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 antigen
CAPi for Chlamydia pneumonia since 11/04. 25yrs CFS & FMSii- Currently: 300mg INHii, 200 Doxycyclinei, 500mg MWF Azithromycini, 1000mg Tiniii daily (Taking a break from continuous protocol)
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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.