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2.
Eur Endod J ; 9(2): 154-160, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38456465

RESUMO

OBJECTIVE: Triple antibiotic paste (TAP) is known to have an essential role in the success of endodontic treatment by eliminating pathogens from the root canal system. Unfortunately, it causes discolouration and cytotoxicity at high concentrations. The objective of this research was to assess and compare the antimicrobial effectiveness of various concentrations (1 mg, 5 mg, 10 mg) of TAP, TAP hydrogel (TAPH), M-TAP, and M-TAP hydrogel (MTAPH) against Enterococcus faecalis. METHODS: The agar well diffusion method was used to assess the antibiotic sensitivity of the following intracanal medicaments: TAP (ciprofloxacin, metronidazole, and minocycline) mixed in a ratio of 1: 1: 1; TAPH, M-TAP (ciprofloxacin, metronidazole, and amoxicillin), M-TAPH and plain hydrogel. Each tested medicament was individually evaluated for its antimicrobial activity against Enterococcus faecalis. Structural and topographical characterisation were analysed using a Scanning Electron Microscope (SEM) and interpreted using ImageJ software. A microdilution broth test was performed to examine the minimum inhibitory concentration and minimum bactericidal concentration (MBC) of M-TAP and TAP. RESULTS: Except for the plain hydrogel, M-TAP and hydrogel and TAP and hydrogel showed significantly varied inhibitory zones at different concentrations. M-TAPH showed the highest mean zone of inhibition of 21.6, 33.33 and 38.0 mm at a concentration of 1, 5, and 10 mg/mL when compared to TAPH, which showed a mean zone of inhibition of 3.3 mm,12.3 mm, 21.3 mm at the respective concentrations. The MIC study shows that more than 75% of Enterococcus faecalis growth was inhibited by M-TAP at a concentration of 5 µg/mL, whereas TAP showed inhibition at a concentration of 35 µg/mL. MBC results indicate that almost 99.9% of the bacterial population was killed at a concentration of 100 µg/mL (10-1) for TAP and 10 µg/mL (10-2) for M-TAP. CONCLUSION: The antibacterial efficacy of M-TAP was significantly higher than TAP. Application of M-TAP at lower doses is advised to overcome the disadvantages seen with TAP.


Assuntos
Anti-Infecciosos , Hidrazonas , Metronidazol , Tiofenos , Metronidazol/farmacologia , Enterococcus faecalis , Hidrogéis/farmacologia , Antibacterianos/farmacologia , Ciprofloxacina , Bacitracina , Polimixina B , Framicetina
3.
Water Sci Technol ; 89(5): 1107-1123, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38483488

RESUMO

In this study, we report a facile hydrothermal synthesis of strontium-doped SnS nanoflowers that were used as a catalyst for the degradation of antibiotic molecules in water. The prepared sample was characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM), and ultraviolet-visible absorption spectroscopy (UV-Vis). The photocatalytic ability of the strontium-doped SnS nanoflowers was evaluated by studying the degradation of metronidazole in an aqueous solution under photocatalytic conditions. The degradation study was conducted for a reaction period of 300 min at neutral pH, and it was found that the degradation of metronidazole reached 91%, indicating the excellent photocatalytic performance of the catalyst. The influence of experimental parameters such as catalyst dosage, initial metronidazole concentration, initial reaction pH, and light source nature was optimized with respect to metronidazole degradation over time. The reusability of the strontium-doped SnS nanoflowers catalyst was investigated, and its photocatalytic efficiency remained unchanged even after four cycles of use.


Assuntos
Poluentes Ambientais , Metronidazol , Antibacterianos , Águas Residuárias , Fotólise , Estrôncio , Água
4.
World J Gastroenterol ; 30(6): 556-564, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38463026

