Background and Objective: Rescue Helicobacter pylori eradication can be challenging. Rifabutin (RBT) demonstrates high activity against Helicobacter pylori and is incorporated into various rescue eradication regimens. This exploratory study was performed to evaluate the efficacy and safety of a rescue regimen comprising RBT, metronidazole (MNZ), and vonoprazan (VPZ). Methods: This prospective, single-center, single-arm, interventional study was performed in Japan. Eligible patients were those who underwent failed primary eradication treatment (7-day treatment with three drugs: VPZ or a proton pump inhibitor [PPI], amoxicillin [AMPC], and clarithromycin) and secondary eradication treatment (7-day treatment with three drugs: VPZ or a PPI, AMPC, and MNZ) and those who were unable to receive first- and second-line therapy because of penicillin allergy. Twenty Helicobacter pylori-positive patients were treated with RBT (150 mg twice daily), MNZ (250 mg twice daily), and VPZ (20 mg twice daily) for 10 days (RBT-MNZ-VPZ therapy). Eradication success was evaluated using the urea breath test. Drug susceptibility test results were available in 16 patients. This study is registered in the Japan Registry of Clinical Trials (jRCT031220504). Results: The intention-to-treat (ITT) and per-protocol (PP) eradication rates of RBT-MNZ-VPZ therapy were 70% (90% confidence interval [CI]: 49.2%-86.0%) and 72.2% (95% CI: 50.2%-88.4%), respectively. In the MNZ-susceptible subgroup, the ITT (n = 8) and PP (n = 7) eradication rates were 100% (90% CI: 68.8%-100%) and 100% (90% CI: 65.2%-100%). In the MNZ-resistant subgroup, the ITT (n = 8) and PP (n = 7) eradication rates were both 62.5% (90% CI: 28.9%-88.9%). All infections were RBT-susceptible. Conclusions: These findings suggest that RBT-MNZ-VPZ therapy may be a promising rescue regimen, especially in MNZ- and RBT-susceptible infections or patients with penicillin allergy.

This study aimed to investigate the impact of storage conditions on the dissolution performance of commercial metronidazole (MTZ) tablets available in Saudi Arabia; these were coded as the reference and Test A, Test B, and Test C products. Moreover, the hardness and the disintegration time were measured. The UV spectrophotometrically analytical technique was utilized to quantify MTZ. All the control tablets, which were tested upon receipt, met the USP requirement as not less than 85 % of the labeled amount of MTZ was dissolved in 60 min. The MTZ reference released 91.79 % ± 1.23 after 60 min, while the products A, B, and C released 87.96 % ± 2.60, 93.26 % ± 2.01, and 88.61 % ± 2.04, respectively. The different dissolution parameters calculated for all the control tablets showed that the MTZ products A and B had optimal dissolution performances and were considered similar to the reference product. The product C showed a significantly reduced dissolution performance and was considered different from the reference. The in vitro dissolution of the MTZ tablets stored at 40oC ± 2 oC/75 % RH ± 5 % for 6 months indicated that the tablets maintained compliance with the USP requirement. The MTZ reference released 89.36 % ± 3.64 after 60 min, while the products A, B, and C released 95.79 % ± 3.91, 88.52 % ± 2.52, and 87.79 % ± 5.04, respectively. However, a slight reduction in the percentage released after 30 min (% DE30) and a slight increase in the mean dissolution time (MDT) were observed during the first 3 months of storage under stressed conditions. These changes were more obvious after 6 months of storage under the same conditions. Furthermore, in vitro dissolution of the product C stored at 40oC ± 2 oC/75 % RH ± 5 % for 3 months with further protection against high humidity revealed an improvement in the dissolution parameters due to the similar protective effects exerted by the two packaging forms. Furthermore, the study shows that storage conditions such as humidity and temperature affect in vitro dissolution of MTZ marketed tablets which may have an impact on efficiency and patient safety.

