Lähettäjä: Soijuv Lähetetty: 20.11.2005 11:52
Itävaltalaisessa tutkimuksessa selvitettiin penisilliinin, keftriaksonin ja doksisykliinin kykyä tuhota borrelia bakteeri. Borreliabakteerin on havaittu selviävän kudoksissa antibiooteista huolimatta. Liikkuvat spirokeetat hävisivät keftriaksonella (Rocephalin). Siitä huolimatta spirokeettojen osia löytyi kystien sisältä. Tämä saattaa selittää kroonisen borrelioosin.
Antimicrob Agents Chemother. 1995 May;39(5):1127-33.
Effects of penicillin, ceftriaxone, and doxycycline on morphology of
Borrelia burgdorferi.
Kersten A, Poitschek C, Rauch S, Aberer E.
Department of Dermatology, University of Vienna, Austria.
Antibiotic therapy with penicillin, doxycycline, and ceftriaxone has proven to be effective for the treatment of Lyme borreliosis. In some patients, however, it was noticed that borreliae can survival in the tissues in spite of seemingly adequate therapy. For a better understanding of this phenomenon, we investigated the different modes of degeneration of Borrelia burgdorferi suspensions during a 96-h exposure to various antibiotics. By dark-field microscopy and ultrastructural investigations, increasing blebbing and the gradual formation of granular and cystic structures could be followed during the exposure time. Although antibiotic concentrations at the MIC at which 90% of organisms are inhibited after 72 h were 80% or even greater, motile organisms were still present after incubation with penicillin and doxycycline but not after incubation with ceftriaxone. By transmission electron microscopy, intact spirochetal parts, mostly situated in cysts, were seen up to 96 h after exposure with all three antibiotics tested. According to experiences from studies with other spirochetes it is suggested that encysted borreliae, granules, and the remaining blebs might be responsible for the ongoing antigenic stimulus leading to complaints of chronic Lyme borreliosis.
PMID: 7625800 [PubMed - indexed for MEDLINE]
ANTIBIOOTTI AUTTAA MUTTA EI AUTA...
Valvojat: Jatta1001, Borrelioosiyhdistys, Bb
ANTIBIOOTTI AUTTAA MUTTA EI AUTA...
Viimeksi muokannut Bb, Pe Maalis 06, 2009 23:57. Yhteensä muokattu 1 kertaa.
Lähettäjä: Soijuv Lähetetty: 20.11.2005 12:13
Raportteja borrelioosin hoidon epäonnistumisesta antibiooteilla raportoidaan toistuvasti. Borreliabakteerin alalajeista B.garinii näytti olevan herkin penisilliinille. Hoitojen epäonnistuminen saattaa selittyä liian alhaisilla antibioottipitoisuuksilla veressä ja kudoksissa (suom. huom. yksi syy muiden lisäksi).
Orv Hetil. 2002 May 26;143(21):1195-8.
Comment in:
Orv Hetil. 2002 May 26;143(21):1223-4.
Borrelia burgdorferi Group: in-vitro antibiotic sensitivity
[Article in Hungarian]
Henneberg JP, Neubert U.
Department of Dermatology, Ludwig-Maximilians-University, Munchen, Germany.
Failures in the antibiotic therapy of Lyme disease have repeatedly been demonstrated by post-treatment isolations of the infecting borreliae. Analyses of the antibiotic susceptibility patterns of borreliae may help to understand the causes of such treatment failures and to develop new therapeutic regimens. AIMS AND METHODS: The three subspecies of Borrelia burgdorferi known to be pathogenic for humans and to differ in their virulence and organ affinity possibly may also show divergent susceptibilities to some common antibacterial agents. In order to get real clues for such probable differences we compared the efficacy of six antimicrobial agents against 24 borrelial tick and skin isolates belonging to the three subspecies of B. burgdorferi sensu lato.
RESULTS: In five comparative evaluations, some significantly different antibiotic sensitivity of the three borrelial species was found. The Borrelia burgdorferi sensu stricto isolates showed lower sensitivity to cephalosporin, tetracycline and ciprofloxacin as well as a higher sensitivity to erythromycin compared to the B. afzelii and B. garinii isolates. The B. garinii isolates proved to be more sensitive to penicillin in comparison to the B. burgdorferi s.s. and B. afzelii isolates.
CONCLUSIONS: In the light of these data, treatment failures may be interpreted by serum and tissue levels of the antibiotic too low for an effective killing of the infecting Spirochetes. However, prolonged treatment regimens applying higher dosages of antibiotics, in order to get complete clearing of the infection, may be linked to aggravated side effects.
PROPOSAL: Therefore, the combination of different antiborrelial agents with synergistic effect seems to be a meaningful alternative and should be included in future studies in vitro as well as in vivo.
PMID: 12073540 [PubMed - indexed for MEDLINE]
Raportteja borrelioosin hoidon epäonnistumisesta antibiooteilla raportoidaan toistuvasti. Borreliabakteerin alalajeista B.garinii näytti olevan herkin penisilliinille. Hoitojen epäonnistuminen saattaa selittyä liian alhaisilla antibioottipitoisuuksilla veressä ja kudoksissa (suom. huom. yksi syy muiden lisäksi).
Orv Hetil. 2002 May 26;143(21):1195-8.
Comment in:
Orv Hetil. 2002 May 26;143(21):1223-4.
Borrelia burgdorferi Group: in-vitro antibiotic sensitivity
[Article in Hungarian]
Henneberg JP, Neubert U.
Department of Dermatology, Ludwig-Maximilians-University, Munchen, Germany.
Failures in the antibiotic therapy of Lyme disease have repeatedly been demonstrated by post-treatment isolations of the infecting borreliae. Analyses of the antibiotic susceptibility patterns of borreliae may help to understand the causes of such treatment failures and to develop new therapeutic regimens. AIMS AND METHODS: The three subspecies of Borrelia burgdorferi known to be pathogenic for humans and to differ in their virulence and organ affinity possibly may also show divergent susceptibilities to some common antibacterial agents. In order to get real clues for such probable differences we compared the efficacy of six antimicrobial agents against 24 borrelial tick and skin isolates belonging to the three subspecies of B. burgdorferi sensu lato.
RESULTS: In five comparative evaluations, some significantly different antibiotic sensitivity of the three borrelial species was found. The Borrelia burgdorferi sensu stricto isolates showed lower sensitivity to cephalosporin, tetracycline and ciprofloxacin as well as a higher sensitivity to erythromycin compared to the B. afzelii and B. garinii isolates. The B. garinii isolates proved to be more sensitive to penicillin in comparison to the B. burgdorferi s.s. and B. afzelii isolates.
CONCLUSIONS: In the light of these data, treatment failures may be interpreted by serum and tissue levels of the antibiotic too low for an effective killing of the infecting Spirochetes. However, prolonged treatment regimens applying higher dosages of antibiotics, in order to get complete clearing of the infection, may be linked to aggravated side effects.
PROPOSAL: Therefore, the combination of different antiborrelial agents with synergistic effect seems to be a meaningful alternative and should be included in future studies in vitro as well as in vivo.
PMID: 12073540 [PubMed - indexed for MEDLINE]
Viimeksi muokannut Bb, Pe Maalis 06, 2009 23:58. Yhteensä muokattu 1 kertaa.
Lähettäjä: Soijuv Lähetetty: 20.11.2005 12:22
Italialaisessa tutkimuksessa havaittiin borrelioosin hoidossa yleisimmin käytettyjen antibioottien (penisilliini, keftriaksoni) aiheuttavan bakteerin muuntumisen kystamuotoon. Makrolidit ja tetrasykliinit saivat vastaavaa muutosta aikaiseksi pienemmässä määrin.
Wien Klin Wochenschr. 2002 Jul 31;114(13-14):574-9.
Cystic forms of Borrelia burgdorferi sensu lato: induction, development, and the role of RpoS.
Murgia R, Piazzetta C, Cinco M.
Dipartimento di Scienze Biomediche, sez. Microbiologia, Universita degli Studi di Trieste, Trieste, Italy. rmurgia@dsbmail.units.it
It has been demonstrated recently that cells of Borrelia burgdorferi sensu lato, the etiological agent of Lyme disease, transform from mobile spirochetes into nonmotile cystic forms in the presence of certain unfavourable conditions, and that cystic forms are able to reconvert to vegetative spirochetes in vitro and in vivo. The purpose of this study was to investigate the kinetics of conversion of borreliae to cysts in different stress conditions such as starvation media or the presence of different antibiotics. Using the same experimental conditions we also investigated the possible role in cyst formation of RpoS, an alternative sigma factor that controls a regulon in response to starvation and transition to stationary phase.
We observed that beta-lactams penicillin G and ceftriaxone, the antibiotics of choice in Lyme borreliosis treatment, favoured the production of cysts when used with serum-depleted BSK medium. In contrast, we observed a low level of cyst formation in the presence of macrolides and tetracyclines. In order to elucidate the role of the rpoS gene in cyst formation we analyzed the reaction of the rpoS mutant strain in comparison with its wild-type in different conditions. Under the same stimuli, both the wild-type borrelia and the rpoS knock-out isogenic strain produced cystic forms with similar kinetics, thus excluding the participation of the gene in this phenomenon.
Our findings suggest that cyst formation is mainly due to a physical-chemical rearrangement of the outer membrane of Borrelia burgdorferi sensu lato leading to membrane fusion and controlled by different regulation mechanisms.
