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1.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 59(7): 672-680, 2024 Jul 09.
Article in Chinese | MEDLINE | ID: mdl-38949135

ABSTRACT

Objective: To investigate the effects of Porphyromonas gingivalis (Pg) persisters (Ps) on immuno-inflammatory responses in macrophages, and to explore the underlying mechanisms. Methods: Pg cells were cultured to the stationary phase (72 h), and subsequently treated by high concentration of metronidazole at 100 mg/L, amoxicillin at 100 mg/L and the combination of them for different time period, named as metronidazole group, amoxicillin group and (metronidazole+amoxicillin) group. Pg cells without treatment were used as Blank control. The survival profile of PgPs cells was measured by colony-forming unit assay. The living state of PgPs was observed by Live/Dead staining. Then, Pg and metronidazole-treated PgPs (M-PgPs) were used to treat macrophages, named as Pg group and M-PgPs group. Transmission electron microscopy (TEM) was used to observe the bacteria in the macrophages. The expression levels of proinflammatory cytokines in macrophages were determined by real-time fluorescence quantitative PCR and enzyme-linked immunosorbent assay. The location of forkhead box transcription factor 1 (FOXO1) was detected by confocal immunofluorescence microscopy. After inhibiting or enhancing the FOXO1 expressions using inhibitors (Fi) or activators (Fa) respectively, the macrophages were treated with Pg and M-PgPs, divided as Blank group, Pg group, M-PgPs group, Fi group, (Fi+Pg) group, (Fi+M-PgPs) group, Fa group, (Fa+Pg) group and (Fa+M-PgPs) group. Then, the expression pattens of proinflammatory cytokines were assessed. Results: Remarkable number of lived PgPs was observed, both in planktonic culture and Pg biofilms either treated with metronidazole, amoxicillin or both, and those persisters could form new colonies. Pg and M-PgPs were able to enter into the macrophages and the protein expression levels of interleukin (IL)-1ß, IL-6, IL-8 and tumor necrosis factor-α (TNF-α) [Pg group: (2 392±188), (162±29), (5 558±661), (789±155) µg/L; M-PgPs group: (2 415±420), (155±3), (5 732±782), (821±176) µg/L] were significantly upregulated than those in Blank group [(485±140), (21±9), (2 332±87), (77±7) µg/L] (P<0.01). Moreover, Pg and M-PgPs could facilitate the nuclear translocation and accumulation of FOXO1. In addition, the relative mRNA expression levels of FOXO1, B-cell lymphoma 6 and Krüppel-like factor 2 were upregulated when compared to Blank group (P<0.05). Furthermore, the protein expression levels of IL-1ß, IL-6, IL-8 and TNF-α in Fi+Pg group [(1 081±168), (70±8), (1 976±544), (420±47) µg/L] were remarkably lower than Pg group [(4 411±137), (179±6), (5 161±929), (934±24) µg/L] (P<0.05). Similarly, the protein expression levels of IL-1ß, IL-6, IL-8 and TNF-α in Fi+M-PgPs group [(1 032±237), (74±10), (1 861±614), (405±32) µg/L] were remarkably lower than M-PgPs group [(4 342±314), (164±17), (4 438±1 374), (957±25) µg/L] (P<0.05). On the contrary, the protein expression levels of IL-1ß, IL-6, IL-8 and TNF-α in Fa+Pg group [(8 198±1 825), (431±28), (8 919±650), (2 186±301) µg/L] and Fa+M-PgPs group [(8 159±2 627), (475±26), (8 995±653), (2 255±387) µg/L] were significantly higher than Pg group and M-PgPs group, respectively (P<0.05). Conclusions: PgPs are highly tolerant to metronidazole and amoxicillin. The M-PgPs could enhance the immuno-inflammatory responses in macrophages by upregulating the FOXO1 signaling pathway, while this effect exhibits no significant difference with Pg.