BACKGROUND: Hoylesella marshii can be isolated from human oral cavities affected by dental pulp and periodontal infections, as well as from the dental plaque of healthy individuals, making it a common bacterium within the oral microbiota. However, its role in causing pleural infections in humans is rare.
METHODS: A case of purulent pleural effusion occurred shortly after discharge in an elderly patient who had undergone surgery for gastric cancer. The infection was identified as being caused by an obligate anaerobe through laboratory culture, and was further identified as Hoylesella marshii causing pleural infection through 16 S rRNA gene sequence analysis. Susceptibility testing guided precise treatment with cefoperazone-sulbactam and metronidazole. The patient\'s clinical symptoms improved rapidly, laboratory test indicators gradually returned to normal, and the patient ultimately recovered.
CONCLUSIONS: Hoylesella marshii can cause pleural infections in humans. Clinical microbiology laboratories should pay special attention to the cultivation of obligate anaerobes when routine aerobic cultures do not show bacterial growth but bacteria are visible on smear staining, and when conventional identification methods fail to identify the bacterium, analysis based on the highly conserved 16 S rRNA gene sequence can accurately and specifically identify the bacterium, guiding clinicians in formulating precise anti-infection strategies.

The development of amoebic liver abscess (ALA) leads to liver necrosis, accompanied by an exacerbated inflammatory response and the formation of multiple granulomas. Adequate management of the infection through the administration of treatment and the timely response of the organ to the damage allows the injury to heal with optimal regeneration without leaving scar tissue, which does not occur in other types of damage such as viral hepatitis that may conducts to fibrosis or cirrhosis. The Hedgehog signaling pathway (Hh) is crucial in the embryonic stage, while in adults it is usually reactivated in response to acute or chronic injuries, regeneration, and wound healing. In this work, we characterized Hh in experimental hepatic amoebiasis model, with the administration of treatment with metronidazole, as well as a pathway inhibitor (cyclopamine), through histological and immunohistochemical analyses including an ultrastructure analysis through transmission electron microscopy. The results showed an increase in the percentage of lesions obtained, a decrease in the presence of newly formed hepatocytes, a generalized inflammatory response, irregular distribution of type I collagen accompanied by the presence of fibroblast-type cells and a decrease in effector cells of this pathway. These results constitute the first evidence of the association of the activation of Hh with the liver regeneration process in experimental amebiasis.

Pleural empyema can lead to significant morbidity and mortality despite chest drainage and antibiotic treatment, necessitating novel and minimally invasive interventions. Fusobacterium nucleatum is an obligate anaerobe found in the human oral and gut microbiota. Advances in sequencing and puncture techniques have made it common to detect anaerobic bacteria in empyema cases. In this report, we describe the case of a 65-year-old man with hypertension who presented with a left-sided encapsulated pleural effusion. Initial fluid analysis using metagenomic next-generation sequencing (mNGS) revealed the presence of Fusobacterium nucleatum and Aspergillus chevalieri. Unfortunately, the patient experienced worsening pleural effusion despite drainage and antimicrobial therapy. Ultimately, successful treatment was achieved through intrapleural metronidazole therapy in conjunction with systemic antibiotics. The present case showed that intrapleural antibiotic therapy is a promising measure for pleural empyema.

In this study, phosphoric acid activation was employed to synthesize nitrogen-doped mesoporous activated carbon (designated as MR1) from Lentinus edodes (shiitake mushroom) residue, while aiming to efficiently remove acetaminophen (APAP), carbamazepine (CBZ), and metronidazole (MNZ) from aqueous solutions. We characterized the physicochemical properties of the produced adsorbents using scanning electron microscopy (SEM), nitrogen adsorption isotherms, and X-ray photoelectron spectroscopy (XPS). MR1, MR2, and MR3 were prepared using phosphoric acid impregnation ratios of 1, 2, and 3 mL/g, respectively. Notably, MR1 exhibited a significant mesoporous structure with a volume of 0.825 cm3/g and a quaternary nitrogen content of 2.6%. This endowed MR1 with a high adsorption capacity for APAP, CBZ, and MNZ, positioning it as a promising candidate for water purification applications. The adsorption behavior of the contaminants followed the Freundlich isotherm model, suggesting a multilayer adsorption process. Notably, MR1 showed excellent durability and recyclability, maintaining 95% of its initial adsorption efficiency after five regeneration cycles and indicating its potential for sustainable use in water treatment processes.

