Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1996 Nov;40(11):2632–2636. doi: 10.1128/aac.40.11.2632

In vivo activities of ceftriaxone and vancomycin against Borrelia spp. in the mouse brain and other sites.

R J Kazragis 1, L L Dever 1, J H Jorgensen 1, A G Barbour 1
PMCID: PMC163589  PMID: 8913478

Abstract

Borrelia burgdorferi, the agent of Lyme disease, and B. turicatae, a neurotropic agent of relapsing fever, are susceptible to vancomycin in vitro, with an MIC of 0.5 microgram/ml. To determine the activity of vancomycin in vivo, particularly in the brain, we infected adult immunocompetent BALB/c and immunodeficient CB-17 scid mice with B. burgdorferi or B. turicatae. The mice were then treated with vancomycin, ceftriaxone as a positive control, or normal saline as a negative control. The effectiveness of treatment was assessed by cultures of blood and brain and other tissues. Ceftriaxone at a dose of 25 mg/kg of body weight administered every 12 h for 7 to 10 days eliminated cultivable B. burgdorferi or B. turicatae from all BALB/c or scid mice in the study. Vancomycin at 30 mg/kg administered every 12 h was effective in eliminating infection from immunodeficient mice if treatment was started within 3 days of the onset of infection. If treatment with vancomycin was delayed for 7 days or more, vancomycin failed to eradicate infection with B. burgdorferi or B. turicatae from immunodeficient mice. The failure of vancomycin in eradicating established infections in immunodeficient mice was associated with the persistence of viable spirochetes in the brain during antibiotic treatment.