Subject(s)
Biofilms , Macrophages , Metronidazole , Porphyromonas gingivalis , Signal Transduction , Macrophages/metabolism , Metronidazole/pharmacology , Biofilms/drug effects , Tumor Necrosis Factor-alpha/metabolism , Interleukin-6/metabolism , Amoxicillin/pharmacology , Up-Regulation , Animals , Interleukin-1beta/metabolism , Mice , Forkhead Box Protein O1/metabolism , Interleukin-8/metabolism , Inflammation , Humans
2.
PLoS One ; 19(7): e0304705, 2024.
Article in English | MEDLINE | ID: mdl-38980858

ABSTRACT

This is a protocol for PPROM-AZM Study, phase II, nonblinded, randomized controlled trial. Bronchopulmonary dysplasia (BPD) at a postmenstrual age of 36 weeks (BPD36) is often observed in infants with preterm premature rupture of the membranes (pPROM). A regimen of ampicillin (ABPC) intravenous infusion for 2 days and subsequent amoxicillin (AMPC) oral administration for 5 days plus erythromycin (EM) intravenous infusion for 2 days followed by EM oral administration for 5 days is standard treatment for pPROM. However, the effect on the prevention of moderate/severe BPD36 using the standard treatment has not been confirmed. Recently, it is reported that ampicillin/sulbactam (ABPC/SBT) plus azithromycin (AZM) was effective for the prevention of moderate/severe BPD36 in pPROM patients with amniotic infection of Ureaplasma species. Therefore, our aim is to evaluate the occurrence rate of the composite outcome of "incidence rate of either moderate/severe BPD36 or intrauterine fetal death, and infantile death at or less than 36 weeks 0 days" comparing subjects to receive ABPC/SBT for 14 days plus AZM for 14 days (intervention group) and those to receive ABPC/SBT for 14 days plus EM for 14 days (control group), in a total of 100 subjects (women with pPROM occurring at 22-27 weeks of gestation) in Japan. The recruit of subjects was started on April 2022, and collection in on-going. We also investigate the association between the detection of Ureaplasma species and occurrence of BPD36. In addition, information on any adverse events for the mother and fetus and serious adverse events for infants are collected during the observation period. We allocate patients at a rate of 1:1 considering two stratification factors: onset of pPROM (22-23 or 24-27 weeks) and presence/absence of a hospital policy for early neonatal administration of caffeine. Trial registration: The trial number in the Japan Registry of Clinical Trials is jRCTs031210631.


Subject(s)
Ampicillin , Anti-Bacterial Agents , Azithromycin , Bronchopulmonary Dysplasia , Erythromycin , Fetal Membranes, Premature Rupture , Adult , Female , Humans , Infant, Newborn , Pregnancy , Amoxicillin/therapeutic use , Amoxicillin/administration & dosage , Ampicillin/administration & dosage , Ampicillin/therapeutic use , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Azithromycin/administration & dosage , Azithromycin/therapeutic use , Bronchopulmonary Dysplasia/prevention & control , Bronchopulmonary Dysplasia/drug therapy , Drug Therapy, Combination , Erythromycin/therapeutic use , Erythromycin/administration & dosage , Fetal Membranes, Premature Rupture/drug therapy , Gestational Age , Japan/epidemiology , Sulbactam/administration & dosage , Sulbactam/therapeutic use , Randomized Controlled Trials as Topic , Multicenter Studies as Topic , Clinical Trials, Phase II as Topic
3.
PLoS One ; 19(7): e0304684, 2024.
Article in English | MEDLINE | ID: mdl-38985698

ABSTRACT

To effectively remove Diazinon (DZ), Amoxicillin (AMX), and Crystal Violet (CV) from aquatic environments, a novel granular activated carbon (GAC) modified with Polyethylene glycol 600 (PEG) was created and manufactured. The chemical properties were investigated using a variety of characteristic analyses, including FT-IR, XRD, FESEM, and N2 adsorption/desorption. The effectiveness of GAC-PEG's adsorption for the removal of DZ, AMX, and CV was assessed under a variety of conditions, including a pH of 4-9 for the solution, 0.003-0.05 g doses of adsorbent, 50-400 ppm starting concentration, and a reaction time of 5-25 min. For DZ, AMX, and CV adsorption, the maximum adsorption capacity (Qmax) was 1163.933, 1163.100, and 1150.300 mg g-1, respectively. The Langmuir isotherm described all of the data from these adsorption experiments, and the pseudo-second-order well explains all-adsorption kinetics. Most contacts between molecules, electrostatic interactions, π-π interactions, hydrogen bonding, and entrapment in the modified CAG network were used to carry out the DZ, AMX, and CV adsorption on the GAC-PEG. The retrievability of the prepared adsorbent was successfully investigated in studies up to two cycles without loss of adsorption efficiency, and it was shown that it can be efficiently separated.


