymptomatic. JS CFS Row 11 Academic physician with a greater than 10 year history of CFS. Cognition problems resulted in his grounding himself as a private pilot. Initial treatment with combination antibiotics results in an apparent Herxheimer reaction with resolution over a two week period with gradual improvement in symptoms. After three months therapy, he piloted a light aircraft under instruments from Florida to North Carolina. He remains on combination antibiotics for over a year and is asymptomatic. PM CFS Row 4 Physician with long-standing CFS. Treated with combination antibiotics with gradual resolution of symptoms. During course of treatment developed cardiac myopathy. Currently asymptomatic from CFS. Cardiac myopathy resolved over six month period on combination antibiotics. MM CFS Row 2 CFS and AD. Resolution of postural tachycardia over 1 month combination antibiotic therapy. Partial reversal of fatigue during this period. Patient non- compliant after one month and lost to follow-up. PH FM Row 1 Three year history of debilitating FM following the stress of being a stalking victim. Patient relatively asymptomatic after nine months combination antibiotic therapy. CN CFS Row 9 Five year history of severe CFS with debilitating cognitive dysfunction and depression. Gradual improvement on combination antibiotics for approximately nine months. Estimated 75% of normal function. PG CFS Ten year history CFS with cognitive dysfunction. Complete response to combination antibiotics over a course of one year. AT CF Row 13 Moderate fatigue and cognitive dysfunction following acute infectious illness. Depression was major problem. During one year course of combination antibiotics fatigue and cognitive dysfunction largely reversed. During mid- course of therapy patient developed acute anxiety attacks relieved by anti- porphyrin therapy. WM CF Row 7 CF following acute stress. Pre-illness serum negative for anti-Chlamydia pneumoniae antibodies which peaked six weeks following stress. Pre-illness PCR was weak positive that became strongly positive. On combination antibiotic therapy at 3 months became asymptomatic. Cessation of antibiotics resulted in symptomatic relapses. Currently asymptomatic with low serum antibodies and negative PCR. HM CF Row 8 Medical student with short history of CF and cognitive dysfunction affecting studies. Combination antibiotics over a multi-month course resulted in complete reversal of symptoms. ST CFS Row 17 Mother of Patient AT. Three year history of CFS with FM. Combination antibiotic therapy has resulted in partial reversal of symptoms allowing her to retain a job in jeopardy. Estimated 80-90% normal function currently. RV CF History of fatigue although non-incapacitating. Combination antibiotic therapy has resulted in 100% return to normal function. EB CFS Teen-ager with long history of CFS resulting in home-bound schooling. On combination antibiotic therapy returned to school and recently graduated. Recovery has not been complete probably secondary to non-compliance in therapy.

Jim K Wed, 2007-08-22 22:06

Dr. Michael Powell: A Rheumatologist Treating Cpn in CFIDS, FM, Lupus and other "auto immune" disorders

Dr. Michael Powell: A Rheumatologist Treating Cpn in CFIDS, FM, Lupus and other "auto immune" disorders

I spoke with a rheumatologist in California, Dr. Michael Powell, who is cautiously using a combination of antibiotics in conjunction with standard therapeutics for the treatment of nanobacterium (including Cpn) in patients suffering from FM, CFS and autoimmune disorders. His results with this treatment program have been encouraging. He faxed me some examples of patient feedback forms, excerpts from which you can see below. Recovery is not instantaneous, but tends to occur over a 6 to 12 month period. The graphs of subjective improvement are drawn from visual analogue scores compiled during each visit. When summarized in this manner these data give a time-lapsed impression of the response to treatment. One of the interesting things he mentioned was in relation to negative patient serology for Cpn when other clinical signs lead him to suspect some involvement. Serologic assays for IgG, IgM and IgA are sent to confirm infection prior to treatment. He would like to see a positive serology in patients before engaging them in a combination antibiotic protocol, but recognizes that patients may not have antibody reactions. This may be due to the ability of intracellular organisms like Cpn to evade a humoral response (antibody production), immunoglobulin depletion, or other factors. In these cases, when there is a high index of suspicion for the infection without a humoral response, he tests the spouse of the partner for Cpn. He sees the "non-symptomatic" partner as a good indicator of Cpn in the patient, given the infectious nature of Cpn. Thus far, most spouses are positive when an ill family member is non-reactive. In our discussion Dr. Powell pointed out the many similarities between TB and Cpn.  Both organisms  can evade our immune system.  Both organisms can be carried from the lungs, the original site of infection, and infect other tissues. Both require prolonged treatment with multiple drugs to eradicate the infection.  Both are sensitive to stress levels. Optimal therapy is being evaluated at various research centers and new medications for Cpn are on the horizon (see activbiotics.com). INH and supplements for endotoxins- Dr. Powell finds most patients improve on a standard combination antibiotic protocol for Cpn. Rheumatologist have apparently been using doxycycline for many years with success for inflammatory arthritis but there is evidence that using doyxcycline in combination with rifampin is even more effective. Some patients plateau after about 8 months of treatment he has found variations in the treatment protocol have made a difference. One protocol he uses involves the use of NAC 600 mg twice daily, INH 300 mg once daily before breakfast, and metronidazole 500 mg twice daily pulsed with 5 days on and two weeks off.  It is essential to start each agent separately and gradually increase the dose over weeks or months as tolerated.  The use of Vitamin C 500 - 1000 mg four times daily (the half life of vitamin C is 30 minutes and little remains after 3 hours) to offset the release of toxins during therapy.  B6 is important to control INH related peripheral neuropathy.  Monthly laboratory evaluation of AST, ALT, Cr, and CBC are recommended for all who engage in this protocol.  It is not uncommon for liver enzymes to show a mild elevation during the initial stages of treatment.  Antibiotic therapy should be temporarily discontinued during periods of toxicity, should it arise. He emphasized the importance of insuring that yeast and fungal infections do not overgrow during protracted antibiotic use. He recommends the use of acidophillus, nystatin, diflucan, oregano oil, and/or grapefruit seed extract as needed to prevent secondary opportunistic infection during treatment. Covering for the possibility of yeast and fungal overgrowth during antibiotic therapy is essential.  If diarrhea develops, stool must be evaluated for antibiotic associated diarrhea (C. difficile).  This is not a simple protocol and it is best if it is guided by an experienced clinician who is familiar with the medications and methods of minimizing toxicity related to killing the nanobacterium. A link to Dr. Powells clinic may be found on our links page. Dr. Powell does do telephone consultations by arrangement and may be a resource for those who have had difficulty finding a Cpn knowledgeable doctor in their area. He requires an initial visit with a physical examination before initiating therapy (lab work can be performed prior to the initial visit to facilitate diagnosis and treatment), and monthly laboratory testing with monthly phone consults are then the norm. Treatment of related hormone imbalances in the thyroid system and nutritional support, temporary antidepressant support as needed, and sleeping medications are useful adjuncts to the antibiotic protocol. It is necessary for patients to have a primary care physician to monitor health matters that are unrelated to FM, CFS and autoimmune disease.  65 year old patient52 year old patient 39 year old patient 

