Randomized trial of secnidazol versus metronidazol in the treatment of intestinal amoebiasis in children

Intestinal amoebiasis of children is an endemic disease in Iraq, and it is one of the leading causes of acute and chronic diarrhea. Noticeable resistance to the usually used antiprotozoal medication, especially in the last years had been repeatedly documented. To determine the effectiveness and safety of [Secnidazol] in the treatment of intestinal amoebiasis in pediatric age group. A study was performed on 200 children aged 10 months -7 years diagnosed as intestinal amoebiasis on the base of clinical ground and microscopical study. The children were allocated at random into one or another equal treatment groups of [100 children for each group]. Therapeutic dose of Metronidazol [40mg/kg/day for 7 days] started for the first group while for the second group, Secnidazol suspension [single dose of 30 mg/Kg/dose] was given. Both groups were followed for one week by clinical assessment and parasitological examination of the stool for the presence of Ent. histolytica [trophozoite and/or cysts]. The study showed that Metronidazol suspension had 18% clinical and 11% parasitological cure at day 1 compared to 83% clinical and 32% parasitological cure when using Secnidazol. These reached 72% clinical and 59% parasitological cure rate after 7 days of using Metronidazol compared to 91% clinical and 89% parasitological cure by effect of Secnidazol suspension. Secnidazol was more effective than Metronidazol for clinical and parasitological treatment of intestinal amoebiasis in children. In addition, Secnidazol is more palatable, and with a shorter duration of treatment [monotherapy] increasing the treatment compliance. Our results recommend to replace Metronidazol with Secnidazol suspension at least in resistant or intransigent cases of intestinal amebiasis

Validation of a modified fluorimetric assay for the screening of trichomonacidal drugs

A fluorimetric microassay that uses a redox dye to determine the viability of the flagellate Trichomonas vaginalis has been optimised to provide a more sensitive method to evaluate potential trichomonacidal compounds. Resazurin has been used in recent years to test drugs against different parasites, including trichomonadid protozoa; however, the reproducibility of these resazurin-based methods in our laboratory has been limited because the flagellate culture medium spontaneously reduces the resazurin. The objective of this work was to refine the fluorimetric microassay method previously developed by other research groups to reduce the fluorescence background generated by the media and increase the sensitivity of the screening assay. The experimental conditions, time of incubation, resazurin concentration and media used in the microtitre plates were adjusted. Different drug sensitivity studies against T. vaginalis were developed using the 5-nitroimidazole reference drugs, new 5-nitroindazolinones and 5-nitroindazole synthetic derivatives. Haemocytometer count results were compared with the resazurin assay using a 10% solution of 3 mM resazurin dissolved in phosphate buffered saline with glucose (1 mg/mL). The fluorimetric assay and the haemocytometer counts resulted in similar percentages of trichomonacidal activity in all the experiments, demonstrating that the fluorimetric microtitre assay has the necessary accuracy for high-throughput screening of new drugs against T. vaginalis.

The activity of a metronidazole analogue and its β-cyclodextrin complex against Trypanosoma cruzi

In this study we prepared an inclusion complex between an iodide analogue of metronidazole (MTZ-I) and cyclodextrin (CD) to develop a safer and more effective method of treating Trypanosoma cruzi infections. According to our results, MTZ-I and MTZ-I:β-CD were 10 times more active than MTZ, demonstrating that the presence of an iodine atom on the side chain increased the trypanocidal activity while maintaining its cytotoxicity. The selective index shows that MTZ-I was 10 times more active against T. cruzi than it was against mammalian cells. The modification of MTZ side chains provides a promising avenue for the development of new drugs.

Prescription of fixed dose combination drugs for diarrhoea.