PMID: 12422604 [PubMed - indexed for MEDLINE]
Italialaisessa tutkimuksessa havaittiin borrelioosin hoidossa yleisimmin käytettyjen antibioottien (penisilliini, keftriaksoni) aiheuttavan bakteerin muuntumisen kystamuotoon. Makrolidit ja tetrasykliinit saivat vastaavaa muutosta aikaiseksi pienemmässä määrin.
Wien Klin Wochenschr. 2002 Jul 31;114(13-14):574-9.
Cystic forms of Borrelia burgdorferi sensu lato: induction, development, and the role of RpoS.
Murgia R, Piazzetta C, Cinco M.
Dipartimento di Scienze Biomediche, sez. Microbiologia, Universita degli Studi di Trieste, Trieste, Italy. rmurgia@dsbmail.units.it
It has been demonstrated recently that cells of Borrelia burgdorferi sensu lato, the etiological agent of Lyme disease, transform from mobile spirochetes into nonmotile cystic forms in the presence of certain unfavourable conditions, and that cystic forms are able to reconvert to vegetative spirochetes in vitro and in vivo. The purpose of this study was to investigate the kinetics of conversion of borreliae to cysts in different stress conditions such as starvation media or the presence of different antibiotics. Using the same experimental conditions we also investigated the possible role in cyst formation of RpoS, an alternative sigma factor that controls a regulon in response to starvation and transition to stationary phase.
We observed that beta-lactams penicillin G and ceftriaxone, the antibiotics of choice in Lyme borreliosis treatment, favoured the production of cysts when used with serum-depleted BSK medium. In contrast, we observed a low level of cyst formation in the presence of macrolides and tetracyclines. In order to elucidate the role of the rpoS gene in cyst formation we analyzed the reaction of the rpoS mutant strain in comparison with its wild-type in different conditions. Under the same stimuli, both the wild-type borrelia and the rpoS knock-out isogenic strain produced cystic forms with similar kinetics, thus excluding the participation of the gene in this phenomenon.
Our findings suggest that cyst formation is mainly due to a physical-chemical rearrangement of the outer membrane of Borrelia burgdorferi sensu lato leading to membrane fusion and controlled by different regulation mechanisms.
PMID: 12422604 [PubMed - indexed for MEDLINE]
Viimeksi muokannut Bb, Pe Maalis 06, 2009 23:59. Yhteensä muokattu 1 kertaa.
Lähettäjä: Soijuv Lähetetty: 20.11.2005 12:32
Saksalaiset tutkivat benzylpenisilliinin vaikutusta borreliabakteerin rakenteeseen. Huomattavaa solujen hajaantumista havaittiin 1mg/l penisilliiniannoksella.
Infection. 1994 Nov-Dec;22(6):401-6.
Ultrastructure of Borrelia burgdorferi after exposure to benzylpenicillin.
Schaller M, Neubert U.
Dermatologische Klinik, Ludwig-Maximilians-Universitat, Munchen, Germany.
The aim of this study was to investigate the morphological changes of Borrelia burgdorferi associated with penicillin treatment. An isolate of B.burgdorferi from an erythema migrans lesion was cultivated in BSK II medium and exposed to increasing concentrations (0.0625 mg/l-2 mg/l) of penicillin G for 5 days. The in vitro minimal inhibitory concentration (MIC) was determined to be 0.5 mg/l by broth dilution method. The morphological structures of untreated spirochetes, as well as their characteristic ultrastructural changes when exposed to penicillin, were observed by electron microscopy. The following alterations were discovered:
(i) Numerous outer sheath blebs at a penicillin concentration of 0.0625 mg/l.
(ii) A characteristic irregular waveform of the borrelial cells and complete loss of the outer sheath at a penicillin concentration of 0.125 mg/l.
(iii) The presence of "spheroplasts" at the same concentration.
(iv) Structural changes of the protoplasmic cylinder complex which showed an irregular pattern at a penicillin concentration of 0.125 mg/l.
(v) Disruption of the protoplasmic cylinder complex into several parts at penicillin concentrations of 0.25 mg/l and 0.5 mg/l.
(vi) Severe cytolysis at penicillin concentrations of 1 mg/l and 2 mg/l.
PMID: 7698837 [PubMed - indexed for MEDLINE]
Saksalaiset tutkivat benzylpenisilliinin vaikutusta borreliabakteerin rakenteeseen. Huomattavaa solujen hajaantumista havaittiin 1mg/l penisilliiniannoksella.
Infection. 1994 Nov-Dec;22(6):401-6.
Ultrastructure of Borrelia burgdorferi after exposure to benzylpenicillin.
Schaller M, Neubert U.
Dermatologische Klinik, Ludwig-Maximilians-Universitat, Munchen, Germany.
The aim of this study was to investigate the morphological changes of Borrelia burgdorferi associated with penicillin treatment. An isolate of B.burgdorferi from an erythema migrans lesion was cultivated in BSK II medium and exposed to increasing concentrations (0.0625 mg/l-2 mg/l) of penicillin G for 5 days. The in vitro minimal inhibitory concentration (MIC) was determined to be 0.5 mg/l by broth dilution method. The morphological structures of untreated spirochetes, as well as their characteristic ultrastructural changes when exposed to penicillin, were observed by electron microscopy. The following alterations were discovered:
(i) Numerous outer sheath blebs at a penicillin concentration of 0.0625 mg/l.
(ii) A characteristic irregular waveform of the borrelial cells and complete loss of the outer sheath at a penicillin concentration of 0.125 mg/l.
(iii) The presence of "spheroplasts" at the same concentration.
(iv) Structural changes of the protoplasmic cylinder complex which showed an irregular pattern at a penicillin concentration of 0.125 mg/l.
(v) Disruption of the protoplasmic cylinder complex into several parts at penicillin concentrations of 0.25 mg/l and 0.5 mg/l.
(vi) Severe cytolysis at penicillin concentrations of 1 mg/l and 2 mg/l.
PMID: 7698837 [PubMed - indexed for MEDLINE]
Viimeksi muokannut Bb, La Maalis 07, 2009 00:01. Yhteensä muokattu 2 kertaa.
Lähettäjä: Soijuv Lähetetty: 21.11.2005 9:56
Tärkeitä tutkimuksia. Selittävät syitä siihen miksi antibioottihoito ei välttämättä auta.
Seuraavissa tutkimuksissa osoitetaan miksi Rocephalin-hoito ei välttämättä ole riittävä hoito borreliabakteerin lopullisessa tuhoamisessa. Siitä johtuen esim. Unkarissa käytetään yhdistelmähoitoa jossa on keftriaksonia 2 x 2 g/pv + Ciprofloksasiinia 3 x 500 mg/pv. In vitro tutkimuksissa flurokinoloneilla oli synergistinen vaikutus käytettynä yhdessä muiden antibioottien kanssa.
1. Fibroblastit suojelevat borreliabakteeria keftriaksonen vaikutuksilta.
Useat eukaryoottiset solut suojelevat spirokeettaa ja mahdollistavat sen selviämisen. Ihmisen solut ovat tyypiltään eukaryoottisia, bakteerien solutyyppi on prokaryoottinen. Tästä on ajateltu olevan hyötyä esim. mikrobilääkkeitä kehitettäessä. Tämän tutkimuksen valossa hyöty ei ole välttämättä ainakaan Bb:n kohdalla kovin hyvä.
2. Borreliabakteerin selviytyminen nivelsolujen sisällä. Keftriaksoni hoito tehosi solujen ulkopuolella oleviin bakteereihin, mutta ei nivelsoluissa oleviin bakteereihin!
3. Keftriaksonihoidon jälkeen näkyvät spirokeetat hävisivät solujen pinnalta, mutta niitä löytyi fibroblasteista (= sidekudossolu).
1. J Infect Dis 1992 Aug;166(2):440-4
Fibroblasts protect the Lyme disease spirochete, Borrelia burgdorferi, from ceftriaxone in vitro.
Georgilis K, Peacocke M, Klempner MS
Department of Medicine, New England Medical Center, Boston, Massachusetts.
The Lyme disease spirochete, Borrelia burgdorferi, can be recovered long after initial infection, even from antibiotic-treated patients, indicating that it resists eradication by host defense mechanisms and antibiotics. Since B. burgdorferi first infects skin, the possible protective effect of skin fibroblasts from an antibiotic commonly used to treat Lyme disease, ceftriaxone, was examined. Human foreskin fibroblasts protected B. burgdorferi from the lethal action of a 2-day exposure to ceftriaxone at 1 microgram/mL, 10-20 x MBC. In the absence of fibroblasts, organisms did not survive. Spirochetes were not protected from ceftriaxone by glutaraldehyde-fixed fibroblasts or fibroblast lysate, suggesting that a living cell was required. The ability of the organism to survive in the presence of fibroblasts was not related to its infectivity. Fibroblasts protected B. burgdorferi for at least 14 days of exposure to ceftriaxone. Mouse keratinocytes, HEp-2 cells, and Vero cells but not Caco-2 cells showed the same protective effect. Thus, several eukaryotic cell types provide the Lyme disease spirochete with a protective environment contributing to its long-term survival. PMID: 1634816, UI: 92340959
--------------------------------------------------------------------------------------------------------------------------
Intracellular persistence of Borrelia burgdorferi in human synovial cells.
Girschick-HJ; Huppertz-HI; Russmann-H; Krenn-V; Karch-H
Children's Hospital, University of Wurzburg, Germany.