RESUMO

BACKGROUND: A cure for Helicobacter pylori (H. pylori) remains a problem of global concern. The prevalence of antimicrobial resistance is widely rising and becoming a challenging issue worldwide. Optimizing sequential therapy seems to be one of the most attractive strategies in terms of efficacy, tolerability and cost. The most common sequential therapy consists of a dual therapy [proton-pump inhibitors (PPIs) and amoxicillin] for the first period (5 to 7 d), followed by a triple therapy for the second period (PPI, clarithromycin and metronidazole). PPIs play a key role in maintaining a gastric pH at a level that allows an optimal efficacy of antibiotics, hence the idea of using new generation molecules. AIM: To compare an optimized sequential therapy with the standard non-bismuth quadruple therapies of 10 and 14 d, in terms of efficacy, incidence of adverse effects (AEs) and cost. METHODS: This open-label prospective study randomized 328 patients with confirmed H. pylori infection into three groups (1:1:1): The first group received quadruple therapy consisting of twice-daily (bid) omeprazole 20 mg, amoxicillin 1 g, clarithromycin 500 mg and metronidazole 500 mg for 10 d (QT-10), the second group received a 14 d quadruple therapy following the same regimen (QT-14), and the third group received an optimized sequential therapy consisting of bid rabeprazole 20 mg plus amoxicillin 1 g for 7 d, followed by bid rabeprazole 20 mg, clarithromycin 500 mg and metronidazole 500 mg for the next 7 d (OST-14). AEs were recorded throughout the study, and the H. pylori eradication rate was determined 4 to 6 wk after the end of treatment, using the 13C urea breath test. RESULTS: In the intention-to-treat and per-protocol analysis, the eradication rate was higher in the OST-14 group compared to the QT-10 group: (93.5%, 85.5% P = 0.04) and (96.2%, 89.5% P = 0.03) respectively. However, there was no statistically significant difference in eradication rates between the OST-14 and QT-14 groups: (93.5%, 91.8% P = 0.34) and (96.2%, 94.4% P = 0.35), respectively. The overall incidence of AEs was significantly lower in the OST-14 group (P = 0.01). Furthermore, OST-14 was the most cost-effective among the three groups. CONCLUSION: The optimized 14-d sequential therapy is a safe and effective alternative. Its eradication rate is comparable to that of the 14-d concomitant therapy while causing fewer AEs and allowing a gain in terms of cost.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Humanos , Metronidazol/efeitos adversos , Claritromicina/efeitos adversos , Rabeprazol/efeitos adversos , Estudos Prospectivos , Quimioterapia Combinada , Antibacterianos/efeitos adversos , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/tratamento farmacológico , Amoxicilina/efeitos adversos , Inibidores da Bomba de Prótons/efeitos adversos
5.
Sci Rep ; 14(1): 5277, 2024 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-38438389

RESUMO

Antibiotic resistance is recognised as one of the biggest global threats to human and animal health. Understanding the influence of antibiotics on the canine microbiome is important to know the potential mid-to-long term effects on dysbiosis and mitigate side-effects such as antibiotic-associated diarrhoea. In this study, metronidazole was prescribed to 22 dogs for suspected giardiasis after exhibiting gastrointestinal symptoms such as diarrhoea and/or vomiting. Faecal samples were collected before, during seven days of treatment, and six months post-cessation. Faecal microbiota was assessed with 16S rRNA sequencing. Shannon diversity was reduced for up to three days after the treatment ended, and an altered community persisted for four to six weeks. All dogs recovered to a similar microbiome composition as pre-treatment. Immediately after receiving metronidazole, an increase in the relative abundance of the genera Lactobacillus, Bifidobacterium, and Enterococcus was observed. This may be due to antibiotic resistance commonly exhibited by these organisms. One-to-two weeks post-cessation, several other genera that were sensitive to the antibiotic recovered in abundances, with taxa belonging to the Erysipelotrichaceae family particularly driving composition change. Many of the bacteria initially reduced were associated with carbohydrate fermentation. This suggests scope exists to explore interventions to augment gastrointestinal health and support the re-establishment of the microbiome.


