Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.899
Filtrar
1.
Dent Mater ; 39(1): 132-139, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36604256

RESUMO

OBJECTIVES: The aim of the present study was to prepare resorbable polylactide fibers for periodontitis treatment using coaxial electrospinning to optimize the release of metronidazole (MNA) by reducing the initial burst effect. METHODS: Poly(L-lactide-co-D,L-lactide) (PLA) fibers mats with different distributions of metronidazole (MNA) were manufactured by coaxial electrospinning (COAX). By COAX spinning the central core of the fiber was enriched with 40% MNA (m/m), while the sheath of the fiber consisted of PLA only (test group). In contrast, fibers of the control group were prepared by conventional electrospinning with the same amount of MNA but with a homogenous drug distribution (HDD - homogenously distributed drug). The release of MNA was determined by analyzing aliquots from the fiber mats using UV-VIS spectroscopy. Agar diffusion tests were carried out to determine the antibacterial effect on periodontopathogenic bacteria. Biocompatibility was tested in direct contact to human gingival fibroblasts (HGF) for two days. RESULTS: The COAX mats showed a retarded drug release compared to the conventional HDD fibers. After 24 h, 64% of total MNA was released cumulatively from the COAX fibers while 90% of the MNA was released from the HDD fibers (controls). The antibacterial effect of COAX fibers was significantly higher after 24 h compared to the HDD fibers. Cell cultivation revealed significant higher numbers of vital cells among the COAX mats. SIGNIFICANCE: COAX fibers showed improved sustained MNA release compared to conventional fibers and can be seen as potential drug delivery systems in local periodontitis treatment.


Assuntos
Nanofibras , Periodontite , Humanos , Metronidazol/farmacologia , Nanofibras/química , Sistemas de Liberação de Medicamentos , Antibacterianos/farmacologia , Antibacterianos/química , Poliésteres/química , Periodontite/tratamento farmacológico , Liberação Controlada de Fármacos
2.
Molecules ; 27(24)2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36558035

RESUMO

Protozoan parasites, such as Giardia lamblia and Trichomonas vaginalis, cause the most prevalent infections in humans in developing countries and provoke significant morbidity and mortality in endemic countries. Despite its side-effects, metronidazole is still the drug of choice as a giardiacidal and trichomonacidal tissue-active agent. However, the emergence of metronidazole resistance and its evolved strategies of parasites to evade innate host defenses have hindered the identification and development of new therapeutic strategies against these parasites. Here, we tested five synthesized benzimidazole derivatives as possible drugs for treating giardiasis and trichomoniasis, probing the bifunctional enzyme glucose 6-phosphate dehydrogenase::6-phosphogluconolactone from G. lamblia (GlG6PD::6PGL) and T. vaginalis (TvG6PD::6PGL) as a drug target. The investigated benzimidazole derivatives were H-B2M1, H-B2M2, H2N-BZM6, O2N-BZM7, and O2N-BZM9. The recombinant enzymes were used in inhibition assays, and in silico computational predictions and spectroscopic studies were applied to follow the structural alteration of the enzymes and identify the possible mechanism of inhibition. We identified two potent benzimidazole compounds (O2N-BZM7 and O2N-BZM9), which are capable of inhibiting both protozoan G6PD::6PGL enzymes and in vitro assays with these parasites, showing that these compounds also affect their viability. These results demonstrate that other therapeutic targets of the compounds are the enzymes GlG6PD::6PGL and TvG6PD::6PGL, which contribute to their antiparasitic effect and their possible use in antigiardial and trichomonacidal therapies.


Assuntos
Antiprotozoários , Giardia lamblia , Parasitos , Trichomonas vaginalis , Animais , Humanos , Metronidazol/farmacologia , Antiparasitários/farmacologia , Benzimidazóis/farmacologia , Antiprotozoários/farmacologia
3.
BMC Microbiol ; 22(1): 321, 2022 12 29.
Artigo em Inglês | MEDLINE | ID: mdl-36581836