Jim K Sun, 2005-11-06 16:33

Comments on CAP variations from Dr. Michael Powell

Comments on CAP variations from Dr. Michael Powell

I asked Dr. Powell to comment directly on concerns that have been mentioned over time as to whether he uses the CAP with his new patients. I received his response a number of weeks ago but have had no time to put it together in a cogent context. But continued posts on these questions has mobilized me to get his comments to our readers here. But context is, as we say, everything. A problem with reading posts on a website such as www.cpnhelp.org is that one does not really have the whole context of that particular person's illness, medical history, the complexity of what is happening in their body as a result of more and more systems being affected by more than one thing going on. While it is perfectly fitting that our site here has it's mission focus of treating Cpn via combined antibiotic (and other relevant antichlamydial agents such as Vitamin D, tocotrienols, etc.), a physician is treating, hopefully, a patient rather than a bacterium. I'm a clinician myself, although a psychologist rather than a physician. One of the things that becomes clear is that the particular clinical population one sees, the kind of clinical practice you have, shapes your understanding of what's needed in order to help people. If you are curious and growing as a professional, you are always learning from the particular complexity of what you see in your patients: what helps them, what doesn't; how general approaches fit and don't fit; and how you need to go beyond the standard approach to respond to what's real, where the standard prescriptive algorithms "You must always do these things and these things only..." fails utterly to help those you must care for.A doctor who sees mostly patients with neurological problems related to chronic infection as from Cpn will get attuned to how those conditions respond and to the complex interactions of treatment with the rest of the person's health process. A physician who sees rheumatological patients learns what works well and what doesn't in that population, and the nuances of attuning treatment to the whole spectrum of patients, even to see the difference of patients who have the same disease label. A physician who sees a lot of complicated cases has two options as a professional. One is to learn to think more broadly and reject the formulaic, in order to account for and encompass, that complexity. The other is to narrow their viewpoint to the accepted practice and say, "Well I do this, I don't know about those other things." The latter is perfectly acceptable to my thinking, as we all need to know our professional limits. But I thank God for those who are willing to grasp the former position, such as Dr. Stratton, Dr. Wheldon, and Dr. Powell amongst others, and dig deeper into things. You see, I'm one of those complicated-type cases, and it has taken a nuanced and complex approach to get treated properly. I'd been sick so long and with so many different systems affected, and likely not just by Cpn, that it has taken a complex clinician to weed through the layers of debris, gradually clearing the tangled mess my health had become. Cpn and the CAP has been at the center of my treatment, hence my devotion to maintaining this website, but it has not been the only thing in my treatment, nor the only concern of my physician. Dr. Powell reflects below on the questions and concerns that have evolved for him through many years of treating Cpn and other infectious inflammatory conditions in his rheumatology practice. He was among the first physicians to use Dr. Stratton's protocol actively in his practice, and has a lot of cases under his belt using the CAP. And he found out about Dr. Stratton's work through his own researches and insistent curiosity. No websites were then available to inform him. That should tell you something about his intellect and curiosity. I think his questions are good ones for any of our readers to ask and consider. They might just help us broaden our thinking the way we hope that our physicians will be willing to broaden theirs. **********************************Dear Jim,Thank you for bringing these concerns to my attention. I am not opposed to treating infected people with antimicrobials. But I do think we all need to ask a few important questions before we start CAP. What is it we expect from CAP? What is CAP this month? Can we clear Cpn? Is Cpn like herpes viruses that can not be cleared, only pushed back? If one has an overgrowth of Cpn does that say something about their immune system? How many other infections does the average Cpn person have? Do you treat the viruses first or second? Could the viruses flare while you are stirring up die off reactions with antibiotics? Does the oxidative stress of these die off reactions have negative consequences to the immune system, neurological system and key infection opposing nutrient levels? For how long do we want to take antibiotics? These are reasonable questions to ask. It is important to understand that:1.) No one knows which CAP combination is optimal.2.) No one knows how long to treat. 3 months? 12 months? 3 years? Longer?3.) No one knows if the infection can be cleared...clearing every elementary body, every cryptic, every reticulocyte form? Is that a realistic expectation? 