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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,

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  • Combined antibiotic curemy experiences with Lyme borreliosis since 1984 Bzsik, Bla Pl, 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, Now is come salvation, and strength, and the kingdom of our God, andthe power of his Christ: for the accuser of our brethren is cast down, which accused them before our God day and night.

  • It is the old enemywhichwill 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 isthe 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 knownsince the ancient times when Man was in close contact with nature.Scleroderma was described by Galenus

  • was estimated to affectAS much as 10 % of the populationat leastBzsik, Lancet 2004Because 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 populationBzsik, Vienna 1985endemicLyme borreliosis

  • The WORLD of The causative agent of Lyme borreliosis Constructed by Baranton, G et workgroup, 2002The genetic plasticity ofBorrelia burgdorferi sensu latoGives it the possibility to change its character Both in nature &Within the bodyduring the whole disease processThe Phylogenetic tree

  • The causative agent of Lyme borreliosis is sensitiveto several well known antibiotics. Therefore,One might assume thatit is easy to cure.However, for this to be true, one needs a firm diagnosis.

  • TREATMENT MAY IMPROVE THE SYMPTOMS OF Lyme borreliosis, WHILE LEAVING OTHER CONDITIONS UNAFFECTED!The uncommon clinical picture of Lyme borreliosis develops as a result of macromolecular immune complexes. Major and minor symptoms undulate, It is time we reevaluated our view on SYNDROMES

  • It is the time to reevaluated our opinion on DIAGNOSISEpidemiologic or Academic principles -in some relation needculture positivity and/or two tiers determinations-could 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 met the surveillance case definition for Lyme disease. (JAMA 2002) so, at least 36% of the sufferings were missed.

  • 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 causerefuse 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.It is the time to think again our opinion on DIAGNOSISTherefore, missed cases of Lyme borreliosis alsoplace an economic burden on society.

  • It is the time to think again our opinion on DIAGNOSISAmerican College of Physicians stated:the diagnosis of Lyme borreliosis depending on epidemiological and clinical data reported from the patients it is really foundedthe 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 processshould be like in my view.

  • It is the time to think again our opinion on DIAGNOSISPatient-centered principles of diagnosis & care based on the latin proverb, on which the medical practice should be founded: Salus aegroti suprema 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 the 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.

  • It is the time to think again our opinion on DIAGNOSISSpecial 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-DECISIONIt is not ultimUM refugium It is real chance for Diagnosis & treatmentIt is Not the last possibility!

  • Thinking again the DIAGNOSISThe 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 DIAGNOSISThe 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 DIAGNOSISHaving answered these questions:The required DURATION of the treatment can be established as 4-6 weeks Unit-time: three weeks Unit-time for cure: FOUR-SIX WEEKS

  • Informations is needed regarding previous treatments with antibiotics:This is the so-calledANTIBIOTIC CASE-HISTORYTHE THERAPEUTIC SCHEDULEALSO BASED ON THIS INFORMATION.The Summary of DIAGNOSISHaving answered the questions:

  • The Summary of DIAGNOSISThe Consequence

  • Which antibiotic should be prescribedOn 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 prescirbedHaving realized this situationthe only option was to investigatecombinations of abx with one ab in the combination licensed andproven to be effective against BorreliaWhat a solution!

  • + : 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 combinationIn vitro effects of antibiotic combinationsSynergistic effect on doxycycline:HUNDRED times

    pefloxacin g/mldoxycycline40,000

    4,0000,4000,0400,00440,00004,0000 *0,4000??0,0400 +**++0,0040?+++0,0004?+++

  • + : 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 combinationIn vitro effects of antibiotic combinations Synergistic effect on ceftriaxon:

    TEN times

    pefloxacin g/mlceftriaxon40,000

    4,0000,4000,0400,00410,00001,0000 0,1000*??0,0100 +**++0,0010?+++0,0001?+++

  • Which antibiotic should be prescirbedThe excessive synergismnoted shed light onthe importanceof DNA-gyrasein Borrelia with plastic geneticmaterial & good adaptationto any environment.What a solution!

  • Borrelia b.persisted inside synovial cells for at least 8 weeks. _Girschick-HJ et al 1996Fibroblasts 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 What antibiotic dosage should be prescirbedintracellular Borrelia to be destroyedit needs as much abx as twenty MIC of abxDoxycycline 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 therapyprevent changes in the genetic material, an indication for using ciprofloxacinewhile 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 brainThis 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 fluoroquinolonesSecond, develop an individualized therapeutic schedule based on the antibiotic case historyThird, 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:

    ciprofloxacine 3 x 250 500 mg/dieAt the same time prescribed:doxycycline 3 x 100 2 x 200 mg/die klarithromycine 3 x 250 500 mg/diejosamycine 3 x 500 1000 mg/dieceftriaxone I.V. 1-2 x 2000 mg/dieklarithromycine I.V. 3 x 2502x1000 mg/diedoxycycline I.V. 2 x 200-400 mg/dieIn combination for individual application SEVERAL PERIODS OF 3-4 WEEKS, SUPPLEMENTED vitamins and trace elements, supporting immune systems, rehabilitate spirite & body

  • A hatkony kezels felttele, hogy a genetikai llomny mdosulsait megakadlyoz-zuk, ezrt is kell ciprofloxacint alkalmaznis egyidejleg a sejtfal felplst, vagy az anyagcsere folyamatokat a krokoz aktulis antibiotikum rzkenysgt anti- biotikum anamnzis flvtelvel valsznstve kro-stsuk, s a krokoz(ka)t A SEJTEKBEN IS, AZ AGY-SZVETBEN IS elpuszttsuk. Az 1990-ben kialaktott, in vitro vizsglattal igazolt , hypothesisemnek ez a lnyege.

  • CURED = Cured Completly and free from any symptoms.

  • OrvHetil2000,141:106-111, 2002,143:1223--1224. EvidenceBased Medicine= Patients without any symptomes were proved as CURED!

  • 17 yr old professional sports-woman (dancer)Numerous tick-bites in Sept 1999 but no ecmvertigo, polyneuritis1st WB: lyme borreliosis (Dr.lakos)rocephin 2g/die for 11 daysschool-acquired infection on the 10th day, 07.12.1999gradual improvement, another infectionmyasthenia begins in feb 2002myasthenia crises (4x)Mestinon, medrol+imuran, plasmapheresisgastrostomaoct and nov 2001 WB_seronegativepositive microscopy resultDg:autoagressive lyme borreliosistwo different medical conditions or complicated LB1st Wb & 4th (feb 2003) seropositivi-ty with newly developed kit supported by the result of pcr (B.burg.s.s)Autoaggressive & seronegative LYME BORRELIOSISclinical evidence of immunocomplex-mediateddamage With infective origin to the neuromuscular junctionend-plate flatteningdecreased signal transductionMyastheniaGravissyndrome&

  • therapeutic schemes & considerationsin the classical senseLyme 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)PLASMAPHERESISGammaglobin i.v.pathogeneticallytherapeutic 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,Psychotherapytreatment for 24 weeksOrsi 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

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

  • Autoaggressive seronegative LYME BORRELIOSISafter 24 weeks of treatment with antibiotics in may 2003 she left the wheelchairAfter 3 years in it (hidden cameras)family happy society satisfied hypothesis provenwildlife park, Budakeszi gorsium, tc

  • in may 2003 she stood up from the wheelchair to start gardeningfamily happy society satisfied new professional approachOrsi D. getting better at the age of 21The best movies her PARENTS & FAMILY have ever seen

  • Av block: treatment with antibiotics instead of a Pacemaker. pt later became a professional sportsman (water polo) again-request for publication rejectedCarditis & 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 completelyRaynauds 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 antibioticsRheumatoid arthritis: _ 5 yrs of pain after ineffective antibiotic therapy (rocephin); complete recovery following effective antibiotic therapy (doxycycline IV.)Guillon-barr syndrome: reatment before surgery _ full recovery treatment after surgery sustained paresismultiple Sclerosis syndromes (LB_labor MS_clinical: without therapy: wheelchair with therapy: no wheelchair, university studentSome of Our Cases withLyme Borreliosis Seronegativa

  • What could be done for the more effective treatment?controllPsychoses could be cured by fever - notes since Hyppocrates & Galenus. Introduced MALA-RIA in curing neurosyphilis byWagner von Jauregg Nobel prize, 1927 Modern possibilities for FEVER therapyfar-infra-red saunaswith 10 nm irradiationbio-energycultivationCSFBrorson O, Brorson SH , 2004

  • What could the future bring?Debate?AGGREMENT?As I HOPE!