RESUMO

BACKGROUND: Helicobacter pylori (H. pylori) infection is associated with remodeling of gut microbiota. Many studies have found H. pylori infection and eradication therapy can alter the gut microbiota. However, few studies explored the impact of eradication therapy containing minocycline and metronidazole on gut microbiota. AIM: The objective of the present study was to explore the changes of gut microbiota after H. pylori infection. Besides, learn more about the dynamic changes of gut microbiota during different stages of eradication treatment containing minocycline, metronidazole, bismuth agents and proton pump inhibitors. METHODS: Sixty stool samples from the patients with H. pylori infection before eradication, 14 and 42 days after eradication, and ten stool samples from non-infected individuals were collected. Subsequently, we performed 16S rRNA gene amplicon sequencing to analyze these samples, and the results were evaluated by using alpha diversity, beta diversity and microbial composition analyses. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States was also used to predict the metabolic pathways according to the Kyoto Encyclopedia of Genes and Genomes database. RESULTS: The alpha and beta diversity of the microbiota changed significantly in H. pylori infected individuals, but returned to baseline 42 days after eradication therapy. At the genus level, the abundances of Bacteroidetes, [Ruminococcus]_gnavus_group, Ruminococcaceae_Incertae_Sedis, Tuzzrealla, Butyricicoccus were significantly lower in the H. pylori infected group. Bacterial abundance was also dynamically changing during eradication treatment. In addition, PICRUST analysis found the levels of uronic acid metabolism, uncharacterized transport system, and biosynthesis of unsaturated fatty acids were higher in H. pylori infected individuals than in the non-infected group. CONCLUSIONS: Intestinal microbiota diversity, composition, functional predictions altered significantly after H. pylori infection, and gradually returned to healthy control levels after the application of eradication therapy containing minocycline and metronidazole in one month and a half.


Assuntos
Microbioma Gastrointestinal , Infecções por Helicobacter , Helicobacter pylori , Humanos , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Metronidazol/farmacologia , Metronidazol/uso terapêutico , Minociclina/farmacologia , Minociclina/uso terapêutico , Helicobacter pylori/genética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , RNA Ribossômico 16S/genética , Filogenia , Quimioterapia Combinada
4.
Int J Mol Sci ; 23(20)2022 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-36293276

RESUMO

Trichomonas vaginalis (TV) is the causative agent of trichomoniasis, the most common nonviral sexually transmitted disease. TV can carry symbionts such as Trichomonas vaginalis virus (TVV) or Mycoplasma hominis. Four distinct strains of TV are known: TVV1, TVV2, TVV3, and TVV4. The aim of the current study was to characterise TV isolates from Austrian patients for the presence of symbionts, and to determine their effect on metronidazole susceptibility and cytotoxicity against HeLa cells. We collected 82 TV isolates and detected presence of TVV (TVV1, TVV2, or TVV3) in 29 of them (35%); no TVV4 was detected. M. hominis was detected in vaginal/urethral swabs by culture in 37% of the TV-positive patients; M. hominis DNA was found in 28% of the TV isolates by PCR. In 15% of the patients, M. hominis was detected in the clinical samples as well as within the respective TV isolates. In 22% of the patients, M. hominis was detected by culture only. In 11 patients, M. hominis was detected only within the respective cultured TV isolates (13%), while the swab samples were negative for M. hominis. Our results provide a first insight into the distribution of symbionts in TV isolates from Austrian patients. We did not observe significant effects of the symbionts on metronidazole susceptibility, cytotoxicity, or severity of symptoms.


Assuntos
Totiviridae , Tricomoníase , Trichomonas vaginalis , Feminino , Humanos , Trichomonas vaginalis/genética , Metronidazol/farmacologia , Células HeLa , Mycoplasma hominis/genética
5.
Bioorg Med Chem Lett ; 76: 129012, 2022 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-36182008

RESUMO

In an effort for fighting with dreadful drug resistance, iminotetraberberine was hybridized with metronidazole to construct a unique type of potential broad-spectrum antibacterial iminotetrahydroberberine-corbelled metronidazoles. Some prepared hybrids exerted promising inhibitory effects against the tested microorganisms in comparison to the natural berberine, clinical metronidazole and norfloxacin. Noticeably, phenyl oxime derivative 8e displayed a broad antibacterial spectrum with a quite low MIC value of 0.024 mM against P. aeruginosa, being 63-, 62- and 2-fold to berberine, metronidazole and norfloxacin, respectively. The active compound 8e with low cytotoxicity under effective bacteriostatic concentration could decrease biofilm viability and show much lower trend to induce the resistant development than norfloxacin in the tested period. Mechanism investigation showed that compound 8e could disturb the bacterial membrane to lead to the leakage of cellular contents, thus exerting potent antibacterial potency. It was also revealed that compound 8e could interact with penicillin binding protein via multi-site non-covalent binding in docking simulation. The above results manifested that iminotetrahydroberberine-corbelled metronidazoles might bring hope for the exploitation of new broad-spectrum antibacterial agents with a membrane-destruction mechanism.