4.) No one knows how many other infections are present and whether it might be better to begin with those, such as by using antivirals, before starting CAP.5.) No one knows what impact genetics are playing in these infections and few people know how to compensate for genetic predisposing factors (e.g supporting methylation defects helps to oppose infection).People need to be realistic when they are considering CAP treatment and make sure they are not approaching these infections with the expectation that taking multiple antibiotics for a few months is going to restore their vitality. Please be sure to mention that you and I have seen CAP fail. I have seen antiviral therapy work tremendously well with some who have failed CAP. That means something. I have seen people recovering faster with sauna, Iodoral and infection-opposing nutrients (weeks rather than months) and that is why I may start with these. When people are done having die off with these measures, they tolerate antivirals and antibiotics better and can get back to working and living full lives faster. If someone comes to me with a 2/10 ratings of their energy and depleted levels of essential nutrients and hormones, the worst thing I can do is send their energy to 0/10 by increasing the demands on their system through premature initiation of antibiotic therapy. I have patients who say that the T3, Vitamin D and infrared sauna have had the largest impact on their health. Some patients respond best to antiviral medication while others respond best to NAC, Zithro, Flagyl. Some patients seem to respond better to NAC, Rifampin, Doxy, Nifedipine. Some patients do very well with IM or IV gammaglobulin if they are hypogammaglobulinemic. Last week I saw a gentleman who failed CAP and antiviral therapy, but he has returned to work feeling better in years after adding niacin therapy. A recent study from Harvard confirms the antibacterial and antiviral properties of niacin, but liver enzymes need to be watched if the dose is increased about the RDA. The doctor can not know in 2008 which modality will work best because we do not know who we are dealing with in terms of these mixed infections and varied genetic mutations.Starting treatment by restoring depleted nutrient levels before starting antibiotics is not a bad idea. Running into battle with your nutritional levels around your ankles is short sighted and likely to cost you more in than preparing properly and building a strong defense before going for the antibiotics and antivirals. I would be surprised if most of the people who dropped out after I recommended sauna actually tried sauna twice daily for 20 minutes as recommended. I have had so many patients swear by this benign method and I have seen recovery occur much faster for those who do daily sauna. Seriously, people tend to respond in weeks rather than months if they are doing daily sauna therapy.In summary, there is no proof that even 3 years of CAP will clear Cpn in humans. I have seen CAP work wonders for those whose illness is linked to Cpn or other polymorphic bacterial infections, which is why I continue to recommend this important therapy. It is wise to minimize antibiotic exposure as much as possible and most patients want to transition from antibiotics to infection opposing supplements as soon as possible. There is no test that can prove to the patient or the physician that Cpn or any other chronic infection is eradicated, so we are forced to use clinical symptoms as a guide. Herpes viruses persist forever, but when herpes is in remission people do not feel the infection. It may be that this is also true for Cpn. We believe the best way to address these infections and restore health is to begin by strengthening the immune system rather than stress the patient's system in the initial stages of treatment. We have tried it both ways and we have better results by starting treatment with measures that support methylation, restore depleted nutrients, increase body temperature and WBC function. Then when the die off from these measures has subsided, antivirals and antibiotics are discussed and can be started more safely. I can't say this enough times, there is no proof that you can ever clear these infections or even know how many different organisms are involved. Check the websites for Lyme, Mycoplasma and other occult infections...relapse is very common. That is why we think it is essential to build one's defenses and improve immune function as the primary focus of therapy. It is wishful thinking to presume that 6-12 months of CAP will restore health in most fatigued patients. If only it were that simple.Best regards,Michael Powell, D.O.

Jim K Sun, 2008-03-09 22:42

Expert Comments

Expert Comments

Note: In a few cases these expert comments may have been superceded by updates to the particular protocols mentioned. Please use the CAP's descriptions in the Cpn Handbook as the most up to date versions of the protocol's using these Expert comments as useful sidebar information where they differ from current practice. Comments by physicians treating various diseases with a Cpn protocol and by scientists and researchers studying Cpn. Comments by David Wheldon Comments by David Wheldon on antibiotics in his protocal and the Vanderbilt protocal Comments by David Wheldon MD on treating MS with Cpn protocal" David Wheldon on Relapse and Pseudo-Relapse treating MS for Cpn David Wheldon comments on Cpn endotoxins & reactionsDavid Wheldon comments on steroid use with Cpn infection  Comments by Dr A Expert close to Vanderbilt work describes thorough treatment of Cpn: an interview. Dr. A comments on EB load and severity of illness.Dr A comments on Flagyl use.  Picture of EB's riding on Red Blood Cells    Dr. Michael Powell   A Rheumatologist Treating Cpn in Chronic Fatigue, Fibromyalgia and other auto immune disorders-  Dr. Powell Comments on Niacin in Cpn Infection and other supplements   Dr. Charles Stratton Indicator of B12 deficiency <!--break-->  

Jim K Wed, 2005-08-24 08:06

First Report: Results of CAP's Treatment Survey #1

First Report: Results of CAP's Treatment Survey #1

Finally we have the results of our first survey of CAP's treatment! The detail hounds might find a few numbers that don't add up. If so, let me know and I'll double check the data. It's as accurate as I could get it given mostly hand tabulation. I'm relying on you to keep me honest, as I'm only one day post Tini and not seeing everything clearly this morning!Please remember that these are small numbers reporting in, and a rather rough set of questions. It's a survey, not a statistical study. The charts are impressive, but should be taken with caution as visual aids can look better than the data set they come from!Find it at:First Report: Results of CAP's Treatment Survey #1 

Jim K Tue, 2006-04-04 10:09

Stratton/Mitchell & Siram Case Reports

Stratton/Mitchell & Siram Case Reports

Does it work?

