Entamoeba histolytica
Dongyou Liu in Handbook of Foodborne Diseases, 2018
Today, dysentery IA is treated with nitroimidazoles (metronidazole or tinidazole), the drug of choice for the treatment of symptomatic and invasive disease.131,132 Metronidazole kills amoebae in the intestine and in tissues, but it does not eradicate intestinal cysts.133 Metronidazole appears to be absorbed into amoebae, producing nitroso intermediates that bind to DNA and enzymes such as thioredoxin reductase forming adducts; antimicrobial effects may result due to the production of free radicals.134 As parasites persist in the intestines of 40%–60% of patients treated with metronidazole, drugs such as paromomycin, diloxanide furoate, or iodoquinol are used to eradicate residual amoebae.135,136 Diloxanide furoate is used alone as a primary agent to treat asymptomatic E. histolytica cyst passers.137 Paromomycin is the drug of choice for treating noninvasive disease.133 Iodoquinol primarily acts in the bowel lumen because it is poorly absorbed.133 Nitroimidazoles with long half-lives (i.e., secnidazole and ornidazole) are also used. Nitroimidazole therapy leads to a clinical response in roughly 90% of patients with mild to moderate IA.131 Nitazoxanide and its active-circulating metabolite tizoxanide are as potent as metronidazole against metronidazole-sensitive isolates of E. histolytica in vitro and have activity against isolates resistant or poorly susceptible to metronidazole.137 Nitazoxanide is effective at treating invasive IA and at preventing the amoebic colonization of the GI tract.138
Tropical infections and infestations
Professor Sir Norman Williams, Professor P. Ronan O’Connell, Professor Andrew W. McCaskie in Bailey & Love's Short Practice of Surgery, 2018
Medical treatment is very effective and should be the first choice in the elective situation, with surgery being reserved for complications. Metronidazole and tinidazole are the effective drugs. After treatment with metronidazole and tinida- zole, diloxanide furoate, which is not effective against hepatic infestation, is used for 10 days to destroy any intestinal amoebae.
Diloxanide Furoate
M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson in Kucers’ The Use of Antibiotics, 2017
Amebiasis is an infection caused by the protozoal organism E. histolytica and is one of the most common parasitic infections worldwide, affecting almost 500 million people and resulting in over 100,000 deaths a year (Walsh, 1986; Swords and Cantey, 2002). These figures may be overestimates, however, given that they are based primarily on examination of the stool for ova and parasites, a technique that does not permit differentiation of E. histolytica from the nonpathogenic, morphologically indistinguishable E. dispar and E. moshkovskii (Haque et al., 2003). Fewer than 10% of individuals who are infected with E. histolytica develop invasive colitis or extraintestinal disease. It is still not clear whether all noninvasive asymptomatic infections should be treated (Farthing, 2006). In areas where the parasite is not endemic, asymptomatic E. histolytica infections should be treated because of the potential for invasive disease and to limit transmission (Jackson, 1987; Haque et al., 2003). Some believe that, given the high rates of infection in highly endemic areas, it is not appropriate or cost-effective to screen or treat all asymptomatic cyst passers. An exception to this approach is patients predisposed to develop severe disease, including pregnant women, very young children, and patients who are malnourished or being treated concurrently with corticosteroids (Ravdin and Stauffer, 2005). Others argue that, given the potential for progression to invasive disease, all individuals with asymptomatic infection should be treated regardless. Outbreaks of refractory intestinal amoebiasis within institutional care facilities have been successfully managed by treatment of asymptomatic carriers of E. histolytica with diloxanide furoate (Fujishima et al., 2010; Nishise et al., 2010). Amebicides are classified according to their site of action, which can be in the bowel lumen, mucosa, and/or extraintestinal tissues. Diloxanide furoate is one of the three principal luminal amebicides that exhibit little or no activity in the bowel wall or extraintestinal tissues. Of the luminal amebicides, diloxanide furoate was favored for many years because of its safety and effectiveness, with cure rates in asymptomatic carriers exceeding 90% (Woodruff and Bell, 1960; Forsyth, 1962; Wilmot et al., 1962; Botero, 1964; Wolfe, 1973; Knight 1980). It is now suggested, however, that paromomycin (a nonabsorbable aminoglycoside; see Chapter 185, Paromomycin) should be the first-line agent of choice, particularly given that it is not absorbed in the bowel and is therefore more likely to be safe for the treatment of pregnant women. Furthermore, it is effective in a shorter duration of therapy (7 days as opposed to 10), has reasonable efficacy, even in symptomatic individuals, and is more widely available (McAuley and Juranek, 1992; McAuley et al., 1992; Blessmann and Tannich, 2002; Farthing, 2006; van Hal et al., 2007; Gilbert et al., 2008).
