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INTRODUCTION: Bacteria and their byproducts are key contributors to the onset and perpetuation of pulpoperiapical pathosis. Intracanal medication is vital in achieving successful endodontic outcomes as it targets and eradicates remaining microorganisms following biomechanical preparation. AIM AND OBJECTIVE: The aim of the study was to compare and evaluate the antimicrobial efficacy of calcium hydroxide (CH) paste, triple antibiotic paste (TAP), and probiotics (PBs) as intracanal medicament in 12-17-year-old children undergoing root canal treatment for the management of infected pulpal tissues in young permanent teeth. MATERIALS AND METHODS: A total of 30 patients aged 12-17 years indicated for endodontic therapy in maxillary incisors and with no systemic complications were selected. They were randomly divided into three groups, i.e., Group I - CH group, Group II - TAP, and Group III - PB allocating 10 teeth in each group. After access opening, the first sample (S1) was collected by inserting a paper point into the root canal, the second sample (S2) was collected immediately after biomechanical preparation, and the third sample (S3) was collected after 7 days, i.e., postintracanal medication. Samples were sent for microbiological analysis to assess the microbial count, and statistical analysis was done for the obtained data. RESULTS: The three intracanal medicaments were successful in reducing the microbial counts of Enterococcus faecalis in the infected root canals. However, according to the results of the study, the PB group demonstrated greater effectiveness against E. faecalis compared to the CH group and displayed similar antimicrobial efficacy as the TAP group. CONCLUSION: PB exhibited antimicrobial efficacy comparable to TAP but greater than Ca (OH) 2 paste. Hence, PB can be utilized as an intracanal medicament in young permanent teeth.
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Antibacterianos , Hidróxido de Calcio , Irrigantes del Conducto Radicular , Humanos , Adolescente , Niño , Hidróxido de Calcio/uso terapéutico , Hidróxido de Calcio/farmacología , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Irrigantes del Conducto Radicular/farmacología , Irrigantes del Conducto Radicular/uso terapéutico , Probióticos/uso terapéutico , Dentición Permanente , Ciprofloxacina/farmacología , Ciprofloxacina/uso terapéutico , Incisivo , Masculino , Metronidazol/farmacología , Metronidazol/uso terapéutico , Femenino , Tratamiento del Conducto Radicular/métodos , Combinación de MedicamentosRESUMEN
Objective: This study aimed to evaluate antibiotic susceptibility and antimicrobial resistance trends among clinically significant anaerobes in Kuwait hospitals from 2013 to 2022, comparing these findings with data from 2002 to 2012. Methods: The study prospectively collected 2,317 anaerobic isolates from various body sites across four Kuwaiti hospitals between January 2013 and December 2022. The minimum inhibitory concentrations for 11 antianaerobic antibiotics were determined using E-test methodology. The study analyzed trends and resistance rates across two periods: 2013-2017 and 2018-2022, using statistical analysis for resistance comparison. Results: Of the 2,317 isolates, most were from wounds (42.2%), fluids (28.0%), and tissues (20.5%). Bacteroides fragilis was the most common pathogen (34.0%), followed by Prevotella bivia (13.4%). Over 90% of isolates were susceptible to imipenem, meropenem, tigecycline, and metronidazole, whereas lower susceptibility was observed for penicillin, amoxicillin-clavulanic acid, and clindamycin. Notable differences in resistance profiles since 2002 were observed, especially in amoxicillin-clavulanic acid, piperacillin, piperacillin-tazobactam, and clindamycin. Conclusion: Owing to detected resistance to all antibiotics, susceptibility testing for anaerobic isolates is recommended in severe infections to ensure effective antimicrobial therapy. Continuous surveillance is crucial for developing antibiotic policies to manage invasive anaerobic infections.
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Antibacterianos , Bacterias Anaerobias , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Bacterias Anaerobias/efectos de los fármacos , Kuwait/epidemiología , Humanos , Estudios Prospectivos , Tigeciclina/farmacología , Farmacorresistencia Bacteriana , Bacteroides fragilis/efectos de los fármacos , Bacteroides fragilis/aislamiento & purificación , Metronidazol/farmacología , Metronidazol/uso terapéuticoRESUMEN
OBJECTIVE: To describe antibiotic prescription patterns in the emergency department (ED) of a tertiary healthcare center in Nepal. METHODS: This was a descriptive cross-sectional study of hospital records of patients who visited the ED. RESULTS: Of the 758 ED patients included in the study, 384 (50.6%) received a total of 536 antibiotic prescriptions. Common indications for antibiotic prescriptions included respiratory infection (37.5%), gastrointestinal infection (19.3%), urinary infection (10.4%), and prophylaxis (29.9%). Antibiotics listed as essential in the National List of Essential Medicines (NLEM) and generic formulations were used in 77.1% and 61.9% of the antibiotic prescriptions, respectively. Injectable antibiotics were prescribed to 54.9% of the 384 patients. Frequently prescribed antibiotics included ceftriaxone (34.1%), metronidazole (18.5%), amoxicillin + clavulanic acid (15.9%), and cefixime (14.3%). Bacterial culture testing was performed in 15.1% of the patients who received antibiotics. CONCLUSIONS: This study showed that overuse of antibiotics, prescription of branded antibiotics, prescription of antibiotics not listed in the NLEM, prophylactic use of antibiotics, and empirical treatment of suspected infections without isolation of pathogens were all prevalent. We recommend more research to determine the causes underlying these practices and develop interventions to limit such practices.