Assuntos
Antibacterianos , Berberina , Antibacterianos/farmacologia , Antibacterianos/química , Metronidazol/farmacologia , Norfloxacino/farmacologia , Testes de Sensibilidade Microbiana , Berberina/farmacologia , Berberina/química , Proteínas de Ligação às Penicilinas , Pseudomonas aeruginosa , Oximas/farmacologia
6.
Sci Rep ; 12(1): 17754, 2022 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-36272980

RESUMO

The increasing rates of antibiotic resistance in Helicobacter pylori (H. pylori) are a major concern of the decreasing eradication rate. Large-scale and long-period studies on antimicrobial susceptibility of H. pylori in children are limited. This study aimed to describe the temporal changes of antibiotic resistance among children in southeast China. Gastric biopsies obtained from children were cultured for H. pylori from 2015 to 2020. Susceptibility to clarithromycin (CLA), amoxicillin (AML), metronidazole (MTZ), furazolidone (FZD), tetracycline (TET) and levofloxacin (LEV) was tested. Data from 2012 to 2014 reported previously were obtained for comparing the change in temporal trends of antibiotic resistance. A total of 1638 (52.7%) H. pylori strains were isolated from 3111 children recruited. The resistance rates to CLA, MTZ and LEV were 32.8%, 81.7% and 22.8%, respectively. There were 52.9% strains resistant to single resistance, 28.7% to double resistance, and 9.0% to triple resistance. The total resistance rate and resistance rates to CLA, MTZ, LEV, CLA + LEV and CLA + MTZ + LEV increased annually in a linear manner. All resistant patterns except single resistance increased obviously from 2015 to 2017 and 2018 to 2020 compared to that from 2012 to 2014. Double resistance to CLA + MTZ increased significantly with age. The resistance rate to CLA and triple resistance to CLA, MTZ and LEV increased in children with prior H. pylori treatment than that from children without prior treatment. The antibiotic resistance rates of H. pylori were high in a large pediatric population in southeast China from 2015 to 2020. Individual treatment based on susceptibility test is imperative and optimal regimens should be chosen in H. pylori eradication therapy.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Criança , Humanos , Claritromicina/farmacologia , Claritromicina/uso terapêutico , Metronidazol/farmacologia , Metronidazol/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/epidemiologia , Levofloxacino/farmacologia , Furazolidona/farmacologia , Farmacorresistência Bacteriana , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Amoxicilina/farmacologia , Amoxicilina/uso terapêutico , Tetraciclinas/farmacologia
7.
ACS Chem Biol ; 17(11): 3077-3085, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36259427

RESUMO

Nitroimidazoles such as metronidazole are used as anti-infective drugs against anaerobic bacteria. Upon in vivo reduction of the nitro group, reactive radicals damage DNA and proteins in the absence of oxygen. Unexpectedly, a recent study of nitroimidazoles linked to an indolin-2-one substituent revealed potent activities against aerobic bacteria. This suggests a different, yet undiscovered mode of action (MoA). To decipher this MoA, we first performed whole proteome analysis of compound-treated cells, revealing an upregulation of bacteriophage-associated proteins, indicative of DNA damage. Since DNA binding of the compound was not observed, we applied activity-based protein profiling (ABPP) for direct target discovery. Labeling studies revealed topoisomerase IV, an essential enzyme for DNA replication, as the most enriched hit in pathogenic Staphylococcus aureus cells. Subsequent topoisomerase assays confirmed the inhibition of DNA decatenation in the presence of indolin-2-one nitroimidazole with an activity comparable to ciprofloxacin, a known inhibitor of this enzyme. Furthermore, we determined significantly increased redox potentials of indolin-2-one nitroimidazoles compared to classic 5-nitroimidazoles such as metronidazole, which facilitates in vivo reduction. Overall, this study unravels that indolin-2-one-functionalized nitroimidazoles feature an unexpected dual MoA: first, the direct inhibition of the topoisomerase IV and second the classic nitroimidazole MoA of reductive bioactivation leading to damaging reactive species. Importantly, this dual MoA impairs resistance development. Given the clinical application of this compound class, the new mechanism could be a starting point to mitigate resistance.


Assuntos
Nitroimidazóis , Nitroimidazóis/química , Antibacterianos/farmacologia , Antibacterianos/química , Metronidazol/metabolismo , Metronidazol/farmacologia , DNA Topoisomerase IV , DNA
8.
Emerg Infect Dis ; 28(11): 2308-2311, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36286226

RESUMO

The plasmid pCD-METRO confers metronidazole resistance in Clostridioides difficile. We showed high sequence similarity among pCD-METRO plasmids from different isolates and identified pCD-METRO and associated metronidazole-resistant isolates in clinical and veterinary reservoirs in the Americas. We recommend using PCR or genomic assays to detect pCD-METRO in metronidazole-resistant C. difficile.


