Combined antibiotic cure my experiences with Lyme borreliosis since 1984

1
Combined antibiotic curemy experiences with
Lyme borreliosis since 1984

• Bózsik, Béla Pál, M. D.
• the Therapeutic Workgroup,
• Lyme Borreliosis Foundation,
• HUNGARY

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GENESIS 3.15 I will put enmity between thee an
d the woman, and between thy seed and her seed
it shall bruise thy head, and thou shalt bruise
his heel. REVELATION 12.1. And there appeared a
great wonder in heaven a woman clothed with th
e sun, and the moon under her feet, and upon her
head a crown of twelve stars
7. And there was war in heaven Mic
hael and his angels fought against the dragon
and the dragon fought and his angels, and
prevailed not neither was their place found any
more in heaven. And the great dragon was cast ou
t, that old serpent, called the Devil, and Sat
an, which deceiveth the whole world
he was cast out into the earth, and his angels
were cast out with him. 10. And I heard a loud
voice saying in heaven, Now is come salvation, a
nd strength, and the kingdom of our God, and
the power of his Christ for the accuser of our
brethren is cast down, which accused them before
our God day and night.
3
It is the old enemy
which
will be defeated
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The best opportunity to fulfill our medical oath
is close at hand Salus aegroti suprema lex est
o
The well-being of the patient is
the most important law, really.
The best example could be Lyme borreliosis it
is endemic, its causative agent is known, it co
uld be determined, its pharmacy is known, so, it
is curable.
5
Lyme borreliosis has been known
since the ancient times when Man was in close co
ntact with nature. Scleroderma was described by
Galenus
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endemic Lyme borreliosis
Bózsik, Vienna 1985
was estimated to affect AS much as 10 of the
population
at least
Bózsik, Lancet 2004
Because of problems with diagnosis and
differential diagnosis, there is no exact
epidemiological data
Due to problems with therapy and
the long persistence of infection,
patients accumulate in the population
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The WORLD of The causative agent of Lyme bo
rreliosis
The Phylogenetic tree
Constructed by Baranton, G et workgroup, 2002
The genetic plasticity of Borrelia burgdorferi se
nsu lato Gives it the possibility to change its
character Both in nature Within the body du
ring the whole disease process
8
The causative agent of Lyme borreliosis is sen
sitive
to several well known antibiotics.
Therefore, One might assume that it is easy to c
ure. However, for this to be true, one needs a
firm diagnosis.
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It is time we reevaluated our view on SYNDROME
S
The uncommon clinical picture of Lyme borreliosis
develops as a result of macromolecular immune
complexes.
Major and minor symptoms undulate,
TREATMENT MAY IMPROVE THE SYMPTOMS OF Lyme
borreliosis, WHILE LEAVING OTHER CONDITIONS
UNAFFECTED!
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It is the time to reevaluated
our opinion on DIAGNOSIS
Epidemiologic or Academic principles -in some
relation need culture positivity and/or two tier
s determinations- could fail the patients with n
egative ELISA as they will not undergo Western-b
lot testing. Some tend to forget that although
these are good scientific tools,
we should not think more of them.
Once again beware Only 64 of the patients
met the surveillance case definition for Lyme
disease. (JAMA 2002) so, at least 36 of the
sufferings were missed.
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It is the time to think again
our opinion on DIAGNOSIS

• Insurance medicine principles of diagnosis
• it missed their original idea about the
  socialised medicine
  
• helping people in distress and rising the level
  of common health
  
• covers expensive investigations,
• accepts wheel chair, but from inexplicably cause
• refuse serologic investigations and/or
• antibiotic treatment(s) all over the world.
• Disability of even the young and the most
  progressive people
  
• of the society is accepted provided, for while
  proper serologic
  
• Investigations treatments are not cover.

Therefore, missed cases of Lyme borreliosis also
place an economic burden on society.
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It is the time to think again
our opinion on DIAGNOSIS
American College of Physicians stated
the diagnosis of Lyme borreliosis depending on
epidemiological and clinical data reported from
the patients it is really founded
the basic principles of the consultative
diagnosis. Despite this statement stopping short
of accepting the possibility of seronegative ca
ses, for instance, it did to introduce clinical
consultation Into the process of making the diag
nosis.
This gets us close to what the evaluation
process
should be like in my view.
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It is the time to think again
our opinion on DIAGNOSIS
Patient-centered principles of diagnosis care
based on the latin proverb, on which the medical
practice should be founded Salus aegroti supre
ma lex, esto. "The well-being of the patient
is the most important law, really."
The well-being of the patient, providing this
well-being making scientific development is th
e best goal, which may be expressed as follows
Evidence Based Medicine in Lyme borreliosis
should involve five years follow-up practice in
each case, as it is in every Spirochetosis.
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It is the time to think again
our opinion on DIAGNOSIS
Special possibility of the patient-centered diag
nosis based on the confidential collaborations
consultation Ex iuvantibus diagnosis, which i
s part of the ART OF MEDICINE DECISION-TREATME
NT-FOLLOW UP-DECISION According to the clinical p
icture!
It is not ultimUM refugium It is real chance fo
r Diagnosis treatment It is Not the last possi
bility!
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Thinking again the DIAGNOSIS The Summary
My remarks Making the appropriate diagnosis
relies more more on laboratory determinations
Indicating the treatment developing the
schedule left to clinical science
Follow up patients both of them.
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Thinking again the DIAGNOSIS The Summary
Recommend the followings questions