Fixed-dose combinations (FDCs) of an antiprotozoal and an antibacterial, for treatment of diarrhoea, have been available in the Indian pharmaceutical market for about a decade. There is little evidence to substantiate this combination therapy. We evaluated 2,163 physician prescriptions for diarrhoea and found that 59 per cent of prescriptions were for FDCs. This is unethical because prescribing such combinations exposes a patient to higher risks of adverse drug reactions and also increases the chances of drug resistance. Physicians' prescribing practices in India are influenced by socioeconomic factors and the pharmaceutical industry's marketing techniques that include giving incentives to physicians to prescribe certain drugs.

Plasma hydroxy-metronidazole/ metronidazole ratio in hepatitis C virus-induced liver disease

It has been suggested that the measurement of metronidazole clearance is a sensitive method for evaluating liver function. The aim of this study was to evaluate the usefulness of plasma hydroxy-metronidazole/metronidazole ratios as indicators of dynamic liver function to detect changes resulting from the various forms of chronic hepatitis C virus (HCV) infection. A total of 139 individuals were studied: 14 healthy volunteers, 22 healthy, asymptomatic, consecutive anti-HCV-positive HCV-RNA negative subjects, 81 patients with chronic hepatitis C (49 with moderate/severe chronic hepatitis and 34 with mild hepatitis), and 20 patients with cirrhosis of the liver. HCV status was determined by the polymerase chain reaction. Plasma concentrations of metronidazole and its hydroxy-metabolite were measured by reverse-phase high-performance liquid chromatography with ultraviolet detection in a blood sample collected 10 min after the end of a metronidazole infusion. Anti-HCV-positive HCV-RNA-negative individuals demonstrated a significantly reduced capacity to metabolize intravenously infused metronidazole compared to healthy individuals (0.0478 ± 0.0044 vs 0.0742 ± 0.0232). Liver cirrhosis patients also had a reduced plasma hydroxy-metronidazole/metronidazole ratio when compared to the other groups of anti-HCV-positive individuals (0.0300 ± 0.0032 vs 0.0438 ± 0.0027 (moderate/severe chronic hepatitis) vs 0.0455 ± 0.0026 (mild chronic hepatitis) and vs 0.0478 ± 0.0044 (anti-HCV-positive, HCV-RNA-negative individuals)). These results suggest an impairment of the metronidazole metabolizing system induced by HCV infection that lasts after viral clearance. In those patients with chronic hepatitis C, this impairment is paralleled by progression of the disease to liver cirrhosis.

Pre and post eradication gastric inflammation in Helicobacter pylori-associated duodenal ulcer.

BACKGROUND: Distribution and nature of gastritis are major determinants of clinical outcome of H. pylori infection. The gastric inflammatory changes associated with this infection in developing countries have not been systematically studied. AIMS: To evaluate the inflammatory changes in gastric antrum and corpus in patients with duodenal ulcer and H. pylori infection, before and after H. pylori eradication therapy. METHODS: Histology and H. pylori density were studied in gastric biopsies obtained from 53 consecutive patients with active duodenal ulcer and H. pylori infection. Biopsies were obtained before and 4 weeks after H. pylori eradication therapy, from the anterior and posterior walls of the antrum and corpus, and were evaluated according to the Sydney system. RESULTS: In the pre-H. py/ori eradication antral biopsies, chronic gastritis, active gastritis, atrophy, intestinal metaplasia (IM) and lymphoid follicles / aggregates were seen in 53 (100%), 49 (92%), 11 (21%), 7 (13%) and 28 (53%) patients, respectively. In the corresponding biopsies from gastric corpus, these changes were seen in 49 (92%), 23 (43%), 2 (4%), 2 (4%) and 8 (15%), respectively. All changes except IM were significantly more frequent and of higher grade in the antrum. The grade of chronic gastritis was significantly higher in antrum than corpus; the frequency of gastritis in the antrum and corpus was similar (100% vs. 92%). H. pylori density was also higher in the antrum and correlated well with the grades of chronic gastritis and activity at both sites. Eradication of H. pylori was achieved in 39 patients (74%), and led to significant decrease in gastritis; no change was seen in patients who did not eradicate the organism. CONCLUSIONS: Antral-predominant chronic gastritis and activity are present in more than 90% of patients with H. pylori infection associated with duodenal ulcer, and the grade of gastritis correlates with the density of the organism. Eradication therapy results in improvement of both chronic gastritis and activity.

