RESUMO
Our objective is to determine the effectiveness of a therapeutic regimen for helicobacter pylori that includes a proton pump inhibitor, doxycycline, furazolidone and bismuth in our location. We carried out a retrospective study, non-randomized, in a private hospital in Lima, Peru. Patients with biopsy and/or rapid urease test proven helicobacter pylori infection after an endoscopy, from January 2017 to October 2022 were included. They received the therapeutic regimen of the study or an alternative triple regimen with a proton pump inhibitor, amoxicillin and levofloxacin and were followed with a urea breath test within 1 to 6 months upon completion of therapy. The quadruple therapy with furazolidone obtained success in 117/122 cases (95.9%) while the triple therapy with levofloxacin only in 5/16 (31.2%) when used for 7 days and 22/38 (57.9%) when used for 10 days, a statistically significant difference with p<0.001. Conclusion: Quadruple therapy with furazolidone reached high effectiveness in our location, while triple therapy with levofloxacin was not an acceptable alternative.
Assuntos
Infecções por Helicobacter , Helicobacter pylori , Humanos , Bismuto/uso terapêutico , Doxiciclina/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Furazolidona/uso terapêutico , Furazolidona/farmacologia , Antibacterianos/uso terapêutico , Levofloxacino/uso terapêutico , Levofloxacino/farmacologia , Estudos Retrospectivos , Quimioterapia Combinada , Amoxicilina/uso terapêutico , Resultado do TratamentoRESUMO
Furazolidone (FZD) is a widely used drug in human and veterinary medicine, and has antibacterial and antiprotozoal action. Although it is widely used as a therapy in various pathological conditions, studies on the efficacy of FZD associated with immune responses are still limited. In this review, we seek to describe which immunopharmacological responses are caused by the administration of FZD. The study followed the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). A systematic review of clinical trials and in vitro and in vivo experimental studies was carried out, which resulted in 943 papers, of which 35 were considered eligible and, of these 35, 4 were selected for analysis. The studies listed indicated that administration of FZD can modulate pro- or anti-inflammatory pathways, with a probable increase in the expression of reactive oxygen species and a modulation of apoptotic pathways.
Assuntos
Imunidade Adaptativa/imunologia , Anti-Infecciosos Locais/farmacologia , Apoptose/imunologia , Furazolidona/farmacologia , Imunidade Inata/imunologia , Imunidade Adaptativa/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/imunologia , Humanos , Imunidade Inata/efeitos dos fármacos , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/imunologia , Espécies Reativas de Oxigênio/metabolismoRESUMO
The combination of bismuth(III) citrate and the antibiotic furazolidone (FDZ) results in a synergetic effect on Helicobacter pylori eradication. However, the problems associated with their oral administration are challenges to overcome. Thus, in the present study, sodium alginate (SA)/carboxymethyl cellulose (CMC) blend hydrogels (SC) were developed for concomitant and controlled release of furazolidone and bismuth(III). The blank formulation (SCblank) and the three drug-loaded hydrogels (SCFDZ, SCBi, and SCFDZ-Bi) were prepared by casting method and characterized by infrared spectroscopy, scanning electron microscopy, differential scanning calorimetry, and X ray powder diffraction analyses. The swelling equilibrium and cumulative release amounts of FDZ and Bi3+ have indicated distinct behaviors of the hydrogels to different pH values. The bismuth-containing sample (SCFDZ-Bi) presents more resistance to degradation on a neutral solution and shows more suitable properties for controlled drug release than the sample without bismuth (SCFDZ). Microbiological studies, using Escherichia coli as a model, show bacteria viability reduction in presence of the drug-loaded samples. The developed system containing furazolidone and bismuth(III) appears to be promising for oral administration with concomitant and controlled release of these drugs aimed at the pharmacological treatment of gastrointestinal disorders.