• Were you or could you bitten by a tick?
• Can you retain that tick(s) for analysis?
• Has Lyme-spot developed on body any time?
• Where were they located geographically
• and anatomically?
• Did the signs fluctuate?
• How long was the cycle of fluctuation
• in weeks time?

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The Summary of DIAGNOSIS Having answered these qu
estions
Unit-time for cure FOUR-SIX WEEKS
Unit-time 2-3 weeks
The required DURATION of the treatment
can be established as 4-6 weeks or more
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The Summary of DIAGNOSIS Having answered the ques
tions

• Informations is needed regarding previous
  treatments with antibiotics
  
• This is the so-called
• ANTIBIOTIC CASE-HISTORY
• THE THERAPEUTIC SCHEDULE
• ALSO BASED ON THIS INFORMATION.

There are no clear-cut ending of the symptoms,
therefore could not applied the old rule Abx
treatment continues up to disappearing the sympt
oms3days
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The Summary of DIAGNOSIS The Consequence
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Which antibiotic should be prescribed

• On the Stockholm Conference (1st with Lyme
  borreliosis term)
  
• there were fiery debate
• for and against the two basic antibiotics
• PENICILLIN its derivatives
• DOXYCYCLINS, and
• FLUOROQUINOLONS were postered
• to have no effect on Borrelia
• ERYTHROMYCINS have no effect in our practice

What a sorrowful situation it was!
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Which antibiotic should be prescirbed
Having realized this situation
the only option was to investigate combinations
of abx with other one, which is registered pr
oven to be effective against Borrelia
What a solution the results was!
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In vitro effects of antibiotic combinations
Synergistic effect on doxycycline HUNDRED times
multiplication of Borrelia burgdorferi is
undisturbed no Borrelia burgdorferi can be
detected ? multiplication of Borrelia burgdo
rferi is partly inhibited inhibitory effec
t expected according to individual
MIC-values(PosC) inhibitory effect observed
in the combination
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In vitro effects of antibiotic combinations
Synergistic effect on ceftriaxon

TEN times
multiplication of Borrelia burgdorferi is
undisturbed no Borrelia burgdorferi can be
detected ? multiplication of Borrelia burgdo
rferi is partly inhibited inhibitory effec
t expected according to individual
MIC-values(PosC) inhibitory effect observed
in the combination
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Which antibiotic should be prescribed
The excessive synergism noted shed light on the
importance of DNA-gyrase in Borrelia with plasti
c genetic material good adaptation to any envi
ronment.
What a solution!
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Which antibiotic should be prescribed
Fibroblasts protected B. burgdorferi for at least
14 days of exposure to ceftriaxone. several
eu-karyotic cell types provide the Lyme disease
spirochete with a protective environment
contributing to its long-term survival. Ceftriaxon
e, Borrelia burgdorferi, Cultivation, in vitro,
fibroblast, protection _ Klempner et al
J-Infect-Dis. 1992
Borrelia b.persisted inside synovial cells for at
least 8 weeks.
_Girschick-HJ et al 1996
Intracellular(!) Borrelia to be destroyed
it needs as much abx as twenty quantity of MIC
Doxycycline in a dose of 200 mg/day
does not produce effective concentrations in CSF

The dose of DOXYCYCLINE is 300 to 400 mg a day
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The keys to effective treatment?
First, prevent adaptation fluoroquinolones
Second, develop an individualized therapeutic
schedule based on the antibiotic dinamics
antibiotic case history Third, determine sub-s
train(s) to aid the develop-ment of an
individualized schedule B.afzelii dox
ycylin, B.burgd.s.s. clarithro
mycin B.garinii penicillin its deri
vatives For this reason there is good chance with
PCR from TICK(removed/regional), patients samp
les Wb concentrated(half of the working dilutio
n) samples to recognize the substrain(s)
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CURED Cured Completly and free from any
symptoms.
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Evidence
Based
Medicine
O
rv
H
etil
2
000,141
1
06
-
111,
2002,143
1223
--
1224.
Patients without any symptomes were proved as
CURED!
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Autoaggressive seronegative LYME BORRELIOSIS

• 17 yr old professional sports-woman (dancer)
• Numerous tick-bites in Sept 1999 but no ecm
• vertigo, polyneuritis
• 1st WB lyme borreliosis (Dr.lakos)
• rocephin 2g/die for 11 days
• school-acquired infection on the 10th day,
  07.12.1999
  