Full Text

The Full Text of this article is available as a PDF (198.9 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Agger W. A., Callister S. M., Jobe D. A. In vitro susceptibilities of Borrelia burgdorferi to five oral cephalosporins and ceftriaxone. Antimicrob Agents Chemother. 1992 Aug;36(8):1788–1790. doi: 10.1128/aac.36.8.1788. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barbour A. G., Fish D. The biological and social phenomenon of Lyme disease. Science. 1993 Jun 11;260(5114):1610–1616. doi: 10.1126/science.8503006. [DOI] [PubMed] [Google Scholar]
  3. Barbour A. G., Hayes S. F. Biology of Borrelia species. Microbiol Rev. 1986 Dec;50(4):381–400. doi: 10.1128/mr.50.4.381-400.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Barbour A. G., Todd W. J., Stoenner H. G. Action of penicillin on Borrelia hermsii. Antimicrob Agents Chemother. 1982 May;21(5):823–829. doi: 10.1128/aac.21.5.823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Barthold S. W., Sidman C. L., Smith A. L. Lyme borreliosis in genetically resistant and susceptible mice with severe combined immunodeficiency. Am J Trop Med Hyg. 1992 Nov;47(5):605–613. doi: 10.4269/ajtmh.1992.47.605. [DOI] [PubMed] [Google Scholar]
  6. Barthold S. W., de Souza M. S., Janotka J. L., Smith A. L., Persing D. H. Chronic Lyme borreliosis in the laboratory mouse. Am J Pathol. 1993 Sep;143(3):959–971. [PMC free article] [PubMed] [Google Scholar]
  7. Beskid G., Christenson J. G., Cleeland R., DeLorenzo W., Trown P. W. In vivo activity of ceftriaxone (Ro 13-9904), a new broad-spectrum semisynthetic cephalosporin. Antimicrob Agents Chemother. 1981 Aug;20(2):159–167. doi: 10.1128/aac.20.2.159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cadavid D., Bundoc V., Barbour A. G. Experimental infection of the mouse brain by a relapsing fever Borrelia species: a molecular analysis. J Infect Dis. 1993 Jul;168(1):143–151. doi: 10.1093/infdis/168.1.143. [DOI] [PubMed] [Google Scholar]
  9. Cadavid D., Thomas D. D., Crawley R., Barbour A. G. Variability of a bacterial surface protein and disease expression in a possible mouse model of systemic Lyme borreliosis. J Exp Med. 1994 Feb 1;179(2):631–642. doi: 10.1084/jem.179.2.631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Delaplane D., Yogev R., Shulman S. T. Ceftriaxone therapy of group B streptococcal bacteraemia and meningitis in infant rats. J Antimicrob Chemother. 1983 Jan;11(1):69–73. doi: 10.1093/jac/11.1.69. [DOI] [PubMed] [Google Scholar]
  11. Dever L. L., Jorgensen J. H., Barbour A. G. In vitro activity of vancomycin against the spirochete Borrelia burgdorferi. Antimicrob Agents Chemother. 1993 May;37(5):1115–1121. doi: 10.1128/aac.37.5.1115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dever L. L., Jorgensen J. H., Barbour A. G. In vitro antimicrobial susceptibility testing of Borrelia burgdorferi: a microdilution MIC method and time-kill studies. J Clin Microbiol. 1992 Oct;30(10):2692–2697. doi: 10.1128/jcm.30.10.2692-2697.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ducharme M. P., Slaughter R. L., Edwards D. J. Vancomycin pharmacokinetics in a patient population: effect of age, gender, and body weight. Ther Drug Monit. 1994 Oct;16(5):513–518. doi: 10.1097/00007691-199410000-00013. [DOI] [PubMed] [Google Scholar]
  14. GERACI J. E., HEILMAN F. R., NICHOLS D. R., ROSS G. T., WELLMAN W. E. Some laboratory and clinical experiences with a new antibiotic, vancomycin. Proc Staff Meet Mayo Clin. 1956 Oct 17;31(21):564–582. [PubMed] [Google Scholar]
  15. Johnson R. C. Isolation techniques for spirochetes and their sensitivity to antibiotics in vitro and in vivo. Rev Infect Dis. 1989 Sep-Oct;11 (Suppl 6):S1505–S1510. doi: 10.1093/clinids/11.supplement_6.s1505. [DOI] [PubMed] [Google Scholar]
  16. Johnson R. C., Kodner C. B., Jurkovich P. J., Collins J. J. Comparative in vitro and in vivo susceptibilities of the Lyme disease spirochete Borrelia burgdorferi to cefuroxime and other antimicrobial agents. Antimicrob Agents Chemother. 1990 Nov;34(11):2133–2136. doi: 10.1128/aac.34.11.2133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Johnson R. C., Kodner C., Russell M. In vitro and in vivo susceptibility of the Lyme disease spirochete, Borrelia burgdorferi, to four antimicrobial agents. Antimicrob Agents Chemother. 1987 Feb;31(2):164–167. doi: 10.1128/aac.31.2.164. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lagast H., Dodion P., Klastersky J. Comparison of pharmacokinetics and bactericidal activity of teicoplanin and vancomycin. J Antimicrob Chemother. 1986 Oct;18(4):513–520. doi: 10.1093/jac/18.4.513. [DOI] [PubMed] [Google Scholar]
  19. Levin J. M., Nelson J. A., Segreti J., Harrison B., Benson C. A., Strle F. In vitro susceptibility of Borrelia burgdorferi to 11 antimicrobial agents. Antimicrob Agents Chemother. 1993 Jul;37(7):1444–1446. doi: 10.1128/aac.37.7.1444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Moellering R. C., Jr Pharmacokinetics of vancomycin. J Antimicrob Chemother. 1984 Dec;14 (Suppl 500):43–52. doi: 10.1093/jac/14.suppl_d.43. [DOI] [PubMed] [Google Scholar]
  21. Moody K. D., Adams R. L., Barthold S. W. Effectiveness of antimicrobial treatment against Borrelia burgdorferi infection in mice. Antimicrob Agents Chemother. 1994 Jul;38(7):1567–1572. doi: 10.1128/aac.38.7.1567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Mursic V. P., Wilske B., Schierz G., Holmburger M., Süss E. In vitro and in vivo susceptibility of Borrelia burgdorferi. Eur J Clin Microbiol. 1987 Aug;6(4):424–426. doi: 10.1007/BF02013102. [DOI] [PubMed] [Google Scholar]
  23. Nicolau D. P., Freeman C. D., Nightingale C. H., Quintiliani R. Pharmacokinetics of minocycline and vancomycin in rabbits. Lab Anim Sci. 1993 Jun;43(3):222–225. [PubMed] [Google Scholar]
  24. Pachner A. R., Ricalton N., Delaney E. Comparison of polymerase chain reaction with culture and serology for diagnosis of murine experimental Lyme borreliosis. J Clin Microbiol. 1993 Feb;31(2):208–214. doi: 10.1128/jcm.31.2.208-214.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Paster B. J., Dewhirst F. E., Weisburg W. G., Tordoff L. A., Fraser G. J., Hespell R. B., Stanton T. B., Zablen L., Mandelco L., Woese C. R. Phylogenetic analysis of the spirochetes. J Bacteriol. 1991 Oct;173(19):6101–6109. doi: 10.1128/jb.173.19.6101-6109.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Patel I. H., Chen S., Parsonnet M., Hackman M. R., Brooks M. A., Konikoff J., Kaplan S. A. Pharmacokinetics of ceftriaxone in humans. Antimicrob Agents Chemother. 1981 Nov;20(5):634–641. doi: 10.1128/aac.20.5.634. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Peetermans W. E., Hoogeterp J. J., Hazekamp-van Dokkum A. M., van den Broek P., Mattie H. Antistaphylococcal activities of teicoplanin and vancomycin in vitro and in an experimental infection. Antimicrob Agents Chemother. 1990 Oct;34(10):1869–1874. doi: 10.1128/aac.34.10.1869. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Sadziene A., Barbour A. G., Rosa P. A., Thomas D. D. An OspB mutant of Borrelia burgdorferi has reduced invasiveness in vitro and reduced infectivity in vivo. Infect Immun. 1993 Sep;61(9):3590–3596. doi: 10.1128/iai.61.9.3590-3596.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Schaible U. E., Gay S., Museteanu C., Kramer M. D., Zimmer G., Eichmann K., Museteanu U., Simon M. M. Lyme borreliosis in the severe combined immunodeficiency (scid) mouse manifests predominantly in the joints, heart, and liver. Am J Pathol. 1990 Oct;137(4):811–820. [PMC free article] [PubMed] [Google Scholar]
  30. Sinsky R. J., Piesman J. Ear punch biopsy method for detection and isolation of Borrelia burgdorferi from rodents. J Clin Microbiol. 1989 Aug;27(8):1723–1727. doi: 10.1128/jcm.27.8.1723-1727.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Steere A. C. Lyme disease. N Engl J Med. 1989 Aug 31;321(9):586–596. doi: 10.1056/NEJM198908313210906. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES