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1.
Chemosphere ; 359: 142279, 2024 Jul.
Article En | MEDLINE | ID: mdl-38723687

The widespread use and misuse of antibiotics in pharmaceuticals and animal farming has resulted in their accumulation in food sources and the environment, posing significant threats to human health, the environment, and the global economy. In this study, we have developed a hypersensitive, and ultra-selective electrochemical sensor, the first of its kind, by integrating a thermally annealed gold-silver alloy nanoporous matrix (TA-Au-Ag-ANpM) with reduced graphene oxide (r-GO) and poly(glycine) at the surface of a glassy carbon electrode (GCE). This sensor aims to detect life-threatening metronidazole (MTZ) residues in food samples. TA-Au-Ag-ANpM/r-GO/poly(glycine)/GCE was thoroughly characterized using a range of analytical techniques, including UV-Vis, FT-IR, XRD, SEM, and EDX. Furthermore, its electrochemical properties were investigated by cyclic voltammetry (CV), square wave voltammetry (SWV), and electrochemical impedance spectroscopy (EIS). The sensor exhibited outstanding performance, with a broad linear range of 2.0 pM-410 µM. The limits of detection (LOD) and quantification (LOQ) were determined to be 0.0312 pM and 0.104 pM, respectively. The TA-Au-Ag-ANpM/r-GO/poly(glycine)/GCE exhibited exceptional reproducibility, repeatability, stability, and resistance to interferences. Moreover, the sensor demonstrated outstanding performance in detecting MTZ residues in milk powder, pork, and chicken meat samples, achieving very good recoveries (96.9%-101.4%) with a relative standard deviation (RSD) below 5%. This performance highlights the potential for practical applications in food safety and quality monitoring. Therefore, the developed sensor contributes to the advancement of electrochemical sensing technology and its application in ensuring food safety and integrity by combating antibiotic residues.


Electrochemical Techniques , Food Contamination , Graphite , Limit of Detection , Metronidazole , Metronidazole/analysis , Graphite/chemistry , Electrochemical Techniques/methods , Food Contamination/analysis , Animals , Electrodes , Gold/chemistry , Food Analysis/methods , Silver/chemistry , Reproducibility of Results , Anti-Bacterial Agents/analysis , Drug Residues/analysis
2.
J Prim Care Community Health ; 15: 21501319241249645, 2024.
Article En | MEDLINE | ID: mdl-38726585

Clostridioides difficile infection (CDI) is one of the most common and severe nosocomial infections worldwide. It can also affect healthy individuals in the community. The incidence of CDI has been on the rise globally for the past decade, necessitating a proactive approach to combat its spread; new strategies are being developed to enhance diagnostic accuracy and optimize treatment outcomes. Implementing the 2-step testing has increased diagnostic specificity, reducing the usage of CD-specific antibiotics with no concomitant increase in surgical complication rates. In 2021, the Infectious Diseases Society of America/Society for Healthcare Epidemiology of America (IDSA/SHEA) shifted its preference for initial treatment to fidaxomicin over vancomycin and metronidazole due to its lower recurrence rate. It also prioritized fidaxomicin for the treatment of recurrent CDI. There are new developments on the frontiers of fecal microbiota therapies, with RBX2660 and SER-109 approved recently by the FDA for prevention, with other microbiome-based therapies in various development and clinical trials. This review offers providers an updated and practical guide for CDI management.


Anti-Bacterial Agents , Clostridioides difficile , Clostridium Infections , Humans , Clostridium Infections/prevention & control , Clostridium Infections/diagnosis , Clostridium Infections/therapy , Anti-Bacterial Agents/therapeutic use , Fecal Microbiota Transplantation , Cross Infection/prevention & control , Practice Guidelines as Topic , Fidaxomicin/therapeutic use , Metronidazole/therapeutic use
3.
J Phys Chem Lett ; 15(20): 5382-5389, 2024 May 23.
Article En | MEDLINE | ID: mdl-38738984

Metronidazole is a prospective hyperpolarized MRI contrast agent with potential hypoxia sensing utility for applications in cancer, stroke, neurodegenerative diseases, etc. We demonstrate a pilot procedure for production of ∼30 mM hyperpolarized [15N3]metronidazole in aqueous media by using a phase-separated SABRE-SHEATH hyperpolarization method, with nitrogen-15 polarization exceeding 2.2% on all three 15N sites achieved in less than 2 min. The 15N polarization T1 of ∼12 min is reported for the 15NO2 group at the clinically relevant field of 1.4 T in the aqueous phase, demonstrating a remarkably long lifetime of the hyperpolarized state. The produced aqueous solution of [15N3]metronidazole that contained only ∼100 µM of residual Ir was deemed biocompatible via validation through the MTT colorimetric test for assessing cell metabolic activity using human embryotic kidney HEK293T cells. This low-cost and ultrafast hyperpolarization procedure represents a major advance for the production of a biocompatible HP [15N3]metronidazole (and potentially other hyperpolarized drugs) formulation for MRI sensing applications.


Metronidazole , Water , Humans , Metronidazole/chemistry , Metronidazole/pharmacology , HEK293 Cells , Water/chemistry , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Hydrogen/chemistry , Nitrogen Isotopes/chemistry , Magnetic Resonance Imaging/methods , Contrast Media/chemistry
4.
Oper Dent ; 49(3): 336-344, 2024 May 01.
Article En | MEDLINE | ID: mdl-38807319

OBJECTIVE: Tooth color matching is challenging, and digital photocolorimetry using eLABor_aid (eLAB) provides objective evaluation through polarized photographs. However, its comparability with spectrophotometry remains unclear. METHODS AND MATERIALS: Bovine incisor root canals (n=30) were prepared to simulate an incomplete root apex. The teeth were randomly assigned to three groups based on intracanal medication: control (without medication); calcium hydroxide/propylene glycol; and triple-antibiotic paste (n=10 each). Tooth color was assessed using both eLAB and spectrophotometry. Measurements were taken at the crown medio-cervical region on five-time intervals (baseline, 1, 3, 7, and 14 days). Statistical analysis included two-way repeated-measures ANOVA, Sidak post hoc and Pearson's correlation test (α=0.05). RESULTS: No significant differences were observed between the two methods for either medication or follow-ups (p>0.05). Triple-antibiotic paste exhibited higher color variation (p<0.05). After 7 days, all groups presented significant color changes (p<0.05). Moderate to high correlations (R2 from 0.51 to 0.84, p<0.0001) were found between both methods for all groups at all intervals. CONCLUSION: The eLAB is a reliable method for detecting tooth color changes, and its results are comparable to spectrophotometry analysis.


Colorimetry , Spectrophotometry , Cattle , Animals , Spectrophotometry/methods , Colorimetry/methods , Anti-Bacterial Agents , Color , In Vitro Techniques , Calcium Hydroxide , Incisor/anatomy & histology , Propylene Glycol , Tooth Discoloration , Root Canal Irrigants/therapeutic use , Metronidazole/therapeutic use , Ciprofloxacin/therapeutic use , Dental Pulp Cavity/anatomy & histology
5.
Sci Rep ; 14(1): 12066, 2024 05 27.
Article En | MEDLINE | ID: mdl-38802465

Heterogeneity of Helicobacter pylori communities contributes to its pathogenicity and diverse clinical outcomes. We conducted drug-susceptibility tests using four antibiotics, clarithromycin (CLR), amoxicillin (AMX), metronidazole and sitafloxacin, to examine H. pylori population diversity. We also analyzed genes associated with resistance to CLR and AMX. We examined multiple isolates from 42 Japanese patients, including 28 patients in whom primary eradication with CLR and AMX had failed, and 14 treatment-naïve patients. We identified some patients with coexistence of drug resistant- and sensitive-isolates (drug-heteroR/S-patients). More than 60% of patients were drug-heteroR/S to all four drugs, indicating extensive heterogeneity. For the four drugs except AMX, the rates of drug-heteroR/S-patients were higher in treatment-naïve patients than in primary eradication-failure patients. In primary eradication-failure patients, isolates multi-resistant to all four drugs existed among other isolates. In primary eradication-failure drug-heteroR/S-patients, CLR- and AMX-resistant isolates were preferentially distributed to the corpus and antrum with different minimum inhibitory concentrations, respectively. We found two mutations in PBP1A, G591K and A480V, and analyzed these in recombinants to directly demonstrate their association with AMX resistance. Assessment of multiple isolates from different stomach regions will improve accurate assessment of H. pylori colonization status in the stomach.


Amoxicillin , Anti-Bacterial Agents , Drug Resistance, Bacterial , Helicobacter Infections , Helicobacter pylori , Microbial Sensitivity Tests , Mutation , Humans , Helicobacter pylori/genetics , Helicobacter pylori/drug effects , Helicobacter pylori/isolation & purification , Helicobacter Infections/microbiology , Helicobacter Infections/drug therapy , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Drug Resistance, Bacterial/genetics , Amoxicillin/pharmacology , Amoxicillin/therapeutic use , Male , Female , Metronidazole/pharmacology , Stomach/microbiology , Clarithromycin/pharmacology , Middle Aged , Aged , Adult , Bacterial Proteins/genetics , Penicillin-Binding Proteins/genetics , Fluoroquinolones/pharmacology , Fluoroquinolones/therapeutic use
6.
Clin Neuropharmacol ; 47(3): 104-107, 2024.
Article En | MEDLINE | ID: mdl-38743605

OBJECTIVES: Metronidazole central nervous system toxicity is a rare finding in patients receiving the medication. We report a peculiar case of metronidazole central nervous system toxicity in which both the underlying condition (Crohn disease) and the drugs used to treat it are potential causes of encephalopathy. METHODS: A 26-year-old female with 6-year history of Crohn's disease for 6 years presented acute-onset encephalopathy. We provide bibliographic evidence to support metronidazole toxicity and potential Crohn disease-associated neurologic involvement. RESULTS: The patient presented dystonia, cerebellar ataxia, and altered mental status. Magnetic resonance imaging of the brain revealed typical findings of metronidazole toxicity and white matter involvement of the centrum semiovale. Immunoelectrophoresis and immunofixation of serum and cerebrospinal fluid proteins were consistent with a systemic inflammatory process. We concluded on an association between drug toxicity and probable Crohn-associated neurologic involvement. Metronidazole was stopped and the patient was placed on vitamin therapy and diazepam to control dystonia. She deteriorated and was transferred to the intensive care unit where she expired. CONCLUSIONS: Acute behavioral changes in a young patient constitute an emergency and differential diagnoses should include infective, inflammatory, metabolic, and toxic causes. Metronidazole is a potential toxic etiology.