Assuntos
Metronidazol , Microbiota , Humanos , Cães , Animais , Metronidazol/farmacologia , Metronidazol/uso terapêutico , RNA Ribossômico 16S/genética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Diarreia
7.
Bioorg Med Chem ; 102: 117679, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38461555

RESUMO

Trichomoniasis, a prevalent sexually transmitted infection (STI) caused by the protozoan Trichomonas vaginalis, has gained increased significance globally. Its relevance has grown in recent years due to its association with a heightened risk of acquiring and transmitting the human immunodeficiency virus (HIV) and other STIs. In addition, many publications have revealed a potential link between trichomoniasis and certain cancers. Metronidazole (MTZ), a nitroimidazole compound developed over 50 years ago, remains the first-choice drug for treatment. However, reports of genotoxicity and side effects underscore the necessity for new compounds to address this pressing global health concern. In this study, we synthesized ten pyrazole-nitroimidazoles 1(a-j) and 4-nitro-1-(hydroxyethyl)-1H-imidazole 2, an analog of metronidazole (MTZ), and assessed their trichomonacidal and cytotoxic effects. All compounds 1(a-j) and 2 exhibited IC50 values ≤ 20 µM and ≤ 41 µM, after 24 h and 48 h, respectively. Compounds 1d (IC50 5.3 µM), 1e (IC50 4.8 µM), and 1i (IC50 5.2 µM) exhibited potencies equivalent to MTZ (IC50 4.9 µM), the reference drug, after 24 h. Notably, compound 1i showed high anti-trichomonas activity after 24 h (IC50 5.2 µM) and 48 h (IC50 2.1 µM). Additionally, all compounds demonstrated either non-cytotoxic to HeLa cells (CC50 > 100 µM) or low cytotoxicity (CC50 between 69 and 100 µM). These findings suggest that pyrazole-nitroimidazole derivatives represent a promising heterocyclic system, serving as a potential lead for further optimization in trichomoniasis chemotherapy.


Assuntos
Antiprotozoários , Nitroimidazóis , Tricomoníase , Trichomonas vaginalis , Humanos , Nitroimidazóis/farmacologia , Metronidazol/farmacologia , Células HeLa , Antiprotozoários/farmacologia , Antiprotozoários/uso terapêutico , Tricomoníase/tratamento farmacológico , Pirazóis/farmacologia , Pirazóis/uso terapêutico
8.
Sci Rep ; 14(1): 5947, 2024 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-38467719

RESUMO

Clostridioides difficile infection (CDI) is the most common cause of infectious diarrhea after allogeneic hematopoietic cell transplantation (allo-HCT). The impact of CDI and its treatment on allo-HCT outcomes and graft-versus-host disease (GVHD), including gastrointestinal GVHD (GI-GVHD) is not well established. This multicenter study assessed real-life data on the first-line treatment of CDI and its impact on allo-HCT outcomes. Retrospective and prospective data of patients with CDI after allo-HCT were assessed. We noted statistically significant increase in the incidence of acute GVHD and acute GI-GVHD after CDI (P = 0.005 and P = 0.016, respectively). The first-line treatment for CDI included metronidazole in 34 patients, vancomycin in 64, and combination therapy in 10. Treatment failure was more common with metronidazole than vancomycin (38.2% vs. 6.2%; P < 0.001). The need to administer second-line treatment was associated with the occurrence or exacerbation of GVHD (P < 0.05) and GI-GVHD (P < 0.001) and reduced overall survival (P < 0.05). In the multivariate analysis, the risk of death was associated with acute GVHD presence before CDI (hazard ratio [HR], 3.19; P = 0.009) and the need to switch to second-line treatment (HR, 4.83; P < 0.001). The efficacy of the initial CDI treatment affects survival and occurrence of immune-mediated GI-GVHD after allo-HCT. Therefore, agents with higher efficacy than metronidazole (vancomycin or fidaxomicin) should be administered as the first-line treatment.


Assuntos
Infecções por Clostridium , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia , Adulto , Humanos , Vancomicina/uso terapêutico , Metronidazol/uso terapêutico , Estudos Retrospectivos , Polônia , Estudos Prospectivos , Doença Enxerto-Hospedeiro/etiologia , Leucemia/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/etiologia
9.
Isr Med Assoc J ; 26(1): 30-33, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38420639

