1. HOW DOES ANTIBIOTIC THERAPY DIFFER FROM
CONVENTIONAL THERAPY?
Antibiotic therapy is based on the theory
that inflammatory rheumatic
diseases such as rheumatoid arthritis, scleroderma,
lupus, juvenile
rheumatoid arthritis, polymyositis, ankylosing
spondylitis, etc. have an
infectious cause, namely mycoplasma and other
bacterial L forms. Using low
dose antibiotics, particularly from the tetracycline
family, the disease is
attacked at its source. This therapy is equally
effective in patients with
severe and/or long standing disease as it
is in those with mild to moderate
disease. Thomas McPherson Brown, M.D. (1906-1989),
a renowned
rheumatologist who practiced in the Washington,
D.C. area, pioneered this
treatment over fifty years ago and successfully
used it to treat over ten
thousand patients. The toxic medications
used in conventional therapy are
prescribed to try and control or suppress
the symptoms. They may or may not
work. If they do work, it is only a matter
of time before they either lose
their effectiveness or the patient develops
side effects, forcing them to
discontinue usage. The patients often are
left worse than before they
started the medication.
2. WHAT ANTIBIOTICS ARE USED AND WHAT IS
THE DOSAGE?
The ultimate decision about antibiotic therapy
for you should be made by
your physician. While this therapy is effective
for the majority of
patients, it will not work for everyone.
Treatment must be tailored to the
individual patient. Typically, patients with
severe and/or long standing
disease are started with a series of daily
intravenous clindamycin for five
to seven days. (Dr. Linda Martin of Plano,
Texas is using lincocin with
equal success.) The first two days, 300 mg.
of clindamycin would be
administered in 250 cc 5% dextrose solution
or 0.9% saline dripped over a
50 to 60 minute period. The third and fourth
day 600 mg., and the fifth and
any subsequent days 900 mg. (* A. Robert
Franco, M.D., a rheumatologist in
Riverside, California often prescribes a
seven day series every five weeks
four times and then reassesses the patients
need.) After the initial daily
series, IVs may be administered weekly, every
other week or as the
physician determines for the individual patient.
The IVs are continued
until all lab figures return to normal. Lab
figures should then be
monitored for a time to be sure patient remains
stable before discontinuing
the IVs. For sensitive patients, a local
anesthetic may be applied to the
injection site. Physicians have reported
some success using clindamycin
orally and in intramuscular injections. Orally,
the single dose is 1200 mg.
once a week. For intramuscular injections,
300 mg to 600 mg. once a week.
When the initial course of IVs is completed,
patients begin oral therapy -
minocycline (Minocin) or doxycycline 100
mg. once or twice daily, or
tetracycline 250 mg. to 500 mg. twice daily
Monday, Wednesday and Friday.
Tetracycline is more apt to react with food
and must be taken on an empty
stomach. The antibiotic and calcium supplements
(including dairy products)
should not be taken at the same time.
Patients with mild to moderate disease are
started with this same oral
therapy. Some reported sensitivities to the
tetracycline drugs may be
caused by the drug being introduced too rapidly
and at too high a dose. A
slow start, 50 mg. Monday and Friday then
gradually building up to the
standard dose, can often avoid this allergic
reaction. Erythromycin can be
substituted for those patients with a sensitivity
to the tetracyclines. For
sensitive stomachs, aloe vera juice has been
found to be helpful - two
ounces three to four times a day.
Exacerbation of systemic lupus erythematosis
has been reported in patients
taking minocycline, as has transient lupus-like
symptoms. However, while
some physicians report they have not had
a problem at the low doses used in
this protocol, other physicians avoid the
risk by prescribing erythromycin
for their lupus patients - 333 mg. twice
a day Monday, Wednesday and Friday
- taken with food. For those patients with
sensitive stomachs, Ery-Tabs may
be prescribed. Erythromycin and clindamycin
should not be taken together.
NOTE: An association has been shown between
Mycoplasma hominus and lupus.
(Cassell GH, Clough W, Septic Arthritis and
Bacteremia Due to Mycoplasma
Resistant to Antimicrobial Therapy in a Patient
with Systemic Lupus
Erythematosus, Clin Infec Dis, 1992; 15:402-407).
M. hominus is resistant
to erythromycin.