Assuntos
Clostridioides difficile , Infecções por Clostridium , Humanos , Metronidazol/farmacologia , Clostridioides difficile/genética , Ribotipagem , Infecções por Clostridium/veterinária , Infecções por Clostridium/tratamento farmacológico , Clostridioides , Farmacorresistência Bacteriana/genética , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico
9.
Int J Mol Sci ; 23(19)2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36232929

RESUMO

Several studies have indicated the beneficial anti-inflammatory effect of butyrate in inflammatory bowel disease (IBD) therapy implying attempts to increase butyrate production in the gut through orally administered dietary supplementation. Through the gut-liver axis, however, butyrate may reach directly the liver and influence the drug-metabolizing ability of hepatic enzymes, and, indirectly, also the outcome of applied pharmacotherapy. The focus of our study was on the liver microsomal cytochrome P450 (CYP) 2A5, which is a mouse orthologue of human CYP2A6 responsible for metabolism of metronidazole, an antibiotic used to treat IBD. Our findings revealed that specific pathogen-free (SPF) and germ-free (GF) mice with dextran sulfate sodium (DSS)-induced colitis varied markedly in enzyme activity of CYP2A and responded differently to butyrate pre-treatment. A significant decrease (to 50%) of the CYP2A activity was observed in SPF mice with colitis; however, an administration of butyrate prior to DSS reversed this inhibition effect. This phenomenon was not observed in GF mice. The results highlight an important role of gut microbiota in the regulation of CYP2A under inflammatory conditions. Due to the role of CYP2A in metronidazole metabolism, this phenomenon may have an impact on the IBD therapy. Butyrate administration, hence, brings promising therapeutic potential for improving symptoms of gut inflammation; however, possible interactions with drug metabolism need to be further studied.


Assuntos
Butiratos , Colite Ulcerativa , Microbioma Gastrointestinal , Animais , Antibacterianos/efeitos adversos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Anti-Inflamatórios/farmacologia , Butiratos/farmacologia , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Sistema Enzimático do Citocromo P-450/metabolismo , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Metronidazol/farmacologia , Camundongos , Camundongos Endogâmicos C57BL
10.
Comput Math Methods Med ; 2022: 1221190, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36267315

RESUMO

The present study was designed to observe the effect of quadruple therapy combined with probiotics on Helicobacter pylori-related peptic ulcer. The patients in the control group (n = 90) were given regular quadruple therapy including proton pump inhibitor ilaprazole enteric-coated tablet + two antibiotics amoxicillin dispersible tablet and metronidazole tablet + colloidal bismuth pectin capsule for 2 weeks. Patients in the study group (n = 90) were given abovementioned quadruple therapy combined with probiotics live combined Bifidobacterium, Lactobacillus, and Enterococcus Capsules, oral for 2 weeks. Then Hp clearance rate, recurrence rate, levels of gastrointestinal hormone makers, and advance reactions between two groups were compared. At the 2nd week after the treatment, the Helicobacter pylori clearance rate in the study group (87.79%) was significantly higher than the control group (78.89%), and the total recurrence rate in the study group (6.67%) was significantly lower than the control group (13.33%) (P < 0.05). Serum gastrin and motilin expression were lower, and somatostatin expressions was significantly higher than those in the control group (P < 0.05). There was no significant difference in the total incidence of adverse reactions between the two groups (P > 0.05). In summary, quadruple therapy combined with probiotics in the treatment of Helicobacter pylori-related peptic ulcer can improve the Helicobacter pylori clearance rate, reduce the Helicobacter pylori recurrence rate, and is beneficial to improving the level of gastrointestinal hormones, with certain safety.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Úlcera Péptica , Probióticos , Humanos , Infecções por Helicobacter/tratamento farmacológico , Bismuto/farmacologia , Bismuto/uso terapêutico , Metronidazol/farmacologia , Metronidazol/uso terapêutico , Inibidores da Bomba de Prótons/farmacologia , Gastrinas/farmacologia , Gastrinas/uso terapêutico , Motilina/farmacologia , Motilina/uso terapêutico , Comprimidos com Revestimento Entérico/farmacologia , Comprimidos com Revestimento Entérico/uso terapêutico , Quimioterapia Combinada , Úlcera Péptica/tratamento farmacológico , Úlcera Péptica/microbiologia , Amoxicilina/uso terapêutico , Amoxicilina/farmacologia , Antibacterianos/uso terapêutico , Probióticos/uso terapêutico , Pectinas/farmacologia , Pectinas/uso terapêutico , Somatostatina/farmacologia , Somatostatina/uso terapêutico
11.
Front Cell Infect Microbiol ; 12: 970630, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36159644

