Submitted by Jim K on Wed, 2007-08-22 22:06

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.