New Treatments | ANTIBIOTICS RECOMMENDED WHEN INDICATED FOR TREATMENT OF GULF WAR ILLNESS/CHRONIC FATIGUE SYNDROME, FIBROMYALGIA SYNDROME, RHEUMATOID ARTHRITIS AND OTHER AUTOIMMUNE ILLNESSES by Prof. Garth L. Nicolson 

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ANTIBIOTICS RECOMMENDED WHEN INDICATED FOR TREATMENT OF GULF WAR ILLNESS/CHRONIC FATIGUE SYNDROME, FIBROMYALGIA SYNDROME, RHEUMATOID ARTHRITIS AND OTHER AUTOIMMUNE ILLNESSES
by Prof. Garth L. Nicolson


Thursday, January 17 2002 - Filed under: General

Sat, 11 Mar 2000



ANTIBIOTICS RECOMMENDED WHEN INDICATED FOR TREATMENT OF GULF WAR
ILLNESS/CHRONIC FATIGUE SYNDROME, FIBROMYALGIA SYNDROME, RHEUMATOID
ARTHRITIS AND OTHER AUTOIMMUNE ILLNESSES


by Prof. Garth L. Nicolson

The Institute for Molecular Medicine, 15162 Triton Lane, Huntington Beach,
California 92649-1041

Tel: (714) 903-2900 Fax: (714) 379-2082 e-mail: gnicimm@ix.netcom.com
Website: www.immed.org

Doxycycline (aka Vibramycin, Doxychel, Doxy-D, Doryx)


Doxycycline is a broad spectrum tetracycline with good lipid solubility
and ability to penetrate the blood-brain-barrier. This antibiotic acts by
inhibiting microorganism protein synthesis; it is readily absorbed by the
(normal) gut, and peak blood concentrations are maintained between 2-18
hrs (half-life, 18-22 hrs) after an oral dose of drug. Food, calcium,
magnesium, antacids and some drugs reduce absorption, and alcohol,
phenytoin Dilantin or barbiturates reduce blood half-life or suppress
the immune system. Minocycline Minocin can be substituted, and for some
illnesses (RA) it is preferred because it penetrates tissues better (same
dose/day).


For GWI/CFS/FMS/RA use, the recommended oral dose is 200-300 mg/day (2-3X
100 mg capsules, 2 in the morning) for 6 months. After 6 months, 6 wk
cycles are suggested. Initially, doxycycline can exacerbate chronic signs
and symptoms (Herxheimer reactions or adverse responses, such as transient
fever, skin, gut discomfort, etc.) but these are usually reduced within a
few wks (see first section). Patients usually start feeling better with
alleviation of major signs and symptoms within 12 wks, but in some
patients’ major symptoms are not alleviated until after 12 wks. Severe
reactions or prior damage to the gastrointestinal track may require i.v.
administration of 100-150 mg/day (rapid i.v. administration must be
avoided) for 2-3 wks, then the remainder of the course should be oral (to
avoid thrombophlebitis and other complications that can occur with
prolonged i.v. therapy). Some patients react to the starch filler in the
capsules and must use Doryx, a granular form of pure doxycycline.
Virtually all patients relapse (show the same major signs and symptoms) if
they stop therapy before 6 months. In a pilot study, ~85% relapsed after
12 weeks of therapy, so the first 6 months without a break is recommended.
Doxycycline has been used successfully in addition to other antibiotics in
situations where either antibiotic alone had minimal effects (ie.,
doxycycline plus ciprofloxacin or doxycycline plus azithromycin).


Doxycycline and minocycline are primarily bacteriostatic and effective
against the following organisms: gram-negative bacteria (N. gonorrhoeae,
Haemophilus influenzae, Shigella species, Yersinia pestis, Brucella
species, Vibrio cholera); gram-positive bacteria (Streptococcus
pneumoniae, Streptococcus pyogenes); mycoplasmas (Mycoplasma pneumoniae,
Mycoplasma fermentans inc. incognitis strain, Mycoplasma penetrans);
others (Bacillus anthracis anthrax, Clostridium species, Chlamydia
species, Actinomyces species, Entamoeba species, Treponema pallidum
syphilis, Plasmodium falciparum malaria and Borrelia Lyme species).