RESUMO

The increasing antibiotic resistance of Helicobacter pylori infection is a globally urging problem. To investigate the H. pylori resistance situation in Nanjing, China, we enrolled patients in Nanjing First Hospital from January 2018 to May 2021. H. pylori strains were isolated from patients who had at least one positive 13C-urea breath or rapid urease result. Subsequently, we performed antibiotic susceptibility tests on the isolated strains to clarithromycin, metronidazole, levofloxacin, amoxicillin, furazolidone and tetracycline. ARMS-PCR was conducted to determine H. pylori clarithromycin resistance gene mutation. Our results demonstrated that the primary resistance rates of metronidazole, clarithromycin, levofloxacin, amoxicillin, furazolidone and tetracycline were 67.19% (1417/2109), 35.99% (759/2109), 24.23% (511/2109), 0.76% (16/2109), 0.28% (6/2109) and 0.09% (2/2109), respectively. The resistance rates of metronidazole, clarithromycin and levofloxacin elevated significantly after treatment and the three antibiotics composed the majority of multi-resistance patterns. However, the resistance rates of amoxicillin, furazolidone and tetracycline were still in low levels after treatment. ARMS-PCR showed a rather good consistency with antibiotic susceptibility test in detecting clarithromycin resistance, with a kappa value of 0.79. Overall, this study revealed the latest complex situation of antibiotic resistance of H. pylori infection in Nanjing and offered suggestions on clinical medication for curing H. pylori.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Amoxicilina/farmacologia , Amoxicilina/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , China/epidemiologia , Claritromicina/farmacologia , Claritromicina/uso terapêutico , Farmacorresistência Bacteriana , Resistência Microbiana a Medicamentos , Furazolidona/farmacologia , Furazolidona/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/epidemiologia , Humanos , Levofloxacino/farmacologia , Levofloxacino/uso terapêutico , Metronidazol/farmacologia , Metronidazol/uso terapêutico , Testes de Sensibilidade Microbiana , Tetraciclina/farmacologia , Tetraciclina/uso terapêutico , Ureia/uso terapêutico , Urease
12.
Pan Afr Med J ; 42: 144, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36160282

RESUMO

Introduction: surveillance data on Helicobacter pylori (H. pylori) antibiotic susceptibilities in Morocco are limited, despite resistance being the key factor in treatment failure. Virulence factors of H. pylori are associated with carcinogenesis and may be also associated with the efficacy of treatment. The aim of our study is to determine the prevalence of H. pylori metronidazole resistance in a Moroccan population infected with H. pylori and to study the impact of their virulence factors CagA and VacA on their resistance to metronidazole. Methods: the susceptibility to metronidazole of 185 isolates was determined by PCR. The isolates were also genotyped for CagA and VacA genes by PCR. Results: the metronidazole resistance rate was 62.70%. No association between resistance to metronidazole and social factors was detected. Regarding the virulence factors, we remarked that the moderate virulent strains s1/m2/i1/d1 with a CagA negative were the most resistant to metronidazole with a rate of 84% compared to the less virulent strains bearing the CagA negative VacA s2m2i2d2 genotype with a rate of 58% and the high virulent strains s1/m1/i1/d1-CagA positive with a rate of 47.06%. Conclusion: our study revealed a very high prevalence of resistance to metronidazole in our population. The resistance ability of H. pylori maybe affected by its virulence intensity. H. pylori eradication regimens should therefore be reevaluated in this setting.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Genótipo , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/epidemiologia , Helicobacter pylori/genética , Humanos , Metronidazol/farmacologia , Fatores de Virulência/genética
13.
Helicobacter ; 27(6): e12932, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36110057

RESUMO

BACKGROUND: One main challenge in Helicobacter pylori (H. pylori) eradication is its increasing antibiotic resistance. Additionally, resistance rates vary between geographic areas and periods. However, data are limited since susceptibility testing is not routinely performed. Thus, it is valuable to gather data regarding H. pylori's resistance rates in Israel that would aid in better adjustment of treatment. MATERIALS AND METHODS: The study included 540 H. pylori isolates, recovered from gastric biopsy samples of patients who had undergone endoscopy, during 2015-2020, at the Padeh Poriya Medical Center. Antibiotic susceptibility testing to amoxicillin, clarithromycin, metronidazole, levofloxacin, rifampicin, and tetracycline was performed using the Etest technique. Data regarding participants' sex, age, and ethnic group were collected. For every antibiotic and for multi-resistance, generalized linear models were used to estimate crude and adjusted estimated differences in mean MIC and odds ratios (ORs) for every year, compared with the reference year 2015. RESULTS: The highest resistance rates were for clarithromycin and metronidazole (46.3% and 16.3%, respectively). Patients above 18 had higher resistance rate to rifampicin and multi-resistance (3.3% and 14.8%), compared with patients under 18 (0.5% and 8.4%, respectively). Resistance rates for levofloxacin, rifampicin, and multi-resistance were significantly higher among Arab patients, compared with Jewish patients. During the 6-year surveillance, a significant annual trend in MIC for metronidazole and in ORs for metronidazole, levofloxacin, and multi-resistance were observed (after adjustment). During 2020 compared with 2015, significant increased ORs were observed for levofloxacin and metronidazole [5.72 (1.03-31.84); 4.28 (1.30-14.14), respectively]. CONCLUSIONS: In light of the remarkable changes in antibiotic resistance of H. pylori during the study's period and the increasing resistance rates to various antibiotics, it is very important to continuously monitor H. pylori antibiotic susceptibly. In order to increase eradication rates of this bacterium, therapy regimes must be based on an updated antibiotic resistance data.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Humanos , Claritromicina/farmacologia , Levofloxacino , Metronidazol/farmacologia , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/microbiologia , Rifampina/farmacologia , Israel/epidemiologia , Testes de Sensibilidade Microbiana , Amoxicilina , Resistência Microbiana a Medicamentos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana
14.
Mar Biotechnol (NY) ; 24(5): 1014-1022, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36102994