• gradual improvement,
• another infection
• myasthenia begins in feb 2002
• myasthenia crises (4x)
• Mestinon, medrolimuran, plasmapheresis
• gastrostoma
• oct and nov 2001 WB_seronegative
• positive microscopy result
• Dgautoagressive lyme borreliosis
• two different medical conditions or complicated
  LB
  
• 1st Wb 4th (feb 2003) seropositivi-ty with
  newly developed kit supported by the result of
  pcr (B.burg.s.s)

Myasthenia Gravis syndrome
clinical evidence of immunocomplex-mediated da
mage With infective origin to the neuromuscular
junction end-plate flattening decreased signal t
ransduction
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therapeutic schemes considerations

• pathogenetically
• therapeutic dilemma medications used in the
  treat-ment of lb contraindicated in myasthenia,
  _ drugs used for myasthenia may exacer-bate
  lyme borreliosis .
• therapy ceftriaxon 2g BID plus ofloxacin 200 mg
  BID,
  
• followed by Doxycycline 200mg BID,
• liver damage!
• followed by Clarithromycin 150mg QID then 500mg
  BID,
  
• Psychotherapy
• treatment for 24 weeks
• Orsi became weaker during the first 8 days of
  treatment but fortunately her breathing was not
  jeopardized. she had pain in her muscles, joints
  and lymph nodes and she chilled with fever. Her
  joints became floppy. she started to get better
  on the 10th day, and by now she can walk
  considerable distances with assistance. She can
  also swallow better, and her balance has
  imporoved, as well.
• Quote from mother, 10 Nov, 2002

• in the classical sense
• Lyme borreliosis was cured or is disregarded
  in the pathogenesis of severe Myasthenia gravis
  
• discontinuation of steroid therapy may extend the
  length of crises or even lead to death
  
• recommended therapy/preven-tion for severe
  Myasthenia gravis
  
• MEDROL/IMURAN (40MG daily for a year in this
  case)
  
• PLASMAPHERESIS
• Gammaglobin i.v.

• Clinical solution (?)
• further evaluation home abroad,
• avoid abx for fear of side effects,
• discontinue steroids
• endanger the patient
• or disregard the opinion stating it is a case
  of myasthenia that has nothing to do with the
  previous Lyme borreliosis

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Autoaggressive seronegative LYME
BORRELIOSISafter 24 weeks of treatment with
antibiotics
gorsium, tác
wildlife park, Budakeszi
in may 2003 she left the wheelchair
After 3 years in it (hidden cameras)
family happy society satisfied hypothesis proven
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Orsi D. getting better at the age of 21
The best movies her PARENTS FAMILY have ever
seen
in may 2003 she stood up from the wheelchair to
start gardening family happy society satisfied
new professional approach
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Some of Our Cases with Lyme Borreliosis Seronegat
iva

• Av block treatment with antibiotics instead of a
  Pacemaker. pt later became a professional
  sportsman (water polo) again
  
• -request for publication rejected
• Carditis myelosuppression _ following
  treatment with ineffec-tive antibiotic
  (Rocephin) _improvement after 1 week treatment
  with effective antibiotic (Tienam) complete
  recovery after 4 week treat-ment with effective
  antibiotic (Tienam) weight loss (16 kg) after
  the discontinuation of steroid therapy. _
  reoccuring lb was denied to treat abx she died
  after the reinstitution of steroid therapy.
• She was a 27 yr old medical student about
  to complete her studies
  
• facial Paresis unwarranted (?!) treatment with
  antibiotics pt, she was a model, recovered
  quickly and completely
  
• Raynauds syndrome symptoms worsened by heat _
  improved after treatment with antibiotics
  (lancet, 1990)
  
• familial Lyme borreliosis mother has RA at the
  age of 18,
  
• daughter has anosmia, son has ptosis
  _ all three of them get better after treatment
  with antibiotics _ anosmia congenitalis milder!
  
• Rheumatoid arthritis After 2 yrs of standard
  therapy the diagnosis of Lyme borreliosis is
  made pt he can ride the bicycle a country-tour
  play tennis after treatment with antibiotics
• Rheumatoid arthritis _ 5 yrs of pain after
  ineffective antibiotic therapy (rocephin)
  complete recovery following effective antibiotic
  therapy (doxycycline IV.)
• Guillon-barré syndrome reatment before surgery _
  full recovery treatment after surgery sustained
  paresis
  
• multiple Sclerosis syndromes (LB_labor
  MS_clinical without therapy wheelchair with
  therapy no wheelchair, university student

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What could be done for the more effective
treatment?
Psychoses could be cured by fever - notes since
Hyppocrates Galenus. Introduced MALA-RIA in
curing neurosyphilis by Wagner von Jauregg Nobe
l prize, 1927
CSF
cultivation
bio-energy
Brorson O, Brorson SH , 2004
Modern possibilities for FEVER therapy far-infr
a-red saunas
with 10 nm irradiation
controll
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What could the future bring?
AGGREMENT?
Debate?
As I HOPE!
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