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Antibacterianos , Servicio de Urgencia en Hospital , Centros de Atención Terciaria , Humanos , Nepal , Antibacterianos/uso terapéutico , Estudios Transversales , Centros de Atención Terciaria/estadística & datos numéricos , Servicio de Urgencia en Hospital/estadística & datos numéricos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Adolescente , Pautas de la Práctica en Medicina/estadística & datos numéricos , Adulto Joven , Prescripciones de Medicamentos/estadística & datos numéricos , Anciano , Niño , Ceftriaxona/uso terapéutico , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Metronidazol/uso terapéutico , Preescolar , Cefixima/uso terapéuticoRESUMEN
BACKGROUND: We compared efficacy of vonoprazan-dual or triple therapies and bismuth-quadruple therapy for treatment-naive Helicobacter pylori (HP) infection in Southern China, where primary resistance rates of clarithromycin and levofloxacin are >30%. METHODS: This was an investigator-initiated, three-arm, randomized clinical trial in Southern China. Between March 2022 and August 2023, treatment-naïve HP-infected adults were randomly assigned to receive one of three 14-day regimens (1:1:1 ratio): vonoprazan-dual (VA-dual; vonoprazan 20 mg twice daily and amoxicillin 1 g thrice daily), vonoprazan-triple (VAC-triple; vonoprazan 20 mg/amoxicillin 1 g/clarithromycin 500 mg twice daily), or bismuth-quadruple therapy containing bismuth, esomeprazole, tetracycline, and metronidazole. Primary outcome was noninferiority in HP eradication, evaluated by UBT 4-6 weeks post-treatment by intention-to-treat (ITT) and per-protocol (PP) analysis (based on subjects who completed 14-day treatment and rechecked UBT). Bonferroni-adjusted p-value of <0.017 was used to determine statistical significance. RESULTS: A total of 298 subjects (mean age: 35.7 ± 8.4 years; male: 134 [45.0%]; VC-dual: 100, VAC-triple: 98, bismuth-quadruple: 100) were enrolled, and 292 (98.0%) had UBT rechecked. ITT analysis showed that both VA-dual (eradication rate of 96.0%) and VAC-triple therapies (95.9%) were noninferior to bismuth-quadruple therapy (92.0%) (difference: 4.0%, 95% CI: -2.9% to 11.5%, p < 0.001; and 3.9%, 95% CI: -3.1% to 11.5%, p < 0.001, respectively). PP analysis also revealed noninferiority (96.7% or 96.7% vs. 97.4%, with difference: -2.9% and -2.9%, p = 0.009 and 0.010, respectively). The frequency of adverse events was 39.0%, 56.1%, and 71.0% in VA-dual, VAC-triple, and bismuth-quadruple therapies, respectively. CONCLUSIONS: VA-dual and VA-triple therapies are highly effective and noninferior to bismuth-quadruple therapy in Southern China. Given the lower adverse effects and fewer antibiotic use, VA-dual therapy is the preferred first-line treatment for HP infection. TRIAL REGISTRATION: Chinese Clinical Trial Registry (No. ChiCTR2200056375). Registered on February 4, 2022, https://www.chictr.org.cn/showproj.aspx?proj=14131.
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Antibacterianos , Bismuto , Quimioterapia Combinada , Infecciones por Helicobacter , Helicobacter pylori , Pirroles , Sulfonamidas , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Sulfonamidas/uso terapéutico , Sulfonamidas/administración & dosificación , Masculino , Femenino , Persona de Mediana Edad , Adulto , Helicobacter pylori/efectos de los fármacos , Bismuto/uso terapéutico , Pirroles/uso terapéutico , Pirroles/administración & dosificación , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , China , Resultado del Tratamiento , Claritromicina/uso terapéutico , Amoxicilina/uso terapéutico , Amoxicilina/administración & dosificación , Metronidazol/uso terapéutico , Inhibidores de la Bomba de Protones/uso terapéutico , Adulto Joven , Esomeprazol/uso terapéutico , Esomeprazol/administración & dosificaciónRESUMEN
BACKGROUND: Metronidazole is a first-line antibiotic to treat Helicobacter pylori infections. However, the Clinical Laboratory Standards Institute guidelines recommend against using antimicrobial susceptibility test (AST) to test metronidazole resistance, due to the unreliable predictive power which can result in treatment failure. OBJECTIVES: The aim of this study was to establish an 8-h, metabolic-phenotype based AST for H. pylori metronidazole susceptibility using D2O-probed Raman microspectroscopy. METHODS: Minimal inhibitory concentration (MIC) measured by conventional AST (E-test) were compared with expedited MIC via metabolic activity (eMIC-MA) for 10 H. pylori isolates. Raman barcodes of cellular-response to stress (RBCS) incorporating protein and carbohydrate Raman bands, were utilized to identify a biomarker to distinguish metronidazole susceptibility. RESULTS: Specifically, eMIC-MA produces metronidazole susceptibility results showing 100% agreement with E-test, and determines the bactericidal dosage for both high- and low-level resistant H. pylori strains. In addition, RBCS not just reliably distinguish between metronidazole-susceptible and -resistant strains, but reveal their distinct mechanisms in bacterial responses to metronidazole. CONCLUSION: The speed, accuracy, low cost, and rich information content that reveals the mode-of-action of drugs suggest the method's value in guiding metronidazole prescriptions for H. pylori eradication and in rapid screening based on drug-resistance mechanism.