Rheumatol-Int. 1996; 16(3): 125-32
To investigate if Borrelia burgdorferi can persist in resident joint cells, an infection model using cell cultures of human synovial cells was establishedand compared to the interaction of Borrelia burgdorferi and human macrophages. Borrelia burgdorferi were found attached to the cell surface or folded into the cell membrane of synovial cells analysed by transmission electron and confocal laser scanning microscopy. In contrast to macrophages, morphologically intact Borrelia burgdorferi were found in the cytosol of synovial cells without engulfment by cell membrane folds or phagosomes. Borrelia burgdorferi were isolated from parallel cultures.
Treatment with ceftriaxone eradicated extracellular Borrelia burgdorferi, but spirochetes were reisolated after lysis of the synovial cells. Borrelia burgdorferi persisted inside synovial cells for at least 8 weeks. These data suggested that Borrelia burgdorferi might be able to persist within resident joint cells in vivo.
-------------------------------------------------------------------------------
Borreliabakteeri tunkeutuu ihon fibroblasteihin.
Invasion of human skin fibroblasts by the Lyme disease spirochete, Borrelia burgdorferi.
Klempner-MS; Noring-R; Rogers-RA
Division of Geographic Medicine and Infectious Diseases, New EnglandMedical Center, Tufts University School of Medicine, Boston, Massachusetts 02111.
J-Infect-Dis. 1993 May; 167(5): 1074-81
The ability of Borrelia burgdorferi to attach to and invade human fibroblasts was investigated by scanning electron and confocal microscopy. By scanning electron microscopy, B. burgdorferi were tightly adherent to fibroblast monolayers after 24-48 h but were eliminated from the cell surface by treatment with ceftriaxone (1 microgram/mL) for 5 days. Despite the absence of visible spirochetes on the cell surface after antibiotic treatment, viable B. burgdorferi were isolated from lysates of the fibroblast monolayers. B.burgdorferi were observed in the perinuclear region within human fibroblasts by laser scanning confocal microscopy. Intracellular spirochetes specifically labeled with monoclonal anti-flagellin antibody were also identified by fluorescent laser scanning confocal microscopy. These observations suggest that B. burgdorferi can adhere to, penetrate, and invade human fibroblasts in organisms that remain viable.
4. Antimicrob Agents Chemother. 1996 Jun;40(6):1552-4.
Eucaryotic cells protect Borrelia burgdorferi from the action of penicillin and ceftriaxone but not from the action of doxycycline and erythromycin.
Brouqui P, Badiaga S, Raoult D.
Unite des Rickettsies, Faculte de Medecine, Centre National de la Recherche Scientifique, Marseille, France.
Despite appropriate antibiotic treatment, Lyme disease patients may have relapses or may develop chronic manifestations. The intracellular location of Borrelia burgdorferi suggests that antibiotics that penetrate cells will have greater efficiency. Doxycycline or erythromycin was more effective than penicillin or ceftriaxone in killing B. burgdorferi when the organism was grown in the presence of eucaryotic cells.
PMID: 8726038 [PubMed - indexed for MEDLINE]
Antibioottihoidosta huolimatta borrelioosia sairastavat saattavat sairastua uudelleen ja sairaus saattaa kroonistua. Yhtenä syynä siihen on bakteerin solunsisäinen sijainti. Eukaryoottiset solut (elimistön solut) suojelevat borrelia bakteereita penisilliinin ja keftriaksonin vaikutuksilta. Siksi sellaiset antibiootit jotka läpäisevät solun (esim. doksisykliini), saattavat olla tehokkaampia bakteerin tuhoamisessa. (Suom. huom. On muistettava että Bb:llä on muitakin selviytymismekanismeja. Esim. kystamuotoon siirtymistä on tavattu myös doksisykliinin kohdalla.)
Tärkeitä tutkimuksia. Selittävät syitä siihen miksi antibioottihoito ei välttämättä auta.
Seuraavissa tutkimuksissa osoitetaan miksi Rocephalin-hoito ei välttämättä ole riittävä hoito borreliabakteerin lopullisessa tuhoamisessa. Siitä johtuen esim. Unkarissa käytetään yhdistelmähoitoa jossa on keftriaksonia 2 x 2 g/pv + Ciprofloksasiinia 3 x 500 mg/pv. In vitro tutkimuksissa flurokinoloneilla oli synergistinen vaikutus käytettynä yhdessä muiden antibioottien kanssa.
1. Fibroblastit suojelevat borreliabakteeria keftriaksonen vaikutuksilta.
Useat eukaryoottiset solut suojelevat spirokeettaa ja mahdollistavat sen selviämisen. Ihmisen solut ovat tyypiltään eukaryoottisia, bakteerien solutyyppi on prokaryoottinen. Tästä on ajateltu olevan hyötyä esim. mikrobilääkkeitä kehitettäessä. Tämän tutkimuksen valossa hyöty ei ole välttämättä ainakaan Bb:n kohdalla kovin hyvä.
2. Borreliabakteerin selviytyminen nivelsolujen sisällä. Keftriaksoni hoito tehosi solujen ulkopuolella oleviin bakteereihin, mutta ei nivelsoluissa oleviin bakteereihin!
3. Keftriaksonihoidon jälkeen näkyvät spirokeetat hävisivät solujen pinnalta, mutta niitä löytyi fibroblasteista (= sidekudossolu).
1. J Infect Dis 1992 Aug;166(2):440-4
Fibroblasts protect the Lyme disease spirochete, Borrelia burgdorferi, from ceftriaxone in vitro.
Georgilis K, Peacocke M, Klempner MS
Department of Medicine, New England Medical Center, Boston, Massachusetts.
The Lyme disease spirochete, Borrelia burgdorferi, can be recovered long after initial infection, even from antibiotic-treated patients, indicating that it resists eradication by host defense mechanisms and antibiotics. Since B. burgdorferi first infects skin, the possible protective effect of skin fibroblasts from an antibiotic commonly used to treat Lyme disease, ceftriaxone, was examined. Human foreskin fibroblasts protected B. burgdorferi from the lethal action of a 2-day exposure to ceftriaxone at 1 microgram/mL, 10-20 x MBC. In the absence of fibroblasts, organisms did not survive. Spirochetes were not protected from ceftriaxone by glutaraldehyde-fixed fibroblasts or fibroblast lysate, suggesting that a living cell was required. The ability of the organism to survive in the presence of fibroblasts was not related to its infectivity. Fibroblasts protected B. burgdorferi for at least 14 days of exposure to ceftriaxone. Mouse keratinocytes, HEp-2 cells, and Vero cells but not Caco-2 cells showed the same protective effect. Thus, several eukaryotic cell types provide the Lyme disease spirochete with a protective environment contributing to its long-term survival. PMID: 1634816, UI: 92340959
--------------------------------------------------------------------------------------------------------------------------
Intracellular persistence of Borrelia burgdorferi in human synovial cells.
Girschick-HJ; Huppertz-HI; Russmann-H; Krenn-V; Karch-H
Children's Hospital, University of Wurzburg, Germany.
Rheumatol-Int. 1996; 16(3): 125-32
To investigate if Borrelia burgdorferi can persist in resident joint cells, an infection model using cell cultures of human synovial cells was establishedand compared to the interaction of Borrelia burgdorferi and human macrophages. Borrelia burgdorferi were found attached to the cell surface or folded into the cell membrane of synovial cells analysed by transmission electron and confocal laser scanning microscopy. In contrast to macrophages, morphologically intact Borrelia burgdorferi were found in the cytosol of synovial cells without engulfment by cell membrane folds or phagosomes. Borrelia burgdorferi were isolated from parallel cultures.
Treatment with ceftriaxone eradicated extracellular Borrelia burgdorferi, but spirochetes were reisolated after lysis of the synovial cells. Borrelia burgdorferi persisted inside synovial cells for at least 8 weeks. These data suggested that Borrelia burgdorferi might be able to persist within resident joint cells in vivo.
-------------------------------------------------------------------------------
Borreliabakteeri tunkeutuu ihon fibroblasteihin.
Invasion of human skin fibroblasts by the Lyme disease spirochete, Borrelia burgdorferi.
Klempner-MS; Noring-R; Rogers-RA
Division of Geographic Medicine and Infectious Diseases, New EnglandMedical Center, Tufts University School of Medicine, Boston, Massachusetts 02111.
J-Infect-Dis. 1993 May; 167(5): 1074-81
The ability of Borrelia burgdorferi to attach to and invade human fibroblasts was investigated by scanning electron and confocal microscopy. By scanning electron microscopy, B. burgdorferi were tightly adherent to fibroblast monolayers after 24-48 h but were eliminated from the cell surface by treatment with ceftriaxone (1 microgram/mL) for 5 days. Despite the absence of visible spirochetes on the cell surface after antibiotic treatment, viable B. burgdorferi were isolated from lysates of the fibroblast monolayers. B.burgdorferi were observed in the perinuclear region within human fibroblasts by laser scanning confocal microscopy. Intracellular spirochetes specifically labeled with monoclonal anti-flagellin antibody were also identified by fluorescent laser scanning confocal microscopy. These observations suggest that B. burgdorferi can adhere to, penetrate, and invade human fibroblasts in organisms that remain viable.
4. Antimicrob Agents Chemother. 1996 Jun;40(6):1552-4.
Eucaryotic cells protect Borrelia burgdorferi from the action of penicillin and ceftriaxone but not from the action of doxycycline and erythromycin.