For children under twelve with juvenile rheumatoid
arthritis, EryPed
(erythromycin), is prescribed in place of
the tetracycline drugs, to avoid
staining of teeth. The dosage is one teaspoon
(200 mg.) three times a day
for 15 to 21 days; then 200 mg. two times
a day thereafter, seven days a
week - taken with food. The patient is kept
on this medication until three
to six months after labs return to normal.
If labs are still normal after
this time, tapering of the drug may begin.
Patients should inform their physician of
any adverse reactions to the
medications.
CAUTION: Some oral generic tetracyclines
have been found to be ineffective
for this therapy.
Thomas McPherson Brown, M.D. et al in Antimycoplasma
Approach to the
Mechanism and the Control of Rheumatoid Disease
from Inflammatory Diseases
and Copper, The Humana Press 1982 states:
"Intraarticular injections of clindamycin
have been very effective when the
reactive state of the joint is so intense
that penetrance (of the
antibiotic) is not achieved by the oral or
IV route. The inflammation must
be reduced in most instances for maximum
clindamycin effect. The usual
treatment plan for large joints, clindamycin
2 cc (300mg.), plus
dexamethasone 1 cc (4 mg.) A reduced amount
of the same combination of
these medications is used for smaller joints.
. . . a program of anti-inflammatory medication
is essential (except early
in the disease) for the maximum effectiveness
of the antibiotic. . . . In
highly allergic individuals antihistamines
and even corticosteroids in very
small doses (less than 5 mg. a day) may be
necessary to activate the
antimycoplasma medication . . ."
3. IS THERE AN ADVANTAGE TO USING MINOCYCLINE
(MINOCIN) OVER THE OTHER
ANTIBIOTICS?
Yes, bacterial cell membranes are surrounded
by a lipid layer (a water
insoluble, fatty substance which surrounds
the cell and provides it with
fuel. As a means of resisting antibiotics,
the cells increase the thickness
of this lipid layer. Minocycline appears
to have greater penetrating
ability. It also has an extended spectrum
of activity and stays in the
system longer and at higher levels than tetracycline.
HOWEVER, there are
patients who have had excellent response
using doxycycline and
tetracycline.
4. ARE THERE SIDE EFFECTS FROM USING ANTIBIOTICS?
The tetracycline antibiotics taken in low
dose, intermittent fashion, can
be used indefinitely without the build-up
of tolerance to the drug and
without the serious side effects of conventional
drugs. However, as with
all medications, side effects may be encountered.
For instance, the
antibiotics cause yeast infections. It is
imperative that patients take a
good acidophilus product such as Metagenics
Flora Plus (1-800-638-4362 for
distributors) or Flora Source (1-800-741-4137
for direct purchase) while on
this therapy. Direct sunlight should be avoided
while on these antibiotics.
Diarrhea is also listed as a side effect,
especially with the clindamycin,
but this has not been encountered at the
dosage used in this therapy. Some
patients' stomachs have become sensitized
from medications prior to
starting this therapy and may experience
nausea. Taking the drug with food
(no dairy products) may help. It has also
been found helpful to start with
a reduced dosage - 50 mg. once or twice a
week for up to several months,
gradually increasing to the recommended dose.
5. WHAT CAN I EXPECT WHEN STARTING ANTIBIOTICS?
The return to health will normally be a slow,
subtle process. In many
cases, the patient will temporarily get worse
before getting better but
over time, the flares will decrease in intensity
and be spaced further
apart until the infectious agent has been
weakened to the point where the
patient's immune system can take over. We
call this the two steps backward,
three steps forward process. Patients have
reported improvement of their
symptoms, including depression, fatigue,
memory, stiff and painful joints,
muscle tone and strength, range of motion,
dry, cracked or tight skin,
bursitis, tendonitis, vasculitis due to inflammation,
skin ulcers,
swallowing difficulties and heartburn. Patients
with Raynauds symptoms have
also experienced improvement.
6. EXPLAIN THE JARISCH HERXHEIMER REACTION.
This drug-induced flare reaction may occur
within hours, the next day or
within the first weeks after the patient
starts the antibiotics - or any
time there is a change in antibiotic or dosage.
It is caused by a die-off
of organisms which in turn create toxins
which circulate in the body. This
will often cause a worsening of symptoms.