RESUMO

BACKGROUND: The management of complicated appendicitis is inconclusive. Guidelines have not been established for the use of personalized antibiotic treatment. OBJECTIVES: To investigate specific risk factors to consider during the initial first-choice antibiotic therapy in children with complicated appendicitis. METHODS: This study included all pediatric patients younger than 18 years of age who underwent a laparoscopic appendectomy during 2012-2022 at a single tertiary medical center. RESULTS: In total, 300 pediatric patients underwent laparoscopic appendectomy due to complicated appendicitis. The patients were treated with ceftriaxone + metronidazole (CM). For 57 (19%) patients, the empirical treatment was changed to tazobactam/piperacillin (TP) due to resistant bacteria or clinical deterioration. The presence of generalized peritonitis during surgery and C-reactive protein (CRP) levels above 20 mg/L at admission were identified as risk factors for changing the antibiotic regimen from CM to TP. CONCLUSIONS: Generalized peritonitis and CRP > 20 gr/L were highly correlated with changing the antibiotic regimen to TP. For such patients, initial treatment with TP may result in clinical improvement and shorter hospitalization.


Assuntos
Apendicite , Peritonite , Humanos , Criança , Apendicite/complicações , Apendicite/tratamento farmacológico , Apendicite/cirurgia , Resultado do Tratamento , Antibacterianos/uso terapêutico , Metronidazol/uso terapêutico , Ceftriaxona/uso terapêutico , Peritonite/etiologia , Peritonite/microbiologia , Combinação Piperacilina e Tazobactam/uso terapêutico , Apendicectomia , Estudos Retrospectivos
10.
Helicobacter ; 29(1): e13057, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38415810

RESUMO

BACKGROUND: Helicobacter pylori antibiotic resistance has undergone vast changes in the last two decades. No systematic review has been done on the prevalence of antibiotic resistant H. pylori in India in the last two decades. We evaluated the pattern of resistance rates across various regions of India. MATERIALS AND METHODS: A systematic review of the geographical variations in antibiotic resistance pattern of H. pylori was conducted using PubMed, Google Scholar, Web of Science, Science Direct, etc. for articles published between January 1, 2000 and May 30, 2023. Random effects-model-based Cochran's Q test, I2 statistics, and chi-squared tests were used to measure heterogeneity. RESULTS: The overall resistance was highest against metronidazole (77.65%) followed by amoxicillin (37.78%), levofloxacin (32.8%), clarithromycin (35.64%), furazolidone (12.03%), and tetracycline (11.63%). 14.7% of the H. pylori isolates were multi-drug resistant. Under meta-analysis of each antibiotic, high heterogeneity levels were observed having I2 ranges from 86.53% to 97.70% at p < 0.0001. In sub-group analysis, Metronidazole has a stable rate of resistance as compared to other antibiotics. Other antibiotics have had a downtrend in the last 5 years except for levofloxacin, which has had an uptrend in the resistance rate for the past 5 years. Hence, one should avoid using metronidazole for any kind of first-line treatment. CONCLUSIONS: Metronidazole resistance is high in most regions of India except Assam and Mumbai while clarithromycin is found to be ineffective in South India, Gujarat, and Kashmir. As compared to other antibiotics, resistance to amoxicillin is generally low except in certain regions (Hyderabad, Chennai, and the Gangetic belt of North India). Tetracycline and Furazolidone have the least resistance rates and should be part of anti- H. pylori regimens. The resurgence of high single and multidrug resistance to the commonly used drugs suggests the need for newer antibiotics and regular resistance surveillance studies.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Humanos , Metronidazol/farmacologia , Metronidazol/uso terapêutico , Claritromicina , Levofloxacino , Furazolidona , Índia/epidemiologia , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/epidemiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Amoxicilina , Tetraciclina , Anticorpos , Resistência Microbiana a Medicamentos
11.
Water Res ; 252: 121212, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38320394