It has been noted that most users of the combination antibiotic protocols commenting here have not been on the treatment long enough to give a big enough pool of reports to feel assured of the efficacy of this approach. I had asked Drs. Stratton, Wheldon, and Powell to perhaps tally up at least some basic numbers from their case experience to help us out with this problem, but this would involve problems of confidentiality and use of private data, etc.   Then, I suddenly realized that we already have a good list of anecdotal reports of response to treatment reported data available to us... right in the Stratton/Mitchell patent materials! (Sheepish, embarrassed grin). So I took it as a project to summarize this data by disease treated. Occasionally I have used the exact wording from the patent materials as they were brief and descriptive. We have the full text referenced in our treatment and links if you want to see more detail. All reported had with positive serology for Cpn using the highly sensitive tests developed by Stratton/Mitchell. I left out a few whose diagnosis was not clear to me, you can see them in the patent materials #6,884,784 All on some form of the combination antibiotic therapy protocol.

MS

  1. EDSS score 8.0- Treatment nine month- EDSS 3.0
  2. EDSS score 8.0 Treatment six months- EDSS 6.5
  3. EDSS score 7.5.  Treatment five months- EDSS 6.5.
  4. EDSS score 8.5  Treatment six months- no further progression of symptoms
  5. 10 years wheel chair  bound  Treatment six months- stands unaided, several steps, dec fatigue and cognitive dysfunction.
  6. Long hx MS with 2-3 year progression   Treatment fourteen months- improved incontinence, stamina, speech. Continues to be wheel chair bound.
  7. One year MS, foot drop, walks with cane.   Treatment four months- no longer requires cane.
  8. One year MS. Cane, rolling gait, fatigue.   Treatment twelve months- no cane, no fatigue on walking

 

RA

Treatment two months. Complete remission of RA symptoms.

IC

Treatment two months. Complete remission of symptoms. Stopped tx, return of IC symptoms.

IBD

  1. Treatment six months. No further evidence of IBD. Bowel habits normal, no steroids, cognitive dysfunction and depression resolved.
  2. Treatment six months. No further evidence of IBD. Neurologic, fatigue, myalias, athralgias, rash resolved.
  3. Six year history of inflammatory bowel disease (uncertain CD or UC) associated with painless rectal bleeding, arthritis, myalgias, skin ulceration, abdominal cramping/diarrhea, and rectal fistulas. She had increasing fatigue. Symptom free (after going off abx on vacation and relapsing) after one year of treatment. On combination antibiotics her ileostomy activity was more regular and less spastic. She claimed to feel better with higher energy levels and ceased antibiotic therapy. Six months post- antibiotic therapy she remained asymptomatic other than a moderate anemia.
  4. On combination antibiotics she experience some symptomatic improvement but failed to completely resolve her IBD symptoms. She discontinued antibiotics due to a probable chronic Herxheimer reaction. Currently she is lost to follow-up.
  5. Colitis with inflamed distal sigmoid colon and proctitis associated with frequent loose stools with significant mucus. Following six weeks of combination antibiotic therapy with a significant reduction in symptoms. Shortly after cessation of antibiotics her symptoms return. Reinstitution of antibiotics resulted in a second remission of the majority of her symptoms with resolution of her proctitis on visual exam.

 

CFS

  1. Insidious onset of debilitating fatigue. This was associated with a severe cognitive dysfunction that disrupted his ability to function. Combination antibiotics with complete reversal of symptoms after six months. He remains asymptomatic.
  2. 10 year history of CFS with severe cognition problems. Herxheimer reaction with resolution over two week period on treatment. He remains on combination antibiotics for over ayear and is asymptomatic.
  3. Physician with long-standing CFS. Treated with combination antibiotics with gradual resolution of symptoms. During course of treatment developed cardiac myopathy. Currently asymptomatic from CFS. Cardiac myopathy resolved over six month period on combination antibiotics.
  4. Five year history of severe CFS with debilitating cognitive dysfunction and depression. Gradual improvement on combination antibiotics for approximately nine months. Estimated 75% of normal function.
  5. Ten year history CFS with cognitive dysfunction. Complete response to combination antibiotics over a course of one year.
  6. Moderate fatigue and cognitive dysfunction following acute infectious illness. Depression was major problem. During one year course of combination antibiotics fatigue and cognitive dysfunction largely reversed. During mid-course of therapy patient developed acute anxiety attacks relieved by anti-porphyrin therapy.
  7. Fatigue following acute stress. On combination antibiotic therapy at 3 months became asymptomatic. Cessation of antibiotics resulted in symptomatic relapses. Currently asymptomatic with low serum antibodies and negative PCR.
  8. Short history of CF and cognitive dysfunction affecting studies. Combination antibiotics over a multi-month course resulted in complete reversal of symptoms.
  9. Three year history of CFS with FM. Combination antibiotic therapy has resulted in partial reversal of symptoms allowing her to retain a job in jeopardy. Estimated 80-90% normal function currently.
  10. History of fatigue although non-incapacitating. Combination antibiotic therapy has resulted in 100% return to normal function.
  11. Teen-ager with long history of CFS resulting in home-bound schooling. On combination antibiotic therapy returned to school and recently graduated. Recovery has not been complete probably secondary to non-compliance in therapy.