Assuntos
Alginatos/química , Bismuto/farmacologia , Carboximetilcelulose Sódica/química , Reagentes de Ligações Cruzadas/química , Furazolidona/farmacologia , Antibacterianos/farmacologia , Varredura Diferencial de Calorimetria , Preparações de Ação Retardada/farmacologia , Liberação Controlada de Fármacos , Escherichia coli/efeitos dos fármacos , Hidrogéis/química , Testes de Sensibilidade Microbiana , Espectroscopia de Infravermelho com Transformada de Fourier , Água/química , Difração de Raios XRESUMO
Recently, there have been numerous cases of leishmaniasis reported in different Brazilian states. The use of furazolidone (FZD) to treat leishmaniasis has been previously described; however, the drug is associated with adverse effects such as anorexia, weight loss, incoordination, and fatigue in dogs. Thus, in the present study, we prepared and evaluated inclusion complexes between FZD and ß-cyclodextrin (ß-CD) to guarantee increased drug solubility and reduce the toxicity associated with high doses. The FZD:ß-CD complexes were prepared by two different techniques (kneading and lyophilization) prior to incorporation in an oral pharmaceutical dosage form. Formation of the complexes was confirmed using appropriate physicochemical methods. Antileishmanial activity against L. amazonensis was tested in vitro via a microplate assay using resazurin dye and cytotoxicity was determined using the fibroblast L929 lineage. Solubility studies showed the formation of complexes with complexation efficiencies lower than 100%. Physicochemical analysis revealed that FZD was inserted into the ß-CD cavity after complexation by both methods. Biological in vitro evaluations demonstrated that free FZD and the FZD:ß-CD complexes presented significant leishmanicidal activity against L. amazonensis with IC50 values of 6.16⯵g/mL and 1.83⯵g/mL for the complexes prepared by kneading and lyophilization, respectively. The data showed that these complexes reduced the survival of promastigotes and presented no toxicity for tested cells. Our results indicate that the new compounds could be a cost-effective alternative for use in the pharmacotherapy of leishmaniasis in dogs infected with L. amazonensis.
Assuntos
Antiprotozoários/farmacologia , Furazolidona/farmacologia , Leishmania mexicana/efeitos dos fármacos , beta-Ciclodextrinas/farmacologia , Animais , Antiprotozoários/efeitos adversos , Brasil , Furazolidona/efeitos adversos , Testes de Sensibilidade Parasitária , Resultado do Tratamento , beta-Ciclodextrinas/efeitos adversosRESUMO
This study was conducted to develop a selective medium for the detection of Leptospira spp. in clinical samples. Serovars of Leptospira spp., environmental bacteria and the fungus from contaminated cultures of patients with suspected leptospirosis were inoculated into EMJH medium containing amphotericin B, 5-fluorouracil (5-FU), furazolidone and neomycin used singly or combined. Medium with 5-FU at the concentration of 200 µg ml-1 did not show any inhibitory effect against the fungus, Gram-negative bacilli and any of the leptospira strains except serovar Pyrogenes. The highest concentration of neomycin and furazolidone that did not inhibit the growth of leptospires was 4 µg ml-1 . All strains of Leptospira spp. grew on 5-FU (100 µg ml-1 ) in combination with neomycin (4 µg ml-1 ) and on 5-FU (100 µg ml-1 ) in combination with furazolidone (4 µg ml-1 ). The highest concentration of amphotericin B (500 µg ml-1 ) that inhibited the growth of the fungus also inhibited the bacteria and most of serovars of Leptospira spp. The most effective antibiotic combinations that inhibited the majority of environmental bacteria growth without affecting leptospiral growth were EMJH with 5-FU (100 µg ml-1 ) in combination with neomycin (4 µg ml-1 ). In conclusion, these findings will help the development of new selective media to isolate leptospires. SIGNIFICANCE AND IMPACT OF THE STUDY: Leptospirosis is one of the most widespread zoonotic diseases in the world. Since certain serovars are often associated with the symptoms and severity of the disease, the isolation and identification of the leptospires usually permits the prediction of sources of infection. Attempts to isolate Leptospira spp. from clinical specimens are often frustrated by overgrowth of the slow-growing bacteria by more rapidly growing contaminants. In this study, we evaluated selective agents to develop a new selective medium to isolate leptospires. The results demonstrated that the association of drugs in concentrations that allowed the growth of leptospires is to be more effective in inhibiting bacterial contaminants.