The structures of three multicomponent crystals formed with imidazole-based drugs, namely metronidazole, ketoconazole and miconazole, in conjunction with trithiocyanuric acid are characterized. Each of the obtained adducts represents a different category of crystalline molecular forms: a cocrystal, a salt and a cocrystal of salt. The structural analysis revealed that in all cases, the N-H...N hydrogen bond is responsible for the formation of acid-base pairs, regardless of whether proton transfer occurs or not, and these molecular pairs are combined to form unique supramolecular motifs by centrosymmetric N-H...S interactions between acid molecules. The complex intermolecular forces acting in characteristic patterns are discussed from the geometric and energetic perspectives, involving Hirshfeld surface analysis, pairwise energy estimation, and natural bond orbital calculations.

UNASSIGNED: Trichomonas vaginalis is a sexually transmitted protozoan parasite that usually causes infections in women. Metronidazole is used as the first choice in the treatment of this parasitic disease, but there is a need for new drugs since 1980\'s with increasing numbers of reported resistance. In this study, it was aimed to determine the antitrichomonal activity of the major components of Cinnamomum zeylanicum (cinnamon) and Thymus vulgaris (thyme) essential oils, cinnamaldehyde, carvacrol and thymol against metronidazole resistant and susceptible T. vaginalis strains, and to determine their interaction with metronidazole by checkerboard method.
UNASSIGNED: Cinnamaldehyde, carvacrol, thymol and metronidazole were obtained commercially. Two clinical isolates and one metronidazole resistant T. vaginalis reference strain were used in the study. MIC50 and MLC values of essential oil components and metronidazole were determined by broth microdilution method. The combinations of essential oil components with metronidazole were determined by the checkerboard method.
UNASSIGNED: According to in vitro activity tests, cinnamaldehyde was determined to be most effective essential oil component. Clinical isolates were susceptible to metronidazole. In combination study, metronidazole showed synergy with cinnamaldehyde and carvacrol, and partial synergy with thymol.
UNASSIGNED: It was determined that cinnamaldehyde, carvacrol and thymol, which are known to have high antimicrobial activity, also have strong activity against T. vaginalis isolates and show a synergistic interaction with metronidazole. The use of metronidazole at lower doses in the synergistic interaction may contribute to the literature in terms of reducing drug side effects, creating a versatile antimicrobial target, and reducing the rate of resistance development.
UNASSIGNED: Trichomonas vaginalis genellikle kadınlarda enfeksiyona neden olan ve cinsel yolla bulaşan bir protozoon parazittir. Parazitin neden olduğu hastalığın tedavisinde ilk tercih olarak metronidazol kullanılmaktadır. Ancak 1980 yılından sonra artan sayılarda direnç gelişiminin rapor edilmesi ile yeni ilaç arayışlarına ihtiyaç duyulmuştur. Bu çalışmada, Cinnamomum zeylanicum (tarçın) ve Thymus vulgaris (kekik) uçucu yağlarının majör bileşenleri olan sinnamaldehit, karvakrol ve timolün metronidazole dirençli ve duyarlı T. vaginalis izolatlarına karşı anti-trichomonal etkinliğinin belirlenmesi ve metronidazol ile etkileşiminin checkerboard (dama tahtası) yöntemi ile gösterilmesi amaçlandı.
UNASSIGNED: Çalışmada kullanılan sinnamaldehit, karvakrol, timol ve metronidazolün saf formları ticari olarak temin edildi. Çalışmada, iki klinik izolat ve bir adet metronidazole dirençli T. vaginalis standart (ATCC 50143) suşu kullanıldı. Uçucu yağ bileşenlerinin ve metronidazolün MIK50 ve MLK (minimum letal konsantrasyonu) değerleri sıvı mikrodilüsyon yöntemi, metronidazol ile kombinasyonu ise checkerboard (dama tahtası) yöntemi ile saptandı.
UNASSIGNED: İn vitro etkinlik testlerine göre, en etkili uçucu yağ bileşeninin sinnamaldehit olduğu belirlendi. Klinik izolatların metronidazole duyarlı olduğu saptandı. Checkerboard yöntemi ile yapılan kombinasyon çalışması değerlendirildiğinde, sinnamaldehit ve karvakrolün metronidazol ile kombinasyonunda sinerji, timolün metronidazol ile kombinasyonunda ise kısmi sinerji görüldü.
UNASSIGNED: Yüksek antimikrobiyal aktiviteye sahip olduğu bilinen sinnamaldehit, karvakrol ve timol’ün T. vaginalis izolatlarına karşı güçlü aktiviteye sahip olduğu ve metronidazol ile sinerjistik etkileşim gösterdiği belirlendi. Sinerjik etkileşimde metronidazolün daha düşük dozlarda kullanılması ilaç yan etkilerinin azaltılması, çok yönlü bir antimikrobiyal hedef oluşturulması ve direnç gelişme hızının düşürülmesi açısından literatüre katkı sağlayabilir.