FM

Three year history of debilitating FM following the stress of being a stalking victim. Patient relatively asymptomatic after nine months combination antibiotic therapy.

Siram's cases

You will find followup reports from Dr. Siram's cases by a man who actually tracked down personally those he could find. These are all MS cases, and all report improvement, some quite spectacular, such as the wheelchair bound tri-pelegic former cop who was able to resume his former job! But please note: some people used flagyl, and other antibiotics only. The inconsistencies of degree of improvement seems mostly due to this factor in my read. Remember that this was in 1994 when the understanding of the importance of the whole protocol, especially the critical importance of flagyl, was still evolving. Click here for link.

Jim K Sat, 2006-01-21 20:33

Summary Chart of Different CAP Protocols

Summary Chart of Different CAP Protocols

We have been preparing this for an eventual overhaul of the Handbook, but there have been a number of requests, especially by new folks, to help clear up confusion. Combination Antibiotic Protocols-These charts are presented to give the brain-fogged an overview of protocols to understand the general approach, and why you may read of people on www.cpnhelp.org as using differing combinations of meds. These charts are meant for clarification only and should not be used as a starting point for doing a CAP protocol. Everyone’s case is different, and requires individual considerations. Also, understanding the many facets of Cpn and treatment reactions is crucial before engaging in treatment. Don’t start any of these without reading further in the Cpn Handbook. Summary chart of different CAP protocolsNote:Jim, I'm sorry not to have read this sooner, but you appear to be making a mistake about David's regime.  You don't mention NACi until way down the list and the first alternative is given appears to be azithromycini by itself, which is incorrect as can be seen here: http://www.davidwheldon.co.uk/ms-treatment1.html

A schedule of treatment.This is one schedule which strikes all stages of the organism's life-cycle. Other equally good schedules are possible. It is preferable that a committed care-giver (for instance, spouse, partner or parent) should ensure that medication is given, and swallowed, consistently.) N-acetyl cysteine (NAC) 600mg - 1,200mg twice a day, should be taken continuously. This is a commonly-taken dietary supplement, available at health-food stores. It is an acetylated sulphur-containing amino-acid, and may be expected to cause chlamydial EBs to open prematurely, exposing them to starvation; more on this and other benefits on page 4. This should be started at the lower dose of 600mg twice a day; the dose should be doubled when well-tolerated. NAC offers liver protection; this may be useful, as rapid bacterial die-off may compromise hepatic function. When NAC is well tolerated, Doxycyclinei 100mg once daily is added. It is taken with plenty of water. When the two above are well tolerated, Azithromycin 250mg orally, three times a week should be added. (Roxithromycini, 150mg twice daily, is an alternative.) When all three agents are well tolerated, the dose of Doxycycline is increased to 200mg daily. The reason for this slow, step-wise introduction of antichlamydials is to minimize any reactions caused by bacterial die-off. These can be unpleasant. NOTE: in rapidly progressive MSi it may be prudent to offset the benefits of stopping progression against the risk of reactions, giving full doses of azithromycin and doxicycline from the beginning. This combination is taken continuously.

Also, The implication might be taken by some people that metronidazolei and tinidazolei are taken during a five day break fro the bacteristatics an this also applies to the Stratton Protocol.  This would seem to answer my query as to why so many newbies were asking me this question..........Sarah    

Jim K Sun, 2007-07-22 11:12

Wheldon Protocol

Wheldon Protocol

David Wheldon MB CHB, FRCPath (Fellow of the Royal College of Pathology) Cpn Protocol

Dr. Wheldon's site has an excellent summary of Cpn and it's implication in disease, especially MS, and a much more complete description of the Cpn and of his treatment protocal than is given here. David updates his site regularly, and it has the best up-to-date information on supplements for Cpn treatment as well. Make sure you consult it for the latest information.

Dr. Wheldon is a consulting medical microbiologist in England whose wife, Sarah, was diagnosed with Multiple Sclerosis. When her worsening condition and lack of useful treatment from conventional medical resources occured, Dr. Wheldon explored the emerging evidense for bacterial causation. Although Sarah did not show any serological results for Cpn, he used the Vanderbilt (Stratton and colleagues) work and his own microbiology knowledge to formulate his own protocol.

His protocol calls for the use of two bacteriostatic agents continuously, both of which can cross the blood-brain barrier and thus are particularly geared to MS, and short pulses of Flagyl (metronidazole) an anearobic bacteriacide.

Sarah, as well as others he has treated, has shown both symptomatic reversal and clear reduction of brain lesions shown by radiological study.

We recommend you read his site in detail and download his treatment pdf before initiating any treatment.

The following is extracted from his website (as of 02/07/06) and may not be complete or up to date. His website is updated frequently with new material and should be read thoroughly by anyone using a CAP for Cpn.

Wheldon Regime

Why doxycycline and roxithromycin (or azithromycin)?

Both are oral, both are active against Chlamydia pneumoniae, both are relatively inexpensive. They are relatively risk-free. They act synergically against test strains of the organism; giving both together would be the equivalent of giving a four-fold increase of each drug were it to be given alone. The drugs work on different steps in the bacterial protein synthesis pathway. Combination therapy reduces the chance of the emergence of resistance. Both drugs pass into the brain. Both reach good levels inside cells. This is very important. Both are well tolerated. Azithromycin is an alternative to roxithromycin. They deplete the organisms slowly: this is very important, as the release of bacterial endotoxins should not be sudden.