Crohn Disease , Encephalitis , Metronidazole , Humans , Metronidazole/adverse effects , Female , Crohn Disease/drug therapy , Crohn Disease/complications , Adult , Encephalitis/chemically induced , Brain Diseases/chemically induced , Magnetic Resonance Imaging , Fatal Outcome
7.
JAMA Netw Open ; 7(5): e248661, 2024 May 01.
Article En | MEDLINE | ID: mdl-38696172

Importance: Bacterial vaginosis (BV) is a common cause of vaginal infection. First-line treatments of BV are metronidazole and clindamycin. Due to the increase in antibiotic resistance, effective nonantibiotic treatments for BV are needed. Objective: To examine whether dequalinium chloride, a broad-spectrum antiseptic, is noninferior to oral metronidazole for the treatment of BV. Design, Setting, and Participants: This phase 4, multicenter, triple-blind, double-dummy, parallel, noninferiority randomized clinical trial was conducted from July 29, 2021, to August 25, 2022, with a 1-month follow-up. Participants were premenopausal women 18 years or older with BV from 11 gynecologic practices and 1 hospital in Poland, Slovakia, and the Czech. Intervention: Patients were randomized to treatment with dequalinium chloride vaginal tablets (10 mg once daily for 6 days) or oral metronidazole (500 mg twice daily for 7 days). Double-dummy medication kits contained vaginal and oral tablets with placebo and active medication. Main Outcomes and Measures: The main outcome was the noninferiority margin (of 15 percentage points) in the absolute difference in clinical cure rates between dequalinium chloride and metronidazole 7 to 11 days after start of treatment (visit 1). Noninferiority was met if the lower 95% CI for the difference in clinical cure rate was less than 15 percentage points at visit 1. Results: A total of 147 women (mean [SD] age, 36.7 [9.0] years) were treated with dequalinium chloride (n = 72) or metronidazole (n = 75). The clinical cure rates at visit 1 were 64 of 69 (92.8%) for dequalinium chloride vs 69 of 74 (93.2%) for metronidazole in the intention-to-treat population, whereas in the per-protocol population, cure rates were 54 of 58 (93.1%) for dequalinium chloride vs 48 of 53 (90.6%) for metronidazole. The treatment differences of -0.5 percentage points (95% CI, -10.8 to 9.8 percentage points; P = .002) in the intention-to-treat population and 2.5 percentage points (95% CI, -9.4 to 14.4 percentage points; P = .001) in the per-protocol population confirmed the noninferiority of dequalinium chloride. The tolerability of dequalinium chloride was rated as very good by 30 of 50 patients (60.0%) but only by 21 of 54 (38.9%) for metronidazole. Three patients in the metronidazole group suspended treatment due to an adverse event. Conclusions and Relevance: This randomized clinical trial showed that dequalinium chloride was not inferior to metronidazole for the treatment of BV. Dequalinium chloride had a similarly high cure rate but with better tolerability and fewer adverse events. With a similar efficacy to metronidazole and clindamycin, dequalinium chloride warrants consideration as first-line treatment for BV to help reduce antibiotic consumption. Trial Registration: EudraCT: 2020-002489-15.


Dequalinium , Metronidazole , Vaginosis, Bacterial , Humans , Female , Metronidazole/therapeutic use , Vaginosis, Bacterial/drug therapy , Adult , Dequalinium/therapeutic use , Treatment Outcome , Double-Blind Method , Middle Aged , Administration, Intravaginal , Anti-Bacterial Agents/therapeutic use , Administration, Oral , Young Adult
8.
Sex Transm Dis ; 51(6): 437-440, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38733973

OBJECTIVES: Live biotherapeutic products (LBPs) containing vaginal Lactobacillus crispatus are promising adjuvant treatments to prevent recurrent bacterial vaginosis (BV) but may depend on the success of initial antibiotic treatment. METHODS: A post hoc analysis of data collected during the phase 2b LACTIN-V randomized control trial (L. crispatus CTV-05) explored the impact of clinical BV cure defined as Amsel criteria 0 of 3 (excluding pH, per 2019 Food and Drug Administration guidance) 2 days after completion of treatment with vaginal metronidazole gel on the effectiveness of an 11-week LACTIN-V dosing regimen to prevent BV recurrence by 12 and 24 weeks. RESULTS: At enrollment, 88% of participants had achieved postantibiotic clinical BV cure. The effect of LACTIN-V on BV recurrence compared with placebo differed by initial clinical BV cure status. The LACTIN-V to placebo risk ratio of BV recurrence by 12 weeks was 0.56 (95% confidence interval, 0.35-0.77) among participants with initial clinical BV cure after metronidazole treatment and 1.34 (95% confidence interval, 0.47-2.23) among participants without postantibiotic clinical BV cure. Among women receiving LACTIN-V, those who had achieved postantibiotic clinical BV cure at enrollment reached higher levels of detectable L. crispatus CTV-05 compared with women failing to achieve postantibiotic clinical BV cure. CONCLUSIONS: LACTIN-V seems to only decrease BV recurrence in women with clinical cure of BV after initial antibiotic treatment. Future trials of LBPs should consider limiting enrollment to these women.


