Summary
For a better understanding of the persistence ofBorrelia burgdorferi sensu lato (s.l.) after antibiotic therapy the kinetics of killingB. burgdorferi s.l. under amoxicillin, doxycycline, cefotaxime, ceftriaxone, azithromycin and penicillin G were determined. The killing effect was investigated in MKP medium and human serum during a 72 h exposure to antibiotics. Twenty clinical isolates were used, including ten strains ofBorrelia afzelii and ten strains ofBorrelia garinii. The results show that the kinetics of killing borreliae differ from antibiotic to antibiotic. The killing rate of a given antibiotic is less dependent on the concentration of the antibiotic than on the reaction time. Furthermore, the data show that the strains ofB. afzelii andB. garinii have a different reaction to antibiotics used in the treatment of Lyme borreliosis and that different reactions to given antibiotics also exist within one species. TheB. garinii strains appear to be more sensitive to antibiotics used in therapy. Furthermore, the persistence ofB. burgdorferi s.l. and clinical recurrences in patients despite seemingly adequate antibiotic treatment is described. The patients had clinical disease with or without diagnostic antibody titers toB. burgdorferi.
Zusammenfassung
Die bakterizide Aktivität von Amoxicillin, Doxycyclin, Cefotaxim, Ceftriaxon, Azithromycin und Penicillin G gegenBorrelia burgdorferi s.l. Stämme wurde in MKP-Medium und Humanserum während der 72 Stunden Einwirkungszeit untersucht. Die Antiborrelienwirkung der Antibiotika wurde an 20 Patientenisolaten, zehnBorrelia afzelii und zehnBorrelia garinii Stämmen, getestet. Der Abtötungseffekt der einzelnen Antibiotika auf getestete Stämme ist sehr unterschiedlich. Die Unterschiede hinsichtlich der Keimreduktion bestehen zwischen den Stämmen derB. afzelii undB. garinii species als auch zwischen den Stämmen innerhalb einer Spezies. Der Anteil der abgetöteten Borrelien ist weniger abhängig von der Konzentration des Antibiotikums als von der Einwirkungszeit. DieB. garinii Stämme sind offensichtlich empfindlicher gegen die in der Therapie eingesetzten Antibiotika. Die Persistenz vonB. burgdorferi s.l. und Rezidive der Erkrankung nach der Antibiotikatherapie werden diskutiert.
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References
Pfister, H.-W., Preac Mursic, V., Wilske, B., Einhäupl, K. M., Weinberger, K. Latent Lyme neuroborreliosis: presence ofBorrelia burgdorferi in the cerebrospinal fluid without concurrent inflammatory signs. Neurology 39 (1989) 1118–1120.
Preac Mursic, V., Weber, K., Pfister, H.-W., Wilske, B., Gross, B., Baumann, A., Prokop, J. Survival ofBorrelia burgdorferi in antibiotically treated patients with Lyme borreliosis. Infection 17 (1989) 355–359.
Liegner, K., Shapiro, J., Ramsay, D. R., Halperin, A. J., Hagrefe, W., Kong, L. Recurrent erythema migrans despite extended antibiotic treatment with minocycline in a patient with persistingBorrelia burgdorferi infection. J. Am. Acad. Dermatol. 28 (1993) 312–314.
Preac Mursic, V., Pfister, H.-W., Spiegel, H., Burk, R., Wilske, B., Reinhardt, S., Boehmer, R. First isolation ofBorrelia burgdorferi from an iris biopsy. J. Clin. Neuroophthalmol. 13 (1993) 155–161.
Johnson, R. C., Kodnes, C., Russel, M. In vitro andin vivo susceptibility of the Lyme disease spirocheteBorrelia burgdorferi to four antimicrobials. Antimicrob. Agents Chemother. 31 (1987) 164–167.
Johnson, R. C. Isolation techniques for spirochetes and their sensitivity to antibioticsin vitro andin vivo. Rev. Infect. Dis. 11 (Suppl. 6) (1989) 1505–1510.