Precautions: Avoid direct sunlight and drink fluids liberally, especially
with oral capsules. Doxycycline or minocycline therapy may result in
overgrowth of fungi or yeast and nonsensitive microorganisms (see
Considerations, first page). Patients on anticoagulants may require lower
anticoagulant doses. Use during pregnancy or in children under 8 years is
not recommended, in the latter case due to tooth discoloration, but lower
doses of doxycycline have proven to be very effective in children with
GWI/CFS (weight 100 lbs or less, 1-2 mg/lb divided into two doses; weight
over 100 lbs use adult dose). Patients with impaired kidney function
should not take doxycycline, and the following drugs should not be taken
with doxycycline: methoxyflurane Penthrane, carbamazepine Tegretol,
digoxin or diuretics. Other drugs can effect uptake or immune systems (see
above). For complicating bacterial infections, 2 wks Augmentin (3X 500
mg/day) can be taken in between courses of antibiotics. For fungal and
yeast complications, please see the instructions above.


Adverse Reactions: In a few patients doxycycline causes gastrointestinal
irritation, anorexia, vomiting, nausea, diarrhea, rashes, mouth dryness,
hoarseness and in rare cases hypersensitivity reactions, hemolytic anemia,
skin hyper-sensitivity and reduced white blood cell counts. In general,
doxycycline is considered a very safe drug, in that there are few adverse
reactions reported in the literature.


Ciprofloxacin (aka Cipro, Cifox, Cifran, Ciloxan, Ciplox)


Ciprofloxacin is a broad spectrum synthetic fluoroquinolone antibiotic
with good absorption characteristics. This drug acts on bacterial DNA
gyrase to inhibit bacterial DNA synthesis. Ciprofloxacin is secreted
rapidly in the urine and has a half-life in the blood of ~4 hrs. Food
delays the absorption (by ~2 hrs) but doesn’t effect total absorption;
antacids containing magnesium, aluminum or other salts as well as various
drugs reduce absorption and should not be taken at the same time of day.


For GWI/CFS/FMS use, the recommended dose is 1,500 mg/day (oral, 3X 500 mg
capsules, 2 in morning) for 6 months, then 6 wk cycles of therapy.
Ciprofloxacin may or may not be taken with meals. Initially, ciprofloxacin
may exacerbate some signs/symptoms (Herxheimer reactions or adverse
antibiotic responses) but these are usually gone within a few wks or so.
Patients report that doses of 1000 mg/day or lower are not effective in
alleviating symptoms. Patients usually start feeling better with
alleviation of major signs/symptoms within 4-6 wks, but in some patients
signs/symptoms are not reduced until after 6 wks. Ciprofloxacin has been
used for patients in which doxycycline cannot be tolerated or in some
patients that no longer respond to doxycycline. In a few cases
ciprofloxacin has been used simultaneously with doxycycline. Herxheimer
reactions, if present, usually pass within days to a few wks; prior damage
to the gastrointestinal system may require i.v. 400-500 mg X2/day (over
one hr per each infusion, rapid i.v. administration is to be avoided) for
2-4 wks, then the remainder on oral antibiotic (oral doses). Virtually all
patients relapse (with major signs/symptoms) if drug is stopped at in 6-12
wk course of therapy. Additional antibiotic courses result in milder
relapses after drug is discontinued. Subsequent cycles of antibiotics may
require the use of doxycycline or other antibiotics. Sparfloxacin, a
fluoroquinolone with better tissue penetration, can be substituted (oral
dose, 400 mg/day).


