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Combined antibiotic cure
–my experiences with Lyme borreliosis since 1984–
Bózsik, Béla Pál, M. D.
& the Therapeutic Workgroup,
Lyme Borreliosis Foundation,
HUNGARY
GENESIS 3.15
… I will put enmity between thee and 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 the sun, and the moon under her feet, and upon
her head a crown of twelve stars:
– …… –
– 7. And there was war in heaven:
Michael 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 out,
that old serpent,
called the Devil, and Satan, 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,
It is the old enemy
which
will be defeated
The best opportunity
to fulfill our medical oath is close at hand:
„Salus aegroti suprema lex esto”
– 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 could be determined,
its pharmacy is known,
so, it is curable.
Lyme borreliosis has been known
since the ancient times when
Man was in close contact
with nature.
Scleroderma was described by Galenus
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
The WORLD
of The causative agent of
Lyme borreliosis
The Phylogenetic tree
Constructed
by
Baranton, G et workgroup,
2002
The genetic plasticity of
Borrelia burgdorferi sensu lato
Gives it the possibility
to change its character
Both in nature &
Within the body
during the whole
disease process
The causative agent
of Lyme borreliosis
is sensitive
to several
well known antibiotics.
Therefore,
One might assume that
it is easy to cure.
However, for this to be true,
one needs a firm diagnosis.
It is time we reevaluated
our view on SYNDROMES
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!
It is the time to reevaluated
our opinion on DIAGNOSIS
pidemiologic or Academic principles -in some relation ne
culture positivity and/or „two tiers” determinationscould fail the patients with negative ELISA
as they will not undergo Western-blot 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
et the surveillance case definition for Lyme disease
o,
(JAMA 2002)
at least 36% of the sufferings were miss
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 h
*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 peo
of the society is accepted & provided, for while proper sero
Investigations & treatments are not cover.
Therefore, missed cases of Lyme borreliosis also
place an economic burden on society.
It is the time to think again
our opinion on DIAGNOSIS
American College of Physicians stated:
he diagnosis of Lyme borreliosis depending on epidemiological an
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 cases, for instance,
it did to introduce clinical consultation
Into the process of making the diagnosis.
This gets us close to what the evaluation process
should be like in my view.
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
ould be founded: Salus aegroti suprema lex, esto. —
he 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 the best goal,
which may be expressed as follows:
Evidence Based Medicine in Lyme borreliosis should involv
five years follow-up practice in each case,
as it is in every Spirochetosis.
It is the time to think again
our opinion on DIAGNOSIS
Special possibility of
the patient-centered diagnosis
based on the confidential collaborations & consultation
Ex iuvantibus diagnosis,
which is part of the
ART OF MEDICINE:
TREATMENT-FOLLOW UP-DECISION
It is not ultimUM refugium
It is real chance for Diagnosis & treatment
It is Not the last possibility!
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.
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?
The Summary of DIAGNOSIS
Having answered these questions:
Unit-time for cure:
FOUR-SIX WEEKS
Unit-time:
three weeks
The required DURATION of the treatment
can be established as 4-6 weeks
The Summary of DIAGNOSIS
Having answered the questions:
Informations is needed regarding
previous treatments with antibiotics:
This is the so-called
ANTIBIOTIC CASE-HISTORY
THE THERAPEUTIC SCHEDULE
ALSO BASED ON THIS INFORMATION.
The Summary of DIAGNOSIS
The Consequence
N sa i d + Ph y si o t h e r a p y
Se d a t i v e a n d /o r a n t i d e p r e ssa n t d r u g s
56
46
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!
Which antibiotic
should be prescirbed
Having realized this situation
the only option was to investigate
combinations of abx with one ab
in the combination licensed and
proven to be effective against Borrelia
What a solution!
In vitro effects of antibiotic combinations
pefloxacin
40,000
0,400
0,040
0,004
µg/ml
doxycycline
40,0000
4,0000
4,000
–
–
–
–
–
–
–*
–
–
–
?
?
– effect
–
0,4000
Synergistic
on– doxycycline:
–
0,0400
0,0040
0,0004
–
+**
+
?
–
HUNDRED
times
+
+
?
–
+
+
+
+
+
+ : multiplication of Borrelia burgdorferi is undisturbed
– : no Borrelia burgdorferi can be detected
? : multiplication of Borrelia burgdorferi is partly inhibited
* : inhibitory effect expected according to individual MIC-values(PosC)
**: inhibitory effect observed in the combination
In vitro effects of antibiotic combinations
pefloxacin
40,000
0,400
0,040
0,004
µg/ml
4,000
ceftriaxon
–
–
–
–
–
–
–*
–
?