RESUMO

The aim of this study was to investigate the removal of metronidazole (MNZ) from seawater using a bioelectrochemical system (BES). Single-chamber BES (i.e., S-BES) and dual-chamber BES (i.e., D-BES) were constructed with carbon brush as the anode and cathode. With the inoculum of sea mud and 2 g/L of glucose as the substrate in seawater, S-BES and D-BES were acclimated to test the MNZ removal. Results showed that S-BES could remove almost 100 % of 200 mg/L MNZ within 120 h and remain stable within 10 cycles of operation (∼50 d) under the applied voltage of 0.8 V. The MNZ removal reached ∼100 % and 60.2 % in the cathodic and anodic chambers of D-BES fed by 100 mg/L MNZ under 0.8 V, respectively. The MNZ concentration of 200 mg/L significantly inhibited the sulfur metabolism, decreased the ratio of live to dead cells in the electrode biofilms, and thus reduced the SO42- removal in the S-BES. The MNZ degradation and S2- oxidation was mainly attributed to the cathodic and anodic biofilms of S-BES, respectively. Three degradation pathways of MNZ were proposed based on the identified intermediates and results of density functional theory calculations. The synergies among different genus species in the bacterial communities of biofilms, and between anodic and cathodic reactions could be responsible for the high performance of S-BES. Results from this study should be not only useful for the MNZ removal but also for effective MNZ inhibition of sulfate-reducing bacteria induced microbiologically influenced corrosion in seawater.


Assuntos
Ácidos Alcanossulfônicos , Bactérias , Metronidazol , Oxirredução , Eletrodos , Água do Mar
12.
Ann Clin Microbiol Antimicrob ; 23(1): 21, 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38402175

RESUMO

BACKGROUND: Pregnancy-related infections are important contributors to maternal sepsis and mortality. We aimed to describe clinical, microbiological characteristics and use of antibiotics by source of infection and country income, among hospitalized women with suspected or confirmed pregnancy-related infections. METHODS: We used data from WHO Global Maternal Sepsis Study (GLOSS) on maternal infections in hospitalized women, in 52 low-middle- and high-income countries conducted between November 28th and December 4th, 2017, to describe the frequencies and medians of maternal demographic, obstetric, and clinical characteristics and outcomes, methods of infection diagnosis and causative pathogens, of single source pregnancy-related infection, other than breast, and initial use of therapeutic antibiotics. We included 1456 women. RESULTS: We found infections of the genital (n = 745/1456, 51.2%) and the urinary tracts (UTI) (n = 531/1456, 36.5%) to be the most frequent. UTI (n = 339/531, 63.8%) and post-caesarean skin and soft tissue infections (SSTI) (n = 99/180, 55.0%) were the sources with more culture samples taken and microbiological confirmations. Escherichia coli was the major uropathogen (n = 103/118, 87.3%) and Staphylococcus aureus (n = 21/44, 47.7%) was the commonest pathogen in SSTI. For 13.1% (n = 191) of women, antibiotics were not prescribed on the same day of infection suspicion. Cephalosporins (n = 283/531, 53.3%) were the commonest antibiotic class prescribed for UTI, while metronidazole (n = 303/925, 32.8%) was the most prescribed for all other sources. Ceftriaxone with metronidazole was the commonest combination for the genital tract (n = 98/745, 13.2%) and SSTI (n = 22/180, 12.2%). Metronidazole (n = 137/235, 58.3%) was the most prescribed antibiotic in low-income countries while cephalosporins and co-amoxiclav (n = 129/186, 69.4%) were more commonly prescribed in high-income countries. CONCLUSIONS: Differences in antibiotics used across countries could be due to availability, local guidelines, prescribing culture, cost, and access to microbiology laboratory, despite having found similar sources and pathogens as previous studies. Better dissemination of recommendations in line with antimicrobial stewardship programmes might improve antibiotic prescription.


Assuntos
Complicações Infecciosas na Gravidez , Infecções Urinárias , Gravidez , Feminino , Humanos , Antibacterianos/uso terapêutico , Metronidazol/uso terapêutico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Cefalosporinas/uso terapêutico , Organização Mundial da Saúde , Infecções Urinárias/tratamento farmacológico
13.
BMC Oral Health ; 24(1): 270, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38395824