The management of Babesia, amoeba and other zoonotic diseases provoked by protozoa
Published in Expert Opinion on Therapeutic Patents, 2023
Clemente Capasso, Claudiu T. Supuran
Although there are ongoing studies, there is currently neither a vaccine nor a wide range of medications that are effective against amebiasis, which remains one of the most severe enteropathogens worldwide [38]. Patients with the clinical disease can be treated with an amoebicidal tissue-active agent or a luminal cysticidal agent to stop the infection and avoid further infections [47,48]. The amoebicidal drug includes the nitroimidazole agents, such as metronidazole 13 and tinidazole 14 (Figure 3), which are the treatment of choice for amebic colitis and amebic liver disease due to their potency against the parasites’ reproductive stages (trophozoites) [47,48]. Tinidazole has a longer half-life and is better tolerated, although metronidazole kills the parasites more efficiently [47,48]. It is necessary to use a luminal agent after using nitroimidazole because it does not eradicate luminal cysts [49–51]. The aminoglycoside paromomycin 15 is utilized as a luminal cysticidal agent, which should not be provided concurrently with the nitroimidazole agent [52]. Alternatives include diloxanide furoate 16 and iodoquinol 17 (Figure 3) [38]. Recently, auranofin, a gold compound used to treat particular cases of rheumatoid arthritis, has entered early clinical drug development as an antiparasitic agent [53]. However, more research is needed to evaluate if auranofin would be a successful treatment of amebiasis and if its usage will be limited by known safety issues such as diarrhea, rash, and bone marrow suppression [53].
Diloxanide furoate binary complexes with β-, methyl-β-, and hydroxypropyl-β-cyclodextrins: inclusion mode, characterization in solution and in solid state and in vitro dissolution studies
Published in Pharmaceutical Development and Technology, 2018
Carolina Aloisio, Marcela Longhi
Pathogenic intestinal protozoa are responsible for clinically important infections in both the developed and the developing world. Amoebiasis affects around 480 million people worldwide, with an annual mortality of 40 000–110 000 persons. These organisms are responsible for both acute and chronic diarrhea, and Entamoeba histolytica, which affects the colon, can spread to involve the liver. Acute amebic colitis ranges from mild to severe, and can be fulminant, leading to colon perforation. The infection can spread from the liver by direct extension into the pleuropulmonary cavity and the pericardial cavity. Occasionally, and most often in immuno-suppressed individuals, the infection might be widely disseminated and affect other organs, including bones and the brain (Farthing 2006). Diloxanide furoate (DF) (Figure 1(a)) is one of the drugs of choice for the treatment of amebic colitis caused by Entamoeba histolytica (Budal et al. 2004; Mishal and Sober 2005; Farthing 2006). DF acts on organisms in the intestinal lumen (Farthing 2006). For this reason, high concentrations of this drug in the intestinal fluids are substantially related to the effectiveness of the drug. Orally administered drugs must have sufficient water solubility to ensure their bioavailability and pharmacological activity (Ojarinta et al. 2017). However, DF presents little solubility in water, which can affect its action against Entamoeba histolytica (Budal et al. 2004). Accordingly, the use of suitable strategies to increase water solubility of DF and dissolution rate in the intestinal fluids may reduce the possibility of the drug precipitating in the lumen, and this would lead to a loss in effectiveness.
Anti-infective treatment of brain abscess
Published in Expert Review of Anti-infective Therapy, 2018
Jacob Bodilsen, Matthijs C. Brouwer, Henrik Nielsen, Diederik Van De Beek
In patients infected with E. histolytica, cerebral amoebiasis has been documented at autopsy among 1.2–2.5%, but in clinical studies this proportion remains less than 0.1%. Treatment includes metronidazole for the brain abscess and diloxanide furoate for clearance of the intestinal stages [103].
Related Knowledge Centers
- Flatulence
- Gastrointestinal Tract
- Metronidazole
- Ribosome
- Tinidazole
- Trophozoite
- Pregnancy
- Amoebiasis
- Paromomycin
- Oral Administration