?
0,0100
–
–
0,0010
–
TEN
0,0001
–
?
10,0000
Synergistic
effect
on
ceftriaxon:
–
–
–
–
–
1,0000
0,1000
?
+**
+
times
+
+
+
+
+
+
+
+ : multiplication of Borrelia burgdorferi is undisturbed
– : no Borrelia burgdorferi can be detected
? : multiplication of Borrelia burgdorferi is partly inhibited
* : inhibitory effect expected according to individual MIC-values(PosC)
**: inhibitory effect observed in the combination
Which antibiotic
should be prescirbed
The excessive synergism
noted shed light on
the importance
of DNA-gyrase
in Borrelia with plastic genetic
material & good adaptation
to any environment.
What a solution!
What antibiotic dosage
should be prescirbed
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. Ceftriaxone, 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 MIC of abx
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
The prerequisites of effective
therapy
•prevent changes in the genetic material,
material an indication
for using ciprofloxacine
while
•
inflict damage on cell wall generation or metabolism (with
the antibiotic case history in mind) in order to kill all
spirochetes, including those intracellularly and in the brain
•This is the sumary of my hypothesis
formed in 1990, and later verified in
vitro & at the bed-side.
The keys to effective
treatment?
First, prevent adaptation fluoroquinolones
Second, develop an individualized
therapeutic schedule based on the
antibiotic case history
Third, determine sub-strain to aid the
development of an individualized
schedule:
B.afzelii:
doxycylin,
B.burgd.s.s.: clarithromycin
B.garinii:
penicillin & its derivatives
Approved schedule
– for individual prescription:
3 x 250 – 500 mg/die
At the same time prescribed:
doxycycline
3 x 100 – 2 x 200 mg/die
klarithromycine
3 x 250 – 500 mg/die
josamycine
3 x 500 –1000 mg/die
ceftriaxone I.V.
1-2 x 2000
mg/die
klarithromycine I.V. 3 x 250–2x1000 mg/die
doxycycline I.V.
2 x 200-400
mg/die
ciprofloxacine
In combination for individual application
 SEVERAL PERIODS OF 3-4 WEEKS,
 SUPPLEMENTED vitamins and trace elements,
 supporting immune systems, rehabilitate spirite & body
CURED = Cured Completly and free from any symptoms.
Evidence
Based
Medicine=
OrvHetil 2000,141:106-111, 2002,143:1223--1224.
Patients without any symptomes were proved as CURED!
Autoaggressive & seronegative LYME BORRELIOSIS
&
Myasthenia
Gravis
syndrome
!
!
!
!
!
!
!
!
!
clinical evidence
!
of immunocomplex-mediated
!
damage With infective origin
to the neuromuscular junction
end-plate flattening
decreased signal transduction
!
!
!
!
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, medrol+imuran, plasmapheresis
gastrostoma
oct and nov 2001 WB_seronegative
positive microscopy result
Dg:autoagressive 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)
therapeutic schemes & considerations
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:
B MEDROL/IMURAN (40MG daily for a year in this case)
B PLASMAPHERESIS
B 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
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
Autoaggressive seronegative LYME BORRELIOSIS
after 24 weeks of treatment with antibiotics
wildlife park, Budakeszi
in may 2003 she left the wheelchair
After 3 years in it (hidden cameras)
family happy– society satisfied– hypothesis proven
gorsium, tác
Orsi D.PARENTS
getting better at&theFAMILY
age of 21 have ever seen
The best movies her
in may 2003 she stood up from the wheelchair to start gardening
family happy– society satisfied– new professional approach
Some of Our Cases with
Lyme Borreliosis Seronegativa
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

facial Paresis: unwarranted (?!) treatment with antibiotics– pt, she was a model, recovered quickly and completely
Raynaud’s syndrome: symptoms worsened by heat _ improved after treatment with antibiotics (lancet, 1990)
familial Lyme borreliosis : mother has RA at the age of 18,
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…






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
What could be done
for the more
effective treatment?
«Psychoses could be cured by
fever» - notes since Hyppocrates
& Galenus. Introduced MALARIA in curing neurosyphilis by
Wagner von Jauregg
CSF
cultivation
Brorson O, Brorson SH , 2004
Nobel prize, 1927
bio-energy
Modern possibilities
controll
for FEVER therapy
far-infra-red saunas
with 10 nm irradiation
What could
the future bring?
AGGREMENT?
Debate?
As I HOPE!