RESUMO

BACKGROUND: Periodontitis is a microbially induced disease destroying structures anchoring teeth to jaw bones. Although metronidazole in combination with spiramycin is the effective conventional treatment of stage III grade C periodontitis, it has several systemic side effects. Laser therapy is widely used nowadays as an adjunct to scaling and root planing (SRP) to modulate inflammatory host response and eradicate microbes, due to bactericidal and detoxifying effects. Since microbiological analysis is one of the diagnostic methods identifying periodontal risk; our research aimed to investigate the efficacy of intra-pocket application of diode laser (980 nm) versus antibiotic therapy in enhancing clinical and microbiological parameters in stage III grade C periodontitis. METHODS: A randomized controlled clinical trial was conducted on fifty patients with stage III grade C periodontitis, divided equally into two groups. We managed test group by SRP with intra-pocket application of diode laser (980 nm) and the control group by SRP with systemic antibiotic administration (spiramycin and metronidazole). Then, we measured periodontal pocket depth (PPD) and clinical attachment loss (CAL) for both groups, before treatment (baseline), four and twelve weeks after. Moreover, we collected gingival crevicular fluid from both groups at baseline, four and twelve weeks after treatment and analyzed by real-time polymerase chain reaction to detect the relative count of Aggregatibacter actinomycetemcomitans and Porhyromonas gingivalis. RESULTS: Compared to baseline, all assessed clinical and microbiological parameters attested improvement at the end of the study period in each group individually with no significant difference between the two studied groups. Although, at twelve weeks, flare up of bacterial levels was detected with systemic antibiotic administration. CONCLUSION: Laser therapy can be considered as an effective treatment modality in stage III grade C periodontitis, avoiding the systemic antibiotic side effects and solving the recurrence problems due to bacterial resistance by long term usage. TRIAL REGISTRATION: NCT05222737 retrospectively on 03/02/2022, Clinicaltrial.gov.


Assuntos
Periodontite Crônica , Periodontite , Espiramicina , Humanos , Metronidazol/uso terapêutico , Espiramicina/uso terapêutico , Lasers Semicondutores/uso terapêutico , Estudos Retrospectivos , Seguimentos , Periodontite/tratamento farmacológico , Periodontite/microbiologia , Antibacterianos/uso terapêutico , Raspagem Dentária/métodos , Aplainamento Radicular/métodos , Periodontite Crônica/terapia
14.
J Dig Dis ; 25(1): 36-43, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38323705

RESUMO

OBJECTIVES: We aimed to explore the efficacy and safety of tailored therapy guided by genotypic resistance in the first-line treatment of Helicobacter pylori (H. pylori) infection in treatment-naive patients. METHODS: Gastric mucosal specimens were taken during gastroscopy, and main mutations of clarithromycin- and levofloxacin-resistant genes were detected by polymerase chain reaction (PCR). Sensitive antibiotics were selected individually for treating H. pylori infection with tailored bismuth-containing quadruple therapy (BQT) consisting of esomeprazole 20 mg twice daily, bismuth potassium citrate 220 mg twice daily, amoxicillin 1 g twice daily, and clarithromycin 500 mg twice daily, or levofloxacin 500 mg once daily, or metronidazole 400 mg four times daily. Safety and patient compliance were assessed 1-3 days after eradication. Treatment outcome was evaluated by urea breath test 4-8 weeks after eradication. RESULTS: One hundred and thirty-two treatment-naive patients with H. pylori infection were included. PCR results suggested resistance rates of 47.7% and 34.9% for clarithromycin and levofloxacin, respectively, and a dual resistance rate of 18.2%. Eradication rates of tailored BQT were 87.1% and 95.8% by intention-to-treat (ITT) analysis and per-protocol (PP) analysis, respectively. There was no statistically significant difference in the efficacy of 7-day clarithromycin-containing, 7-day levofloxacin-containing, and 14-day full-dose metronidazole-containing BQT (ITT analysis: P = 0.488; PP analysis: P = 0.833). The incidence of adverse events was 19.7%, and patient compliance was 97.7%. CONCLUSION: Tailored BQT guided by genotypic resistance can achieve satisfactory efficacy, safety, and patient compliance in the first-line treatment of H. pylori infection.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Humanos , Infecções por Helicobacter/tratamento farmacológico , Claritromicina/farmacologia , Claritromicina/uso terapêutico , Levofloxacino/efeitos adversos , Helicobacter pylori/genética , Bismuto/uso terapêutico , Metronidazol/uso terapêutico , Quimioterapia Combinada , Antibacterianos/efeitos adversos , Amoxicilina/uso terapêutico , Resultado do Tratamento , Reação em Cadeia da Polimerase
16.
Artigo em Inglês | MEDLINE | ID: mdl-38301337

