FREQUENTLY ASKED QUESTIONS ABOUT ANTIBIOTIC THERAPY

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. (Some doctors are using lincocin with equal success.) The first two days, 300 mg. of clindamycin would be administered in 250 cc 0.9% saline dripped over a 50 to 60 minute period. (D5W is not used because of the yeast overgrowth found in most of these patients.) The third and fourth day 600 mg. is given, 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 patient's need. In some of his patients with rheumatoid arthritis, Dr. Franco is substituting Zithromax 250 mg. twice daily two days a week in place of the IV clindamycin.) 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. This dosage is effective for most patients. However, five or even seven-day a week doses may be necessary in some cases. 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. Some patients may need to take doxycycline with food. Be careful to avoid dairy products and calcium supplements. For sensitive stomachs, aloe vera juice has been found to be helpful - two ounces three to four times a day.

Exacerbation of system 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 inflammatory rheumatic disease, 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 (300 mg.), 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 ANY 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 can cause yeast infections. Drugs such as the NSAIDS, gold, Plaquenil, methotrexate, steroids, antibiotics, etc. kill off the necessary good bacteria in the intestinal tract. Patients should be tested for candida antibodies at the start of this antibiotic therapy, and if found, appropriate treatment should be prescribed. Conventional therapy would include the anti-fungals Nystatin or Diflucan. Natural therapies would include olive leaf extract (a good product is available from East Park Research along with slippery elm, l. glutamine and grapefruit seed extract. (See Section 11 for list of laboratories testing for candida antibodies.) It is extremely important 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 to replace the good bacteria destroyed by the antibiotics. It is also recommended that patients avoid direct sunlight 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, vaculitis due to inflammation, skin ulcers, swallowing difficulties and heartburn. Patients with Raynaud's 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 that 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, hives, skin rashes, depression and short term memory loss. Hives and rash are sometimes mistaken for an allergic reaction. 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 may 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 web page 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 the joints, 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 at a slow rate.

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 doctor's 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 that 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, intestinal tract, etc. that may be impeding your progress and must be addressed for optimum benefit from this therapy. The first area to check is the intestinal tract for candida overgrowth and leaky gut. There are special labs that perform these tests - Immuno-Science Lab in Beverly Hills, CA. (http://www.immuno-sci-lab.com), and Antibody Assay Laboratories in Santa Ana, CA. (phone -800-522-2611) run candida antibody tests, and Great Smokies Lab runs the lactulose mannitol test for leaky gut. (http://www.gsdl.com or http://www.greatsmokies-lab.com)

g. 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.

h. Are you deficient in antibody? Perhaps intravenous immunoglobulin is necessary.

i. 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.

Three laboratories performing this special testing are listed on http://rheumatic.org in the Doctors' Corner.

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 that 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 is enormously helpful at determining the cause of the decreased WBC. The company Body Bio (888-320-8338) can provide a clinician that 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, your physician may be reluctant to discontinue it. The antibiotic therapy can be started and then eventually gradually the patient is tapered off the drug. 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. Posted in the section of our web page titled "Interesting Topics" is another program used by a fibromyalgia patient that put her disease in remission.

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 need for intravenous infusion. 900 mg. vials of Cleocin or clindamycin 250cc 0.9%NS or lactated ringers. D5W should not be used because of the candida overgrowth found in these patients. 10cc syringe with 21 gauge needle to draw up medication and insert in delivery solution. IV tubing set IV needle or catheter (recommend 23gauge butterfly). Always ask for extras. Tourniquet, antiseptic pads, bandaids, and tape (paper, silk, or adhesive). Sometimes these are available as an "IV start kit".

Our thanks to Dr. M. R. Coker-Vann, Ph.D. Director, Arthritis Research Center
504 E. Diamond Ave.
Gathersburg, MD 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. First revision May 1998 Second revision July 1999 *

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