Assuntos
Antibacterianos/farmacologia , Meios de Cultura/farmacologia , Fluoruracila/farmacologia , Leptospira/efeitos dos fármacos , Leptospira/isolamento & purificação , Neomicina/farmacologia , Anfotericina B/farmacologia , Animais , Meios de Cultura/química , Furazolidona/farmacologia , Humanos , Leptospirose/microbiologiaRESUMO
In seeking substitutions for the current Chagas disease treatment, which has several relevant side effects, new therapeutic candidates have been extensively investigated. In this context, a balanced interaction between mediators of the host immune response seems to be a key element for therapeutic success, as a proinflammatory microenvironment modulated by interleukin-10 (IL-10) is shown to be relevant to potentiate anti-Trypanosoma cruzi drug activity. This study aimed to identify the potential immunomodulatory activities of the anti-T. cruzi K777, pyronaridine (PYR), and furazolidone (FUR) compounds in peripheral blood mononuclear cells (PBMC) from noninfected (NI) subjects and chronic Chagas disease (CD) patients. Our results showed low cytotoxicity to PBMC populations, with 50% cytotoxic concentrations (CC50) of 71.0 µM (K777), 9.0 µM (PYR), and greater than 20 µM (FUR). In addition, K777 showed no impact on the exposure index (EI) of phytohemagglutinin-stimulated leukocytes (PHA), while PYR and FUR treatments induced increased EI of monocytes and T lymphocytes at late stages of apoptosis in NI subjects. Moreover, K777 induced a more prominent proinflammatory response (tumor necrosis factor alpha-positive [TNF-α+] CD8+/CD4+, gamma interferon-positive [IFN-γ+] CD4+/CD8+ modulated by interleukin-10-positive [IL-10+] CD4+ T/CD8+ T) than did PYR (TNF-α+ CD8+, IL-10+ CD8+) and FUR (TNF-α+ CD8+, IL-10+ CD8+). Signature analysis of intracytoplasmic cytokines corroborated the proinflammatory/modulated (K777) and proinflammatory (PYR and FUR) profiles previously found. In conclusion, the lead compound K777 may induce beneficial changes in the immunological profile of patients presenting the chronic phase of Chagas disease and may contribute to a more effective therapy against the disease.
Assuntos
Fatores Imunológicos/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Doença de Chagas/prevenção & controle , Furazolidona/farmacologia , Leucócitos/efeitos dos fármacos , Naftiridinas/farmacologia , Fito-Hemaglutininas/farmacologiaRESUMO
OBJECTIVE: The aim of the present study was to assess the primary and secondary resistance of Helicobacter pylori strains to clarithromycin, amoxicillin, furazolidone, tetracycline, and metronidazole, the conventional antibiotics presently used in Brazilian children and adolescents. METHODS: Seventy-seven consecutive H pylori strains, 71 of 77 strains obtained from patients without previous eradication treatment for H pylori infection, and 6 strains from patients in whom previous eradication treatment had failed. RESULTS: Global rate of resistance was 49.3% (38/77): 40% of strains were resistant to metronidazole, 19.5% to clarithromycin, and 10.4% to amoxicillin. All of the tested H pylori strains were susceptible to furazolidone and tetracycline. Multiple resistance were detected in 18.2% (14/77 patients) of the strains: 6 of 14 (43%) simultaneously resistant to clarithromycin and metronidazole; 5 of 14 (36%) to amoxicillin and metronidazole; 2 of 14 (14%) to amoxicillin, clarithromycin, and metronidazole; and 1 of 14 (7%) to clarithromycin and amoxicillin. CONCLUSIONS: The high resistance rate to metronidazole and clarithromycin observed in clinical H pylori isolates can exclude these antimicrobials in empirical eradication treatment in Brazil. Otherwise, furazolidone and tetracycline presented no resistance. Properly assessing the risks and benefits, these 2 antimicrobials and their derivatives could be used in empirical eradication schedules, both associated with amoxicillin, which showed a low resistance rate despite its wide use in pediatric patients.
Assuntos
Antibacterianos/farmacocinética , Claritromicina/farmacologia , Farmacorresistência Bacteriana , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Metronidazol/farmacologia , Adolescente , Adulto , Amoxicilina/farmacologia , Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Brasil , Criança , Pré-Escolar , Claritromicina/uso terapêutico , Países em Desenvolvimento , Erradicação de Doenças , Farmacorresistência Bacteriana Múltipla , Feminino , Furazolidona/farmacologia , Furazolidona/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/prevenção & controle , Helicobacter pylori/crescimento & desenvolvimento , Humanos , Masculino , Metronidazol/uso terapêutico , Testes de Sensibilidade Microbiana , Tetraciclina/farmacologia , Tetraciclina/uso terapêutico , Adulto JovemRESUMO
The current treatment for leishmaniasis is unsatisfactory due to toxic side effects, high cost, and problems with drug resistance. Various approaches have been used to identify novel drug candidates to treat Leishmania sp. parasites including the use of re-purposed drugs. Furazolidone is a nitrofuran derivative with antiprotozoal and antibacterial activity and is used for the treatment of giardiasis. In the present work, we determined the in vitro antileishmanial activity of furazolidone and its ability to induce ultrastructural alterations of parasites. Promastigotes of Leishmania (L.) chagasi, Leishmania (V.) braziliensis, Leishmania (L.) major, and Leishmania (L.) amazonensis were highly susceptible to furazolidone, with IC(50) values ranging between 0.47 and 0.73 microg/mL. Furazolidone was also very effective against L. chagasi intracellular amastigotes, and despite mammalian cytotoxicity, the selectivity index was 8.0 in human monocytes. The drug also had limited toxicity in mice erythrocytes. Furazolidone demonstrated specific activity against Leishmania, a potential consequence of the lack of macrophage nitric oxide activation. As determined by electron transmission microscopy, drug treatment induced severe damage to the parasite mitochondria and nucleus. This older oral drug is an effective agent for the treatment of L. (L.) chagasi in vitro and is a novel candidate for further experimental studies.