Ciprofloxacin is effective against the following organisms: gram-negative
bacteria (Shigella species, Citrobacter diversus, Citrobacter freundii,
Escherichia coli, Klebisella pneumoniae, Haemophilus influenzae,
Enterobacter species, Proteus vulgaris, Psuedomonas aeruginosa, Yersinia
pestis, Vibrio cholera), Moraxella catarrhalis; gram-positive bacteria
(Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus hominis,
Staphylococcus aureus, Staphylococcus saprophytieus); mycoplasmas,
moderately active (Mycoplasma species); others (Clostridium species,
Chlamydia species, Mycobacterium tuberculosis).


Precautions: Direct sunlight is to be avoided, especially with
sparfloxacin, and patients should not take floxacin and theophylline
concurrently. Ciprofloxacin therapy may result in drug crystals in the
urine in rare cases, and patients should be well hydrated to prevent
concentration of urine. Pregnant women and children should not use this
drug due to reduction in bone and cartilage development.


Adverse Reactions: Adverse antibiotic responses resulted in discontinuing
drug in ~3.5% of patients, and such reactions included nausea (5%),
diarrhea (2%), vomiting (2%) abdominal pain (1.7%), headache (1.2%) and
rash (1.1%). In rare cases cirprofloxacin may cause cardiovascular
problems (<1%) and central nervous system (dizziness, insomnia, tremor,
confusion, convulsions and other reactions (<1%). Small numbers of
patients have experienced hypersensitivity (anaphylactic) reactions which
have required immediate emergency treatment. Other drugs may effect
absorption and immune systems.


Azithromycin (aka Zithromax)


Azithromycin is a azalide (macrolide) antibiotic with good absorption and
a serum half-life of ~68 hrs. This class of drug acts by binding to the
50S ribosomal subunit of susceptible organisms where it interferes with
protein synthesis. Food decreases absorption rate, but absorption is
unaffected by antacids containing magnesium, aluminum or other salts;
other drugs may affect absorption (see above).


For GWI/CFS/FMS use, the recommended dose is 500 mg/day (oral, 2X 250 mg
capsules taken at once) for each 6-wk cycle of therapy. Azithromycin
should not be taken with meals (1 hr before or 1 hr after). Initially,
azithromycin may exacerbate some symptoms but these are usually gone
within a few weeks. Patients usually start feeling better with alleviation
of most major signs/symptoms within several weeks, but in some patients
major symptoms are not alleviated within months. Azithromycin has been
used for patients in which doxycycline cannot be tolerated or in patients
that no longer respond to doxycycline. Herxheimer reactions usually pass
within a few days to weeks. Virtually all patients relapse (show the same
major signs/symptoms) after terminating therapy in less than 12 wks.
Additional cycles of antibiotic result in milder relapses after drug is
discontinued. Azithromycin has been shown to be safe for pediatric use (10
mg/kg/day is recommended for children under 14, but see below).


Azithromycin is effective against the following organisms: gram-negative
bacteria (Bordetella pertussis, Shigella species, Haemophilus influenzae,
Chlamydia species, Yersinia pestis, Brucella species, Vibrio cholera);
gram-positive bacteria (Streptococci group C, F, G); mycoplasmas
(Mycoplasma species); others (Clostridium species, Treponema pallidum
syphilis, and Borrelia species).


Precautions: Azithromycin is principally absorbed by the liver, and
caution should be exercised with patients with impaired liver function.
Antacids containing magnesium, aluminum or other salts should not be taken
at the same time of day with azithromycin. Other drugs can also interfere.
Macrolides plus terfenadine Seldane or astemizole Hismaral may
dangeriously elevate plasma antihistamine and cause arrhythmias and
increase serum theophyline levels in some patients, particularly those
receiving methylated xanthine causing nausea, vomiting, seizures. Plasma
levels of carbamazepine Tegretol can also be elevated, leading to
carbamazepine toxicity and nausea, vomiting, drowsiness and ataxia.