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Antibacterianos , Infecciones por Helicobacter , Helicobacter pylori , Metronidazol , Pruebas de Sensibilidad Microbiana , Espectrometría Raman , Helicobacter pylori/efectos de los fármacos , Metronidazol/farmacología , Espectrometría Raman/métodos , Pruebas de Sensibilidad Microbiana/métodos , Humanos , Antibacterianos/farmacología , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/diagnóstico , Análisis de la Célula Individual/métodos , Farmacorresistencia BacterianaRESUMEN
Introduction: The decreasing Helicobacter pylori eradication rate is primarily attributed to antibiotic resistance, and further exacerbated by uniform drug administration disregarding a host's metabolic capability. Consequently, applying personalized treatment based on antibiotic resistance-associated variants and the host's metabolic phenotype can potentially increase the eradication rate. Method: A custom next-generation sequencing panel for personalized H. pylori eradication treatment (NGS-PHET) was designed which targeted the regions for amoxicillin, clarithromycin, metronidazole, tetracycline, and levofloxacin-resistance in H. pylori and human proton-pump inhibitor (PPI) metabolism. The libraries were constructed following customized methods and sequenced simultaneously. The customized framework criteria, grounded in previously reported antibiotic resistance associated variants and the host's PPI metabolism, was applied to the NGS-PHET results and suggested a personalized treatment for each subject, which was validated through each subject's actual eradication outcome. Results: Both previously reported and novel variants were identified from H. pylori sequencing results. Concurrently, five CYP2C19 homozygous extensive metabolizers and three CYP3A4 intermediate metabolizers were identified. Among the total of 12 subjects, clarithromycin triple therapy was suggested for five subjects, bismuth quadruple therapy was suggested for six subjects, and rifabutin triple therapy was suggested for one subject by following the customized framework criteria. The treatment suggestion for nine of the 12 subjects was consistent with the treatment that each subject achieved eradication with. Discussion: Applying the methodology using the NGS-PHET and customized framework helps to perform eradication treatment quickly and effectively in most patients with antibiotic-resistant H. pylori strains, and is also useful in research to find novel antibiotic-resistance candidates.
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Antibacterianos , Infecciones por Helicobacter , Helicobacter pylori , Secuenciación de Nucleótidos de Alto Rendimiento , Medicina de Precisión , Humanos , Helicobacter pylori/efectos de los fármacos , Helicobacter pylori/genética , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/microbiología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Medicina de Precisión/métodos , Inhibidores de la Bomba de Protones/uso terapéutico , Claritromicina/farmacología , Claritromicina/uso terapéutico , Masculino , Farmacorresistencia Bacteriana/genética , Persona de Mediana Edad , Femenino , Adulto , Quimioterapia Combinada , Metronidazol/farmacología , Metronidazol/uso terapéutico , Amoxicilina/uso terapéutico , Amoxicilina/farmacología , Citocromo P-450 CYP2C19/genética , Pruebas de Sensibilidad Microbiana , Levofloxacino/farmacología , Levofloxacino/uso terapéutico , Tetraciclina/farmacología , Tetraciclina/uso terapéutico , Resultado del TratamientoRESUMEN
Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare, benign, vasoproliferative tumour. We report a 25-year-old female patient who reported in 2021 to a dermatology clinic in Rustaq, Oman, with multiple, grouped, erythematous dome-shaped papules and nodules of 6 months duration on the left temporo-occipital region. Biopsy findings were consistent with a diagnosis of ALHE with evidence of Demodex mite infestation in the sebaceous ducts. The patient demonstrated significant improvement following 7 weeks of treatment with multiple cryotherapy sessions and topical application of metronidazole gel. This case suggests that scalp demodicosis may represent a novel trigger for the development of ALHE.
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Hiperplasia Angiolinfoide con Eosinofilia , Crioterapia , Metronidazol , Infestaciones por Ácaros , Humanos , Femenino , Adulto , Crioterapia/métodos , Metronidazol/uso terapéutico , Infestaciones por Ácaros/tratamiento farmacológico , Hiperplasia Angiolinfoide con Eosinofilia/tratamiento farmacológico , Hiperplasia Angiolinfoide con Eosinofilia/diagnóstico , Omán , Administración Tópica , Cuero CabelludoRESUMEN
The understanding of how central metabolism and fermentation pathways regulate antimicrobial susceptibility in the anaerobic pathogen Bacteroides fragilis is still incomplete. Our study reveals that B. fragilis encodes two iron-dependent, redox-sensitive regulatory pirin protein genes, pir1 and pir2. The mRNA expression of these genes increases when exposed to oxygen and during growth in iron-limiting conditions. These proteins, Pir1 and Pir2, influence the production of short-chain fatty acids and modify the susceptibility to metronidazole and amixicile, a new inhibitor of pyruvate: ferredoxin oxidoreductase in anaerobes. We have demonstrated that Pir1 and Pir2 interact directly with this oxidoreductase, as confirmed by two-hybrid system assays. Furthermore, structural analysis using AlphaFold2 predicts that Pir1 and Pir2 interact stably with several central metabolism enzymes, including the 2-ketoglutarate:ferredoxin oxidoreductases Kor1AB and Kor2CDAEBG. We used a series of metabolic mutants and electron transport chain inhibitors to demonstrate the extensive impact of bacterial metabolism on metronidazole and amixicile susceptibility. We also show that amixicile is an effective antimicrobial against B. fragilis in an experimental model of intra-abdominal infection. Our investigation led to the discovery that the kor2AEBG genes are essential for growth and have dual functions, including the formation of 2-ketoglutarate via the reverse TCA cycle. However, the metabolic activity that bypasses the function of Kor2AEBG following the addition of phospholipids or fatty acids remains undefined. Overall, our study provides new insights into the central metabolism of B. fragilis and its regulation by pirin proteins, which could be exploited for the development of new narrow-spectrum antimicrobials in the future.
