Clarithromycin therapy of experimental Treponema pallidum infections in hamsters

Abstract

Clarithromycin was shown to be effective therapy for Treponena paUlidum infections in hamsters. Clarithromycin therapy was effective when initiated either 1 or 8 days after infection. The delay in initiation of therapy allowed an active infection to develop. The treponemal burden in lymph tissue of treated hamsters was eradicated, as determined by dark-field microscopy and by inoculation of lymph material into susceptible hamsters. Treatments with clarithromycin and the 14-hydroxy metabolite of clarithromycin were equally effective. Therapy with clarithromycin and penicillin was not antagonistic and did not appear to be synergistic when the two drugs were given concurrently. Pharmacokinetic evaluation of clarithromycin in hamsters showed that the doses which produced effective therapy yielded concentrations in serum similar to those routinely achieved in human sera. These findings demonstrate that clarithromycin is effective in treating active or incubating syphilis in the hamster model and could be useful in treating humans.

Clarithromycin Treatment Failure due to Macrolide Resistance in Treponema pallidum in a Patient with Primary Syphilis

“…Multiple doses of erythromycin decrease treponema counts by greater than 300-fold, which is similar to the efficacy of penicillin (5). darithromycin was found to be effective in treating syphilis in the hamster model, and several human studies report that azithromycin can effectively replace penicillin therapy (6,7). Nevertheless, treatment failure after administration of azithromycin in syphilis has been reported, and the genetic background of macrolide resistance was identified in clinical isolates as A2058G and A2059G mutations in the 23S ribosomal RNA gene of Treponema pallidum (8)(9)(10)(11).…”

The Experimental Use of Syrian Hamsters

“…Experimental infection of hamsters with T. pallidum provides a model to study syphilis infection and drug therapy. Daily clarithromycin given over 7 days successfully eliminates infection in hamsters (Alder et al, 1993). Success is confirmed by failure to infect susceptible hamsters following inoculation with lymph node material from treated hamsters (Alder et al, 1993).…”

Tight binding of clarithromycin, its 14-(R)-hydroxy metabolite, and erythromycin to Helicobacter pylori ribosomes

“…Clarithromycin is a recently approved 14-membered macrolide with increased stability in acid and improved pharmacokinetics, including the appearance of a microbiologically active metabolite in humans (8). Clarithromycin possesses broad-spectrum antimicrobial activity, inhibiting a range of gram-positive and gram-negative organisms, some anaerobes, and atypical pathogens (1,3,14,16,25), in many cases with greater in vitro activity than erythromycin.…”