Brouqui P, Badiaga S, Raoult D.
Unite des Rickettsies, Faculte de Medecine, Centre National de la Recherche Scientifique, Marseille, France.
Despite appropriate antibiotic treatment, Lyme disease patients may have relapses or may develop chronic manifestations. The intracellular location of Borrelia burgdorferi suggests that antibiotics that penetrate cells will have greater efficiency. Doxycycline or erythromycin was more effective than penicillin or ceftriaxone in killing B. burgdorferi when the organism was grown in the presence of eucaryotic cells.
PMID: 8726038 [PubMed - indexed for MEDLINE]
Antibioottihoidosta huolimatta borrelioosia sairastavat saattavat sairastua uudelleen ja sairaus saattaa kroonistua. Yhtenä syynä siihen on bakteerin solunsisäinen sijainti. Eukaryoottiset solut (elimistön solut) suojelevat borrelia bakteereita penisilliinin ja keftriaksonin vaikutuksilta. Siksi sellaiset antibiootit jotka läpäisevät solun (esim. doksisykliini), saattavat olla tehokkaampia bakteerin tuhoamisessa. (Suom. huom. On muistettava että Bb:llä on muitakin selviytymismekanismeja. Esim. kystamuotoon siirtymistä on tavattu myös doksisykliinin kohdalla.)
Viimeksi muokannut Bb, La Maalis 07, 2009 00:04. Yhteensä muokattu 1 kertaa.
Lähettäjä: Sar_Ani Lähetetty: 21.11.2005 13:59
Doksisykliinin annostuksia...
Syfiliksessä 400 mg päivässä ja borrelioosissa 200 mg päivässä. Vastaavat CNS pitoisuudet ovat
1.3 micrograms/ml / 0.4 to 2.5 microgram/ml.
Borrelian herkkyys doksille eli MIC vaihtelee tutkijasta riippuen, MIC of doxycycline 0.12 microgram/ml:sta MIC of doxycycline 2micrograms/ml :aan
1: Antimicrob Agents Chemother. 1996 May;40(5):1104-7. Related Articles, Links
Concentrations of doxycycline and penicillin G in sera and cerebrospinal fluid of patients treated for neuroborreliosis.
Karlsson M, Hammers S, Nilsson-Ehle I, Malmborg AS, Wretlind B.
Department of Infectious Diseases, Danderyd Hospital, Stockholm, Sweden.
Concentrations of doxycycline and penicillin G in serum and cerebrospinal fluid (CSF) were analyzed in 46 patients during treatment for neuroborreliosis. Twenty patients were treated intravenously with penicillin G at 3 g every 6 h (q6h), and 26 patients were treated orally with doxycycline at 200 mg q24h. All samples were collected on day 13 of treatment. The median concentrations of penicillin G in serum were 0.5, 37, and 5.6 micrograms/ml before and 1 and 3 h after drug administration, and that in CSF was 0.5 (range, 0.3 to 1.6) microgram/ml after 2 to 3 h. The median concentrations of doxycycline in serum were 2.1, 6.1, and 4.7 micrograms/ml before and 2 and 6 h after drug administration, and that in CSF was 0.6 (range, 0.4 to 2.5) microgram/ml after 4 h. All patients had concentrations of penicillin G or doxycycline in CSF above the lowest reported MICs of penicillin G (0.003 microgram/ml) and doxycycline (0.12 microgram/ml) for Borrelia burgdorferi. However, no patients had a drug concentration in CSF above the highest reported MIC of penicillin G (8 micrograms/ml), and only one had a drug concentration in CSF above the highest reported MIC of doxycycline (2 micrograms/ml), despite good clinical response to treatment. No treatment failure or relapse was observed during a 1-year follow-up, although one patient treated with penicillin G and one treated with doxycycline were retreated because of residual pain. The chosen dosages of penicillin G and doxycycline seem to give sufficient concentrations in serum and CSF for the treatment of neuroborreliosis.
Publication Types:
* Clinical Trial
* Randomized Controlled Trial
PMID: 8723448 [PubMed - indexed for MEDLINE]
Antimicrob Agents Chemother. 1985 Aug;28(2):347-8. Related Articles, Links
Penetration of oral doxycycline into the cerebrospinal fluid of patients with latent or neurosyphilis.
Yim CW, Flynn NM, Fitzgerald FT.
Five patients with laboratory evidence of latent or neurosyphilis were treated orally with doxycycline (200 mg) twice a day for 21 days. After the seventh dose, the mean level of doxycycline in serum was 5.8 micrograms/ml, with a mean drug level in cerebrospinal fluid of 1.3 micrograms/ml. The mean penetration into cerebrospinal fluid was 26%. These preliminary findings suggest that doxycycline, administered orally at a dose of 200 mg twice a day, reaches a sufficient concentration in cerebrospinal fluid to be worthy of further evaluation as an alternative regimen to penicillin therapy for latent or neurosyphilis.
PMID: 3834836 [PubMed - indexed for MEDLINE]
Doksisykliinin annostuksia...
Syfiliksessä 400 mg päivässä ja borrelioosissa 200 mg päivässä. Vastaavat CNS pitoisuudet ovat
1.3 micrograms/ml / 0.4 to 2.5 microgram/ml.
Borrelian herkkyys doksille eli MIC vaihtelee tutkijasta riippuen, MIC of doxycycline 0.12 microgram/ml:sta MIC of doxycycline 2micrograms/ml :aan
1: Antimicrob Agents Chemother. 1996 May;40(5):1104-7. Related Articles, Links
Concentrations of doxycycline and penicillin G in sera and cerebrospinal fluid of patients treated for neuroborreliosis.
Karlsson M, Hammers S, Nilsson-Ehle I, Malmborg AS, Wretlind B.
Department of Infectious Diseases, Danderyd Hospital, Stockholm, Sweden.
Concentrations of doxycycline and penicillin G in serum and cerebrospinal fluid (CSF) were analyzed in 46 patients during treatment for neuroborreliosis. Twenty patients were treated intravenously with penicillin G at 3 g every 6 h (q6h), and 26 patients were treated orally with doxycycline at 200 mg q24h. All samples were collected on day 13 of treatment. The median concentrations of penicillin G in serum were 0.5, 37, and 5.6 micrograms/ml before and 1 and 3 h after drug administration, and that in CSF was 0.5 (range, 0.3 to 1.6) microgram/ml after 2 to 3 h. The median concentrations of doxycycline in serum were 2.1, 6.1, and 4.7 micrograms/ml before and 2 and 6 h after drug administration, and that in CSF was 0.6 (range, 0.4 to 2.5) microgram/ml after 4 h. All patients had concentrations of penicillin G or doxycycline in CSF above the lowest reported MICs of penicillin G (0.003 microgram/ml) and doxycycline (0.12 microgram/ml) for Borrelia burgdorferi. However, no patients had a drug concentration in CSF above the highest reported MIC of penicillin G (8 micrograms/ml), and only one had a drug concentration in CSF above the highest reported MIC of doxycycline (2 micrograms/ml), despite good clinical response to treatment. No treatment failure or relapse was observed during a 1-year follow-up, although one patient treated with penicillin G and one treated with doxycycline were retreated because of residual pain. The chosen dosages of penicillin G and doxycycline seem to give sufficient concentrations in serum and CSF for the treatment of neuroborreliosis.
Publication Types:
* Clinical Trial
* Randomized Controlled Trial
PMID: 8723448 [PubMed - indexed for MEDLINE]
Antimicrob Agents Chemother. 1985 Aug;28(2):347-8. Related Articles, Links
Penetration of oral doxycycline into the cerebrospinal fluid of patients with latent or neurosyphilis.
Yim CW, Flynn NM, Fitzgerald FT.
Five patients with laboratory evidence of latent or neurosyphilis were treated orally with doxycycline (200 mg) twice a day for 21 days. After the seventh dose, the mean level of doxycycline in serum was 5.8 micrograms/ml, with a mean drug level in cerebrospinal fluid of 1.3 micrograms/ml. The mean penetration into cerebrospinal fluid was 26%. These preliminary findings suggest that doxycycline, administered orally at a dose of 200 mg twice a day, reaches a sufficient concentration in cerebrospinal fluid to be worthy of further evaluation as an alternative regimen to penicillin therapy for latent or neurosyphilis.
PMID: 3834836 [PubMed - indexed for MEDLINE]
Viimeksi muokannut Bb, La Maalis 07, 2009 00:06. Yhteensä muokattu 1 kertaa.
Lähettäjä: Sar_Ani Lähetetty: 2.1.2006 20:10
lainaus ekasta artikkelista:
By transmission electron microscopy, intact spirochetal parts, mostly situated in cysts, were seen up to 96 h after exposure with all three antibiotics tested.
Yritän vielä toistaiseksi näänny ttää borrelioita doksilla, lemput tuli sairaalasta. Vaikea tapaus.
_____________________________________________________________
Lähettäjä: iippo Lähetetty: 5.1.2006 14:31
Vai tuli lemput sairaalasta. Minullekin lääkäri sanoi, ettei aio enää minulle antibioottia määrätä. Eilen päättyi 5 viikon IV Rocephalin ja olo parani huomattavasti. Sitä ennen puoli vuotta klaritromysiiniä. Toivottavasti en repsahda kun menen puolivälissä kuuta takaisin töihin.
