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Antimicrobial Agents and Chemotherapy, November 1998, p. 2877-2882, Vol. 42, No. 11
Department of Pathobiology, College of
Veterinary Medicine, Auburn University, Auburn, Alabama
36849-55191;
Department of Pathology,
School of Medicine, University of North Carolina at Chapel Hill, Chapel
Hill, North Carolina 275992; and
Department of Chemistry, Georgia State University, Atlanta,
Georgia 303033
Received 27 April 1998/Returned for modification 12 June
1998/Accepted 25 August 1998
The efficacies of dicationic carbazole compounds, nitazoxanide
(NTZ), and paromomycin were evaluated against the AUCp1 isolate of
Cryptosporidium parvum by using a neonatal mouse model.
Compounds were solubilized or suspended in deionized water and
administered orally by gavage to neonatal mice at a constant dose rate
on days 0 to 5 (treatment started on day 0). Dose rates varied for
individual carbazole compounds but ranged from 0.65 to 20 mg/kg of body
weight. NTZ was tested at 100 and 150 mg/kg, and paromomycin was tested at 50 mg/kg. Efficacies were determined by comparing numbers of oocysts
present in treated versus control mice at necropsy examination on day
6. Demonstrable efficacy was observed for several carbazole compounds,
based on significant reductions in the numbers of oocysts recovered
from treated mice versus control mice. Compounds 1, 7, and 10 (19.0 mg/kg) reduced oocyst passage in treated mice to less than 5% of that
in control mice. Treatment with compounds 6, 8, and 9 (17.0 mg/kg)
resulted in reductions of oocyst output to less than 10% of that in
controls. Although they were not comparable in efficacy to compounds 1, 6, 7, 8, 9, and 10, treatment with other carbazole compounds resulted
in statistically significant reductions in oocyst output in treated
versus control mice. Compound 1 retained efficacy resulted in reduction
of oocyst output to approximately 6% of that in controls when the dose
was reduced to 5 mg/kg. Further reductions in the dose rate resulted in
considerable reductions in anticryposporidial activity. Likewise, the
efficacies of compounds 9 and 10 were reduced substantially when the
doses were lowered to one-half the screening dose. Paromomycin yielded excellent activity (reduction of oocyst output to <2% of that in
controls) at a dose of 50 mg/kg. NTZ yielded moderate efficacy as
powder and injectable formulations administered at 100 mg/kg orally
(reduction of oocyst output to 42 and 26% of that in controls, respectively). Oral administration of the injectable formulation of NTZ at a dose of 150 mg/kg resulted in improved efficacy (oocyst output, <5% of that in controls).
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Comparative Efficacy Evaluation of Dicationic
Carbazole Compounds, Nitazoxanide, and Paromomycin against
Cryptosporidium parvum Infections in a Neonatal
Mouse Model
*
Corresponding author. Mailing address: Department of
Pathobiology, College of Veterinary Medicine, Auburn University,
Auburn, Alabama 36849-5519. Phone: (334) 844-2702. Fax: (334) 844-2652. E-mail: blagbbl{at}vetmed.auburn.edu.
Antimicrobial Agents and Chemotherapy, November 1998, p. 2877-2882, Vol. 42, No. 11
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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