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