_____________________________________________________________
Lähettäjä: jukka61 Lähetetty: 5.1.2006 21:28
Aikamoinen "Onneniippo" olet, jos olet saanut Rochedalinia 5 vkoa ja sitä ennen ½-v klaritromysiiniä. Taitaa lääkärisi olla melko harvinainen tapaus, pääsääntöhän on 3 vkoa max 4 vkoa ei yhtään enempää.
_____________________________________________________________
Lähettäjä: iippo Lähetetty: 7.1.2006 18:01
Niin se oli minullakin että 3 viikkoa, mutta kun oli ollut apua, niin päätettiin jatkaa vielä pari viikkoa kun veriarvot olivat ok. Hemoglobiini tosin 194, mutta ei se menoa haittaa. Sain metronidatsoli reseptinkin (clostrum difficile tms) mutta kun näytteistä eivät tulokset olleet valmistuneet Jouluksi, niin aloitin sen oma-aloitteisesti, tosin se kuuri oli vain 10 päivän mittainen. Taitaa olla sittenkin hyötyä kuljettaa lääkäriin Jenkkitohtoreitten luento DVD:tä ja artikkeleita tai sitten tämä on taisteluväsymystä lääkärin puolelta
lainaus ekasta artikkelista:
By transmission electron microscopy, intact spirochetal parts, mostly situated in cysts, were seen up to 96 h after exposure with all three antibiotics tested.
Yritän vielä toistaiseksi näänny ttää borrelioita doksilla, lemput tuli sairaalasta. Vaikea tapaus.
_____________________________________________________________
Lähettäjä: iippo Lähetetty: 5.1.2006 14:31
Vai tuli lemput sairaalasta. Minullekin lääkäri sanoi, ettei aio enää minulle antibioottia määrätä. Eilen päättyi 5 viikon IV Rocephalin ja olo parani huomattavasti. Sitä ennen puoli vuotta klaritromysiiniä. Toivottavasti en repsahda kun menen puolivälissä kuuta takaisin töihin.
_____________________________________________________________
Lähettäjä: jukka61 Lähetetty: 5.1.2006 21:28
Aikamoinen "Onneniippo" olet, jos olet saanut Rochedalinia 5 vkoa ja sitä ennen ½-v klaritromysiiniä. Taitaa lääkärisi olla melko harvinainen tapaus, pääsääntöhän on 3 vkoa max 4 vkoa ei yhtään enempää.
_____________________________________________________________
Lähettäjä: iippo Lähetetty: 7.1.2006 18:01
Niin se oli minullakin että 3 viikkoa, mutta kun oli ollut apua, niin päätettiin jatkaa vielä pari viikkoa kun veriarvot olivat ok. Hemoglobiini tosin 194, mutta ei se menoa haittaa. Sain metronidatsoli reseptinkin (clostrum difficile tms) mutta kun näytteistä eivät tulokset olleet valmistuneet Jouluksi, niin aloitin sen oma-aloitteisesti, tosin se kuuri oli vain 10 päivän mittainen. Taitaa olla sittenkin hyötyä kuljettaa lääkäriin Jenkkitohtoreitten luento DVD:tä ja artikkeleita tai sitten tämä on taisteluväsymystä lääkärin puolelta
Lähettäjä: Soijuv Lähetetty: 6.2.2006 9:45
Suurin osa eurooppalaisista borrelioosia sairastavista kärsii neuroborrelioosista. Antibiootit läpäisevät kuitenkin veri-aivoesteen (BBB) huonosti. Seuraavan tutkimuksen mukaan kinolonit (norfloksasiini, ofloksasiini tai siprofloksasiini) läpäisevät esteen beta-laktaameja paremmin (=borrelioosin hoidossa yleisimmin käytetty antibioottiryhmä eli penisilliinit ja keftriaksoni). Niiden läpäisevyys ei ole riippuvainen tulehduksesta kuten beta-laktaamien kohdalla asianlaita on.
(Suom. huom. Kinolonien on toisaalta havaittu aiheuttavan toisinaan jännevaurioita.)
Clin Infect Dis. 1998 Nov;27(5):1117-27, quiz 1128-9.
Antibiotic pharmacodynamics in cerebrospinal fluid.
Lutsar I, McCracken GH Jr, Friedland IR.
Department of Pediatrics, University of Texas, Southwestern Medical Center, Dallas, USA.
The CSF half-lives of lipophilic agents, such as quinolones, are similar to those in serum and peak concentrations in CSF are achieved relatively quickly. In contrast, the pharmacokinetics of hydrophilic agents (beta-lactams and vancomycin) in CSF often differ from those in serum.
In particular, the half-lives of these agents in CSF tend to be extended, and the time to achieve peak concentrations in CSF is delayed. Hydrophilic antibiotics, such as beta-lactams, penetrate poorly through the BBB, but CSF penetration is significantly increased in the presence of inflammation. In contrast, lipophilic antibiotics, such as quinolones, enter the CSF more efficiently and their penetration is not inflammation dependent. The pharmacodynamic properties of antibiotics in CSF are generally similar to those in other body sites; beta-lactam agents and vancomycin are time-dependent, whereas the quinolones and aminoglycosides are concentration-dependent.
However, a notable difference from infections in other sites is that quinolones have a short PAE in CSF and need to continually exceed the MBC for maximal effectiveness. Thus, in CSF, quinolones demonstrate features of both concentration-dependency and time-dependency, evidence that the AUC/MBC is an important predictor of effectiveness.
With the exception of quinolones, many antibiotics appear to have prolonged sub-MIC effects and longer half-lives in CSF than in serum, suggesting that dosing intervals longer than those used traditionally would be effective in meningitis. However, this requires clinical verification.
Suurin osa eurooppalaisista borrelioosia sairastavista kärsii neuroborrelioosista. Antibiootit läpäisevät kuitenkin veri-aivoesteen (BBB) huonosti. Seuraavan tutkimuksen mukaan kinolonit (norfloksasiini, ofloksasiini tai siprofloksasiini) läpäisevät esteen beta-laktaameja paremmin (=borrelioosin hoidossa yleisimmin käytetty antibioottiryhmä eli penisilliinit ja keftriaksoni). Niiden läpäisevyys ei ole riippuvainen tulehduksesta kuten beta-laktaamien kohdalla asianlaita on.
(Suom. huom. Kinolonien on toisaalta havaittu aiheuttavan toisinaan jännevaurioita.)
Clin Infect Dis. 1998 Nov;27(5):1117-27, quiz 1128-9.
Antibiotic pharmacodynamics in cerebrospinal fluid.
Lutsar I, McCracken GH Jr, Friedland IR.
Department of Pediatrics, University of Texas, Southwestern Medical Center, Dallas, USA.
The CSF half-lives of lipophilic agents, such as quinolones, are similar to those in serum and peak concentrations in CSF are achieved relatively quickly. In contrast, the pharmacokinetics of hydrophilic agents (beta-lactams and vancomycin) in CSF often differ from those in serum.
In particular, the half-lives of these agents in CSF tend to be extended, and the time to achieve peak concentrations in CSF is delayed. Hydrophilic antibiotics, such as beta-lactams, penetrate poorly through the BBB, but CSF penetration is significantly increased in the presence of inflammation. In contrast, lipophilic antibiotics, such as quinolones, enter the CSF more efficiently and their penetration is not inflammation dependent. The pharmacodynamic properties of antibiotics in CSF are generally similar to those in other body sites; beta-lactam agents and vancomycin are time-dependent, whereas the quinolones and aminoglycosides are concentration-dependent.
However, a notable difference from infections in other sites is that quinolones have a short PAE in CSF and need to continually exceed the MBC for maximal effectiveness. Thus, in CSF, quinolones demonstrate features of both concentration-dependency and time-dependency, evidence that the AUC/MBC is an important predictor of effectiveness.
With the exception of quinolones, many antibiotics appear to have prolonged sub-MIC effects and longer half-lives in CSF than in serum, suggesting that dosing intervals longer than those used traditionally would be effective in meningitis. However, this requires clinical verification.
Viimeksi muokannut Bb, La Maalis 07, 2009 00:07. Yhteensä muokattu 1 kertaa.
Lähettäjä: Soijuv Lähetetty: 7.2.2006 9:36
Saksalaisen tutkimuksen mukaan antibioottihoito ei välttämättä auta edes varhaisvaiheen borrelioosiin. Hoitojen epäonnistumisia on tavattu useita eri antibiootteja kohtaan useissa tutkimuksissa.
Antimicrob Agents Chemother. 2005 April; 49(4): 12941301.
doi: 10.1128/AAC.49.4.1294-1301.2005.
Copyright © 2005, American Society for Microbiology
In Vitro Susceptibility Testing of Borrelia burgdorferi Sensu Lato Isolates
Cultured from Patients with Erythema Migrans before and after Antimicrobial Chemotherapy
Klaus-Peter Hunfeld,1,2* Eva Ruzic-Sabljic,3 Douglas E. Norris,2 Peter
Kraiczy,1 and Franc Strle4
Institute of Medical Microbiology, University Hospital of Frankfurt,
Frankfurt/Main, Germany,1 Institute of Microbiology and Immunology, Medical
Faculty, University of Ljubljana,3 Department of Infectious Diseases,
University Medical Centre, Ljubljana, Slovenia,4 The Harry W. Feinstone
Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg
School of Public Health, Baltimore, Maryland2
*Corresponding author. Mailing address: Institute of Medical Microbiology,
University Hospital of Frankfurt, Paul-Ehrlich Str. 40, D-60596
Frankfurt/Main, Germany. Phone: 49-69-6301-6441. Fax: 49-69-6301-5767.