RESUMO

The integration of molecular imprinting technique with chromatographic one has a great impact on the assay's selectivity and sensitivity. Herein, a molecularly imprinted solid-phase extraction associated with high performance liquid chromatography (MISPE-HPLC) was employed for simultaneous determination of the co-formulated drugs; tetracycline hydrochloride (TET) and metronidazole (MET), in plasma and in their anti-H-pylori drug for the first time. Two sorts of molecularly imprinted polymers (MIPs) were fabricated using TET and MET as the template molecules, while ethylene glycol dimethacrylate and methacrylic acid were used as a cross-linker and a monomer, respectively. The synthesized MIPs were identified using different techniques. The adsorption-desorption capability of each template was investigated towards its corresponding MIP. The extraction conditions of MISPE was optimized with respect to TET/MIP and MET/MIP sorbent. Bismuth subcitrate (BSC), the third co-formulated drug was analyzed in spiked human plasma using an atomic absorption spectrometric (AAS) method. The performance of the developed methods was assured as per ICH guidelines for analyzing the studied drugs in their pharmaceutical dosage form along with two of their official impurities. In addition, bioanalytical method validation was conducted where linearity was achieved at 2.0-40.0 µg mL-1, 2.0-40.0 µg mL-1 and 5.0-80.0 µg mL-1 for TET, MET and BSC, respectively.


Assuntos
Metronidazol , Impressão Molecular , Compostos Organometálicos , Humanos , Cromatografia Líquida de Alta Pressão/métodos , Espectrofotometria Atômica , Tetraciclina , Extração em Fase Sólida/métodos , Preparações Farmacêuticas , Impressão Molecular/métodos , Adsorção
17.
Chemosphere ; 352: 141382, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38331262

RESUMO

The purpose of the present study was to investigate the cardiotoxic effects of Metronidazole (Mtz) in albino mice. The mice were divided into four experimental groups: Gp.I (control group): saline, Gp.II:125 mg/kg b.w Mtz, Gp.III:250 mg/kg b.w, Gp.IV:500 mg/kg b.w Mtz. Heart weight ratio, markers of cardiac injury, markers of oxidative stress, histopathological examinations, DNA fragmentation and spectral analysis were used to determine cardiotoxicity. Administration of 125-500 mg/kg Mtz caused an increase in heart weight and a decrease in body weight. Administration of 500 mg/kg Mtz increased heart weight by 35.5% and decreased body weight by 21.9% compared with control. Mtz-treated mice showed a significant increase in cardiac injury biomarkers and serious alterations in cardiac oxidative stress markers. Histopathological changes of cardiac tissues observed in mice treated with Mtz include myocardial hypertrophy, fibrosis, myocarditis, separation of the muscle fibers, congestion-narrowing in vessels, necrosis, myocardium-vacuolation, myocytolysis, myocyte degeneration, nuclear aggregation, cytoplasmic fragmentation and prevalent nuclei. Mtz treatment already resulted in a significant decrease in the percentage of head DNA and an increase in the percentage of tail DNA. The most striking tail formation among the Mtz-treated groups was observed in the group receiving 500 mg/kg Mtz. In the presence of Mtz, there was a hypochromic shift in the absorption spectrum of DNA, and the potential DNA-Mtz interaction was found to occur in the intercalation mode. These results show that Mtz used against anaerobic bacteria and protozoa in gastrointestinal infections can cause severe cardiotoxic findings in albino mice and cause fragmentation in DNA.


Assuntos
Metronidazol , Estresse Oxidativo , Animais , Camundongos , Metronidazol/toxicidade , Fragmentação do DNA , DNA , Peso Corporal
18.
Antimicrob Agents Chemother ; 68(3): e0162123, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38364016