Randomized double-blind trial of metronidazole versus secnidazole in amebic liver abscess.

OBJECTIVE: To compare the efficacy of secnidazole with metronidazole in the treatment of amebic liver abscess. METHODS: Thirty two patients with uncomplicated liver abscesses were studied in a randomized, double-blind trial. Fifteen received metronidazole (400 mg t.i.d. for 7 days) and 17 secnidazole (500 mg t.i.d. for 5 days). All abscesses were aspirated on day 1 and laboratory tests and ultrasonographic examination were done on days 1 and 10. RESULTS: One patient in the metronidazole group developed intraperitoneal rupture. The other 31 patients had 40 abscesses (19 in metronidazole group, 21 in secnidazole group). Complete resolution of signs occurred by day 10 in 10 patients on metronidazole and 12 on secnidazole, and in all others by day 28. On day 10 ultrasonography in the metronidazole group showed complete disappearance of abscess in one patient, decrease in 8 and increase in 5 (versus 2, 12 and 3, respectively in the secnidazole group). After 6 months, four asymptomatic patients (two from each group) had small abscess cavities on ultrasonography; there were no recurrences. CONCLUSIONS: Secnidazole is as effective in the treatment of amebic liver abscess as metronidazole; it is equally well tolerated.

Itraconazol + Secnidazol* cápsulas vs. óvulos vaginales Acetónido de Fluocinolona 0.05 mg, Nistatina 100,000 U y Metronidazol 500 mg en el tratamiento sintomático de la vaginitis / Itraconazol + Secnidazol* capsules Vs. Acetónido of Fluocinolona 0.05 mg, Nistatina 100,000 U and Metronidazol 500 mg vaginal ovules, en the symptomatic treat of vaginitis

Objetivo: Evaluar la eficacia del tratamiento oral en las vaginitis y la vaginosis con intraconazol y secnidazol, comparándolo con el tratamiento tópico con óvulos vaginales de acetónido de fluocinolona, nistatina 100 000 U. y metronidazol 500 mg. Diseño: Estudios comparativos, longitudinal, prospectivo y abierto Lugar: Servicio de Reproducción Humana. Centro Médico Nacional "20 de Noviembre" I.S.S.S.T.E. Material y métodos: Fueron incluidas 40 pacientes del sexo femenino que asistieron a la consulta externa del Servicio de Reproducción humana con diagnóstico de vaginitis y vaginosis, se dividieron al azar en dos grupos. Grupo 1 (20 pacientes) que recibieron tratamiento oral con Itraconazol y secnidazol y el grupo 2 (20 pacientes) que recibieron tratamiento tópico con fluocinolona, nistatina y metronidazol. Se citaron a las pacientes a los 7 y 14 días después de iniciado el tratamiento valorando la intensidad de la sintomatología clínica y la eficacia del tratamiento. Resultados: Las características poblacionales de ambos grupos no mostraron diferencias. La leucorrea fue el síntoma más importante en ambos grupos el cual fue de intensidad moderada severa, y mostró una diferencia en la evaluación post-tratamiento estadísticamente significativa a favor de las pacientes tratadas con itraconazol y secnidazol. En cuanto al ardor, prurito, dispareunia y disuria no mostraron diferencias en la evaluación post-tratamiento, sin embargo la mejoría fue estadísticamente significativa entre el día 1 y 7 de tratamiento en favor del grupo tratado con Itraconazol y Secnidazol. conclusión. El tratamiento con Itraconazol y Secnidazol ofrece mejoría en menor tiempo y la comodidad que ofrece en cuanto a la facilidad de administración lo hacen un medicamento adecuado para el tratamiento de la vaginitis y la vaginosis o ambas