E-mail: K.Hunfeld@em.uni-frankfurt.de.
Abstract
Clinical treatment failures have been reported to occur in early Lyme borreliosis (LB) for many suitable antimicrobial agents. Investigations of possible resistance mechanisms of the Borrelia burgdorferi complex must analyze clinical isolates obtained from LB patients, despite their receiving antibiotic treatment.
Here, borrelial isolates obtained from five patients with erythema migrans (EM) before the start of antibiotic therapy and again after the conclusion of treatment were investigated. The 10 isolates were characterized by restriction fragment length polymorphism analysis and plasmid profile analysis and subjected to susceptibility testing against a variety of antimicrobial agents including those used for initial chemotherapy. Four out of five patients were infected by the same genospecies (Borrelia afzelii, n = 3; Borrelia garinii, n = 1) at the site of the EM lesion before and after antimicrobial therapy. In one patient the genospecies of the initial isolate (B. afzelii) differed from that of the follow-up isolate (B. garinii). No significant changes in the in vitro susceptibilities became obvious for corresponding clinical isolates before the start and after the conclusion of antimicrobial therapy. This holds true for the antimicrobial agents used for specific chemotherapy of the patients, as well as for any of the additional agents tested in vitro.
Our study substantiates borrelial persistence in some EM patients at the site of the infectious lesion despite antibiotic treatment over a reasonable time period. Borrelial persistence, however, was not caused by increasing MICs or minimal borreliacidal concentrations in these isolates. Therefore, resistance mechanisms other than acquired resistance to antimicrobial agents should be considered in patients with LB resistant to treatment.
Saksalaisen tutkimuksen mukaan antibioottihoito ei välttämättä auta edes varhaisvaiheen borrelioosiin. Hoitojen epäonnistumisia on tavattu useita eri antibiootteja kohtaan useissa tutkimuksissa.
Antimicrob Agents Chemother. 2005 April; 49(4): 12941301.
doi: 10.1128/AAC.49.4.1294-1301.2005.
Copyright © 2005, American Society for Microbiology
In Vitro Susceptibility Testing of Borrelia burgdorferi Sensu Lato Isolates
Cultured from Patients with Erythema Migrans before and after Antimicrobial Chemotherapy
Klaus-Peter Hunfeld,1,2* Eva Ruzic-Sabljic,3 Douglas E. Norris,2 Peter
Kraiczy,1 and Franc Strle4
Institute of Medical Microbiology, University Hospital of Frankfurt,
Frankfurt/Main, Germany,1 Institute of Microbiology and Immunology, Medical
Faculty, University of Ljubljana,3 Department of Infectious Diseases,
University Medical Centre, Ljubljana, Slovenia,4 The Harry W. Feinstone
Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg
School of Public Health, Baltimore, Maryland2
*Corresponding author. Mailing address: Institute of Medical Microbiology,
University Hospital of Frankfurt, Paul-Ehrlich Str. 40, D-60596
Frankfurt/Main, Germany. Phone: 49-69-6301-6441. Fax: 49-69-6301-5767.
E-mail: K.Hunfeld@em.uni-frankfurt.de.
Abstract
Clinical treatment failures have been reported to occur in early Lyme borreliosis (LB) for many suitable antimicrobial agents. Investigations of possible resistance mechanisms of the Borrelia burgdorferi complex must analyze clinical isolates obtained from LB patients, despite their receiving antibiotic treatment.
Here, borrelial isolates obtained from five patients with erythema migrans (EM) before the start of antibiotic therapy and again after the conclusion of treatment were investigated. The 10 isolates were characterized by restriction fragment length polymorphism analysis and plasmid profile analysis and subjected to susceptibility testing against a variety of antimicrobial agents including those used for initial chemotherapy. Four out of five patients were infected by the same genospecies (Borrelia afzelii, n = 3; Borrelia garinii, n = 1) at the site of the EM lesion before and after antimicrobial therapy. In one patient the genospecies of the initial isolate (B. afzelii) differed from that of the follow-up isolate (B. garinii). No significant changes in the in vitro susceptibilities became obvious for corresponding clinical isolates before the start and after the conclusion of antimicrobial therapy. This holds true for the antimicrobial agents used for specific chemotherapy of the patients, as well as for any of the additional agents tested in vitro.
Our study substantiates borrelial persistence in some EM patients at the site of the infectious lesion despite antibiotic treatment over a reasonable time period. Borrelial persistence, however, was not caused by increasing MICs or minimal borreliacidal concentrations in these isolates. Therefore, resistance mechanisms other than acquired resistance to antimicrobial agents should be considered in patients with LB resistant to treatment.
Viimeksi muokannut Bb, La Maalis 07, 2009 00:09. Yhteensä muokattu 1 kertaa.
Lähettäjä: Soijuv Lähetetty: 14.2.2006 11:15
"Borreliabakteeri leviää joka puolelle elimistöä aiheuttaen ajoittaisia niveltulehduksia ja kroonisen infektion. Spirokeetta selviää antibioottihoidoista ja tauti uusiutui sellaisilla, joiden immuunijärjestelmä heikkeni, esim. koirilla joille annettiin kortisonia." (Itävaltalainen tutkimus)
Wien Klin Wochenschr. 1998 Dec 23;110(24):874-81.
Clinical manifestations, pathogenesis, and effect of antibiotic treatment on
Lyme borreliosis in dogs.
Straubinger RK, Straubinger AF, Summers BA, Jacobson RH, Erb HN.
James A. Baker Institute for Animal Health, Ithaca, New York, USA.
rks4@cornell.edu
BACKGROUND: Borrelia burgdorferi, the causative agent of Lyme disease,
infects humans and animals. In humans, the disease primarily affects the
skin, large joints, and the nervous system days to months after infection.
Data generated with appropriate animal model help to understand the
fundamental mechanisms of the disease.
OBJECTIVE: 1) More clearly define the
clinical manifestation and pathogenetic mechanisms of Lyme disease in dogs;
2) evaluate the effect of antibiotics in dogs infected with B. burgdorferi;
3) describe the effects of corticosteroids on dogs persistently infected
with B. burgdorferi.
DESIGN: Specific-pathogen-free beagles were infected
with B. burgdorferi using ticks collected in an endemic Lyme disease area.
Clinical signs were recorded daily. Antibody titers were measured by ELISA
at two-week intervals. B. burgdorferi organisms were detected in tissues by
culture and PCR. Synovial fluids were evaluated microscopically and with a
chemotaxis cell migration assay. Histological sections were examined for
pathological lesions. Specific cytokine up-regulation in tissues was
detected by RT-PCR.
INTERVENTIONS: In three separate experiments, B.
burgdorferi-infected dogs received antibiotic treatment (amoxicillin;
azithromycin; ceftriaxone; doxycycline) for 30 consecutive days. Two
subclinical persistently infected dogs received oral prednisone for 14
consecutive days starting at day 420 post-infection.
RESULTS: Dogs developed
acute arthritis in the joints closest to the tick bites after a median
incubation period of 68 days. Synovial membranes of lame and non-lame dogs
produced the chemokine IL-8 in response to B. burgdorferi. Antibiotic
treatment prevented or resolved episodes of acute arthritis, but failed to
eliminate the bacterium from infected dogs. Corticosteroid treatment
reactivated Lyme disease in persistently infected dogs, which had not
received antibiotics previously.
CONCLUSIONS: B. burgdorferi disseminates
through tissue by migration following tick inoculation, produces episodes of
acute arthritis, and establishes persistent infection. The spirochete
survives antibiotic treatment and disease can be reactivated in
immunosuppressed animals.
PMID: 10048169 [PubMed - indexed for MEDLINE]
"Borreliabakteeri leviää joka puolelle elimistöä aiheuttaen ajoittaisia niveltulehduksia ja kroonisen infektion. Spirokeetta selviää antibioottihoidoista ja tauti uusiutui sellaisilla, joiden immuunijärjestelmä heikkeni, esim. koirilla joille annettiin kortisonia." (Itävaltalainen tutkimus)
Wien Klin Wochenschr. 1998 Dec 23;110(24):874-81.
Clinical manifestations, pathogenesis, and effect of antibiotic treatment on
Lyme borreliosis in dogs.
Straubinger RK, Straubinger AF, Summers BA, Jacobson RH, Erb HN.
James A. Baker Institute for Animal Health, Ithaca, New York, USA.
rks4@cornell.edu
BACKGROUND: Borrelia burgdorferi, the causative agent of Lyme disease,
infects humans and animals. In humans, the disease primarily affects the
skin, large joints, and the nervous system days to months after infection.
Data generated with appropriate animal model help to understand the
fundamental mechanisms of the disease.
OBJECTIVE: 1) More clearly define the
clinical manifestation and pathogenetic mechanisms of Lyme disease in dogs;
2) evaluate the effect of antibiotics in dogs infected with B. burgdorferi;
3) describe the effects of corticosteroids on dogs persistently infected
with B. burgdorferi.
DESIGN: Specific-pathogen-free beagles were infected
with B. burgdorferi using ticks collected in an endemic Lyme disease area.
Clinical signs were recorded daily. Antibody titers were measured by ELISA
at two-week intervals. B. burgdorferi organisms were detected in tissues by
culture and PCR. Synovial fluids were evaluated microscopically and with a
chemotaxis cell migration assay. Histological sections were examined for
pathological lesions. Specific cytokine up-regulation in tissues was
detected by RT-PCR.
INTERVENTIONS: In three separate experiments, B.
burgdorferi-infected dogs received antibiotic treatment (amoxicillin;
azithromycin; ceftriaxone; doxycycline) for 30 consecutive days. Two
subclinical persistently infected dogs received oral prednisone for 14
consecutive days starting at day 420 post-infection.
RESULTS: Dogs developed
acute arthritis in the joints closest to the tick bites after a median
incubation period of 68 days. Synovial membranes of lame and non-lame dogs
produced the chemokine IL-8 in response to B. burgdorferi. Antibiotic
treatment prevented or resolved episodes of acute arthritis, but failed to
eliminate the bacterium from infected dogs. Corticosteroid treatment
reactivated Lyme disease in persistently infected dogs, which had not
received antibiotics previously.
CONCLUSIONS: B. burgdorferi disseminates
through tissue by migration following tick inoculation, produces episodes of
acute arthritis, and establishes persistent infection. The spirochete
survives antibiotic treatment and disease can be reactivated in
immunosuppressed animals.
PMID: 10048169 [PubMed - indexed for MEDLINE]
Viimeksi muokannut Bb, La Maalis 07, 2009 00:11. Yhteensä muokattu 1 kertaa.
Lähettäjä: Soijuv Lähetetty: 16.2.2006 13:30
Glaxon (=Britannian suurin lääketehdas) johtaja myöntää että suurin osa eri sairauksia sairastavista ei saa hyötyä lääkkeistä. Esim. alzheimerin taudin hoitoon käytetyistä lääkkeistä saa hyötyä vain alle kolmasosa, syöpälääkkeistä neljäsosa, niveltulehdus-, migreeni- ja osteoporoosilääkkeistä noin puolet.
Published on Monday, December 8, 2003 by the lndependent/UK
Glaxo Chief: Our Drugs Do Not Work on Most Patients
by Steve Connor
A senior executive with Britain's biggest drugs
company has admitted that most prescription
medicines do not work on most people who take
them.
Allen Roses, worldwide vice-president of genetics
at GlaxoSmithKline (GSK), said fewer than half of
the patients prescribed some of the most
expensive drugs actually derived any benefit from
them.
It is an open secret within the drugs industry
that most of its products are ineffective in most
patients but this is the first time that such a
senior drugs boss has gone public. His comments
come days after it emerged that the NHS drugs
bill has soared by nearly 50 per cent in three
years, rising by £2.3bn a year to an annual cost
to the taxpayer of £7.2bn. GSK announced last
week that it had 20 or more new drugs under
development that could each earn the company up
to $1bn (£600m) a year.
Dr Roses, an academic geneticist from Duke
University in North Carolina, spoke at a recent
scientific meeting in London where he cited
figures on how well different classes of drugs
work in real patients.
Drugs for Alzheimer's disease work in fewer than
one in three patients, whereas those for cancer
are only effective in a quarter of patients.
Drugs for migraines, for osteoporosis, and
arthritis work in about half the patients, Dr
Roses said. Most drugs work in fewer than one in
two patients mainly because the recipients carry
genes that interfere in some way with the
medicine, he said.
"The vast majority of drugs - more than 90 per
cent - only work in 30 or 50 per cent of the
people," Dr Roses said. "I wouldn't say that most
drugs don't work. I would say that most drugs
work in 30 to 50 per cent of people. Drugs out
there on the market work, but they don't work in
everybody."
Some industry analysts said Dr Roses's comments
were reminiscent of the 1991 gaffe by Gerald
Ratner, the jewelry boss, who famously said that
his high street shops are successful because they
sold "total crap". But others believe Dr Roses
deserves credit for being honest about a
little-publicized fact known to the drugs
industry for many years.
"Roses is a smart guy and what he is saying will
surprise the public but not his colleagues," said
one industry scientist. "He is a pioneer of a new
culture within the drugs business based on using
genes to test for who can benefit from a
particular drug."
Dr Roses has a formidable reputation in the field
of "pharmacogenomics" - the application of human
genetics to drug development - and his comments
can be seen as an attempt to make the industry
realize that its future rests on being able to
target drugs to a smaller number of patients with
specific genes.
The idea is to identify "responders" - people who
benefit from the drug - with a simple and cheap
genetic test that can be used to eliminate those
non-responders who might benefit from another
drug.
This goes against a marketing culture within the
industry that has relied on selling as many drugs
as possible to the widest number of patients - a
culture that has made GSK one of the most
profitable pharmaceuticals companies, but which
has also meant that most of its drugs are at best
useless, and even possibly dangerous, for many
patients.
Dr Roses said doctors treating patients routinely
applied the trial-and-error approach which says
that if one drug does not work there is always
another one. "I think everybody has it in their
experience that multiple drugs have been used for
their headache or multiple drugs have been used
for their backache or whatever.
"It's in their experience, but they don't quite
understand why. The reason why is because they
have different susceptibilities to the effect of
that drug and that's genetic," he said.
"Neither those who pay for medical care nor
patients want drugs to be prescribed that do not
benefit the recipient. Pharmacogenetics has the
promise of removing much of the uncertainty."
Response rates
Therapeutic area: drug efficacy rate in per cent
* Alzheimer's: 30
* Analgesics (Cox-2): 80
* Asthma: 60
* Cardiac Arrhythmias: 60
* Depression (SSRI): 62
* Diabetes: 57
* Hepatitis C (HCV): 47
* Incontinence: 40
* Migraine (acute): 52
* Migraine (prophylaxis)50
* Oncology: 25
* Rheumatoid arthritis50
* Schizophrenia: 60
© 2003 Independent Digital (UK) Ltd
http://www.commondreams.org/headlines03/1208-02.htm
Also See:
Demolished: The Myth That Allows Drugs Giants to Sell More
http://www.commondreams.org/headlines03/1208-01.htm
Glaxon (=Britannian suurin lääketehdas) johtaja myöntää että suurin osa eri sairauksia sairastavista ei saa hyötyä lääkkeistä. Esim. alzheimerin taudin hoitoon käytetyistä lääkkeistä saa hyötyä vain alle kolmasosa, syöpälääkkeistä neljäsosa, niveltulehdus-, migreeni- ja osteoporoosilääkkeistä noin puolet.
Published on Monday, December 8, 2003 by the lndependent/UK
Glaxo Chief: Our Drugs Do Not Work on Most Patients
by Steve Connor
A senior executive with Britain's biggest drugs
company has admitted that most prescription
medicines do not work on most people who take
them.
Allen Roses, worldwide vice-president of genetics
at GlaxoSmithKline (GSK), said fewer than half of
the patients prescribed some of the most
expensive drugs actually derived any benefit from
them.
It is an open secret within the drugs industry
that most of its products are ineffective in most
patients but this is the first time that such a
senior drugs boss has gone public. His comments
come days after it emerged that the NHS drugs
bill has soared by nearly 50 per cent in three
years, rising by £2.3bn a year to an annual cost
to the taxpayer of £7.2bn. GSK announced last
week that it had 20 or more new drugs under
development that could each earn the company up
to $1bn (£600m) a year.
Dr Roses, an academic geneticist from Duke
University in North Carolina, spoke at a recent
scientific meeting in London where he cited
figures on how well different classes of drugs
work in real patients.
Drugs for Alzheimer's disease work in fewer than
one in three patients, whereas those for cancer
are only effective in a quarter of patients.
Drugs for migraines, for osteoporosis, and
arthritis work in about half the patients, Dr
Roses said. Most drugs work in fewer than one in
two patients mainly because the recipients carry
genes that interfere in some way with the
medicine, he said.
"The vast majority of drugs - more than 90 per
cent - only work in 30 or 50 per cent of the
people," Dr Roses said. "I wouldn't say that most
drugs don't work. I would say that most drugs
work in 30 to 50 per cent of people. Drugs out
there on the market work, but they don't work in
everybody."
Some industry analysts said Dr Roses's comments
were reminiscent of the 1991 gaffe by Gerald
Ratner, the jewelry boss, who famously said that
his high street shops are successful because they
sold "total crap". But others believe Dr Roses
deserves credit for being honest about a
little-publicized fact known to the drugs
industry for many years.
"Roses is a smart guy and what he is saying will
surprise the public but not his colleagues," said
one industry scientist. "He is a pioneer of a new
culture within the drugs business based on using
genes to test for who can benefit from a
particular drug."
Dr Roses has a formidable reputation in the field
of "pharmacogenomics" - the application of human
genetics to drug development - and his comments
can be seen as an attempt to make the industry
realize that its future rests on being able to
target drugs to a smaller number of patients with
specific genes.
The idea is to identify "responders" - people who
benefit from the drug - with a simple and cheap
genetic test that can be used to eliminate those
non-responders who might benefit from another
drug.
This goes against a marketing culture within the
industry that has relied on selling as many drugs
as possible to the widest number of patients - a
culture that has made GSK one of the most
profitable pharmaceuticals companies, but which
has also meant that most of its drugs are at best
useless, and even possibly dangerous, for many
patients.
Dr Roses said doctors treating patients routinely
applied the trial-and-error approach which says
that if one drug does not work there is always
another one. "I think everybody has it in their
experience that multiple drugs have been used for
their headache or multiple drugs have been used
for their backache or whatever.