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Antibacterianos , Bacteroides fragilis , Metronidazol , Bacteroides fragilis/genética , Bacteroides fragilis/efectos de los fármacos , Bacteroides fragilis/enzimología , Bacteroides fragilis/metabolismo , Metronidazol/farmacología , Metronidazol/metabolismo , Antibacterianos/farmacología , Antibacterianos/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Pruebas de Sensibilidad Microbiana , Regulación Bacteriana de la Expresión GénicaRESUMEN
The present investigation aimed to quantitatively assess the level of parasitemia in dogs using qPCR.The dogs selected for this study were infected with the haemoprotozoan parasite Babesia gibsoni. In the study, dogs diagnosed with babesiosis were divided into two groups (n = 12) and subjected to distinct treatment strategies. The first group received clindamycin-metronidazole-doxycycline (CMD) therapy, while the second group was treated with a combination of buparvaquone-azithromycin (BPV-AZM). The level of parasitemia in the infected dogs was determined using an absolute quantification-based qPCR method. This assessment was conducted both prior to initiating the treatment and on the 10th day following the commencement of the treatment protocols. On the tenth day after the initiation of treatment, the CMD group exhibited a lower level of parasitemia in comparison to the BPV-AZM group. In the CMD treated groups, the mean parasitemia decreased from 4.9E + 06 to 3.4E + 06, indicating a reduction in parasitic load. Conversely, in the BPV-AZM treatment groups, the mean parasitemia increased from 1.62E + 06 to 2.87E + 06, suggesting an increase in parasitic load. On the 10th day, the CMD-treated group demonstrated a statistically significant decline in the level of parasitemia, with a P-value of ≤0.001. This indicates a strong and significant reduction in parasitic load following the CMD treatment. Therefore, the absolute quantification-based qPCR method could effectively assess the initial treatment response by measuring the level of parasitemia.
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Babesia , Babesiosis , Clindamicina , Enfermedades de los Perros , Carga de Parásitos , Parasitemia , Reacción en Cadena en Tiempo Real de la Polimerasa , Animales , Perros , Enfermedades de los Perros/parasitología , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/tratamiento farmacológico , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Babesia/genética , Babesia/aislamiento & purificación , Parasitemia/parasitología , Parasitemia/veterinaria , Babesiosis/parasitología , Babesiosis/diagnóstico , Clindamicina/uso terapéutico , Carga de Parásitos/métodos , Doxiciclina/uso terapéutico , Azitromicina/uso terapéutico , Metronidazol/uso terapéutico , Antiprotozoarios/uso terapéutico , NaftoquinonasRESUMEN
Excisional haemorrhoidectomy is the gold standard for operating haemorrhoids, but it is accompanied by a significant problem: postoperative pain. Several strategies have been adopted to minimize this condition. Oral metronidazole has been proven to reduce postoperative pain but with some complications. This systematic review was conducted to investigate the effects and general efficacy of topical metronidazole administration and to evaluate its potential superiority over the oral formula. A systematic review of the literature was carried out. Randomized controlled trials published until September 2023 on PubMed, Central, and Web of Science were considered. The primary outcome considered was postoperative pain, which was evaluated using visual analogue scores. The secondary outcomes were analgesic use, return to work, and complications. Six randomized controlled trials were included, with a total of 536 patients. Topical metronidazole was compared with placebo in two studies, with oral formula in three studies, and with placebo and oral administration in one study. Topical metronidazole was found to be effective for treating postoperative pain when compared to a placebo but had no significant advantage over the oral formula. No complications were reported in the studies. Topical and oral metronidazole are effective solutions for postoperative pain after excisional haemorrhoidectomy. No superiority was demonstrated based on the route of administration, and complications were marginal for both formulas. Further studies are required to determine the best metronidazole solution.
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Hemorreoidectomía , Metronidazol , Dolor Postoperatorio , Humanos , Administración Oral , Administración Tópica , Hemorreoidectomía/métodos , Hemorreoidectomía/efectos adversos , Hemorroides/cirugía , Metronidazol/administración & dosificación , Dimensión del Dolor , Dolor Postoperatorio/prevención & control , Dolor Postoperatorio/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
Bacterial vaginosis (BV) is an imbalance of the vaginal microbiome in which there are limited lactobacilli and an overgrowth of anaerobic and fastidious bacteria such as Gardnerella. The propensity for BV recurrence is high, and therapies involving multiple treatment modalities are emerging to meet this need. However, current treatments requiring frequent therapeutic administration are challenging for patients and impact user compliance. Three-dimensional (3D)-printing offers a novel alternative to customize platforms to facilitate sustained therapeutic delivery to the vaginal tract. This study designed a novel vehicle intended for dual sustained delivery of both antibiotic and probiotic. 3D-printed compartmental scaffolds consisting of an antibiotic-containing silicone shell and a core containing probiotic Lactobacillus were developed with multiple formulations including biomaterials sodium alginate (SA), polyethylene glycol (PEG), polyvinyl alcohol (PVA), polyethylene oxide (PEO), and kappa-carrageenan (KC). The vehicles were loaded with 50 µg of metronidazole/mg polymer and 5 × 107 CFU of L. crispatus/mg scaffold. Metronidazole-containing shells exhibited cumulative drug release of 324.2 ± 31.2 µg/mL after 14 days. Multiple polymeric formulations for the probiotic core demonstrated cumulative L. crispatus recovery of >5 × 107 CFU/mg scaffold during this timeframe. L. crispatus-loaded polymeric formulations exhibited ≥2 log CFU/mL reduction in free Gardnerella in the presence of VK2/E6E7 vaginal epithelial cells. As a first step towards the goal of facilitating patient compliance, this study demonstrates in vitro effect of a novel 3D-printed dual antibiotic and probiotic delivery platform to target BV.
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Lactobacillus crispatus , Metronidazol , Impresión Tridimensional , Probióticos , Siliconas , Humanos , Siliconas/química , Metronidazol/farmacología , Metronidazol/administración & dosificación , Metronidazol/química , Femenino , Probióticos/administración & dosificación , Vaginosis Bacteriana/tratamiento farmacológico , Vaginosis Bacteriana/microbiología , Vaginosis Bacteriana/terapia , Antibacterianos/farmacología , Antibacterianos/administración & dosificación , Antibacterianos/química , Preparaciones de Acción Retardada , Liberación de Fármacos , Sistemas de Liberación de Medicamentos/métodosRESUMEN
Trichomonas vaginalis is the etiologic agent of trichomoniasis, a worldwide distributed sexually transmitted infection (STI) that affects the genitourinary tract. Even though this disease already has a treatment in the prescription of drugs of the 5-nitroimidazole class, described low treatments adhesion, adverse side effects and cases of resistant isolates demonstrate the need for new formulations. With this in mind, chalcones emerge as a potential alternative to be tested, being compounds widely distributed in nature, easy to chemically synthesize and presenting several biological activities already reported. In this experiment, we evaluated the antiparasitic activity of 10 chalcone at a concentration of 100 µM against ATCC 30236 T. vaginalis isolates, considering negative (live trophozoites), positive (Metronidazole 100 µM) and vehicle (DMSO 0.6%) controls. Compounds 3a, 3c, 3 g and 3i showed promising results, with MICs set at 70 µM, 80 µM, 90 µM and 90 µM, respectively (p < 0,05). Cytotoxicity assays were performed on VERO and HMVII cell lines and revealed low inhibition rates at concentrations bellow 20 µM. To elucidate a possible mechanism of action for these molecules, the DPPH, ABTS and FRAP assays were performed, in which none of the four compounds presented antioxidant activity. Assays to verify ROS and lipid peroxidation in the parasite membrane were performed. None of the tested compounds identified ROS accumulation after incubation with trophozoites. 3 g molecule promoted an increase in MDA production after incubation. Results presented in this paper demonstrate the promising trichomonicidal profile, although further tests are still needed to optimize their performance and better elucidate the mechanisms of action involved.
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Chalconas , Trichomonas vaginalis , Trichomonas vaginalis/efectos de los fármacos , Animales , Chalconas/farmacología , Chalconas/química , Chlorocebus aethiops , Células Vero , Humanos , Línea Celular , Especies Reactivas de Oxígeno/metabolismo , Metronidazol/farmacología , Peroxidación de Lípido/efectos de los fármacos , Pruebas de Sensibilidad MicrobianaRESUMEN
BACKGROUND: Giardiasis, caused by the protozoan parasite Giardia intestinalis, often presents a treatment challenge, particularly in terms of resistance to metronidazole. Despite extensive research, markers for metronidazole resistance have not yet been identified. METHODS: This study analysed 28 clinical samples of G. intestinalis from sub-assemblage AII, characterised by varying responses to metronidazole treatment. We focussed on copy number variation (CNV) of the multi-copy flavohemoprotein gene, analysed using digital polymerase chain reaction (dPCR) and next generation sequencing (NGS). Additionally, chromosomal ploidy was tested in 18 of these samples. Flavohemoprotein CNV was also assessed in 17 samples from other sub-assemblages. RESULTS: Analyses revealed variable CNVs of the flavohemoprotein gene among the isolates, with no correlation to clinical metronidazole resistance. Discrepancies in CNVs detected from NGS data were attributed to biases linked to the whole genome amplification. However, dPCR helped to clarify these discrepancies by providing more consistent CNV data. Significant differences in flavohemoprotein CNVs were observed across different G. intestinalis sub-assemblages. Notably, Giardia exhibits a propensity for aneuploidy, contributing to genomic variability within and between sub-assemblages. CONCLUSIONS: The complexity of the clinical metronidazole resistance in Giardia is influenced by multiple genetic factors, including CNVs and aneuploidy. No significant differences in the CNV of the flavohemoprotein gene between isolates from metronidazole-resistant and metronidazole-sensitive cases of giardiasis were found, underscoring the need for further research to identify reliable genetic markers for resistance. We demonstrate that dPCR and NGS are robust methods for analysing CNVs and provide cross-validating results, highlighting their utility in the genetic analyses of this parasite.
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Antiprotozoarios , Variaciones en el Número de Copia de ADN , Resistencia a Medicamentos , Giardia lamblia , Giardiasis , Metronidazol , Giardia lamblia/genética , Giardia lamblia/efectos de los fármacos , Metronidazol/farmacología , Resistencia a Medicamentos/genética , Humanos , Giardiasis/parasitología , Giardiasis/tratamiento farmacológico , Antiprotozoarios/farmacología , Secuenciación de Nucleótidos de Alto Rendimiento , Proteínas Protozoarias/genéticaRESUMEN
Background: Helicobacter pylori (Hp) infection predisposes to malignant and non-malignant diseases warranting eradication. In Belgium, resistance rates for clarithromycin demonstrate regional variations making the use of standard triple therapy (STT) borderline acceptable. According to a recent Belgian survey, STT and bismuth-based quadruple therapy (BQT), are equally frequent prescribed as first line treatment for treatment naïve Hp positive patients. This study aims to evaluate the eradication rates (ER) of BQT versus STT. Methods: Multicentre, non-blinded randomized, prospective study comparing ER in treatment-naïve Hp positive patients. ER were compared by intention to treat (ITT) and per protocol (PP) analysis. Results: Overall 250 patients were included (STT 126, BQT 124). Seventeen patients were lost to follow-up (6,8%). No significant difference in ER between BQT and STT was observed in ITT (73% vs 68%, p= 0,54) neither in PP analysis (81% vs 75%, p= 0,33). Side effects and endoscopic findings were comparable between groups. Post-hoc analysis showed no differences according to gender or site allocation. Conclusion: The numerical advantage of BQT did not translate in a significant improvement of ER when compared with STT. These results question the cost-effectiveness of BQT, while confirming the suboptimal eradication rates on STT. A nationwide monitoring of resistance patterns, maximal investments in treatment adherence as well as a detailed follow-up of the changing treatment landscape are mandatory to continuously optimise Hp ER in Belgium.
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Antibacterianos , Bismuto , Quimioterapia Combinada , Infecciones por Helicobacter , Helicobacter pylori , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Femenino , Masculino , Bélgica , Helicobacter pylori/efectos de los fármacos , Persona de Mediana Edad , Bismuto/uso terapéutico , Estudios Prospectivos , Antibacterianos/uso terapéutico , Adulto , Inhibidores de la Bomba de Protones/uso terapéutico , Inhibidores de la Bomba de Protones/administración & dosificación , Anciano , Claritromicina/uso terapéutico , Amoxicilina/uso terapéutico , Amoxicilina/administración & dosificación , Metronidazol/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND AND AIM: Bismuth and non-bismuth quadruple therapy are the guideline-recommended first-line therapy in children with Helicobacter pylori infection in areas with high antibiotic resistance. However, their efficacy in children is uncertain and there are few well-designed studies. Here, we evaluated the eradication rates of standard triple therapy, bismuth-based quadruple therapy and sequential therapy in children with H. pylori infection. METHODS: A randomised controlled trial was conducted in children infected with H. pylori in West China Second Hospital. They were randomly assigned to 14-day standard triple therapy (omeprazole + amoxicillin + clarithromycin), 14-day bismuth quadruple therapy (bismuth + omeprazole + amoxicillin + clarithromycin) and 10-day sequential therapy (omeprazole + amoxicillin for 5 days followed by omeprazole + clarithromycin + metronidazole for 5 days). The eradication rate was assessed by a 13C-urea breath test 4 to 6 weeks after therapy completion. Symptom improvement and adverse events were compared among the groups. RESULTS: In total, 132 patients were enrolled. The eradication rates of 14-day standard triple therapy, 14-day bismuth quadruple therapy and 10-day sequential therapy were 70.0%, 78.9% and 50.0% in per-protocol analysis and 63.6%, 68.2% and 43.2% in intention-to-treat analysis, respectively. Symptom improvement and adverse drug event rates were similar in the three groups. CONCLUSION: The three therapeutic regimens evaluated in this study are equally not recommendable for H. pylori infection treatment due to unsatisfactory eradication rates. The high prevalence of clarithromycin resistance makes the use of clarithromycin-based quadruple therapy not advisable, even in combination with amoxicillin and bismuth salts.
Asunto(s)
Amoxicilina , Antibacterianos , Bismuto , Claritromicina , Quimioterapia Combinada , Infecciones por Helicobacter , Helicobacter pylori , Metronidazol , Omeprazol , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Femenino , Masculino , Niño , Omeprazol/administración & dosificación , Omeprazol/uso terapéutico , Metronidazol/administración & dosificación , Metronidazol/uso terapéutico , Amoxicilina/administración & dosificación , Claritromicina/administración & dosificación , Claritromicina/uso terapéutico , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Bismuto/administración & dosificación , Bismuto/uso terapéutico , Adolescente , Resultado del Tratamiento , Esquema de Medicación , Preescolar , Pruebas Respiratorias , Inhibidores de la Bomba de Protones/administración & dosificación , Inhibidores de la Bomba de Protones/uso terapéuticoRESUMEN
BACKGROUND: The optimal duration of regimens for tailored therapy based on genotypic resistance for clarithromycin has yet to be established. AIM: This study was a nationwide, multicenter, randomized trial comparing empirical therapy with tailored therapy based on genotypic resistance for first-line eradication of Helicobacter pylori. We also compared the eradication rates of 7- and 14-day regimens for each group. PATIENTS AND METHODS: Patients with H. pylori infection were first randomized to receive empirical or tailored therapy. Patients in each group were further randomized into 7- or 14-day regimens. Empirical therapy consisted of a triple therapy (TT) regimen (twice-daily doses of pantoprazole 40 mg, amoxicillin 1 g, and clarithromycin 500 mg) for 7 or 14 days. Tailored therapy consisted of TT of 7 or 14 days in patients without genotypic resistance. Patients with genotypic resistance were treated with bismuth quadruple therapy (BQT) regimens (twice-daily doses of pantoprazole 40 mg, three daily doses of metronidazole 500 mg, and four times daily doses of bismuth 300 mg and tetracycline 500 mg) for 7 or 14 days. A 13C-urea breath test assessed eradication rates. The primary outcome was eradication rates of each group. RESULTS: A total of 593 patients were included in the study. The eradication rates were 65.7% (201/306) in the empirical therapy group and 81.9% (235/287) in the tailored therapy group for intention-to-treat analysis (p < 0.001). In the per-protocol analysis, the eradication rates of the empirical therapy and tailored groups were 70.3% (201/286) and 85.5% (235/274) (p < 0.001), respectively. There was no difference in compliance between the two groups. The rate of adverse events was higher in the tailored group compared to the empirical group (p < 0.001). DISCUSSION: Our study confirmed that tailored therapy based on genotypic resistance was more effective than empirical therapy for H. pylori eradication in Korea. However, no significant difference was found between 7- and 14-day regimens for each group. Future studies are needed to determine the optimal duration of therapy for empirical and tailored therapy regimens.