Rifampicin may also be considered. It, too, is synergic with doxycycline, penetrates the brain and is active intracellularly. It is not suitable for intermittent use. It is highly active, and, in patients with a large bacterial load, it may give rise to intense reactions.
 


 

Why are later short courses of metronidazole to be taken together with these antimicrobials?

Chlamydiae are complex organisms. Long ago their ancestors must once have been free-living bacteria which possessed their own energy-generating pathways. The transformation from EB to RB is an active change, and an active change implies the retention of at least some of these pathways. The ones with the most utility for this purpose would be anaerobic, and thus susceptible to metronidazole.

Doxycycline and roxithromycin block the replicating phase by inhibiting protein synthesis and may be expected to force the organism to maintain itself by using its own primitive anaerobic respiratory mechanisms. In this suspended state it would be susceptible to anti-anaerobic agents such as metronidazole.

This is borne out by clinical evidence. The administration of metronidazole after doxycycline in a patient with likely high-load Chl pneumoniae infection causes a bacteriolytic reaction more severe than that following the original administration of doxycycline.

However, there is a difference: in this leg of treatment there is no risk of the emergence of resistance, for the organism is unable to replicate. Metronidazole need thus be given in courses only as long as can be tolerated.

Five-day courses of metronidazole at three-week intervals, during continuous treatment with doxycycline and roxithromycin, would seem reasonable; at first, metronidazole may be limited to one or two doses on one or two days to judge the severity of reaction.

The eventual aim would be to give all three agents intermittently. This, the final leg of treatment, would entail a 14 day course of doxycycline and roxithromycin, with metronidazole given from day five for five days. (The reason for continuing doxycycline and roxithromycin for a few days after the metronidazole has been stopped is because these drugs both possess anti-inflammatory activity which may prevent a reaction to the organisms killed by metronidazole.) This course would be given once a month. After several months the intervals between the antibiotics would be cautiously extended.
 


Why this complex antibiotic regime?

The literature is filled with instances of treatment-failure in serologically-proven chronic Chl pneumoniae infections of non-CNS systems, whether macrolides, tetracyclines or rifampicin have been used. When the drug is stopped, even after months of treatment, serology rises, and the patient relapses.

The intensive cyclical regime of combined antimicrobials outlined here corrals the pathogen, initially halting replication, then eliminating stalled intracellular forms. Extracellular forms may be depleted by giving N-acetyl cysteine (see below.)

No single antimicrobial agent can be expected to achieve this effectiveness against every phase of the organism's life.

 


 

What are the expected reactions to the antibiotics?

There seems to be two components to the reactions experienced on taking the antibiotics.

The first is caused by elimination of bacterial fragments — endotoxins — and is characterised by shivering, influenzal symptoms and general malaise.

The second is caused by the release of metabolic toxins; waves of giddiness and feelings of unreality are quite common. They are alarming if not known about and understood. The strength and duration of these reactions depends largely on the bacterial load. In MS, particularly early relapsing-remitting MS, the bacterial load is likely to be small, and the reaction brief. In other conditions, particularly those with multi-system involvement, the bacterial load may be large and the reaction to antibiotics unpleasant and prolonged.

It may seem unlikely that doxycycline, roxithromycin and rifampicin can kill chlamydiae; they are, after all, considered to be bacteriostatic agents — normally they inhibit rather than kill bacteria. However, intracellular Chlamydia pneumoniae must continuously elaborate proteins to ensure its own survival within the host-cell.

The reaction to the metronidazole component of treatment is particularly severe as at this stage numerous bacteria are being killed. For this reason it may be best to give an initial course of one single day, followed by review. Prochlorperazine, 10mg orally, may be useful.

The patient can be reassured that a reaction to the antimicrobials are evidence of bacterial destruction and that they will end. And, too, the morale induced by physical improvement has to be set against them.
 


 

Isn’t giving antibiotics for a long time is a bad thing?

That depends on the illness. Long-term doxycycline is used fairly routinely for certain kinds of gum disease and for acne. Doxycycline is also used long-term in malaria prophylaxis.

 

Long-term use of these antibiotics engenders no real risk of an increase of resistance in other bacteria within the wider community.

What might a schedule of treatment comprise?

 

What might a schedule of treatment comprise?

Antimicrobials
Doxycycline
200mg once daily with plenty of water.
Roxithromycin 150mg twice daily or Azithromycin 250mg three times a week.
These are maintained without a break for at least six months.

N-acetyl cysteine 600mg - 1,200mg twice a day, should be taken continuously. This is a commonly-taken dietary supplement, available at health-food stores. It is an acetylated sulphur-containing amino-acid, and may be expected to cause chlamydial EBs to open prematurely, exposing them to starvation; more on this and other benefits here.

Two or three months into the treatment regimen, or when the patient is experiencing few problems with reactions, three-weekly cycles of intermittent oral Metronidazole are added. During the first cycle metronidazole is given only for the first day. If problems with reactions are found, the period of administration is kept short. When metronidazole is well tolerated the period of administration in each cycle is increased to five days.

The dosage of metronidazole is 400mg three times a day. If it is suspected that a patient may have a heavy chlamydial load a smaller daily dose may be given.

The eventual aim is to give all three agents intermittently so that the patient has a respite from antibiotics. This, the final leg of treatment, may entail a 14 day course of doxycycline and roxithromycin, with a five day course of metronidazole in the middle. This course is given once a month. After several months the intervals between the antibiotics may be cautiously extended.