RESUMO

Antimicrobial resistance is emerging in clinical strains of Clostridioides difficile. Ibezapolstat (IBZ) is a DNA polymerase IIIC inhibitor that has completed phase II clinical trials. IBZ has potent in vitro activity against wild-type, susceptible strains but its effect on C. difficile strains with reduced susceptibility to metronidazole (MTZ), vancomycin (VAN), or fidaxomicin (FDX) has not been tested. The primary objective of this study was to test the antibacterial properties of IBZ against multidrug-resistant C. difficile strains. The in vitro activity, bactericidal, and time-kill activity of IBZ versus comparators were evaluated against 100 clinical strains of which 59 had reduced susceptibility to other C. difficile antibiotics. Morphologic changes against a multidrug resistance strain were visualized by light and scanning electron microscopy. The overall IBZ MIC50/90 values (µg/mL) for evaluated C. difficile strains were 4/8, compared with 2/4 for VAN, 0.5/1 for FDX, and 0.25/4 for MTZ. IBZ MIC50/90 values did not differ based on non-susceptibility to antibiotic class or number of classes to which strains were non-susceptible. IBZ bactericidal activity was similar to the minimum inhibitory concentration (MIC) and maintained in wild-type and non-susceptible strains. Time-kill assays against two laboratory wild-type and two clinical non-susceptible strains demonstrated sustained IBZ activity despite reduced killing by comparator antibiotics for IBZ and VAN non-susceptible strains. Microscopy visualized increased cell lengthening and cellular damage in multidrug-resistant strains exposed to IBZ sub-MIC concentrations. This study demonstrated the potent antibacterial activity of IBZ against a large collection of C. difficile strains including multidrug-resistant strains. This study highlights the therapeutic potential of IBZ against multidrug-resistant strains of C. difficile.


Assuntos
Anti-Infecciosos , Clostridioides difficile , Infecções por Clostridium , Nucleosídeos de Purina , Humanos , Clostridioides , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Anti-Infecciosos/farmacologia , Vancomicina/farmacologia , Vancomicina/uso terapêutico , Metronidazol/farmacologia , Metronidazol/uso terapêutico , Fidaxomicina/farmacologia , Fidaxomicina/uso terapêutico , Testes de Sensibilidade Microbiana
19.
Sci Rep ; 14(1): 4912, 2024 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-38418852

RESUMO

Helicobacter pylori (H. pylori) resistance is the most important risk factor for eradication failure. However, in most regions, antibiotic resistance rates of H. pylori in patients with different types of gastric mucosal lesions are still unclear. An 8-year clinical retrospective cohort study involving 2847 patients was performed. In this study, we first summarized and compared the resistance status of H. pylori in different years, ages, sexes, and gastric diseases. The resistance profiles of amoxicillin (AMX), clarithromycin (CLR), levofloxacin (LVX) and furazolidone (FR) and their changing trends in the clinic were described. Then, multiple antibiotic resistance in different gastric diseases and years were described and compared. The relationship between proton pump inhibitor (PPI) medication history and antibiotic resistance in H. pylori was also explored. Finally, an antibiotic resistance risk model was constructed for clinical resistance risk prediction. The overall resistance rates of AMX, CLR, LVX and FR in gastric diseases were 8.18%, 38.11%, 43.98%, and 13.73%, respectively. The mono resistance, double resistance, triple resistance, and quadruple resistance rates were 30.17%, 25.96%, 6.46%, and 0.63%, respectively. Compared with the period from 2014 to 2016, the rates of mono-resistance and multiple resistance all showed relatively downward trends in the past 5 years. Factors including age, sex, type of gastric lesions and recent PPI treatment history are associated with the antibiotic resistance rate of H. pylori. Atrophic gastritis is an important clinical feature of high-risk antibiotic resistance in H. pylori-infected patients. Patients with atrophic gastritis have higher risk of resistant strains infection. In this study, our data provide the association between antibiotic resistance of H. pylori and gastritis pattern, which indicate the higher risk of resistant strain infection if the patients with atrophic gastritis, PPI history and older age.


Assuntos
Gastrite Atrófica , Infecções por Helicobacter , Helicobacter pylori , Gastropatias , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/epidemiologia , Estudos Retrospectivos , Amoxicilina/farmacologia , Claritromicina/uso terapêutico , Gastropatias/tratamento farmacológico , Levofloxacino/farmacologia , Inibidores da Bomba de Prótons/uso terapêutico , Inibidores da Bomba de Prótons/farmacologia , Furazolidona/farmacologia , Furazolidona/uso terapêutico , Farmacorresistência Bacteriana , Metronidazol/farmacologia
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