Adverse Reactions: Adverse antibiotic responses were mild to moderate in
clinical trials and included diarrhea (5%), nausea (3%), abdominal pain
(3%). In rare cases (<1%) azithromycin may cause cardiovascular problems
(palpitations, tachycardia, chest pain) and central nervous system
(dizziness, headache, vertigo), allergic (rash, photosensitivity,
angioderma), fatigue and other reactions (<1%). In pediatric patients >80%
of the adverse responses were gastrointestinal. In children, doses above
the suggested 10 mg/kg/day have been shown to produce hearing loss in some
patients.


Clarithromycin (aka Biaxin)


Clarithromycin is a broad spectrum macrolide antibiotic with good
absorption and serum half-life. This drug acts by binding to the 50S
ribosomal subunit of susceptible organisms and interfering with protein
synthesis. The drug is mostly bacterostatic but high concentrations can be
bactericidal. Food decreases absorption rate, but absorption is unaffected
by antacids containing magnesium, aluminum or other salts. Some drugs may
interfere with absorption or depress immune systems (see above).


The recommended dose is 500-750 mg/day (oral, 2-3X 250 mg capsules, 2
taken in morning) for 6 months of therapy, then 6-wk cycles.
Clarithromycin should not be taken with meals (1 hr before or 1 hr after).
Initially, clarithromycin may exacerbate some symptoms due to Herxheimer
reactions and bacterial death but these are usually gone within wks.
Patients usually start feeling better with alleviation of most major signs
and symptoms within 1-2 wks, but in some patients major symptoms are not
alleviated until after 12 wks or so. Clarithromycin has been used for
patients that do not respond or cannot tolerate doxycycline. Herxheimer
reactions usually pass within days to wks. Virtually all patients relapse
(show the same major signs/symptoms) when therapy is stopped within 12
wks. Additional cycles of antibiotic result in milder relapses after drug
is discontinued. For children, the recommended dose is 15 mg/kg/day X2; at
this dose some children have gastrointestinal problems.


Clarithromycin is effective against the following organisms: gram-negative
bacteria (Neisseria gonorrhoeae, N. menigitidis, Moraxella catarrhalis,
Campylobacter jejuni, Eikenella corrodens, Haemophilus ducreyi, Bordetella
pertussis, Shigella species, Salmonella species, Haemophilus influenzae,
Chlamydia species, Yersinia pestis, Brucella species, Vibrio cholera,
Aeromonos species, E. coli, gram-positive bacteria (Streptococcus
pyogenes, S. pneumeniae, anerobic Streptococci, Enterococcus faccalis,
Staphlococcus aureus, S. epidermidis, Bacillus anthracis, Corynebacterium
diptheriae, C. minutissimum, Listeria monocytogenes, Actinomyces
israelii); mycoplasmas (Mycoplasma species, M. pneumoniae, Ureaplasma
urealyticum); others (Clostridium species, Treponema pallidum syphilis,
Legionella pneumophilia, L. micdadei, Mycobacterium avium, M. chelonae, M.
chelonae absessus, M. fortuitim, Rickettsia species and Borrelia species).
Yeasts, fungi and viruses are resistant.


Precautions: Clarithromycin is principally absorbed by the liver, and
caution should be exercised with patients with impaired liver function.
Antacids containing magnesium, aluminum or other salts should not be taken
at the same of day as azithromycin. Other drugs may also interfere (see
above). Macrolides plus terfenadine Seldane or astemizole Hismaral may
dangerously elevate plasma antihistamine and cause arrhythmias and
increase serum theophyline levels in some patients, particularly those
receiving methylated xanthine causing nausea, vomiting, seizures. Plasma
levels of carbamazepine Tegretol can also be elevated, leading to
carbamazepine toxicity and nausea, vomiting, drowsiness and ataxia.
Macrolides like clarithromycin should not be used with cyclosporin
Sandimmune.


