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Azithromycin versus doxycycline for treatment of erythema migrans: Clinical and microbiological findings

Azithromycin versus Doxycyclin bei Erythema migrans: klinische und mikrobiologische Befunde

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Summary

The effectiveness of azithromycin and doxycycline in the treatment of erythema migrans was compared in a prospective randomized trial. One hundred seven adult patients with typical erythema migrans, examined in the Lyme Borreliosis Outpatients' Clinic, University Department of Infectious Diseases in Ljubljana, were included in the study. Fifty-five patients received azithromycin (500 mg twice daily for the first day, followed by 500 mg once daily for four days) and 52 patients received doxycycline (100 mg twice daily for 14 days). The mean duration of skin lesions after the beginning of treatment was 7.5±5.9 days (median value 5, range 2–28 days) in the azithromycin group and 11.4±7.8 days (median value 9, range 2 days — 8 weeks) in the doxycycline group (p<0.05).Borrelia burgdorferi was isolated from erythema migrans in 28 patients before therapy: in 13 out of 52 in the doxycycline group and in 15 out of 55 in the azithromycin group. Three months after therapy, the culture was positive in four out of 13 patients treated with doxycycline and in one of the 15 patients who received azithromycin. A biopsy was repeated in all the patients with a positive isolation from the first skin specimen. During the first 12 months' follow-up, three patients treated with doxycycline but none in the azithromycin group developed major manifestations of Lyme borreliosis, while 15 doxycycline recipients and 10 azithromycin recipients developed minor consecutive manifestations.

Zusammenfassung

In einer prospektiven, randomisierten Studie wurde die Wirksamkeit von Azithromycin und Doxycyclin bei Erythema migrans verglichen. In die Studie, die in der Lyme-Borreliose-Ambulanz der Infektiologischen Abteilung der Universtitätsklinik Ljubljana durchgeführt wurde, wurden 107 Patienten mit typischem Erythema migrans aufgenommen. Mit Azithromycin (500 mg zweimal täglich am ersten und 500 mg einmal täglich an den folgenden 4 Tagen) wurden 55 Patienten behandelt, mit Doxycyclin (200 mg zweimal täglich für 14 Tage) 52 Patienten. In der Azithromycin-Gruppe verschwanden die Hautläsionen nach Therapiebeginn im Mittel nach 7,5±5,9 (Medianwert 5; Bereich 2–28) Tagen, in der Doxycyclin-Gruppe nach 11,4±7,8 Tagen (Medianwert 9; Bereich 2 Tage bis 8 Wochen); (p<0,05). Bei 28 Patienten konnteBorrelia burgdorferi aus dem Bereich des Erythema migrans vor Therapiebeginn isoliert werden (13/52 Patienten der Doxycyclin-Gruppe und 15 von 55 Patienten der Azithromycin-Gruppe). Drei Monate nach Therapie waren die Kulturen in der Doxycyclin-Gruppe noch in vier von 13 und in der Azithromycin-Gruppe in einem von 15 Fällen positiv. Bei allen Patienten mit positiver Kultur in der ersten Hautbiopsie war auch eine Kontrollbiopsie vorgenommen und die Erregerisolierung durchgeführt worden. Während der ersten 12 Monate der Nachbeobachtungsphase hatten drei mit Doxycyclin behandelte Patienten bedeutende Manifestationsformen der Lyme Borreliose entwickelt. In der Azithromycin-Gruppe war dies in keinem Fall erfolgt. Weniger gravierende Manifestationsformen folgten bei 15 mit Doxycyclin und bei 10 mit Azithromycin behandelten Patienten.

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References

  1. Stanek, G., Pletschette, M., Flamm, H., Hirschl, A. M., Aberer, E., Kristoferitsch, W., Schmutzhard, E. European Lyme borreliosis. Ann. N. Y. Acad. Sci. 539 (1988) 274–282.

    Google Scholar 

  2. Ciesielski, C. A., Markowitz, L. E., Horsley, R., Hightower, A. R., Russell, H., Broome, C. V. The geographic distribution of Lyme disease in the United States. Ann. N. Y. Acad. Sci. 539 (1988) 283–288.