Preac Mursic, V., Wilske, B., Schierz, G., Holmburger, M., Süß, E. In vitro andin vivo susceptibility ofBorrelia burgdorferi. Eur. J. Clin. Microbiol. 6 (1987) 424–426.
Preac Mursic, V. Antibiotic susceptibility ofBorrelia burgdorferi. In vitro andin vivo. In:Weber, K., Burgdorfer, W. (eds.): Aspects of Lyme borreliosis. Springer, Berlin, Heidelberg, New York 1993, pp. 301–311.
Levin, J. M., Nelson, J. A., Segreti, J., Harrison, B., Benson, C. A., Strle, F. In vitro susceptibility ofBorrelia burgdorferi to 11 antimicrobial agents. Antimicrob. Agents Chemother. 37 (1993) 1444–1446.
Schmidli, J., Hunziker, T., Moesli, P., Schaad, U. B. Cultivation ofBorrelia burgdorferi from joint fluid three months after treatment of facial palsy due to Lyme borreliosis. J. Infect. Dis. 158 (1988) 905–906.
Häupl, T., Hahn, G., Rittig, M., Krause, A., Schoerner, C., Schönherr, U., Kalden, J. R., Burmester, G. R. Persistence ofBorrelia burgdorferi in ligamentous tissue from a patient with chronic Lyme borreliosis. Arthritis Rheum. 36 (1993) 1621–1626.
Liegner, K. B. Treatment of late Lyme disease: a challenge to accept. J. Clin. Microbiol. 32 (1994) 1415–1416.
Preac Mursic, V., Wilske, B., Schierz, G. EuropeanBorrelia burgdorferi isolated from humans and ticks: culture conditions and antibiotic susceptibility. Zbl. Bakt. Hyg. A 263 (1986) 112–118.
Wilske, B., Preac-Mursic, V. Microbiological diagnosis of Lyme borreliosis. reliosis. In:Weber, K., Burgdorfer, W. (eds.): Aspects of Lyme borreliosis. Springer, Berlin, Heidelberg, New York 1993, pp. 267–300.
Preac Mursic, V., Wilske, B. Biology ofBorrelia burgdorferi. In:Weber, K., Burgdorfer, W. (eds.): Aspects of Lyme borreliosis. Springer, Berlin, Heidelberg, New York 1993, pp. 44–58.
Wilske, B., Preac Mursic, V., Fuchs, R., Bruckbauer, H., Hofmann, A., Zumstein, G., Jauris, S., Soutschek, E., Motz, M. Immunodominant proteins ofBorrelia burgdorferi; implications for improving serodiagnosis of Lyme borreliosis. In:Neu, H. C. (ed.): New antibacterial strategies. Churchill Livingstone, London 1990, pp. 47–63.
Casjens, S., Huang, W. M. Linear chromosomal physical and genetic map ofBorrelia burgdorferi, the Lyme disease agent. Molec. Microbiol. 8 (1993) 967–980.
Busch, U., Teufel, C. H., Boehmer, R., Wilske, B., Preac-Mursic, V. Molecular characterization ofBorrelia burgdorferi sensu lato strains by pulsed-field gel electrophoresis. Electrophoresis 16 (1995) 744–747.
Asbrink, E., Olsson, I., Hovmark, A. Erythema chronicum migrans afzelius in Sweden. A study on 231 patients. Zbl. Bakt. Hyg. A 263 (1986) 229–236.
Steere, A. C., Schoen, R. T., Taylor, E. The clinical evolution of Lyme arthritis. Ann. Intern. Med. 107 (1987) 725–731.
Steere, A. C., Levin, R. E., Molloy, P. J., Kalish, R. A., Abraham III, J. H., Lui, N. Y., Schmid, C. H. Treatment of Lyme arthritis. Arthritis Rheum. 37 (1994) 878–888.
Radolf, J. D., Bourell, K. W., Akins, D. R., Brusca, J. S., Norgard, M. V. Analysis ofBorrelia burgdorferi membrane architecture by freeze-fracture electron microscopy. J. Bacteriol. 176 (1994) 21–31.