Assuntos
Antiprotozoários/farmacologia , Furazolidona/farmacologia , Leishmania/efeitos dos fármacos , Leishmania/ultraestrutura , Animais , Antiprotozoários/toxicidade , Linhagem Celular , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/ultraestrutura , Cricetinae , Eritrócitos/efeitos dos fármacos , Feminino , Furazolidona/toxicidade , Concentração Inibidora 50 , Mesocricetus , Camundongos , Camundongos Endogâmicos BALB C , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/ultraestrutura , Monócitos/efeitos dos fármacosRESUMO
The protozoon Giardia lamblia infects millions of people worldwide, most of them in underdeveloped countries, where it is frequently a hyperendemic disease. The search for an effective anti-Giardia treatment has been intense, but recurrent infections, virulence factors, and drug resistance imposed obstacles in the achievement of an efficient medication. Most papers about drug effects in Giardia are related to the trophozoite form, although viable cysts, the infective forms, are continuously eliminated in the stools during the treatment. Supported by this knowledge, we analyzed the inhibitory effects of metronidazole (MZ) and furazolidone (FZ) on the differentiation of Giardia into cysts and its viability. The presence of cavities, lamellar bodies and thread-like structures were the most frequent morphological alterations. The results showed also that FZ was more effective by 50% than MZ in inhibiting in vitro cyst differentiation.
Assuntos
Antiprotozoários/farmacologia , Furazolidona/farmacologia , Giardia lamblia/efeitos dos fármacos , Metronidazol/farmacologia , Animais , Giardia lamblia/fisiologia , Giardia lamblia/ultraestrutura , Microscopia Eletrônica de TransmissãoRESUMO
The effects of metronidazole and furazolidone on Giardia lamblia trophozoites were analyzed by video-light and transmission electron microscopy. In addition, growth curves were drawn based on four concentrations of the drugs. The IC50 was 4.6 microM for metronidazole and 2.9 microM for furazolidone. By light microscopy we observed that metronidazole-treated cells maintained the characteristic body shape, but many showed bubbles in the dorsal and ventral surfaces. The effects of furazolidone include changes in the morphology (the cells were roundish) and also cytoplasmic extrusions. When observed by transmission microscopy, cells treated with metronidazole appeared rounder than usual and membranous structures were observed in the cytoplasm. Cells treated with furazolidone showed the cytoplasm depleted of its contents and great changes in volume. Our results show that furazolidone was more effective than metronidazole and its effects were observed in cells treated with 1 microg/ml (the lowest concentration) as early as 6 h after the start of exposure.
Assuntos
Antiprotozoários/farmacologia , Furazolidona/farmacologia , Giardia lamblia/efeitos dos fármacos , Metronidazol/farmacologia , Animais , Relação Dose-Resposta a Droga , Giardia lamblia/crescimento & desenvolvimento , Giardia lamblia/ultraestrutura , Giardíase/parasitologia , Giardíase/patologia , Microscopia Eletrônica/métodos , Microscopia de Vídeo/métodosRESUMO
BACKGROUND: Helicobacter pylori infection is associated with a wide range of digestive diseases and is very prevalent in developing countries, although few data exist on the susceptibility of H. pylori to antimicrobials commonly used in eradication schedules in these countries. The aim of this study was to evaluate the resistance of H. pylori to metronidazole, clarithromycin, amoxicillin, tetracycline, and furazolidone in dyspeptic Brazilian patients. Material and Methods. Ninety consecutive H. pylori-positive patients were enrolled. Resistance was evaluated by an agar dilution test. RESULTS: Resistance to metronidazole was detected in 38 patients (42%); to amoxicillin in 26 individuals (29%); to clarithromycin in 6 patients (7%); to tetracycline in 6 patients (7%); and to furazolidone in 4 individuals (4%). Thirteen strains were resistant to two agents, and eight strains were resistant to three antimicrobials. CONCLUSIONS: These results confirm the need for culture and susceptibility testing to define H. pylori resistance patterns in particular geographical areas before the general use of an eradication schedule. They also suggest the possibility of resistance to such antimicrobials as amoxicillin or tetracycline in geographical areas with a high prevalence of H. pylori infection and still not fully evaluated for antimicrobial susceptibility.