Susceptibility of helicobacter pylori to metronidazole and its bioactive derivatives

The hydroxy derivative of metronidazole can exhibit equal or greater activity to the parent drug against several bacteria. The susceptibility status of 22 H. pylon strains to these breakdown compounds was determined in order to determine their possible role in the therapy of H. pylori-associated peptic ulcer disease. The susceptibility was determined using the agar dilution method and substantial activity [MlC[90] = 0.33 micro g/mI] for the hydroxy metabolite of metronidazole versus H. pylori was observed. The findings define a role for the hydroxy derivative of metronidazole in peptic ulcer disease and support the limited data on the possibility of cooperative interactions between the parent compound, its main derivatives and related companion drugs in this condition

Ensaio terapêutico na infecção por Giardia muris em camundongo com metronidazole, tinidazole, secnidazole e furazolidone / A therapeutic trial in Giardia muris infection in the mouse with metronidazole, tinidazole, secnidazole and furazolidone

Foi testado in vivo a sensibilidade de Giardia muris a quatro drogas comumente usadas no tratamento da giardíase humana. Foram utilizados 7 grupos de animais, com 12 camundongos cada, sendo que o grupo controle recebeu apenas solução salina 0,15M (0,5ml/animal). Os demais grupos receberam em dose única: metronidazole e furazolidone (500mg/kg), tinidazole e secnidazole (200mg/kg). A eficácia das drogas foi avaliada através da contagem de cistos nas fezes e pela ausência de trofozoítos no intestino. O metronidazole foi a droga mais eficaz. Os cortes histológicos mostraram diferenças entre o padrão da mucosa intestinal de animais normais e parasitados. No entanto, não se observou diferença entre o padrão de mucosa de animais infectados tratados e não tratados, o que sugere que estas alterações podem ser causadas pelo parasito e não pelas drogas.

A comparative study about the effectiveness of metronidazole, tinidazole, secnidazole and furazolidone was performed on Giardia muris from mice naturally infected. Groups of 12 animals each was constituted: the control treated with saline; one treated with metronidazole; one treated with furazolidone; one treated with tinidazole; one treated with secnidazole; histological normal control; histological infected. Samples of three stools were examined before and after treatment with quantification of cysts. Animals were cured when the trophozoites was not seen in the small bowel. The curative activity of drugs was 58.3% for metronidazole, 50% for furazolidone, 40% for secnidazole and 16% for tinidazole. It was also showed that there was a different pattern of the intestinal mucosa from the control and infected groups, treated or not, suggesting that the alterations encountered in the mucosa of infected animals were due to the parasitism either the action of the drugs.

Respuesta al tratamiento con secnidazol en niños parasitados por Giardia Lambia / Response to treatment with secnidazole in children infected with giardia lamblia

Se informa de los resultados del tratamiento son secnidazol de 100 niños entre uno y 12 años. El medicamento se dio a razón de 30 mg/Kg/día, por tres días. El resultado del tratamiento se valoró 10 días después en 95 niños; en ocho la G. lamblia aún estaba presente en las heces por lo que se estimó una efectividad de 84 por ciento. La manifestación indeseable al medicamento que se presentó con mayor frecuencia (36.8 por ciento) fue el ®mal sabor¼

Vaginose bacteriana / Bacterial vaginosis

Estudando-se 116 pacientes conclui-se que o metronidazol continua sendo a droga de escolha para o tratamento da Vaginose Bacteriana (VB). Entretanto, pela comodidade posológica, baixo índice de efeitos colaterais e eficácia de aproximadamente 70 por cento, mesmo após 3 meses de tratamento, o secnidazol administrado em dose única de 2g pode ser boa alternativa de tratamento para um número significativo de pacientes. O tratamento dos parceiros näo influenciou nos resultados. O uso da dosagem do pH, de contagem do lactobacilo e do Flagytest säo de valia no diagnóstico e controle de cura da BV