Anti-Bacterial Agents , Lactobacillus crispatus , Metronidazole , Probiotics , Vaginosis, Bacterial , Humans , Female , Vaginosis, Bacterial/drug therapy , Vaginosis, Bacterial/prevention & control , Vaginosis, Bacterial/microbiology , Metronidazole/administration & dosage , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Adult , Lactobacillus crispatus/physiology , Probiotics/administration & dosage , Treatment Outcome , Recurrence , Secondary Prevention , Administration, Intravaginal , Young Adult , Vagina/microbiology , Double-Blind Method
9.
Front Cell Infect Microbiol ; 14: 1368684, 2024.
Article En | MEDLINE | ID: mdl-38779565

Introduction: Quorum-quenching enzyme Est816 hydrolyzes the lactone rings of N-acyl homoserine lactones, effectively blocking the biofilm formation and development of Gram-negative bacteria. However, its applications in the oral field is limited. This study aimed to evaluate the efficacy of enzyme Est816 in combination with antibiotics against periodontitis induced by Aggregatibacter actinomycetemcomitans in vitro and in vivo. Methods: The antimicrobial efficacy of enzyme Est816 in combination with minocycline, metronidazole, and amoxicillin was determined using the minimum inhibitory concentration test. The anti-biofilm effect of enzyme Est816 was assessed using scanning electron microscopy, live/dead bacterial staining, crystal violet staining, and real-time quantitative PCR. Biocompatibility of enzyme Est816 was assessed in human gingival fibroblasts (HGF) by staining. A rat model of periodontitis was established to evaluate the effect of enzyme Est816 combined with minocycline using micro-computed tomography and histological staining. Results: Compared to minocycline, metronidazole, and amoxicillin treatment alone, simultaneous treatment with enzyme Est816 increased the sensitivity of biofilm bacteria to antibiotics. Enzyme Est816 with minocycline exhibited the highest rate of biofilm clearance and high biocompatibility. Moreover, the combination of enzyme Est816 with antibiotics improved the antibiofilm effects of the antibiotics synergistically, reducing the expression of the virulence factor leukotoxin gene (ltxA) and fimbria-associated gene (rcpA). Likewise, the combination of enzyme Est816 with minocycline exhibited a remarkable inhibitory effect on bone resorption and inflammation damage in a rat model of periodontitis. Discussion: The combination of enzyme Est816 with antibiotics represents a prospective anti-biofilm strategy with the potential to treat periodontitis.


Aggregatibacter actinomycetemcomitans , Anti-Bacterial Agents , Biofilms , Disease Models, Animal , Metronidazole , Microbial Sensitivity Tests , Periodontitis , Quorum Sensing , Animals , Aggregatibacter actinomycetemcomitans/drug effects , Biofilms/drug effects , Anti-Bacterial Agents/pharmacology , Periodontitis/drug therapy , Periodontitis/microbiology , Rats , Humans , Metronidazole/pharmacology , Quorum Sensing/drug effects , Minocycline/pharmacology , Amoxicillin/pharmacology , Rats, Sprague-Dawley , Male , Fibroblasts/drug effects , Gingiva/microbiology
10.
Sci Rep ; 14(1): 11430, 2024 05 20.
Article En | MEDLINE | ID: mdl-38769330

Liver abscess is a potentially life-threatening medical emergency. Prompt empirical antimicrobial with or without percutaneous aspiration or drainage is therapeutic. The rational for using empirical intravenous broad-spectrum antimicrobials upfront instead of oral Fluoroquinolone or Cephalosporin is contentious. In this double blind randomized control clinical trial 69 participants received Ciprofloxacin (500 mg q 12 hourly) and 71 participants received Cefixime (200 mg q 12 hourly) orally for 2 weeks. Both the group received oral Metronidazole (800 mg q 8 hourly) for 2 weeks and percutaneous drainage or aspiration of the abscess was done as per indication and followed-up for 8 weeks. Out of 140 participants, 89.3% (N = 125) achieved clinical cure, 59 (85.5%) in Ciprofloxacin group and 66 (93%) in Cefixime group (p = 0.154). Mean duration of antimicrobial therapy was 16.2 ± 4.3 days, 15.1 ± 4.5 days in Ciprofloxacin group and 16.0 ± 4.2 days in Cefixime group (p = 0.223). Total 15 (10.7%) participants had treatment failure, 10 (14.5%) in Ciprofloxacin group and 5 (7.0%) in Cefixime group (p = 0.154). The most common reason for treatment failure was need of prolong (> 4 weeks) antimicrobial therapy due to persistent hepatic collection requiring drainage, which was significantly (p = 0.036) higher in Ciprofloxacin (14.5%, N = 10) group, compared to the Cefixime (4.2%, N = 3) group. In conclusion, both, the Ciprofloxacin or Cefixime plus Metronidazole for duration of 2-3 weeks were efficacious as empirical oral antimicrobial regimen along with prompt percutaneous drainage or aspiration for the treatment of uncomplicated liver abscess with similar efficacy. Oral Cefixime was better than Ciprofloxacin in term of lesser chance of treatment failure due to persistent collection which is required to be investigated further in larger clinical trial.Trial registration: clinicaltrials.gov PRS ID: NCT03969758, 31/05/2019.