RESUMO

Trichomoniasis is the most common non-viral sexually transmitted infection (STI) in the world caused by Trichomonas vaginalis. Failures in the treatment with the 5-nitroimidazole class including parasite resistance to metronidazole elicit new alternatives. Marine natural products are sources of several relevant molecules, presenting a variety of metabolites with numerous biological activities. In this work, we evaluated the anti-T. vaginalis activity of fungi associated with marine invertebrates by mass spectrometry-based metabolomics approaches. After screening of six marine fungi, extract from Penicillium citrinum FMPV 15 has shown to be 100% active against T. vaginalis, and the gel permeation column on Sephadex LH-20® yielded twelve organic fractions which five showed to be active. Metabolomics and statistical analyses were performed with all the samples (extract and fractions), and several compounds were suggested to be related to the activity. These components include citrinin, dicitrinin C, citreoisocoumarin, dihydrocitrinone, decarboxycitrinin, penicitrinone C, and others. The minimum inhibitory concentration (MIC) value of anti-T. vaginalis activity of citrinin was 200 µM. The marine fungi metabolites show potential as new alternatives to overcome drug resistance in T. vaginalis infections.


Assuntos
Produtos Biológicos , Citrinina , Trichomonas vaginalis , Fungos , Espectrometria de Massas , Metronidazol/farmacologia , Extratos Vegetais
15.
Parasit Vectors ; 15(1): 313, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36064639

RESUMO

BACKGROUND: Blastocystis sp. is one of the most common colonisers of the intestinal tract that demonstrate strong interaction with accompanying gut bacteria. Previously, the protozoan isolated from individuals with irritable bowel syndrome (IBS) showed altered phenotypic features suggesting that it can be triggered to become pathogenic. Previous studies reported altered gut microbiota and high prevalence of Blastocystis sp. in schizophrenia patients. However, the phenotypic characteristics of Blastocystis sp. isolated from individuals with SZ have yet to be described. METHODS: In this study, faecal samples from 50 patients with severe schizophrenia (SZ) and 100 non-schizophrenic (NS) individuals were screened for Blastocystis sp. INFECTION: Positive isolates were subjected to genotypic and phenotypic characterization. RESULTS: We found that 12 out of 50 (24%) SZ and 5 out of 100 (5%) NS individuals were detected Blastocystis sp. positive using both in vitro culture and PCR method with no significant association to age and gender. Out of the 15 sequenced isolates, ST3 was the most prevalent subtype (66.7%) followed by ST1 (20%) and ST6 (13.3%). The isolates from SZ individuals demonstrated significant slower growth rate (34.9 ± 15.6 h) and larger range of cell diameter (3.3-140 µm). We detected higher amoebic forms and metronidazole resistance among SZ isolates with variation in cell surface glycoprotein where 98% of cells from SZ showed consistent medium to high binding affinity (+ 2 to + 3) to Concavalin A staining compared to NS isolates that demonstrated only 76% high lectin (+ 3) binding affinity. Cysteine and serine protease levels were predominantly found among SZ isolates. We also demonstrate the presence of metalloprotease in Blastocystis sp. especially among NS isolates. Introduction of solubilised antigens from SZ isolates increased the cell proliferation of HCT116 cells by two fold when compared to NS isolates. CONCLUSION: Our findings demonstrated Blastocystis sp. isolated from SZ individuals showed variation in phenotype specifically in morphology and drug resistance. The findings indicate that the gut environment (SZ and NS) and treatment of SZ could have influenced the phenotype of Blastocystis sp.


Assuntos
Infecções por Blastocystis , Blastocystis , Síndrome do Intestino Irritável , Blastocystis/genética , Infecções por Blastocystis/epidemiologia , Fezes , Humanos , Síndrome do Intestino Irritável/epidemiologia , Metronidazol/farmacologia , Metronidazol/uso terapêutico
16.
ChemMedChem ; 17(21): e202200341, 2022 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-36085254