Patients may experience a range
of symptoms from mild fatigue and sleepiness
to flu-like symptoms - chills,
low grade fever, night sweats, muscle aches,
aching and swollen joints,
nausea, skin rashes, increased pain, depression
and short term memory loss.
When this occurs it is a good indicator that
the antibiotic is reaching its
target - a very positive sign. The length
of time for this reaction varies
from patient to patient. About twenty percent
of patients do not experience
the Herxheimer reaction. Scleroderma patients
seem to experience the
Herxheimer reaction less often than RA patients.
Oxidative therapy appears
to be useful in reducing these symptoms.
Garth Nicholson, M.D., director of
The Institute for Molecular Medicine in Huntington
Beach, California
recommends peroxide baths (four 16 oz. bottles
of 3% hydrogen peroxide in
20 inch bath or Jacuzzi, with 2 cups of Epsom
salt). Patient soaks in hot
water plus the epsom salt for five minutes
until pores are open, then adds
the peroxide solution. This should be repeated
three times a week at
bedtime. No vitamins should be taken 8 hours
before bath. The peroxide can
also be directly applied to the skin after
a hot shower/tub. The peroxide
should be left on for 5 minutes and then
washed off. Another useful
suggestion from Dr. Nicholson - blend one
whole lemon, then add 1 cup fruit
juice or water and 1 tablespoon of olive
oil. Strain and drink liquid. Diet
and supplements are extremely important.
Nutritional recommendations are on
this webpage and include avoidance of sugar,
caffeine, dairy, fatty or acid
forming foods, but an increase in fresh vegetables
- especially the
cruciferous vegetables - organic if possible.
Patients should drink no less
than two quarts of water a day to flush the
toxins out of the system,
lubricate and carry nutrients through the
body; and should have two to
three bowel movements a day. If the Herxheimer
reaction is severe, the
medication may be stopped and a small dose
of prednisone (no more than 10
mg.) may be prescribed. When the flare subsides,
the medication is
re-introduced slowly.
7. HOW LONG DOES IT TAKE BEFORE I START SEEING
IMPROVEMENT?
The length of time a patient has had the
disease and the strength of their
immune system will determine the recovery
time frame. Some patients see
significant benefits in months, but for others
it may take several years.
Dr. Pnina Langevitz of Israel reported that
the longer patients stayed on
the antibiotics the greater improvement they
experienced. Patients can
safely remain on these antibiotics for years
without building up resistance
to them.
8. CAN I EXPECT TO BE ABLE TO DISCONTINUE
MEDICATION EVENTUALLY?
Some patients may find this treatment provides
a permanent remission and no
further medication is needed, but most will
need to stay on a maintenance
dose to keep the disease under control. If
symptoms should return at any
time a short course of 100 mg. of minocycline
or doxycycline, or 500 mg to
1,000 mg. of tetracycline three times a day
for three days will usually
re-establish the remission for an indefinite
period. For some patients a
return to normal lab figures occurs before
they reach a symptom free
remission. For others the reverse is true
- the symptoms leave first and
then the lab figures return to normal.
9. WHY ARE THE IVs NECESSARY IN SEVERE OR
LONG STANDING DISEASE?
In severe or long standing disease, or in
very resistant cases, the oral
route may be inadequate for the antibiotic
to reach its target and suppress
antigen formation. The intravenous clindamycin
would then be required. The
IV clindamycin jump-starts the therapy, eradicating
long-standing
microorganisms in the gut, respiratory tract
and other areas, creating
greater receptivity for the tetracycline
drug. IV clindamycin therapy is
recommended in the treatment of all scleroderma
patients from mild to
severe. When lab figures return to normal,
these patients may still require
occasional IVs or a weekly dose of oral clindamycin
to remain stable.
10. WHAT LAB TESTS SHOULD BE DONE TO MONITOR
MY PROGRESS?
Laboratory tests are done to help in the
diagnosis of the disease and to
provide a baseline from which to measure
progress after antibiotic therapy
has begun. These include a complete blood
count (CBC), rheumatoid factor
(RF), erythrocyte sedimentation rate (ESR),
C reactive protein (CRP),
antinuclear antibody (ANA), antistreptolysin-O
titer (ASO), and mycoplasma
complement fixation (MCF). These tests can
be repeated at your doctors
discretion to follow your progress. Running
an ASO titer is very important.
