Journal of Antimicrobial Chemotherapy, Vol 41, 57-62, Copyright © 1998 by The British Society for Antimicrobial Chemotherapy
M Brun-Pascaud, F Chau, F Derouin and PM Girard
We have developed a dual infection model in immunosuppressed rats for
evaluating drugs against Pneumocystis carinii and Toxoplasma gondii, two
important opportunistic pathogens in patients with AIDS. Using this model,
we reported that the macrolide roxithromycin was effective at a daily dose
of 400 mg/kg in preventing the development of T. gondii infection but did
not have a prophylactic effect against P. carinii in the same rats. A lower
dose (200 mg/kg/day) had only marginal effects. Extending these
experiments, we have now shown that roxithromycin at doses of 400 or 200
mg/kg/day combined with dapsone at doses of 5, 25 or 50 mg/kg/day
completely prevented the development of T. gondii infection, with no
parasites being detected in any of the tissues sampled. Roxithromycin at
either dose combined with dapsone at 25 or 50 mg/kg/day was also effective
in preventing the development of P. carinii infection in the lungs. The
lowest dose of dapsone (5 mg/kg/day) was not fully effective.
Pyrimethamine-dapsone, a combination used clinically, was tested in the
same experiment, and gave results comparable to those with
roxithromycin-dapsone combinations. In a further experiment combining
roxithromycin with sulphamethoxazole, roxithromycin was effective in
preventing the T. gondii infection, even when given at only 200 mg/kg/day
with 20 mg/kg/day of sulphamethoxazole. When the dose of sulphamethoxazole
was reduced to 2 mg/kg/day and given with roxithromycin 200 mg/kg/day, T.
gondii infection developed in two of the five rats treated. P. carinii
infection was prevented by sulphamethoxazole at 20 mg/kg/day but not
completely by 2 mg/kg/day. Roxithromycin also has activity against
Mycobacterium avium, another important cause of opportunistic infections in
AIDS patients, and the compound penetrates mammalian cells well. Taken
together with the favourable pharmacokinetic profile of roxithromycin,
these results suggest that it may have a clinical utility, when used with
other agents, in controlling the development of opportunistic infections
caused by M. avium complex, T. gondii and P. carinii in HIV-infected
individuals.
ORIGINAL ARTICLES
Experimental evaluation of roxithromycin combined with dapsone or sulphamethoxazole on Pneumocystis carinii and Toxoplasma gondii dual infections in a rat model
Inserm U13, Hopital Bichat-Claude Bernard, Paris, France.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. A. Khan and J. R. Wingard Infection and Mucosal Injury in Cancer Treatment J Natl Cancer Inst Monographs, October 1, 2001; 2001(29): 31 - 36. [Abstract] [Full Text] [PDF]
|
|