"It's in their experience, but they don't quite
understand why. The reason why is because they
have different susceptibilities to the effect of
that drug and that's genetic," he said.
"Neither those who pay for medical care nor
patients want drugs to be prescribed that do not
benefit the recipient. Pharmacogenetics has the
promise of removing much of the uncertainty."
Response rates
Therapeutic area: drug efficacy rate in per cent
* Alzheimer's: 30
* Analgesics (Cox-2): 80
* Asthma: 60
* Cardiac Arrhythmias: 60
* Depression (SSRI): 62
* Diabetes: 57
* Hepatitis C (HCV): 47
* Incontinence: 40
* Migraine (acute): 52
* Migraine (prophylaxis)50
* Oncology: 25
* Rheumatoid arthritis50
* Schizophrenia: 60
© 2003 Independent Digital (UK) Ltd
http://www.commondreams.org/headlines03/1208-02.htm
Also See:
Demolished: The Myth That Allows Drugs Giants to Sell More
http://www.commondreams.org/headlines03/1208-01.htm
Viimeksi muokannut Bb, La Maalis 07, 2009 00:11. Yhteensä muokattu 1 kertaa.
Lähettäjä: Soijuv Lähetetty: 28.3.2006 10:44
Tutkimusten mukaan antibioottihoito ei välttämättä auta edes borrelioosin varhaisvaiheessa - erytheemavaiheessa. Syynä ei kuitenkaan todennäköisesti ole antibioottiresistenssi sillä hoidon epäonnistumisia on havaittu lähes kaikkien antibioottien kohdalla.
Int J Med Microbiol. 2006 Mar 8;
Risk of culture-confirmed borrelial persistence in patients treated for erythema migrans and possible mechanisms of resistance.
Hunfeld KP, Ruzic-Sabljic E, Norris DE, Kraiczy P, Strle F.
Institute of Medical Microbiology, University Hospital of Frankfurt, Paul-Ehrlich Str. 40, D-60596 Frankfurt/Main, Germany; The W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, USA.
Erythema migrans (EM) develops at the site of the tick bite in 77-90% of Lyme borreliosis (LB) patients and is therefore a common manifestation of early disease. Clinical treatment failures have been reported in early LB cases for almost every suitable antimicrobial agent. The exact risk of resistance to antibiotic treatment in patients with EM, however, is not known and there are few published cases of culture-proven treatment failure. Moreover, currently available diagnostic techniques cannot reliably discriminate between possible reinfection, true endogenous relapse and co-infection with other tick-borne pathogens. These drawbacks together with the phenomenon of resistance to therapy in individual patients undoubtedly contribute to the inconsistencies surrounding the optimal treatment regimens for LB and are often misinterpreted and misused to support prolonged antibiotic treatment regimens. The question for the underlying mechanisms of possible antimicrobial resistance in Borrelia burgdorferi sensu lato remains unresolved but a better understanding of such genetic or phenotypic mechanisms would be helpful for the treatment of LB and other spirochetal diseases. Investigations on this issue, at best, should start with borrelial isolates cultured from patients before the start of antibiotic therapy and again after the conclusion of treatment. This task, however, remains challenging insofar, as culture is rarely successful under routine laboratory conditions after antimicrobial therapy. Here, we review recent clinical and experimental data on treatment resistance in EM patients suggesting that, although rare, borrelial persistence does occur at the site of the infectious lesion after antibiotic treatment. Borrelial persistence, however, is unlikely to result from acquired resistance against antimicrobial agents that were used for initial specific chemotherapy.
PMID: 16530006 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/entrez/quer ... med_docsum
Tutkimusten mukaan antibioottihoito ei välttämättä auta edes borrelioosin varhaisvaiheessa - erytheemavaiheessa. Syynä ei kuitenkaan todennäköisesti ole antibioottiresistenssi sillä hoidon epäonnistumisia on havaittu lähes kaikkien antibioottien kohdalla.
Int J Med Microbiol. 2006 Mar 8;
Risk of culture-confirmed borrelial persistence in patients treated for erythema migrans and possible mechanisms of resistance.
Hunfeld KP, Ruzic-Sabljic E, Norris DE, Kraiczy P, Strle F.
Institute of Medical Microbiology, University Hospital of Frankfurt, Paul-Ehrlich Str. 40, D-60596 Frankfurt/Main, Germany; The W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, USA.
Erythema migrans (EM) develops at the site of the tick bite in 77-90% of Lyme borreliosis (LB) patients and is therefore a common manifestation of early disease. Clinical treatment failures have been reported in early LB cases for almost every suitable antimicrobial agent. The exact risk of resistance to antibiotic treatment in patients with EM, however, is not known and there are few published cases of culture-proven treatment failure. Moreover, currently available diagnostic techniques cannot reliably discriminate between possible reinfection, true endogenous relapse and co-infection with other tick-borne pathogens. These drawbacks together with the phenomenon of resistance to therapy in individual patients undoubtedly contribute to the inconsistencies surrounding the optimal treatment regimens for LB and are often misinterpreted and misused to support prolonged antibiotic treatment regimens. The question for the underlying mechanisms of possible antimicrobial resistance in Borrelia burgdorferi sensu lato remains unresolved but a better understanding of such genetic or phenotypic mechanisms would be helpful for the treatment of LB and other spirochetal diseases. Investigations on this issue, at best, should start with borrelial isolates cultured from patients before the start of antibiotic therapy and again after the conclusion of treatment. This task, however, remains challenging insofar, as culture is rarely successful under routine laboratory conditions after antimicrobial therapy. Here, we review recent clinical and experimental data on treatment resistance in EM patients suggesting that, although rare, borrelial persistence does occur at the site of the infectious lesion after antibiotic treatment. Borrelial persistence, however, is unlikely to result from acquired resistance against antimicrobial agents that were used for initial specific chemotherapy.
PMID: 16530006 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/entrez/quer ... med_docsum
Viimeksi muokannut Bb, La Maalis 07, 2009 00:12. Yhteensä muokattu 1 kertaa.
Lähettäjä: Soijuv Lähetetty: 5.4.2006 11:25
Minosykliini saattaa olla tehokasta varhaisvaiheen borrelioosissa seuraavan viime vuosikymmenen tutkimuksen mukaan:
Arch Dermatol. 1995 Jun;131(6):678-82.
No detection of Borrelia burgdorferi-specific DNA in erythema migrans
lesions after minocycline treatment.
Muellegger RR, Zoechling N, Soyer HP, Hoedl S, Wienecke R, Volkenandt M,
Kerl H.
Department of Dermatology, Karl-Franzens University, Graz, Austria.
BACKGROUND AND DESIGN: Early treatment of erythema migrans is important
to prevent late complications. Minocycline possesses several attributes,
making it potentially useful in the treatment of borrelial infections. In
our study, minocycline was administered to 14 patients with erythema
migrans. Punch biopsy specimens were obtained from the (affected) skin of
all patients before and after therapy. The formalin-fixed, paraffin-embedded
specimens were analyzed by polymerase chain reaction for the presence of
Borrelia burgdorferi-specific DNA. RESULTS: Polymerase chain reaction assay
succeeded in amplifying B burgdorferi-specific DNA from the first biopsy
specimen, obtained from the border of erythema migrans before initiating
treatment, in eight (57%) of 14 patients. At the end of minocycline therapy,
however, polymerase chain reaction analysis disclosed no B
burgdorferi-specific DNA in any of the 14 patients. The good clinical
response of our patients with erythema migrans substantiates our molecular
findings. CONCLUSIONS: The presented polymerase chain reaction data,
together with the clinical outcome, indicate that minocycline may be useful
for treatment of early Lyme borreliosis.
PMID: 7778919 [PubMed - indexed for MEDLINE]
Minosykliini saattaa olla tehokasta varhaisvaiheen borrelioosissa seuraavan viime vuosikymmenen tutkimuksen mukaan:
Arch Dermatol. 1995 Jun;131(6):678-82.
No detection of Borrelia burgdorferi-specific DNA in erythema migrans
lesions after minocycline treatment.
Muellegger RR, Zoechling N, Soyer HP, Hoedl S, Wienecke R, Volkenandt M,
Kerl H.
Department of Dermatology, Karl-Franzens University, Graz, Austria.
BACKGROUND AND DESIGN: Early treatment of erythema migrans is important
to prevent late complications. Minocycline possesses several attributes,
making it potentially useful in the treatment of borrelial infections. In
our study, minocycline was administered to 14 patients with erythema
migrans. Punch biopsy specimens were obtained from the (affected) skin of
all patients before and after therapy. The formalin-fixed, paraffin-embedded
specimens were analyzed by polymerase chain reaction for the presence of
Borrelia burgdorferi-specific DNA. RESULTS: Polymerase chain reaction assay
succeeded in amplifying B burgdorferi-specific DNA from the first biopsy
specimen, obtained from the border of erythema migrans before initiating
treatment, in eight (57%) of 14 patients. At the end of minocycline therapy,
however, polymerase chain reaction analysis disclosed no B
burgdorferi-specific DNA in any of the 14 patients. The good clinical
response of our patients with erythema migrans substantiates our molecular
findings. CONCLUSIONS: The presented polymerase chain reaction data,
together with the clinical outcome, indicate that minocycline may be useful
for treatment of early Lyme borreliosis.
PMID: 7778919 [PubMed - indexed for MEDLINE]