If elevated, amoxicillin or ampicillin is
prescribed. Once the ASO titer
returns to normal, patient should be monitored
for recurrence. Some
patients may need to stay on medication until
a negative titer is achieved.
11. I HAVE BEEN ON 100 MG. OF MINOCYCLINE
MONDAY, WEDNESDAY AND FRIDAY FOR
SIX MONTHS AND HAVE SEEN NO RESPONSE. CAN
I STILL EXPECT IMPROVEMENT?
Yes, however you should have some indication
by this time that the
antibiotic is working for you. Your doctor
needs to do a little detective
work at this point. Here are some things
to check:
a. Laboratory tests should be run again.
Often improvement in these tests
will precede improvement of symptoms.
b. If you are on a generic minocycline, change
manufacturers or switch to
the brand name. Patients have discovered
not all generic minocycline (or
doxycycline) is therapeutically equivalent.
Many physicians prescribe the
brand name to avoid this risk.
c. Try a different antibiotic. All patients
may not respond to minocycline
(Minocin).
d. Try one antibiotic in the morning and
a different one at night, or
sequence them taking one for six weeks and
then switching to another for
six weeks.
e. If your disease is severe, long standing
or very resistant, and you are
only on oral antibiotics, you will need to
add intravenous therapy.
f. Look for other infections in the sinuses,
allergies, root canals, gut,
etc. that may be impeding your progress.
Check for systemic candida and
leaky gut. Did you have an elevated ASO titer?
If so, it must be treated as
well. The strep organism is difficult to
eradicate and even after the ASO
titer returns to normal, the patient should
be monitored for some time for
recurrence. The goal of the therapy is to
remove antigen wherever it may be
found in the body in order to achieve optimum
benefit from this therapy.
g. Are you deficient in antibody? Perhaps
intravenous immunoglobulin is
necessary.
h. Did your doctor have the mycoplasma test
run? It should be run for the
entire panel and not just for M. pneumoniae.
The first test may be negative
if the immune system is too weak to mount
an antibody attack to the
organism. Therefore, it is important to repeat
the test within 3 to 6
months. If it is still negative, the medication
should be changed. The
tetracycline antibiotic still works in some
instances of a negative
reading. If the cause is viral the antibiotic
therapy may fail.
Additionally, the cause could be streptococcus
infection compounded with a
mycoplasma infection or vice versa.
Some patients have reported they had absolutely
no indication the
antibiotic was working for them, but they
continued with the protocol, and
in time improvement began.
12. MY DOCTOR HAS TOLD ME TO STOP THE MINOCYCLINE
(MINOCIN) BECAUSE OF A
LOW WHITE BLOOD COUNT.
White blood cells are used to fight infection.
A low white blood cell count
is clinically called leukopenia. This occurs
when there is a reduction in
the normal number of circulating white blood
cells in the blood stream.
This condition involves the blood and the
bone marrow. Patients may
demonstrate a low white cell count before
commencing the antibiotics. This
can be due to the nature of their illness,
or previous therapy such as
methotrexate which causes suppression of
white blood cells, platelets and
red blood cells. This is caused by increased
destruction or impaired
production of these cells. Poor quality protein
intake or digestion
(impaired pancreatic enzyme or HCI production),
inadequate trace mineral or
essential fatty acid intake are other causes.
A blood test called the
Carbon test (800-722-8327) is enormously
helpful at determining the cause
of the decreased WBC. The company can provide
a clinician who can perform
the test in your area. A doctor may be cautious
and suggest that you cease
the minocycline therapy. This is to check
that this is not the trigger of
the leukopenia. If the white count returns
to normal then one can resume
the minocycline and observe if the WBC count
decreases again. If it
decreases again it probably is not wise to
continue with the Minocin. The
minocycline assists the body in clearing
the infection and once the
infectious trigger which stimulates the increased
production of white blood
cells is gone, the WBC will drop to its normal
non-infectious level.
13. MY DOCTOR HAS ME ON METHOTREXATE. DO
I STAY ON THIS MEDICATION ALONG
WITH THE ANTIBIOTICS?