Anti-Bacterial Agents , Cefixime , Ciprofloxacin , Liver Abscess , Metronidazole , Humans , Ciprofloxacin/administration & dosage , Ciprofloxacin/therapeutic use , Metronidazole/administration & dosage , Metronidazole/therapeutic use , Cefixime/therapeutic use , Cefixime/administration & dosage , Male , Female , Middle Aged , Adult , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Liver Abscess/drug therapy , Liver Abscess/microbiology , Treatment Outcome , Double-Blind Method , Drug Therapy, Combination , Drainage , Aged
11.
BMC Microbiol ; 24(1): 177, 2024 May 23.
Article En | MEDLINE | ID: mdl-38783194

BACKGROUND: Clostridioides difficile is the main pathogen of antimicrobial-associated diarrhoea and health care facility-associated infectious diarrhoea. This study aimed to investigate the prevalence, toxin genotypes, and antibiotic resistance of C. difficile among hospitalized patients in Xi'an, China. RESULTS: We isolated and cultured 156 strains of C. difficile, representing 12.67% of the 1231 inpatient stool samples collected. Among the isolates, tcdA + B + strains were predominant, accounting for 78.2% (122/156), followed by 27 tcdA-B + strains (27/156, 17.3%) and 6 binary toxin gene-positive strains. The positive rates of three regulatory genes, tcdC, tcdR, and tcdE, were 89.1% (139/156), 96.8% (151/156), and 100%, respectively. All isolates were sensitive to metronidazole, and the resistance rates to clindamycin and cephalosporins were also high. Six strains were found to be resistant to vancomycin. CONCLUSION: Currently, the prevalence rate of C. difficile infection (CDI) in Xi'an is 12.67% (156/1231), with the major toxin genotype of the isolates being tcdA + tcdB + cdtA-/B-. Metronidazole and vancomycin were still effective drugs for the treatment of CDI, but we should pay attention to antibiotic management and epidemiological surveillance of CDI.


Anti-Bacterial Agents , Bacterial Toxins , Clostridioides difficile , Clostridium Infections , Feces , Genotype , Hospitals , Clostridioides difficile/genetics , Clostridioides difficile/drug effects , Clostridioides difficile/isolation & purification , Clostridioides difficile/classification , Humans , China/epidemiology , Anti-Bacterial Agents/pharmacology , Clostridium Infections/microbiology , Clostridium Infections/epidemiology , Bacterial Toxins/genetics , Hospitals/statistics & numerical data , Feces/microbiology , Drug Resistance, Bacterial/genetics , Prevalence , Microbial Sensitivity Tests , Female , Middle Aged , Male , Aged , Adult , Bacterial Proteins/genetics , Diarrhea/microbiology , Diarrhea/epidemiology , Metronidazole/pharmacology , Young Adult , Enterotoxins/genetics , Adolescent , Vancomycin/pharmacology , Clindamycin/pharmacology , Aged, 80 and over
12.
Int J Mol Sci ; 25(10)2024 May 07.
Article En | MEDLINE | ID: mdl-38791121

Melanoma, arguably the deadliest form of skin cancer, is responsible for the majority of skin-cancer-related fatalities. Innovative strategies concentrate on new therapies that avoid the undesirable effects of pharmacological or medical treatment. This article discusses the chemical structures of [(MTZ)2AgNO3], [(MTZ)2Ag]2SO4, [Ag(MCZ)2NO3], [Ag(MCZ)2BF4], [Ag(MCZ)2SbF6] and [Ag(MCZ)2ClO4] (MTZ-metronidazole; MCZ-miconazole) silver(I) compounds and the possible relationship between the molecules and their cytostatic activity against melanoma cells. Molecular Hirshfeld surface analysis and computational methods were used to examine the possible association between the structure and anticancer activity of the silver(I) complexes and compare the cytotoxicity of the silver(I) complexes of metronidazole and miconazole with that of silver(I) nitrate, cisplatin, metronidazole and miconazole complexes against A375 and BJ cells. Additionally, these preliminary biological studies found the greatest IC50 values against the A375 line were demonstrated by [Ag(MCZ)2NO3] and [(MTZ)2AgNO3]. The compound [(MTZ)2AgNO3] was three-fold more toxic to the A375 cells than the reference (cisplatin) and 15 times more cytotoxic against the A375 cells than the normal BJ cells. Complexes of metronidazole with Ag(I) are considered biocompatible at a concentration below 50 µmol/L.