Rifampicin is not suitable for intermittent use, and azithromycin may be given instead.

 


 

Adjuncts

The brain has extraordinary powers of repair, but must be provided with the building-blocks by which to do it. This infection is intracellular; the organism interferes with mitochondria, the cells' powerhouses. Many of the symptoms of the disease - particularly the fatigue - may be due to mitochondrial exhaustion. Toxins known as free radicals are released as various synthetic pathways are disrupted. If this oxidative stress continues unchecked for too long irreversible mitochondrial damage may occur. A combined dietary supplementation of antioxidants is strongly recommended. (See Syburra C, Passi S. Oxidative stress in patients with multiple sclerosis. Ukr Biokhim Zh. 1999 May-Jun;71(3):112-5.)

Vitamin C 1G daily
E 800iu daily
Omega 3 fish oil daily
Evening primrose oil 1G daily
Acetyl L-Carnitine 500mg daily
Alpha Lipoic acid 150mg daily
Ubiquinone (Coenzyme Q10) 200mg daily
Selenium 200 micrograms daily.
N-acetyl cysteine 600mg twice daily
melatonin 1.5mg at night may be considered.

This may seem like polypharmacy, but there are good reasons to consider these agents. This is because the mitochondrial membrane is the bottle-neck for numerous key cellular reactions, and it is exactly here that chlamydiae hover as they control the host cell and steal its vital molecules via tiny projections. These agents are available at health food stores and are obtainable on-line.

More details on how antioxidants can act synergistically to enhance their effects, and to regenerate each other can be found on this page.

Apart from mitochondrial support, Vitamin D is needed. There is evidence that a relative Vitamin D deficiency is common in MS, and may allow the disease process to begin. High dose supplementation - 4000iu is recommended. (less may be needed in infections other than MS) A page on this is given here.

In addition, B complex, Magnesium, 300mg and Calcium 500mg supplements in the evening (remote from the time of taking doxycycline) daily.

Vitamin B12 injections once weekly for 3 months, then monthly for the duration of continuous treatment; B12, (together with B6 and folate) counteracts the hyperhomocysteinaemia which accompanies chronic Chl pneumoniae infection and which is thought to cause connective tissue damage. (There is now evidence that oral B12 is satisfactorily absorbed, except in patients with pernicious anaemia. High dose supplementation is recommended.)

Regular Lactobacillus acidophilus, daily, either as a supplement or in capsules. This is to maintain bowel flora in the face of antibiotic treatment. Tablets of Lactobacillus sporogenes spores may be considered. These have the advantage of getting into the small bowel in large numbers.

It would be wise to avoid foods containing artificial trans-fats. These are hard fats made from unsaturated oils which, after heating under pressure, are hydrogenated in the presence of a catalyst. They are widely used because they have a long shelf life and are inexpensive. With certain exceptions hydrogenated fats are not found in nature, and are metabolized with difficulty in the body. They alter cell and mitochondrial membrane functions. Two studies in animal models have found that artificial trans-fats affect mitochondrial efficiency as measured by a reduction of ATP synthesis. [Blomstrand R, Svensson L. The effects of partially hydrogenated marine oils on the mitochondrial function and membrane phospholipid fatty acids in rat heart. Lipids. 1983 Mar;18(3):151-70; De Schrijver R, Privett OS. Energetic efficiency and mitochondrial function in rats fed trans fatty acids. J Nutr. 1984 Jul;114(7):1183-91.] Dietary intake of trans-fats increases systemic inflammatory markers in humans. [Mozaffarian D, Pischon T, Hankinson SE, et al. Dietary intake of trans-fatty acids and systemic inflammation in women. Am J Clin Nutr. 2004;79:606–12.; Baer DJ, Judd JT, Clevidence BA, Tracy RP. Dietary fatty acids affect plasma markers of inflammation in healthy men fed controlled diets: a randomized crossover study. Am J Clin Nutr. 2004;79:969–73.] If the words 'hydrogenated oil' or 'partially hydrogenated oil' appear in a list of ingredients then trans-fats are likely to be present. (It may be noted that dairy products and animal fats also contain a small proportion of trans-fats, but these naturally occurring trans-fats are digestible and were beneficial in animal studies; evidence is less clear-cut in humans. [reviewed by Wang Y, Jones PJ. Dietary conjugated linoleic acid and body composition. Am J Clin Nutr. 2004 Jun; 79(6 Suppl): 1153S - 1158S.])

Turmeric, the yellow spice used in Indian cooking, may be very useful. The active ingredient, curcumin, moderates the pro-inflammatory effects of bacterial endotoxin, probably by restraining the activation of nuclear factor-kappa B. 'Nuclear factor kappa B has been implicated in autoimmune and inflammatory diseases, infection, cell survival, and cell transformation with subsequent promotion of cancer.' [Reviewed by Holmes-McNary M. Nuclear factor kappa B signaling in catabolic disorders. Curr Opin Clin Nutr Metab Care. 2002 May;5(3):255-63.]

 

 

 

Why this complex antibiotic regime?

The literature is filled with instances of treatment-failure in serologically-proven chronic Chlamydia pneumoniae infections of non-CNS systems, whether macrolides, tetracyclines or rifampicin have been used. When the drug is stopped, even after months of treatment, serology rises, and the patient relapses. The intensive cyclical regime of combined antimicrobials outlined here corrals the pathogen, initially halting replication, then eliminating stalled intracellular forms. Over a number of cycles it is expected that the load of extracellular forms will be reduced to negligible levels. There is evidence that in persistent infections the extracellular forms are scarce. No single antimicrobial agent can be expected to achieve this.