Swain, R. H. A. Electron microscopic studies of the morphology of pathogenic spirochaetes. J. Path. Bact. Vol. LXIX (1955) 117–128.
Charache, P. Atypical bacterial forms in human disease. In:Guze, L. B. (ed.): Microbial protoplasts, spheroplasts and L-forms. Williams and Wilkins, Baltimore 1968, p. 484.
Stanek, G., Klein, J., Bittner, R., Glogar, D. Isolation ofBorrelia burgdorferi from the myocardium of a patient with longstanding cardiomyopathy. N. Engl. J. Med. 322 (1990) 249–252.
Detmar, U., Maciejewski, W. Borrelial dermatomyositis-like syndrome. In:Weber, K., Burgdorfer, W. (eds.): Aspects of Lyme borreliosis. Springer, Berlin, Heidelberg, New York 1993, 259–266.
Cimmino, M., Azzolini, A., Tobia, F., Pesce, C. Spirochetes in the spleen of a patient with chronic Lyme disease. Am. J. Clin. Pathol. 91 (1989) 95–97.
MacDonald, A. B. Borrelia in the brains of patients dying with dementia. JAMA 256 (1986) 2195–2196.
Dattwyler, R. J., Halperin, J. J., Volkman, D. J., Luft, B. J. Treatment of late Lyme borreliosis — randomised comparison of ceftriaxone and penicillin. Lancet ii (1988) 1191–1194.
Pal, G. S., Baker, J. T., Wright, D. J. M. Penicillin-resistant borrelia encephalitis responding to cefotaxime. Lancet i (1988) 50–51.
Hassler, D., Zöller, L., Haude, M., Hufnagel, H.-D., Heinrich, F., Sonntag, H.-G. Cefotaxime versus penicillin in the late stage of Lyme disease — prospective, randomized therapeutic study. Infection 18 (1990) 16–20.
Kristoferitsch, W., Baumhackl, U., Sluga, E., Stanek, G., Zeller, K. High-dose penicillin in meningopolyneuritis Garin-Bujadoux-Bannwarth. Zbl. Bakt. Hyg. A 263 (1986) 357–364.
Pfister, H.-W., Preac-Mursic, V., Einhäupl, K. M., Wilske, B. Cefotaxime versus penicillin G for acute neurological manifestations of Lyme borreliosis: a prospective randomized study. Arch. Neurol. 46 (1989) 1190–1194.
Weber, K., Preac-Mursic, V., Wilske, B., Thurmayr, R., Neubert, U., Scherwitz, C. A randomized trial of ceftriaxone versus oral penicillin for treatment of early Lyme borreliosis. Infection 18 (1990) 91–96.
Karlsson, M., Hammers-Berggren, S., Lindquist, L., Stiernstedt, G., Svenungsson, B. Comparison of intravenous penicillin G and oral doxycycline for treatment of Lyme neuroborreliosis. Neurology 44 (1994) 1203–1207.
Strle, F., Stanek, G., Ruzic, E., Michieli, M. S.: Erythema migrans: comparison of treatment with azithromycin, doxycycline and phenoxymethylpenicillin. Congress for Infectious Diseases, Montreal, Canada, 1990.
Pfister, H.-W., Preac Mursic, V., Wilske, B., Schielke, E., Soergel, F., Einhäupl, K. M. Randomized comparison of ceftriaxone and cefotaxime in Lyme neuroborreliosis. J. Infect. Dis. 163 (1991) 311–318.
Ying, M., Sturrock, A., Weis, J. J. Intracellular localization ofBorrelia burgdorferi within human emdothelial cells. Infect. Immun. 59 (1991) 671–678.
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This article is the expanded version of a lecture delivered in Portoroz on 14 May 1995. See also page 59.
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Mursic, V.P., Busch, U., Marget, W. et al. Kill kinetics ofBorrelia burgdorferi and bacterial findings in relation to the treatment of lyme borreliosis. Infection 24, 9–16 (1996). https://doi.org/10.1007/BF01780643
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DOI: https://doi.org/10.1007/BF01780643