RESUMO

From four focused compound libraries based on the known anticoccidial agent robenidine, 44 compounds total were synthesised and screened for antigiardial activity. All active compounds were counter-screened for antibiotic and cytotoxic action. Of the analogues examined, 21 displayed IC50 <5 µM, seven with IC50 <1.0 µM. Most active were 2,2'-bis{[4-(trifluoromethoxy)phenyl]methylene}carbonimidic dihydrazide hydrochloride (30), 2,2'-bis{[4-(trifluoromethylsulfanyl)phenyl]methylene}carbonimidic dihydrazide hydrochloride (32), and 2,2'-bis[(2-bromo-4,5-dimethoxyphenyl)methylene]carbonimidic dihydrazide hydrochloride (41) with IC50 =0.2 µM. The maximal observed activity was a 5 h IC50 value of 0.2 µM for 41. The clinically used metronidazole was inactive at this timepoint at a concentration of 25 µM. Robenidine off-target effects at bacteria and cell line toxicity were removed. Analogue 41 was well tolerated in mice treated orally (100 mg/kg). Following 5 h treatment with 41, no Giardia regrowth was noted after 48 h.


Assuntos
Guanidinas , Robenidina , Animais , Camundongos , Guanidina , Metronidazol/farmacologia , Antibacterianos/farmacologia
17.
PLoS Pathog ; 18(9): e1010840, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36166467

RESUMO

Giardia duodenalis causes giardiasis, a major diarrheal disease in humans worldwide whose treatment relies mainly on metronidazole (MTZ) and albendazole (ABZ). The emergence of ABZ resistance in this parasite has prompted studies to elucidate the molecular mechanisms underlying this phenomenon. G. duodenalis trophozoites convert ABZ into its sulfoxide (ABZSO) and sulfone (ABZSOO) forms, despite lacking canonical enzymes involved in these processes, such as cytochrome P450s (CYP450s) and flavin-containing monooxygenases (FMOs). This study aims to identify the enzyme responsible for ABZ metabolism and its role in ABZ resistance in G. duodenalis. We first determined that the iron-containing cofactor heme induces higher mRNA expression levels of flavohemoglobin (gFlHb) in Giardia trophozoites. Molecular docking analyses predict favorable interactions of gFlHb with ABZ, ABZSO and ABZSOO. Spectral analyses of recombinant gFlHb in the presence of ABZ, ABZSO and ABZSOO showed high affinities for each of these compounds with Kd values of 22.7, 19.1 and 23.8 nM respectively. ABZ and ABZSO enhanced gFlHb NADH oxidase activity (turnover number 14.5 min-1), whereas LC-MS/MS analyses of the reaction products showed that gFlHb slowly oxygenates ABZ into ABZSO at a much lower rate (turnover number 0.01 min-1). Further spectroscopic analyses showed that ABZ is indirectly oxidized to ABZSO by superoxide generated from the NADH oxidase activity of gFlHb. In a similar manner, the superoxide-generating enzyme xanthine oxidase was able to produce ABZSO in the presence of xanthine and ABZ. Interestingly, we find that gFlHb mRNA expression is lower in albendazole-resistant clones compared to those that are sensitive to this drug. Furthermore, all albendazole-resistant clones transfected to overexpress gFlHb displayed higher susceptibility to the drug than the parent clones. Collectively these findings indicate a role for gFlHb in ABZ conversion to its sulfoxide and that gFlHb down-regulation acts as a passive pharmacokinetic mechanism of resistance in this parasite.


Assuntos
Anti-Helmínticos , Giardia lamblia , Albendazol/química , Albendazol/farmacocinética , Animais , Anti-Helmínticos/farmacologia , Biotransformação , Cromatografia Líquida , Citocromos/metabolismo , Flavinas/metabolismo , Giardia lamblia/genética , Giardia lamblia/metabolismo , Heme/metabolismo , Humanos , Ferro , Metronidazol/farmacologia , Oxigenases de Função Mista/metabolismo , Simulação de Acoplamento Molecular , RNA Mensageiro/metabolismo , Sulfonas , Sulfóxidos/metabolismo , Superóxidos , Espectrometria de Massas em Tandem , Trofozoítos/metabolismo , Xantina Oxidase/metabolismo , Xantinas
18.
Parasitol Res ; 121(12): 3503-3512, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36171407

RESUMO

The parasite Trichomonas vaginalis is the aetiologic agent of trichomoniasis, the most common non-viral sexually transmitted disease worldwide. This infection often remains asymptomatic and is related to several health complications. The traditional treatment for trichomoniasis uses drugs of the 5-nitroimidazole family, such as metronidazole; however, scientific reports indicate an increasing number of drug-resistant strains. Antimicrobial peptides could be an alternative or complementary treatment. In this sense, one attractive candidate is the human cathelicidin, being LL-37 its active form. LL-37 possesses microbicidal activity against many microorganisms such as bacteria, Candida albicans, and Entamoeba histolytica. Shorter sequences derived from this peptide, such as KR-20, FK-13 and KR-12, have been shown to possess a higher microbicidal effect than LL-37. In this study, we determined the activity of LL-37 and its derivatives against T. vaginalis, which was unknown. The results showed that the four peptides (LL-37, KR-20, FK-13-NH2 and KR-12) decreased the viability of T. vaginalis on a 5-nitroimidazole-sensitive and a 5-nitroimidazole-resistant strain; however, KR-20 was the most effective peptide, followed by FK-13-NH2. Low concentrations of all peptides showed a better effect when combined with metronidazole in the sensitive and resistant T. vaginalis strains. These results are promising for potential future therapeutic uses.