Physicians should be cautious about possible
antagonism between drugs,
which could cause severe side effects. Response
to antibiotic therapy
depends to a large degree on the strength
of the immune system.
Methotrexate is a toxic, immune suppressing
drug, and physicians most
experienced in the use of this therapy take
patients off the drug. Ideally,
a six week wash out period is recommended
between stopping the methotrexate
and starting the antibiotic therapy.
However, if you are receiving benefit from
the methotrexate, some
physicians will start the antibiotics and
then eventually gradually taper
the patient off the methotrexate. If you
are receiving no benefit from the
methotrexate, it should be discontinued.
14. DOES THIS TREATMENT WORK FOR FIBROMYALGIA?
Garth Nicholson, M.D. of the Institute of
Molecular Medicine at Huntington
Beach, CA., and Daryl See, M.D. of the University
of California College of
Medicine at Irvine, CA are finding strong
evidence of mycoplasmal blood
infections in a majority of their fibromyalgia
patients. Other chronic
infections may also be a source. They recommend
long term antibiotic
therapy. Click here for further information
from Dr. Nicholson.
Dr. Lida Mattman, a leading microbiologist,
retired from Wayne State
University and now running a laboratory with
Dr. Seldon Nelson in Warren,
Michigan, reports she is finding the Lyme
Disease spirochete, Borrelia
burgdorferi, in 40% of the fibromyalgia patients
she tests. Dr. Mattman
says should the strep organism be causing
a problem, it will not be found
until the Lyme Disease is treated - these
organisms overgrow each other.
15. GENERAL INFORMATION
a) From the Physicians Desk Reference:
"Concurrent use of tetracycline may
render oral contraceptives less
effective. Minocin pellet-filled capsules,
like other tetracycline-class
antibiotics, can cause fetal harm when administered
to a pregnant woman. .
. . The use of drugs of the tetracycline
class during tooth development
(last half of pregnancy, infancy, and childhood
to the age of 8 years) may
cause permanent discoloration of the teeth
- yellow-gray-brown).
b) List of supplies needed for intravenous
infusion:
900 mg. vials of Cleocin or clindamycin
250cc D5W or .9%NS
10cc syringe with 21 gauge needle to draw
up medication and insert in
delivery solution.
IV tubing set
IV needle or catheter (recommend 23 gauge
butterfly). Always ask for
extras.
Tourniquet, antiseptic pads, bandaids, and
tape (paper, silk, or adhesive).
Sometimes these are available as an IV start
kit.
* IMPORTANT MESSAGE from A. Robert Franco,
MD, Arthritis Center of
Riverside, Riverside, California.
Dear Patients,
I often find that patients that come to see
me for diagnosis and treatment
for rheumatic diseases have already started
on antibiotic treatment.
Although this may be helpful to the patient,
it would be best when
applicable to have the appropriate work-up
PRIOR to starting antibiotic
treatment. I am referring especially to the
mycoplasma and Chlamydia PCR
test (generic fingerprint).
Antibiotics may render this test negative
and thereby often making useless
this great diagnostic tool, especially in
view of the fact that patients
will be obligated to use antibiotics for
several years exposing themselves
to some potential toxic side effects. If
you have already started
antibiotics, you should continue and consider
going off for 4 weeks prior
to your visit to the Arthritis Center of
Riverside, or your physician's
office where these tests may be done.
If it is possible to do the above, you will
increase your chances of
confirming the infectious cause of your rheumatic
disease. Even more so by
doing the test prior to initiating antibiotic
treatment. Additionally, your
insurance company will be more likely to
authorize and pay for IV treatment
if you have a positive mycoplasma PCR test.
I hope this information proves useful to
you.
Sincerely, A. Robert Franco, MD
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Our thanks to:
Dr. M. R. Coker-Vann Ph.D.,
Director, Arthritis Research Center,
504 E. Diamond Ave.,
Gaithersburg, Maryland 20877,
phone (301) 216-1231,
for her assistance in compiling the answers
to the above questions. Dr.
Coker-Vann was research director of Dr. Thomas
McPherson Brown's Arthritis
Institute at the time of his death in 1989.
Revised May, 1998
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FOR MORE INFORMATION PLEASE SEE THE ARTICLE
ENTITLED
"GETTING STARTED ON ANTIBIOTICS"
ON THE MAIN PAGE.
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