Asunto(s)
Antibacterianos , Quimioterapia Combinada , Infecciones por Helicobacter , Helicobacter pylori , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/microbiología , Helicobacter pylori/efectos de los fármacos , Helicobacter pylori/genética , Masculino , Femenino , Persona de Mediana Edad , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , República de Corea , Adulto , Anciano , Resultado del Tratamiento , Farmacorresistencia Bacteriana , Amoxicilina/uso terapéutico , Amoxicilina/administración & dosificación , Claritromicina/uso terapéutico , Metronidazol/uso terapéutico , Pantoprazol/uso terapéutico , Genotipo , Adulto JovenRESUMEN
The presence of metronidazole (MNZ) and acetaminophen (ACE) in aquatic environments has raised growing concerns regarding their potential impact on human health. Incorporating various patterns into a photocatalytic material is considered a critical approach to achieving enhanced photocatalytic efficiency in the photocatalysis process. In this study, WO3 nanoparticles, which were immobilized onto ferromagnetic multi-walled carbon nanotubes that were functionalized using (3-glycidyloxypropyl)trimethoxysilane (FMMWCNTs@GLYMO@WO3), exhibited remarkable efficiency in removing MNZ and ACE (93% and 97%) in only 15 min. In addition, the new visible-light FMMWCNTs@GLYMO@WO3 nanoparticles as a magnetically separable photocatalyst were characterized by Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction analysis (XRD), transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectroscopy (EDS), EDS-mapping, vibrating sample magnetometry (VSM), thermogravimetric analysis (TGA), diffuse reflectance spectroscopy (DRS), high-performance liquid chromatography (HPLC), and total organic carbon (TOC) due to detailed studies (morphological, structural, magnetic and optical properties) of the photocatalyst. In-depth spectroscopic and microscopic characterization of the newly developed ferromagnetic FMMWCNTs@GLYMO@WO3 (III) photocatalyst revealed a spherical morphology, with nanoparticle diameters averaging between 23 and 39 nm. Compared to conventional multiwall carbon nanotube and WO3 photocatalysts, FMMWCNTs@GLYMO@WO3 (III) demonstrated superior photocatalytic activity. Remarkably, it exhibited excellent reusability, maintaining its efficiency over a minimum of five cycles in the degradation of metronidazole (MNZ) and acetaminophen (ACE).
Asunto(s)
Acetaminofén , Metronidazol , Fotólisis , Tungsteno , Acetaminofén/química , Metronidazol/química , Tungsteno/química , Catálisis , Nanotubos de Carbono/química , Contaminantes Químicos del Agua/química , Óxidos/químicaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Helicobacter pylori (H. pylori) infections are on the rise, presenting a significant global health challenge. Mass Galla chinesis et camelliae Fermentata (Chinese gall leaven, CGL), a traditional Chinese medicinal product made from the fermentation of Rhus chinensis Mill., is frequently employed to address digestive system ailments. Contemporary pharmacological research reveals that CGL exhibits anti-inflammatory, anti-diarrheal, and enzyme-inhibitory activities and holds potential as a treatment for H. pylori infections. However, the precise mechanisms underlying CGL's efficacy against H. pylori remain to be fully elucidated. AIM: The objective of the study is to evaluate CGL's ability to disrupt the H. pylori biofilm and to explore its synergistic potential with antibiotics in targeting the biofilm-efflux pump system, a mechanism implicated in bacterial resistance. METHORDS: The study determined the Minimum Inhibitory Concentration (MIC) of CGL and metronidazole against H. pylori and evaluated their effects on H. pylori biofilms using an in vitro model. Structural changes induced by drug interventions were compared to those in untreated and antibiotic-treated models through scanning electron microscopy and laser confocal microscopy. The accumulation of H33342 dye in planktonic and biofilm H. pylori before and after drug treatment was assessed to evaluate cell viability and biofilm disruption. The study also involved adding experimental drugs to a biofilm H. pylori medium containing D-glucose, measuring glucose concentrations post-intervention using the glucose oxidase method, and calculating changes in glucose uptake. Finally, the relative expression levels of several genes in planktonic and biofilm H. pylori treated with CGL alone or in combination with antibiotics were measured to understand the impact on the biofilm-efflux pump system. RESULTS: Both CGL alone and in combination with metronidazole demonstrated effective disruption of H. pylori biofilms. The combination therapy was particularly effective in reducing the biofilm transfer-enhancing effect of metronidazole and decreasing SpoT expression in the 'SpoT-(p)ppGpp' pathway, especially in biofilms. It showed a greater inhibition of the 'σ54-gluP-sugar uptake' pathway, with significant reductions in rpoN and gluP expression under biofilm conditions compared to CGL or metronidazole alone. The treatment also suppressed H. pylori proliferation and may have altered glucose uptake mechanisms. Moreover, it significantly inhibited the 'hp0939/hp0497/hp0471-RND efflux pump' pathway, with a notable reduction in gene expression compared to the 1/2 MIC metronidazole treatment. CONCLUSION: This study demonstrates that CGL effectively hinders the development of drug resistance in H. pylori by targeting biofilm formation and critical molecular pathways associated with antibiotic resistance. The synergistic effect of combining CGL with metronidazole notably enhances biofilm disruption and inhibits the bacterium's metabolic and reparative mechanisms. Further in vivo studies are needed to confirm these results and to investigate additional mechanisms of CGL's action.
