Comparative efficacy evaluation of dicationic carbazole compounds, nitazoxanide, and paromomycin against Cryptosporidium parvum infections in a neonatal mouse model

被引:58
作者
Blagburn, BL [1 ]
Drain, KL
Land, TM
Kinard, RG
Moore, PH
Lindsay, DS
Patrick, DA
Boykin, DW
Tidwell, RR
机构
[1] Auburn Univ, Coll Vet Med, Dept Pathobiol, Auburn, AL 36849 USA
[2] Univ N Carolina, Sch Med, Dept Pathol, Chapel Hill, NC 27599 USA
[3] Georgia State Univ, Dept Chem, Atlanta, GA 30303 USA
关键词
D O I
10.1128/AAC.42.11.2877
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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 mgikg) 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,vith 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 mgikg. 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 mgikg. NTZ yielded moderate efficacy as powder and injectable formulations administered at 100 mgikg 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 mgikg resulted in improved efficacy (oocyst output, <5% of that in controls).
引用
收藏
页码:2877 / 2882
页数:6
相关论文
共 26 条
[1]  
[Anonymous], CRYPTOSPORIDIUM CRYP
[2]  
BELL CA, 1993, ANTIMICROB AGENTS CH, V37, P2668, DOI 10.1128/AAC.37.12.2668
[3]  
BLAGBURN B, IN PRESS J PARASITOL
[4]   INHIBITION OF CRYPTOSPORIDIUM-PARVUM IN NEONATAL HSD-(ICR)BR SWISS MICE BY POLYETHER IONOPHORES AND AROMATIC AMIDINES [J].
BLAGBURN, BL ;
SUNDERMANN, CA ;
LINDSAY, DS ;
HALL, JE ;
TIDWELL, RR .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1991, 35 (07) :1520-1523
[5]  
BLAGBURN BL, 1997, CRYPTOSPORIDIUM CRYP, P111
[6]   DICATIONIC DIARYLFURANS AS ANTIPNEUMOCYSTIS CARINII AGENTS [J].
BOYKIN, DW ;
KUMAR, A ;
SPYCHALA, J ;
ZHOU, M ;
LOMBARDY, RJ ;
WILSON, WD ;
DYKSTRA, CC ;
JONES, SK ;
HALL, JE ;
TIDWELL, RR ;
LAUGHTON, C ;
NUNN, CM ;
NEIDLE, S .
JOURNAL OF MEDICINAL CHEMISTRY, 1995, 38 (06) :912-916
[7]  
CASEMORE DP, 1997, CRYPTOSPORIDIUM CRYP, P65
[8]   PENTAMIDINE CONGENERS .2. 2-BUTENE-BRIDGED AROMATIC DIAMIDINES AND DIIMIDAZOLINES AS POTENTIAL ANTIPNEUMOCYSTIS CARINII PNEUMONIA AGENTS [J].
DONKOR, IO ;
TIDWELL, RR ;
JONES, SK .
JOURNAL OF MEDICINAL CHEMISTRY, 1994, 37 (26) :4554-4557
[9]   Nitazoxanide in the treatment of cryptosporidial diarrhea and other intestinal parasitic infections associated with acquired immunodeficiency syndrome in tropical Africa [J].
Doumbo, O ;
Rossignol, JF ;
Pichard, E ;
Traore, HA ;
Dembele, M ;
Diakite, M ;
Traore, F ;
Diallo, DA .
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, 1997, 56 (06) :637-639
[10]   INHIBITION OF RESPIRATORY SYNCYTIAL VIRUS-HOST CELL-INTERACTIONS BY MONOAMIDINES AND DIAMIDINES [J].
DUBOVI, EJ ;
GERATZ, JD ;
SHAVER, SR ;
TIDWELL, RR .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1981, 19 (04) :649-656