    Google Scholar 

  3. Burgdorfer, W., Barbour, A. G., Hayes, S. F., Benach, J. L., Grunwaldt, E., Davis, J. P. Lyme disease: a tick-borne spirochetosis? Science 216 (1982) 1317–1319.

    Google Scholar 

  4. Steere, A. C., Bartenhagen, N. H., Craft, J. E., Hutchinson, G. J., Newman, J. H., Pachner, A. R., Rahn, D. W., Sigal, L. H., Taylor, E., Malawista, S. E. Clinical manifestations of Lyme disease. Zbl. Bakt. Hyg. A 263 (1986) 201–205.

    Google Scholar 

  5. Steere, A. C., Malawista, S. E., Bartenhagen, N. H., Spieler, P. N., Newman, J. H., Rahn, D. W., Hutchinson, G. J., Green, J., Snydman, D. R., Taylor, E. The clinical spectrum and treatment of Lyme disease. Yale J. Biol. Med. 57 (1984) 453–461.

    Google Scholar 

  6. Steere, A. C., Hutchinson, G. J., Rahn, D. W. A., Sigal, L. H., Craft, J. E., DeSanna, E. T., Malawista, S. E. Treatment of the early manifestations of Lyme disease. Ann. Intern. Med. 99 (1983) 22–26.

    Google Scholar 

  7. Weber, K., Neubert, U., Thurmayr, R. Antibiotic therapy in early erythema migrans disease and related disorders. Zbl. Bakt. Hyg. A 263 (1986) 377–388.

    Google Scholar 

  8. Berger, B. W. Treatment of erythema chronicum migrans of Lyme disease. Ann. N. Y. Acad. Sci. 539 (1988) 346–351.

    Google Scholar 

  9. Weber, K., Preac-Mursic, V., Neubert, U., Thurmayr, R., Herzer, P., Wilske, B., Schierz, G., Marget, W. Antibiotic therapy of early European Lyme borreliosis and acrodermatitis chronica atrophicans. Ann. N. Y. Acad. Sci. 539 (1988) 324–345.

    Google Scholar 

  10. Preac-Mursic, A., 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.

    Google Scholar 

  11. Foulds, G., Shepard, R. M., Johnson, R. B. The pharmacokinetics of azithromycin in human serum and tissues. J. Antimicrob. Chemother. 25 Suppl. A (1990) 73–82.

    Google Scholar 

  12. Preac-Mursic, V., Wilske, B., Schierz, G., Suss, E., Gross, B. Comparative antimicrobial activity of the new macrolides againstBorrelia burgdorferi. Eur. J. Clin. Microbiol. 8 (1989) 651–653.

    Google Scholar 

  13. Johnson, R. C., Kodner, C., Russell, M.: In vitro andin vivo susceptibility ofBorrelia burgdorferi to three antimicrobial agents. 4th European Congress of Clinical Microbiology, Nice 1989, Abstract No. 941, p. 43.

  14. Johnson, R. C., Kodner, C., Russell, M., Girard, D. In-vitro andin-vivo susceptibility ofBorrelia burgdorferi to azithromycin. J. Antimicrob. Chemother. 25 Suppl. A (1990) 33–38.

    Google Scholar 

  15. Strle, F., Ružič, E., Cimperman, J. Erythema migrans: comparison of treatment with azithromycin, doxycycline and phenoxymethylpenicillin. J. Antimicrob. Chemother. 30 (1992) 543–550.

    Google Scholar 

  16. Massarotti, E. M., Luger, S. W., Rahn, D. W., Messner, R. P., Wong, J. B., Johnson, R. C., Steere, A. C. Treatment of early Lyme disease. Am. J. Med. 92 (1992) 396–403.

    Google Scholar 

  17. 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.

    Google Scholar 

  18. Steere, A. C., Malawista, S. E., Newman, J. H., Spieler, P. N., Bartenhagen, N. H. Antibiotic therapy in Lyme disease. Ann. Intern. Med. 93 (1980) 1–8.