What are the expected reactions to the antibiotics?

There seems to be two components to the reactions experienced on taking the antibiotics.

The first is caused by elimination of bacterial fragments — endotoxins — and is characterised by shivering, influenzal symptoms and general malaise. The second is caused by the release of metabolic toxins; waves of giddiness and feelings of unreality are quite common. They are alarming if not known about and understood. The strength and duration of these reactions depends largely on the bacterial load. In MS, particularly early relapsing-remitting MS, the bacterial load is likely to be small, and the reaction brief. In other conditions, particularly those with multi-system involvement, the bacterial load may be large and the reaction to antibiotics unpleasant and prolonged.

The early bacteriolytic (Herxheimer) reaction can be alarming. And, as Sarah found, as-yet unorganised repair can cause function to worsen in the short term. This could easily lead to an early impression that antibiotics were unhelpful or even harmful and could have led to their discontinuance.

Jim K Tue, 2005-08-23 22:08

Clinical Outcomes: a small data-set

27 Apr 2018
Author
D W
Title

Clinical Outcomes: a small data-set

Body

Clinical outcomes.

Comments

Thank you, David.  The part I like best is "In all 7 the resolution continues".   The part I am sorry about is so little faith, so little compliance.  Personally, I have other things I would rather do, but the trade-off is  -  let me see, should I make a list beginning with thinking, dressing, swallowing, walking..........17 months, every day  and my list continues to grow.

Rica 

Ignorance is voluntary bad luck.  Lauritz S.   A true Viking

If you come to a fork in the road, take it. Yogi Berra

3/9 Symptoms returning. Began 5 abx protocol 5/9 Rifampin 600, Amox 1000, Doxy 200, MWF Azith 250, flagyl 1000 daily. Began Sept 04 PPMS EDSS 6.7 Now good days EDSS 1 Mind, like parachute, work only when open. Charlie Chan  In for the duration.&am

 David- Thanks for posting this. Really important to have actual data sets available. So many of us "in process" here that it's hard to stand back and know how powerful this work is. These results are unheard of for MS. Guess this isn't just a pet theory, huh? This goes in the Handbook!

On Wheldon/Stratton protocol for Cpn in CFS/FMS since December 2004.

Here is a very interesting and very positive 9-month-long trial for spondyloarthropathy in which chlamydial involvement was suspected. Doxy alone did very little. The patients in the "real" treatment arm, doxy plus rifampin, saw ~2x reductions in multiple measures - pain (visual analog scale), morning stiffness (hours), tender joint count, swollen joint count.

J Rheumatol 31.10.1973-80, 2004.

I think there are also some negative trials out there for a similar patient population. One would want to examine whether the regimes used in such trials might simply have been far too weak.

More great news - thank-you so much for the report!

 

 

 

On Wheldon protocol for MS since April, 2006.  LDN 1994

5oo mgs Ceftin 2 x/day, 500 mgs Zithromax, 500 mgs 2 x tini pulses,100 mg diflucan, 4.5 ldn; Wheldon protocol for MS April, 2006 to May 2008. 2008 MRI shows NO NEW DISEASE ACTIVITY, 2012 MRI no new disease activity.

D W

David Wheldon Comments on How Flagyl/Tinidazole works on Cpn

David Wheldon Comments on How Flagyl/Tinidazole works on Cpn

There are reasons for thinking that the MBC (Minimum Bacteriocidal Concentration) of metronidazole against cpn 'frozen' by protein-synthesis inhibitors may be quite low. Metronidazole enters the bacterial cell by passive diffusion. Of itself it has little antibacterial activity, but in susceptible bacteria its highly reactive metabolites break the bacterial DNA at the AT base-pair; these are single-strand breaks, and are repairable. In ordinary anaerobic bacteria the outcome (death or survival) is decided by the equation of breakage versus repair. Under normal circumstances, the organism, at the first sign of DNA damage, will switch on its 'last chance saloon' repair mechanism. However, this repair mechanism requires the synthesis of at least 15 proteins. The 'frozen' organism is unable to make them. Thus DNA damage is likely to be ongoing and remain unrepaired. New metronidazole is also entering the bacterial cell by passive diffusion all the time, there being a concentration-gradient across the bacterial cell-wall as the intracellulari metronidazole is converted to active metabolite. Further, one might postulate that the endosome is likely to maintain a high concentration of active metabolite: the organism's refuge becomes its death-chamber. If this is the case, one could make an argument for a sustained rather than a high-dose medication. Speaking from my own experience I experienced little during my first five-day pulse of metronidazole (400mg three times a day): the fireworks came on day 4 of the second pulse, and continued long after stopping the drug. And what fireworks they were. I wish I had filmed the muscle fasciculationsi. Metronidazole does not now affect me, apart from its rather nauseating taste.The metronidazole is active against chlamydia only when protein-synthesis inhibitors have forced the chlamydia to switch to a sluggish anaerobic pathway. The same protein-synthesis inhibitors then prevent repair of DNA damage caused by metronidazole-metabolite. Synergy on two fronts: I have to say it again - it's one of the neatest concepts in antimicrobial therapeutics. My admiration goes to the Vanderbilt workers who first considered this.

Jim K Fri, 2006-03-03 22:09

Cpn Handbook Table of Contents

Cpn Handbook Table of Contents Jim K Sat, 2006-02-18 22:25