Antineoplastic Agents , Coordination Complexes , Melanoma , Metronidazole , Miconazole , Silver , Humans , Melanoma/drug therapy , Melanoma/metabolism , Melanoma/pathology , Miconazole/pharmacology , Miconazole/chemistry , Silver/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Metronidazole/chemistry , Metronidazole/pharmacology , Cell Line, Tumor , Coordination Complexes/pharmacology , Coordination Complexes/chemistry , Cell Survival/drug effects , Skin Neoplasms/drug therapy , Skin Neoplasms/pathology
14.
Helicobacter ; 29(2): e13060, 2024.
Article En | MEDLINE | ID: mdl-38581134

BACKGROUND: Treatment of Helicobacter pylori gastric infection is complex and associated with increased rates of therapeutic failure. This research aimed to characterize the H. pylori infection status, strain resistance to antimicrobial agents, and the predominant lesion pattern in the gastroduodenal mucosa of patients with clinical suspicion of refractoriness to first- and second-line treatment who were diagnosed and treated in a health center in Guayaquil, Ecuador. METHODS: A total of 374 patients with upper gastrointestinal symptoms and H. pylori infection were preselected and prescribed one of three triple therapy regimens for primary infection, as judged by the treating physician. Subsequently, 121 patients who returned to the follow-up visit with persistent symptoms after treatment were studied. RESULTS: All patients had H. pylori infection. Histopathological examination diagnosed chronic active gastritis in 91.7% of cases; premalignant lesions were observed in 15.8%. The three triple therapy schemes applied showed suboptimal efficacy (between 47.6% and 77.2%), with the best performance corresponding to the scheme consisting of a proton pump inhibitor + amoxicillin + levofloxacin. Bacterial strains showed very high phenotypic resistance to all five antimicrobials tested: clarithromycin, 82.9%; metronidazole, 69.7%; amoxicillin and levofloxacin, almost 50%; tetracycline, 38.2%. Concurrent resistance to clarithromycin-amoxicillin was 43.4%, to tetracycline-metronidazole 30.3%, to amoxicillin-levofloxacin 27.6%, and to clarithromycin-metronidazole 59.2%. CONCLUSIONS: In vitro testing revealed resistance to all five antibiotics, indicating that H. pylori exhibited resistance phenotypes to these antibiotics. Consequently, the effectiveness of triple treatments may be compromised, and further studies are needed to assess refractoriness in quadruple and concomitant therapies.


Anti-Infective Agents , Helicobacter Infections , Helicobacter pylori , Humans , Clarithromycin/pharmacology , Clarithromycin/therapeutic use , Metronidazole/pharmacology , Helicobacter Infections/drug therapy , Helicobacter Infections/microbiology , Levofloxacin/pharmacology , Ecuador , Anti-Bacterial Agents/pharmacology , Amoxicillin/pharmacology , Tetracycline/therapeutic use , Tetracycline/pharmacology , Drug Therapy, Combination
15.
Korean J Gastroenterol ; 83(4): 150-156, 2024 Apr 25.
Article En | MEDLINE | ID: mdl-38659251

Background/Aims: Helicobacter pylori (H. pylori) is the most prevalent infection in the world and is strongly associated with gastric adenocarcinoma, lymphoma and gastric or duodenal ulcers. Different regimens have been used for H. pylori eradication. We aimed to compare the efficacy of two different regimens as first-line H. pylori eradication regimens, in an area with high antibiotic resistance. Methods: In this RCT, we assigned 223 patients with H. pylori infection, who were naïve to treatment. They were randomly divided into two groups to receive either 12-day concomitant quadruple therapy (consisting of pantoprazole 40 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg every 12 hours) or 14-day high dose dual therapy (consisting of esomeprazole 40 mg and amoxicillin 1 g TDS). H. pylori eradication was assessed eight weeks after the end of treatment. Results: H. pylori eradication rate by PP analysis for 12-day concomitant quadruple therapy and 14-day high dose dual therapy were 90.4% and 79.1%, respectively (p=0.02). According to ITT analysis, the eradication rates were 86.2% and 76.3%, respectively (p=0.06). Adverse drug reactions were 12.3% in high dose dual therapy and 36.8% in concomitant quadruple therapy (p<0.001). Conclusions: Twelve-day concomitant therapy seems to be an acceptable regimen for first-line H. pylori eradication in Iran, a country with a high rate of antibiotic resistance. Although, high dose dual therapy did not result in an ideal eradication rate, but it had fewer drug side effects than the 12-day concomitant regimen.


Amoxicillin , Anti-Bacterial Agents , Clarithromycin , Drug Therapy, Combination , Esomeprazole , Helicobacter Infections , Helicobacter pylori , Metronidazole , Adult , Aged , Female , Humans , Male , Middle Aged , Amoxicillin/therapeutic use , Anti-Bacterial Agents/therapeutic use , Clarithromycin/therapeutic use , Clarithromycin/administration & dosage , Drug Administration Schedule , Esomeprazole/therapeutic use , Esomeprazole/administration & dosage , Helicobacter Infections/drug therapy , Helicobacter pylori/drug effects , Metronidazole/therapeutic use , Pantoprazole/therapeutic use , Proton Pump Inhibitors/therapeutic use , Treatment Outcome
16.
Sci Rep ; 14(1): 8986, 2024 04 18.
Article En | MEDLINE | ID: mdl-38637591