Adverse Reactions: Adverse antibiotic responses were mild to moderate in
clinical trials and included diarrhea, nausea, and abdominal pain. In rare
cases (<1%) azithromycin may cause cardiovascular problems (palpitations,
tachycardia, chest pain) and central nervous system (dizziness, headache,
vertigo), allergic (rash, photosensitivity, angioderma) and fatigue.


Clindamycin (aka Cleocin, Dalacin, Lacin)


Clindamycin is a semisynthetic antibiotic made from lincomycin and is
effective against severe anaerobic infections. It is primarily
bacteriostatic against a wide range of Gram-positive and anaerobic
pathogens, including some protozoa. It has good absorption and tissue
penetration; its half-life is ~3 hrs in adults and ~2 hrs in children.
Since clindamycin use can result in severe colitis even weeks after
cessation of the drug, it should not be used as primary therapy. Food does
not adversely affect absorption rate, but absorption is affected by
antacids containing magnesium, aluminum or other salts. Some drugs may
interfere with absorption or depress immune systems (see above).


The recommended dose is 600-1200 mg/day (oral, 4-8 X 150 mg capsules, in
three divided doses) for 6-wk cycles of therapy. Herxheimer reactions may
exacerbate signs/symptoms but these are usually gone within days-weeks.
Patients usually start feeling better with alleviation of most major signs
and symptoms within days-weeks, but in some patients major symptoms are
not alleviated until after several weeks or so. For children, the
recommended dose is 8-16 mg/kg/day divided into 3-4 doses.


Precautions: Clindamycin should not be used for patients with nonbacterial
(viral, fungal) infections. Its use is associated in some patients with
colitis and severe, persistent diarrhea and abdominal cramps, and when
this occurs the drug should be discontinued. It must not be used with
opiates or diphenoxylate with atropine Lomotil. Patients with hepatic or
renal problems require dosage adjustment. Antidiarrheal drugs that reduce
peristalsis, such as dipenoxylate, loperamide or opioids, should be
avoided. If prolonged therapy is used, periodic liver and kidney function
tests and blood counts should be performed. Clindamycin should not be used
by pregnant women, and prolonged use can result in overgrowth of yeasts
and other nonsusceptible microorganisms. Cholestyramine or colestipol
resins bind clindamycin and should not be administered simultaneously.


Adverse Reactions: Adverse antibiotic responses were mainly diarrhea in
2-20% of cases, some severe and dangerous (colitis). Psuedomembranous
colitis may develop during or several weeks after therapy. This can be
serious if ignored. Other gastrointestinal effects of the drug have been
reported (nausea, vomiting, esophagitis, abdominal pain or cramps), and
hypersensitivity reactions, including skin rashes occur in up to 10% of
patients. Mild cases of colitis should be managed promptly with fluid,
electrolyte and protein supplementation as indicated. Other effects
include transient leucopenia, polyarthritis and abnormal liver function
(jaundice and hepatic damage rarely occur). Clindamycin should not be used
with erythromycin. Clindamycin has been shown to have neuromuscular
blocking properties that may enhance the action of other neuromuscular
drugs. Clindamycin should only be used with caution in patients receiving
such drugs.


Final Comments


Recovery will be gradual not rapid, and almost all patients experience
initial Herxheimer reactions that can be quite severe and can last for
weeks. You will have to be patient and not abandon therapy prematurely,
because few patients recover in less than one year of therapy. Do not take
antibiotics at the same time of day as vitamins, minerals, supplements,
etc. Vitamins and minerals should be taken 3 hrs after antibiotics to
prevent interference with antibiotic uptake. Stop antibiotics if adverse
reactions continue. You will experience cycles of relapse when severely
physically or mentally stressed, and you should not be alarmed if some
signs and symptoms occasionally return or worsen. This is not unusual.
Eventually you will be off antibiotics but you will need to continue
various supplements to maintain your immune system



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