Asunto(s)
Antibacterianos , Biopelículas , Helicobacter pylori , Pruebas de Sensibilidad Microbiana , Biopelículas/efectos de los fármacos , Helicobacter pylori/efectos de los fármacos , Antibacterianos/farmacología , Metronidazol/farmacología , Rhus/química , Farmacorresistencia Bacteriana/efectos de los fármacos , Sinergismo Farmacológico , Extractos Vegetales/farmacología , Medicamentos Herbarios Chinos , TaninosRESUMEN
BACKGROUND: Universal surgical prophylaxis for pancreatoduodenectomy (PD) is practiced, with cephalosporins recommended in most guidelines. Recent studies suggest piperacillin-tazobactam (PTZ) prophylaxis in biliary-stented patients is superior in preventing surgical site infections (SSIs). This study aims to refine surgical prophylaxis recommendations based on the local microbial profile and evaluate the clinical outcomes of biliary-stented compared with non-stented patients. METHODS: This was a retrospective study of all consecutive PD patients at Singapore General Hospital between January 2013 to December 2019. The primary outcome was post-operative SSI rates. Secondary outcomes included rates of ceftriaxone-resistant Klebsiella pneumoniae, Escherichia coli, and Enterococcus species from intraoperative bile cultures and 30-day mortality. RESULTS: There were 130 biliary-stented and 211 non-stented patients included. Majority of biliary-stented patients received ceftriaxone ± metronidazole prophylaxis (83/130, 63.8 %) while 30/130 (23.8 %) received PTZ. Most non-stented patients received ceftriaxone ± metronidazole prophylaxis (163/211, 77.3 %). Between biliary-stented and non-stented patients, post-operative SSIs (40.8 % vs 38.4 %, p = 0.662), and 30-day mortality rates (1.5 % vs 1.4 %, p = 1.000) were comparable. The adjusted odds of post-operative SSIs was significantly lower in biliary-stented patients prescribed PTZ as compared to non-PTZ prophylaxis (0.29, 95 % CI (0.10-0.79), p = 0.015). Ceftriaxone-resistant Klebsiella spp. and/or Escherichia coli (27.6 % vs 3.8 %, p < 0.001) as well as Enterococcus species (46.1 % vs 11.5 %, p < 0.001), were more prevalent in intraoperative bile cultures of biliary-stented patients, while frequencies in non-stented patients were low. CONCLUSION: PTZ prophylaxis effectively reduced SSIs in stented patients post-pancreatoduodenectomy. Based on the local microbial profile, ceftriaxone prophylaxis may be used for prophylaxis in non-stented patients.
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Antibacterianos , Profilaxis Antibiótica , Pancreaticoduodenectomía , Stents , Infección de la Herida Quirúrgica , Humanos , Masculino , Femenino , Estudios Retrospectivos , Anciano , Infección de la Herida Quirúrgica/prevención & control , Antibacterianos/uso terapéutico , Persona de Mediana Edad , Profilaxis Antibiótica/métodos , Ceftriaxona/uso terapéutico , Cefalosporinas/uso terapéutico , Combinación Piperacilina y Tazobactam/uso terapéutico , Metronidazol/uso terapéutico , Anciano de 80 o más Años , Bilis , Escherichia coli/efectos de los fármacosRESUMEN
BACKGROUND: Pericoronitis, an inflammation near wisdom teeth, often occurs when they are partially emerged, especially in the lower jaw. Commonly, the gingiva partially envelops the tooth. Treatments vary from gingival surgery to extraction. This study assessed the efficacy of a mouthwash with Chlorhexidine, Benzydamine, Nanosilver, Amoxicillin, and Metronidazole for pain reduction and enhancement of maximum mouth opening in acute pericoronitis cases. MATERIALS AND METHODS: In this randomized controlled clinical trial conducted at the Gorgan Dental Faculty, 48 pericoronitis patients were randomized into two groups. The control group used a 0.12% chlorhexidine mouthwash, while the case group used a mouthwash containing Chlorhexidine, Benzydamine, Nanosilver, Amoxicillin, and Metronidazole. The study recorded Visual Analog Scale (VAS) scores for 7 days, and Maximum mouth opening (MMO) was measured at the start and after 7 days. The analysis was performed using SPSS v20. RESULTS: In this study, we compared the effects of a combined mouthwash with those of a chlorhexidine mouthwash on pericoronitis in 48 patients, with an average age of 21.56 years. No significant difference in pain reduction was observed between the groups; however, both groups exhibited decreased pain and improved MMO post-treatment. The gender distribution was balanced across both groups. CONCLUSION: The results indicate that both chlorhexidine mouthwash and combined mouthwash significantly improved maximum mouth opening. Nonetheless, there were no notable differences in efficacy between the two groups. These findings suggest that these mouthwashes may be beneficial for oral hygiene, warranting further in-depth research. TRIAL REGISTRATION: Registered on 12/03/2023, registration number IRCT20230104057046N1.