Potassium-competitive acid blockers (P-CABs) provide potent acid inhibition, yet studies on P-CAB-based quadruple therapy for H. pylori eradication are limited. We theorized that integrating bismuth subsalicylate into a quadruple therapy regimen could enhance eradication rates. However, data on the efficacy of vonoprazan bismuth quadruple therapy are notably scarce. Therefore, the aim of this study was to evaluate the efficacy of vonoprazan-based bismuth quadruple therapy in areas with high clarithromycin and levofloxacin resistance. This was a prospective, single-center, randomized trial conducted to compare the efficacy of 7-day and 14-day vonoprazan-based bismuth quadruple therapy for H. pylori eradication between June 1, 2021, and March 31, 2022. Qualified patients were randomly assigned to the 7-day or 14-day regimen (1:1 ratio by computer-generated randomized list as follows: 51 patients for the 7-day regimen and 50 patients for the 14-day regimen). The regimens consisted of vonoprazan (20 mg) twice daily, bismuth subsalicylate (1024 mg) twice daily, metronidazole (400 mg) three times daily, and tetracycline (500 mg) four times daily. CYP3A4/5 genotyping and antibiotic susceptibility tests were also performed. Successful eradication was defined as 13negative C-UBTs 4 weeks after treatment. The primary endpoint was to compare the efficacy of 7-day and 14-day regimens as first-line treatments, which were assessed by intention-to-treat (ITT) and per-protocol (PP) analyses. The secondary endpoints included adverse effects. A total of 337 dyspeptic patients who underwent gastroscopy were included; 105 patients (31.1%) were diagnosed with H. pylori infection, and 101 patients were randomly assigned to each regimen. No dropouts were detected. The antibiotic resistance rate was 33.3% for clarithromycin, 29.4% for metronidazole, and 27.7% for levofloxacin. The CYP3A4 genotype was associated with 100% rapid metabolism. The H. pylori eradication rates for the 7-day and 14-day regimens were 84.4%, 95% CI 74.3-94.2 and 94%, 95% CI 87.4-100, respectively (RR difference 0.25, 95% CI 0.03-0.53, p value = 0.11). Interestingly, the 14-day regimen led to 100% eradication in the clarithromycin-resistant group. Among the patients in the 7-day regimen group, only two exhibited resistance to clarithromycin; unfortunately, neither of them achieved a cure from H. pylori infection. The incidence of adverse events was similar in both treatment groups, occurring in 29.4% (15/51) and 28% (14/50) of patients in the 7-day and 14-day regimens, respectively. No serious adverse reactions were reported. In conclusion, 14 days of vonoprazan-based bismuth quadruple therapy is highly effective for H. pylori eradication in areas with high levels of dual clarithromycin and levofloxacin resistance.


Helicobacter Infections , Helicobacter pylori , Organometallic Compounds , Pyrroles , Salicylates , Sulfonamides , Humans , Clarithromycin/pharmacology , Bismuth/therapeutic use , Bismuth/adverse effects , Levofloxacin/adverse effects , Metronidazole/adverse effects , Prospective Studies , Cytochrome P-450 CYP3A , Anti-Bacterial Agents/adverse effects , Helicobacter Infections/genetics , Drug Therapy, Combination , Treatment Outcome
17.
J Colloid Interface Sci ; 666: 512-528, 2024 Jul 15.
Article En | MEDLINE | ID: mdl-38613974

Metronidazole (MNZ), a commonly used antibiotic, poses risks to water bodies and human health due to its potential carcinogenic, mutagenic, and genotoxic effects. In this study, mesoporous cobalt-manganese layered double hydroxides (CoxMny-LDH) with abundant oxygen vacancies (Ov) were successfully synthesized using the co-precipitation method and used to activate calcium sulfite (CaSO3) with slight soluble in water for MNZ degradation. The characterization results revealed that Co2Mn-LDH had higher specific areas and exhibited good crystallinity. Co2Mn-LDH/CaSO3 exhibited the best catalytic performance under optimal conditions, achieving a remarkable MNZ degradation efficiency of up to 98.1 % in only 8 min. Quenching experiments and electron paramagnetic resonance (EPR) tests showed that SO4•- and 1O2 played pivotal roles in the MNZ degradation process by activated CaSO3, while the redox cycles of Co2+/Co3+ and Mn3+/Mn4+ on the catalyst surface accelerated electron transfer, promoting radical generation. Three MNZ degradation routes were put forward based on the density functional theory (DFT) and liquid chromatography-mass spectrometer (LC-MS) analysis. Meanwhile, the toxicity analysis result demonstrated that the toxicity of intermediates post-catalytic reaction was decreased. Furthermore, the Co2Mn-LDH/CaSO3 system displayed excellent stability, reusability, and anti-interference capability, and achieved a comparably high removal efficiency across various organic pollutant water bodies. This study provides valuable insights into the development and optimization of effective heterogeneous catalysts for treating antibiotic-contaminated wastewater.


Cobalt , Hydroxides , Manganese , Metronidazole , Cobalt/chemistry , Metronidazole/chemistry , Hydroxides/chemistry , Manganese/chemistry , Porosity , Surface Properties , Sulfites/chemistry , Catalysis , Particle Size , Density Functional Theory , Water Pollutants, Chemical/chemistry
18.
Environ Res ; 252(Pt 3): 119029, 2024 Jul 01.
Article En | MEDLINE | ID: mdl-38685299

