Abstract
The efficacy of azithromycin administered alone or combined with pyrimethamine or sulfadiazine was examined in a murine model of acute toxoplasmosis. Outbred Swiss mice acutely infected with tachyzoites of the virulent RH strain were treated for 10 days from day +1 postinfection. The efficacy of each regimen was assessed in terms of survival rates and sequential titration of parasites in blood, brain, and lungs by using a tissue culture method. Administration of azithromycin at 300, 150, or 75 mg/kg of body weight per day resulted in prolonged survival relative to that of untreated controls; sequential examination of parasite burden showed early eradiaction of Toxoplasma gondii from the lungs, whereas dissemination to the brain was not prevented. A remarkable synergistic effect was observed when azithromycin (150 mg/kg/day) was administered in combination with pyrimethamine or sulfadiazine at noncurative dosages, i.e., 12.5 and 200 mg/kg/day, respectively. In mice treated with azithromycin plus sulfadiazine and azithromycin plus pyrimethamine, parasite burdens in blood and organs, relapses after cessation of therapy, and mortality were all markedly reduced relative to mice treated with any of the agents alone. These results show that azithromycin, which is remarkably active on pulmonary Toxoplasma infection, significantly potentiates the curative effect of sulfadiazine or pyrimethamine.
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Selected References
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- Araujo F. G., Guptill D. R., Remington J. S. Azithromycin, a macrolide antibiotic with potent activity against Toxoplasma gondii. Antimicrob Agents Chemother. 1988 May;32(5):755–757. doi: 10.1128/aac.32.5.755. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Araujo F. G., Shepard R. M., Remington J. S. In vivo activity of the macrolide antibiotics azithromycin, roxithromycin and spiramycin against Toxoplasma gondii. Eur J Clin Microbiol Infect Dis. 1991 Jun;10(6):519–524. doi: 10.1007/BF01963942. [DOI] [PubMed] [Google Scholar]
- Chamberland S., Kirst H. A., Current W. L. Comparative activity of macrolides against Toxoplasma gondii demonstrating utility of an in vitro microassay. Antimicrob Agents Chemother. 1991 May;35(5):903–909. doi: 10.1128/aac.35.5.903. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chang H. R., Pechère J. C. In vitro effects of four macrolides (roxithromycin, spiramycin, azithromycin [CP-62,993], and A-56268) on Toxoplasma gondii. Antimicrob Agents Chemother. 1988 Apr;32(4):524–529. doi: 10.1128/aac.32.4.524. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Derouin F., Chastang C. Activity in vitro against Toxoplasma gondii of azithromycin and clarithromycin alone and with pyrimethamine. J Antimicrob Chemother. 1990 Apr;25(4):708–711. doi: 10.1093/jac/25.4.708. [DOI] [PubMed] [Google Scholar]
- Derouin F., Nalpas J., Chastang C. Mesure in vitro de l'effet inhibiteur de macrolides, lincosamides et synergestines sur la croissance de Toxoplasma gondii. Pathol Biol (Paris) 1988 Dec;36(10):1204–1210. [PubMed] [Google Scholar]
- Girard A. E., Girard D., English A. R., Gootz T. D., Cimochowski C. R., Faiella J. A., Haskell S. L., Retsema J. A. Pharmacokinetic and in vivo studies with azithromycin (CP-62,993), a new macrolide with an extended half-life and excellent tissue distribution. Antimicrob Agents Chemother. 1987 Dec;31(12):1948–1954. doi: 10.1128/aac.31.12.1948. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gladue R. P., Bright G. M., Isaacson R. E., Newborg M. F. In vitro and in vivo uptake of azithromycin (CP-62,993) by phagocytic cells: possible mechanism of delivery and release at sites of infection. Antimicrob Agents Chemother. 1989 Mar;33(3):277–282. doi: 10.1128/aac.33.3.277. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Huskinson-Mark J., Araujo F. G., Remington J. S. Evaluation of the effect of drugs on the cyst form of Toxoplasma gondii. J Infect Dis. 1991 Jul;164(1):170–171. doi: 10.1093/infdis/164.1.170. [DOI] [PubMed] [Google Scholar]
- Kirst H. A., Sides G. D. New directions for macrolide antibiotics: pharmacokinetics and clinical efficacy. Antimicrob Agents Chemother. 1989 Sep;33(9):1419–1422. doi: 10.1128/aac.33.9.1419. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Piketty C., Derouin F., Rouveix B., Pocidalo J. J. In vivo assessment of antimicrobial agents against Toxoplasma gondii by quantification of parasites in the blood, lungs, and brain of infected mice. Antimicrob Agents Chemother. 1990 Aug;34(8):1467–1472. doi: 10.1128/aac.34.8.1467. [DOI] [PMC free article] [PubMed] [Google Scholar]