Assuntos
Antibacterianos/farmacologia , Resistência a Múltiplos Medicamentos/fisiologia , Dispepsia/microbiologia , Helicobacter pylori/efeitos dos fármacos , Adolescente , Adulto , Idoso , Amoxicilina/farmacologia , Brasil , Resistência Microbiana a Medicamentos , Feminino , Furazolidona/farmacologia , Humanos , Masculino , Metronidazol/farmacologia , Pessoa de Meia-Idade , Penicilinas/farmacologiaRESUMO
Se describen los resultados clínicos e histopatológicos de un grupo de pacientes con DNU, quienes consultaron únicamente por dolor de "tipo ulceroso" y fueron tratados con la asociación de subsalicilato de bismuto más furazolidona dirigido contra el Helicobacter Pylori (grupo I) o sucralfate, un conocido citoprotector de la mucosa gástrica (grupo II). Se encontró una mejoría significativa con los dos tipos de tratamiento, sinembargo, en el grupo que recibió el tratamiento dirigido a eliminar la colonización gástrica por Helicobacter Pylori, la mejoría histológica fue superior que la observada en el grupo tratado con sucralfate. La disminución de los cambios inflamatoria encontrada en el grupo de sucralfate podría estar relacionada con sus propiedades citoprotectoras y con la disminución de la adhesión del Helicobacter pylori a las células epiteliales del estómago. Los hallazgos sugieren que el Helicobacter pylori puede ser la causa de síntomas dispépticos y en un grupo adecuadamente seleccionado de pacientes con DNU, un tratamiento de erradicación mejora los síntomas
Assuntos
Humanos , Bismuto/uso terapêutico , Dispepsia/tratamento farmacológico , Furazolidona/uso terapêutico , Helicobacter pylori/efeitos dos fármacos , Bismuto/farmacologia , Dispepsia/microbiologia , Furazolidona/farmacologiaRESUMO
Se estudiaron 42 pacientes con síntomas dispépticos con hallazgos endoscópicos sugestivos de gastritis erosiva crónica. La mitad fueron tratados con la asociación de bismuto más furazolidona y el resto con Famotidina. Se encontró mejoría endoscópica significativa con los dos tratamientos, pero la mejoría histológica fue mayor con el primer tratamiento, el cual se asoció a desaparición del Helicobacter pylori. Los resultados anteriores sugieren una etiología múltiple de los cambios observados en la mucosa gástrica en esta entidad
Assuntos
Humanos , Bismuto/uso terapêutico , Furazolidona/uso terapêutico , Gastrite/tratamento farmacológico , Bismuto/farmacologia , Furazolidona/farmacologia , Helicobacter pylori/efeitos dos fármacosRESUMO
Se caracterizaron 26922 cepas de Vibrio cholerae aisladas en México de 1991 a 1993, el patrón fenotípico demostró que 100 por ciento pertenece al biovar El Tor y fueron sensibles a los antibióticos, excepto a la furazolidona, la estreptomicina y el sulfixosasol probados en 1993. Se empleó como marcadores epidemiológicos al 97 por ciento de las cepas que fueorn resistentes. Se observó un cambio drástico en la frecuencia de los serotipo Inaba; en 1991 el 99.5 por ciento de las cepas fueron Inaba mientras que para 1992, el 95.0 por ciento fueron del serotipo Ogawa, fueron toxigénicas, y las no 01 dieron negativa la prueba de ELISA, PCR y los cultivos celulares para investigar toxina colérica. Los ribotipos correspondieron en su mayoría al patrón 5, un lote pequeño a la 6a y dos al ribotipo 12. En este estudio se buscó el ribotipo 2, que se ha relacionado con las cepas aisladas del Golfo de México entre las cepas hemolíticas, pero hasta ahora no se ha identificado ninguna cepa con dicho patrón. Para estudios fenotípicos y genotípicos en apoyo al análisis epidemilógico de la enfermedad, es conveniente continuar haciendo el cultivo en una fracción de las muestras para recuperar cepas puras, aunque se utilicen pruebas rápidas para el diagnóstico de cólera