Antibiotics released into water sources pose significant risks to both human health and the environment. This comprehensive review meticulously examines the ecotoxicological impacts of three prevalent antibiotics-ciprofloxacin, metronidazole, and sulfamethoxazole-on the ecosystems. Within this framework, our primary focus revolves around the key remediation technologies: adsorption and advanced oxidation processes (AOPs). In this context, an array of adsorbents is explored, spanning diverse classes such as biomass-derived biosorbents, graphene-based adsorbents, MXene-based adsorbents, silica gels, carbon nanotubes, carbon-based adsorbents, metal-organic frameworks (MOFs), carbon nanofibers, biochar, metal oxides, and nanocomposites. On the flip side, the review meticulously examines the main AOPs widely employed in water treatment. This includes a thorough analysis of ozonation (O3), the photo-Fenton process, UV/hydrogen peroxide (UV/H2O2), TiO2 photocatalysis, ozone/UV (O3/UV), radiation-induced AOPs, and sonolysis. Furthermore, the review provides in-depth insights into equilibrium isotherm and kinetic models as well as prospects and challenges inherent in these cutting-edge processes. By doing so, this review aims to empower readers with a profound understanding, enabling them to determine research gaps and pioneer innovative treatment methodologies for water contaminated with antibiotics.


Anti-Bacterial Agents , Ciprofloxacin , Oxidation-Reduction , Sulfamethoxazole , Wastewater , Water Pollutants, Chemical , Water Purification , Water Pollutants, Chemical/chemistry , Water Pollutants, Chemical/analysis , Sulfamethoxazole/chemistry , Adsorption , Anti-Bacterial Agents/chemistry , Water Purification/methods , Wastewater/chemistry , Ciprofloxacin/chemistry , Metronidazole/chemistry
19.
J Antimicrob Chemother ; 79(6): 1320-1328, 2024 Jun 03.
Article En | MEDLINE | ID: mdl-38598696

OBJECTIVES: To determine the frequencies and clonal distributions of putative genetic determinants of resistance to antimicrobials applied for treatment of Clostridioides difficile infection (CDI), as documented in the genomic record. METHODS: We scanned 26 557 C. difficile genome sequences publicly available from the EnteroBase platform for plasmids, point mutations and gene truncations previously reported to reduce susceptibility to vancomycin, fidaxomicin or metronidazole, respectively. We measured the antimicrobial susceptibility of 143 selected C. difficile isolates. RESULTS: The frequency of mutations causing reduced susceptibility to vancomycin and metronidazole, respectively, increased strongly after 2000, peaking at up to 52% of all sequenced C. difficile genomes. However, both mutations declined sharply more recently, reflecting major changes in CDI epidemiology. We detected mutations associated with fidaxomicin resistance in several major genotypes, but found no evidence of international spread of resistant clones. The pCD-METRO plasmid, conferring metronidazole resistance, was detected in a single previously unreported C. difficile isolate, recovered from a hospital patient in Germany in 2008. The pX18-498 plasmid, putatively associated with decreased vancomycin susceptibility, was confined to related, recent isolates from the USA. Phenotype measurements confirmed that most of those genetic features were useful predictors of antibiotic susceptibility, even though ranges of MICs typically overlapped among isolates with and without specific mutations. CONCLUSIONS: Genomic data suggested that resistance to therapeutic antimicrobial drugs is rare in C. difficile. Public antimicrobial resistance marker databases were not equipped to detect most of the genetic determinants relevant to antibiotic therapy of CDI.


Anti-Bacterial Agents , Clostridioides difficile , Drug Resistance, Bacterial , Genome, Bacterial , Microbial Sensitivity Tests , Plasmids , Clostridioides difficile/genetics , Clostridioides difficile/drug effects , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Drug Resistance, Bacterial/genetics , Plasmids/genetics , Clostridium Infections/drug therapy , Clostridium Infections/microbiology , Vancomycin/pharmacology , Vancomycin/therapeutic use , Metronidazole/pharmacology , Metronidazole/therapeutic use , Genotype , Mutation
20.
Nanotechnology ; 35(31)2024 May 13.
Article En | MEDLINE | ID: mdl-38663370

The overuse of antibiotics currently results in the presence of various antibiotics being detected in water bodies, which poses potential risks to human health and the environment. Therefore, it is highly significant to remove antibiotics from water. In this study, we developed novel rod-like NiCo-phyllosilicate hybrid catalysts on calcined natural zeolite (NiCo@C-zeolite) via a facile one-pot process. The presence of the zeolite served as both a silicon source and a support, maintaining a high specific surface area of the NiCo@C-zeolite. Remarkably, NiCo@C-zeolite exhibited outstanding catalytic performance in antibiotic degradation under PMS activation. Within just 5 min, the degradation rate of metronidazole (MNZ) reached 96.14%, ultimately achieving a final degradation rate of 99.28%. Furthermore, we investigated the influence of catalyst dosage, PMS dosage, MNZ concentration, initial pH value, and various inorganic anions on the degradation efficiency of MNZ. The results demonstrated that NiCo@C-zeolite displayed outstanding efficacy in degrading MNZ under diverse conditions and maintained a degradation rate of 94.86% at 60 min after three consecutive cycles of degradation. Free radical quenching experiments revealed that SO•-4played a significant role in the presence of NiCo@C-zeolite-PMS system. These findings indicate that the novel rod-like NiCo-phyllosilicate hybrid catalysts had excellent performance in antibiotic degradation.


Anti-Bacterial Agents , Zeolites , Zeolites/chemistry , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Catalysis , Water Pollutants, Chemical/chemistry , Metronidazole/chemistry , Water Purification/methods , Silicates/chemistry
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