    Google Scholar 

  19. Berger, B. W. Treating erythema chronicum migrans of Lyme disease. J. Am. Acad. Dermatol. 15 (1986) 459–463.

    Google Scholar 

  20. Dattwyler, R. J., Halperin, J. J. Failure of tetracycline therapy in early Lyme disease. Arthritis Rheumat. 30 (1987) 448–450.

    Google Scholar 

  21. Preac-Mursic, V., Wilske, B., Schierz, G., Holmburger, M., Suss, E. In vitro andin vivo susceptibility ofBorrelia burgdorferi. Eur. J. Clin. Microbiol. 6 (1987) 424–426.

    Google Scholar 

  22. Wretlind, B., Johnson, R. C., Hansen, K., Preac-Mursic, V. Antibiotic susceptibility ofBorrelia burgdorferi inin vitro and animal models. Scand. J. Infect. Dis. Suppl. 77 (1991) 143–144.

    Google Scholar 

  23. Johnson, R. C., Kodner, C., Russell, M., Duray, H. P. Experimental infection of the hamster withBorrelia burgdorferi. N. Y. Acad. Sci. 539 (1988) 258–263.

    Google Scholar 

  24. Standiford, H. C. Tetracyclines and chloramphenicol. In:Mandell, G. L., Douglas, R. G. Jr., Bennett, J. E. (eds.): Principles and practice of infectious diseases. Churchill Livingstone, New York 1990, pp. 284–295.

    Google Scholar 

  25. Dotevall, L., Alestig, K., Hanner, P., Norkrans, G., Hagberg, L. The use of doxycycline in nervous systemBorrelia burgdorferi infection. Scand. J. Infect. Dis. 53 (1988) 74–79.

    Google Scholar 

  26. Dotevall, L., Hagberg, L. Penetration of doxycycline into cerebrospinal fluid in patients treated for suspected Lyme neuroborreliosis. Antimicrob. Agents Chemother. 33 (1989) 1078–1080.

    Google Scholar 

  27. Bright, G. M., Nagel, A. A., Bordner, J., Desai, K. A., Dibrino, J. N., Nowakowska, J., Vincent, L., Watrous, R. M., Sciavolino, F. C., English, A. R., Retsema, J. A., Anderson, M. R., Brennan, L. A., Borovoy, R. J., Cimochowski, C. R., Faiella, J. A., Girard, A. E., Girard, D., Herbert, C., Manousos, M., Mason, R. Synthesis,in vitro andin vivo activity of novel 9-deoxo-9a-aza-9a homoerythromycin A derivates: a new class of macrolide antibiotics, the azalides. J. Antibiotics 41 (1988) 1029–1047.

    Google Scholar 

  28. Girard, A. E., Girard, D, Retsema, J. A. Correlation of the extravascular pharmacokinetics of azithromycin within vivo efficacy in models of localized infection. J. Antimicrob. Chemother. 25 Suppl. A (1990) 61–71.

    Google Scholar 

  29. Shepard, R. M., Falkner, F. C. Pharmacokinetics of azithromycin in rats and dogs. J. Antimicrob. Chemother. 25 Suppl. A (1990) 49–60.

    Google Scholar 

  30. Retsema, J. A., Girard, A. E., Girard, D., Milisen, W. P. Relationship of high tissue concentrations of azithromycin to bactericidal activity and efficacyin vivo. J. Antimicrob. Chemother. 25 Suppl. A (1990) 83–89.

    Google Scholar 

  31. Weber, K., Preac-Mursic, V., Wilske, B., Thurmayr, R., Neubert, U., Scherwitz, C. A randomized trial of ceftriaxone versus oral penicillin for the treatment of early European Lyme borreliosis. Infection 18 (1990) 91–96.

    Google Scholar 

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Strle, F., Cimperman, J., Maraspin, V. et al. Azithromycin versus doxycycline for treatment of erythema migrans: Clinical and microbiological findings. Infection 21, 83–88 (1993). https://doi.org/10.1007/BF01710737

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