This study investigates the potential applications of incorporating 2D bacterial cellulose microfibers (BCM) biochar into chitosan/polyethyleneimine beads as a semi-natural sorbent for the efficient removal of tetracycline (TET) and metronidazole (MET) antibiotics. Batch adsorption experiments and characterization techniques evaluate removal performance and synthesized adsorbent properties. The adsorbent eliminated 99.13 % and 90 % of TET and MET at a 10 mg.L-1 concentration with optimal pH values of 8 and 6, respectively, for 90 min. Under optimum conditions and a 400 mg.L-1 concentration, MET and TET have possessed the maximum adsorption capacities of 691.325 and 960.778 mg.g-1, respectively. According to the isothermal analysis, the adsorption of TET fundamentally follows the Temkin (R2 = 0.997), Redlich-Peterson (R2 = 0.996), and Langmuir (R2 = 0.996) models. In contrast, the MET adsorption can be described by the Langmuir (R2 = 0.997), and Toth (R2 = 0.991) models. The pseudo-second-order (R2 = 0.998, 0.992) and Avrami (R2 = 0.999, 0.999) kinetic models were well-fitted with the kinetic results for MET and TET respectively. Diffusion models recommend that pore, liquid-film, and intraparticle diffusion govern the rate of the adsorption process. The developed semi-natural sorbent demonstrated exceptional adsorption capacity over eleven cycles due to its porous bead structure, making it a potential candidate for wastewater remediation.

Bacterial nitroreductase enzymes capable of activating imaging probes and prodrugs are valuable tools for gene-directed enzyme prodrug therapies and targeted cell ablation models. We recently engineered a nitroreductase (E. coli NfsB F70A/F108Y) for the substantially enhanced reduction of the 5-nitroimidazole PET-capable probe, SN33623, which permits the theranostic imaging of vectors labeled with oxygen-insensitive bacterial nitroreductases. This mutant enzyme also shows improved activation of the DNA-alkylation prodrugs CB1954 and metronidazole. To elucidate the mechanism behind these enhancements, we resolved the crystal structure of the mutant enzyme to 1.98 Å and compared it to the wild-type enzyme. Structural analysis revealed an expanded substrate access channel and new hydrogen bonding interactions. Additionally, computational modeling of SN33623, CB1954, and metronidazole binding in the active sites of both the mutant and wild-type enzymes revealed key differences in substrate orientations and interactions, with improvements in activity being mirrored by reduced distances between the N5-H of isoalloxazine and the substrate nitro group oxygen in the mutant models. These findings deepen our understanding of nitroreductase substrate specificity and catalytic mechanisms and have potential implications for developing more effective theranostic imaging strategies in cancer treatment.