Assuntos
Antiprotozoários , Tricomoníase , Trichomonas vaginalis , Humanos , Metronidazol/farmacologia , Peptídeos Antimicrobianos , Resistência a Medicamentos , Antiprotozoários/farmacologia
19.
Int J Infect Dis ; 124: 118-123, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36155825

RESUMO

Recently, the recommendations for the treatment of Clostridioides difficile infection (CDI) have been updated. However, in addition to the clinical efficacy data, the drug of choice should ideally represent optimal antimicrobial stewardship, with an emphasis on rapid restoration of the gut microbiota to minimize the risk of infection relapses. Oral administration of metronidazole results in low concentration in stool, and interaction with fecal microbiota reduces its antimicrobial bioactivity. Reported elevated minimum inhibitory concentrations of metronidazole in epidemic C. difficile ribotypes and the emergence of plasmid-mediated resistance to metronidazole represent additional potential risks for clinical failure. If metronidazole is the only CDI treatment option, antimicrobial susceptibility testing on agar containing heme should be performed in C. difficile isolate. Compared with metronidazole, oral vancomycin and fidaxomicin reach very high concentrations in the stool, and therefore can quickly reduce C. difficile shedding. Health care facilities with higher CDI incidence and/or occurrence of epidemic ribotypes should not use metronidazole because prolonged C. difficile shedding can increase the risk for further C. difficile transmission. Only fidaxomicin has a narrow spectrum of antimicrobial activity, which might be, together with persistence on spores, the main contributing factor to reduce the recurrent CDI rates.


Assuntos
Clostridioides difficile , Infecções por Clostridium , Humanos , Fidaxomicina/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Metronidazol/farmacologia , Metronidazol/uso terapêutico , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/epidemiologia , Infecções por Clostridium/microbiologia
20.
Helicobacter ; 27(6): e12930, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36156332

RESUMO

BACKGROUND & AIMS: Antibiotic resistance of Helicobacter pylori (H. pylori) is increasing worldwide, and bismuth quadruple therapy has been recommended as a first-line regimen in many areas. This study aimed to investigate whether bismuth would improve the eradication rate (ER) of clarithromycin-/metronidazole-/levofloxacin-resistant H. pylori strains and how much additional efficacy bismuth could achieve. METHODS: PubMed, EMBASE, Web of Science, and Cochrane Central databases for randomized controlled trials were systematically searched by two independent reviewers until 15 January 2022. Pooled ERs of clarithromycin-/metronidazole-/levofloxacin-resistant H. pylori strains were compared between bismuth-containing and non-bismuth therapies. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model. RESULTS: Eight studies enrolling 340 individuals were included. The RRs of pooled ERs compared between bismuth-containing and non-bismuth therapies were 1.83 for clarithromycin-resistant strains (95% CI 1.16-2.89, pooled ER: 76.9% vs. 36.6%, p = .009, I2  = 0%), 1.39 for metronidazole-resistant strains (95% CI 1.09-1.78, pooled ER: 86.8% vs. 60.9%, p = .008, I2  = 37%), 2.75 for dual clarithromycin/metronidazole-resistant strains (95% CI 1.01-7.52, pooled ER: 76.9% vs. 18.2%, p = .05, I2  = 0%), and 1.04 for levofloxacin-resistant strains (95% CI 0.56-1.93, pooled ER: 63.4% vs. 54.3%, p = .90; I2  = 60%). Bismuth significantly increased the ERs of clarithromycin-, metronidazole-, and dual-resistant strains by 40%, 26%, and 59%, respectively. Subgroup analysis of treatment duration showed that the significantly higher eradication rate for antibiotic-resistant strains in bismuth-containing therapy than non-bismuth therapy was only observed in 14-day treatment regimens and not in 7-day regimens (p = .02 and .17, respectively). CONCLUSIONS: Bismuth was most effective in improving the ERs of dual-resistant H. pylori strains, followed by clarithromycin- and metronidazole-resistant strains. Prolonged treatment duration might effectively improve the efficacy of bismuth in overcoming antibiotic resistance.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Humanos , Bismuto/farmacologia , Bismuto/uso terapêutico , Claritromicina/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Metronidazol/farmacologia , Metronidazol/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Levofloxacino/uso terapêutico , Quimioterapia Combinada , Amoxicilina/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...