Tinidazole: A nitroimidazole antiprotozoal agent

Fung, Horatio B.; Doan, Thien-Ly

doi:10.1016/j.clinthera.2005.12.012

Cited by 135 publications

(75 citation statements)

References 67 publications

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“…Although metronidazole and related 5-nitroimidazoles are no longer used for swine applications, they are used for treating anaerobic infections of nonfood animals (44). Nitroimidazole antibiotics are commonly used to treat human intestinal diseases caused by anaerobic bacteria and parasitic protozoa (4,21,45).…”

Section: Discussionmentioning

confidence: 99%

Collateral Effects of Antibiotics: Carbadox and Metronidazole Induce VSH-1 and Facilitate Gene Transfer among Brachyspira hyodysenteriae Strains

Stanton

Humphrey

Sharma

et al. 2008

Appl Environ Microbiol

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Brachyspira hyodysenteriae is an anaerobic spirochete and the etiologic agent of swine dysentery. The genome of this spirochete contains a mitomycin C-inducible, prophage-like gene transfer agent designated VSH-1. VSH-1 particles package random 7.5-kb fragments of the B. hyodysenteriae genome and transfer genes between B. hyodysenteriae cells. The chemicals and conditions inducing VSH-1 production are largely unknown. Antibiotics used in swine management and stressors inducing traditional prophages might induce VSH-1 and thereby stimulate lateral gene transfer between B. hyodysenteriae cells. In these studies, VSH-1 induction was initially detected by a quantitative real-time reverse transcriptase PCR assay evaluating increased transcription of hvp38 (VSH-1 head protein gene). VSH-1 induction was confirmed by detecting VSH-1-associated 7.5-kb DNA and VSH-1 particles in B. hyodysenteriae cultures. Nine antibiotics (chlortetracycline, lincomycin, tylosin, tiamulin, virginiamycin, ampicillin, ceftriaxone, vancomycin, and florfenicol) at concentrations affecting B. hyodysenteriae growth did not induce VSH-1 production. By contrast, VSH-1 was detected in B. hyodysenteriae cultures treated with mitomycin C (10 g/ml), carbadox (0.5 g/ml), metronidazole (0.5 g/ml), and H 2 O 2 (300 M). Carbadox-and metronidazole-induced VSH-1 particles transmitted tylosin and chloramphenicol resistance determinants between B. hyodysenteriae strains. The results of these studies suggest that certain antibiotics may induce the production of prophage or prophage-like elements by intestinal bacteria and thereby impact intestinal microbial ecology.In the United States, various antimicrobials are added to feed to prevent diseases and to promote growth or to enhance the feeding efficiency of swine (14, 28). Antibiotics commonly used in feed for swine include tetracyclines, carbadox, macrolides, and lincosamides (19). At higher concentrations, carbadox, lincomycin, tylosin, and tiamulin are added to feed or drinking water for the treatment of swine intestinal diseases, notably swine dysentery (25,28). In Australia and some European countries, nitroimidazole antibiotics, such as metronidazole, ronidazole, and dimetridazole, have been used to treat swine dysentery (22,25; D. Trott, personal communication), although legislation in several countries has restricted the use of these antibiotics in food animals (2, 44).The etiologic agent of swine dysentery is the anaerobic spirochete Brachyspira hyodysenteriae. Within their genome, B. hyodysenteriae cells carry a mitomycin C-inducible prophagelike element, designated VSH-1 (30, 31, 63). Unlike traditional prophages, VSH-1 particles contain random 7.5-kb fragments of the B. hyodysenteriae genome. VSH-1 head, tail, and lysis genes total at least 16.3 kb of DNA (38). Consequently, an individual VSH-1 particle is incapable of lytic growth, and there are no bioassays (i.e., plaque formation) for measuring VSH-1 production. Although VSH-1 particles do not selfpropagate, they transfer genes between B. hyody...

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Section: Discussionmentioning

confidence: 99%

Collateral Effects of Antibiotics: Carbadox and Metronidazole Induce VSH-1 and Facilitate Gene Transfer among Brachyspira hyodysenteriae Strains

Stanton

Humphrey

Sharma

et al. 2008

Appl Environ Microbiol

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“…In addition, follow-up treatment with a second drug, such as paromomycin, is recommended for amebiasis to prevent prolonged retention and excretion of cysts (20). Newer metronidazole derivatives, such as tinidazole (21) and nitazoxanide, a nitrothiazoly-salicylamide derivative (22), have fewer side effects and shorter treatment courses. Other drugs, such as furazolidone, albendazole, and paromomycin, are used for giardiasis to a lesser extent, with similar or lower success rates.…”

Section: T He Protozoan Intestinal Parasites Entamoeba Histolytica Andmentioning

confidence: 99%

Hsp90 Inhibitors as New Leads To Target Parasitic Diarrheal Diseases

Debnath

Shahinas

Bryant

et al. 2014

Antimicrob Agents Chemother

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Entamoeba histolytica and Giardia lamblia are anaerobic protozoan parasites that cause amebiasis and giardiasis, two of the most common diarrheal diseases worldwide. Current therapy relies on metronidazole, but resistance has been reported and the drug has significant adverse effects. Therefore, it is critical to search for effective, better-tolerated antiamebic and antigiardial drugs. We synthesized several examples of a recently reported class of Hsp90 inhibitors and evaluated these compounds as potential leads for antiparasitic chemotherapy. Several of these inhibitors showed strong in vitro activity against both E. histolytica and G. lamblia trophozoites. The inhibitors were rescreened to discriminate between amebicidal and giardicidal activity and general cytotoxicity toward a mammalian cell line. No mammalian cytotoxicity was found at >100 M for 48 h for any of the inhibitors. To understand the mechanism of action, a competitive binding assay was performed using the fluorescent ATP analogue bis-ANS (4,4=-dianilino-1,1=-binaphthyl-5,5=-disulfonic acid dipotassium salt) and recombinant E. histolytica Hsp90 preincubated in both the presence and absence of Hsp90 inhibitors. There was significant reduction in fluorescence compared to the level in the control, suggesting that E. histolytica Hsp90 is a selective target. The in vivo efficacy and safety of one Hsp90 inhibitor in a mouse model of amebic colitis and giardiasis was demonstrated by significant inhibition of parasite growth at a single oral dose of 5 mg/kg of body weight/day for 7 days and 10 mg/kg/day for 3 days. Considering the results for in vitro activity and in vivo efficacy, Hsp90 inhibitors represent a promising therapeutic option for amebiasis and giardiasis.

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“…The first-line drugs for invasive amebiasis and giardiasis chemotherapy are nitroimidazoles, with the prototype, metronidazole, being the most common drug used worldwide. 13 Newer metronidazole derivatives such as tinidazole 14 and nitazoxanide, a nitrothiazoly-salicylamide derivative, 15 have fewer side-effects and are shorter treatment courses. Other drugs, such as furazolidone, albendazole and paromomycin are used for giardiasis to a lesser extent with similar and/or lower success rates.…”

Section: Killing Three Parasites With One Drugmentioning

confidence: 99%