Subject(s)
Charcoal , Polyethylene Glycols , Wastewater , Water Pollutants, Chemical , Water Purification , Polyethylene Glycols/chemistry , Wastewater/chemistry , Kinetics , Water Pollutants, Chemical/chemistry , Water Pollutants, Chemical/isolation & purification , Adsorption , Charcoal/chemistry , Water Purification/methods , Amoxicillin/chemistry , Hydrogen-Ion Concentration , Gentian Violet/chemistry , Gentian Violet/isolation & purification , Spectroscopy, Fourier Transform Infrared
4.
Helicobacter ; 29(4): e13079, 2024.
Article in English | MEDLINE | ID: mdl-38984661

ABSTRACT

BACKGROUND: Eradicating Helicobacter pylori infection by bismuth quadruple therapy (BQT) is effective. However, the effect of BQT and subsequent fecal microbiota transplant (FMT) on the gut microbiota is less known. MATERIALS AND METHODS: This prospective randomized controlled trial was conducted at a tertiary hospital in China from January 2019 to October 2020, with the primary endpoints the effect of BQT on the gut microbiota and the effect of FMT on the gut microbiota after bismuth quadruple therapy eradication therapy. A 14-day BQT with amoxicillin and clarithromycin was administered to H. pylori-positive subjects, and after eradication therapy, patients received a one-time FMT or placebo treatment. We then collected stool samples to assess the effects of 14-day BQT and FMT on the gut microbiota. 16 s rDNA and metagenomic sequencing were used to analyze the structure and function of intestinal flora. We also used Gastrointestinal Symptom Rating Scale (GSRS) to evaluate gastrointestinal symptom during treatment. RESULTS: A total of 30 patients were recruited and 15 were assigned to either FMT or placebo groups. After eradication therapy, alpha-diversity was decreased in both groups. At the phylum level, the abundance of Bacteroidetes and Firmicutes decreased, while Proteobacteria increased. At the genus level, the abundance of beneficial bacteria decreased, while pathogenic bacteria increased. Eradication therapy reduced some resistance genes abundance while increased the resistance genes abundance linked to Escherichia coli. While they all returned to baseline by Week 10. Besides, the difference was observed in Week 10 by the diarrhea score between two groups. Compared to Week 2, the GSRS total score and diarrhea score decreased in Week 3 only in FMT group. CONCLUSIONS: The balance of intestinal flora in patients can be considerably impacted by BQT in the short term, but it has reverted back to baseline by Week 10. FMT can alleviate gastrointestinal symptoms even if there was no evidence it promoted restoration of intestinal flora.


Subject(s)
Anti-Bacterial Agents , Bismuth , Fecal Microbiota Transplantation , Gastrointestinal Microbiome , Helicobacter Infections , Helicobacter pylori , Humans , Helicobacter Infections/therapy , Helicobacter Infections/microbiology , Helicobacter Infections/drug therapy , Gastrointestinal Microbiome/drug effects , Fecal Microbiota Transplantation/methods , Male , Female , Middle Aged , Helicobacter pylori/drug effects , Adult , Anti-Bacterial Agents/therapeutic use , Prospective Studies , Bismuth/therapeutic use , Drug Therapy, Combination , China , Amoxicillin/therapeutic use , Clarithromycin/therapeutic use , Treatment Outcome , Aged , Feces/microbiology
5.
Signal Transduct Target Ther ; 9(1): 183, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38972904

ABSTRACT

Helicobacter pylori (H. pylori) is currently recognized as the primary carcinogenic pathogen associated with gastric tumorigenesis, and its high prevalence and resistance make it difficult to tackle. A graph neural network-based deep learning model, employing different training sets of 13,638 molecules for pre-training and fine-tuning, was aided in predicting and exploring novel molecules against H. pylori. A positively predicted novel berberine derivative 8 with 3,13-disubstituted alkene exhibited a potency against all tested drug-susceptible and resistant H. pylori strains with minimum inhibitory concentrations (MICs) of 0.25-0.5 µg/mL. Pharmacokinetic studies demonstrated an ideal gastric retention of 8, with the stomach concentration significantly higher than its MIC at 24 h post dose. Oral administration of 8 and omeprazole (OPZ) showed a comparable gastric bacterial reduction (2.2-log reduction) to the triple-therapy, namely OPZ + amoxicillin (AMX) + clarithromycin (CLA) without obvious disturbance on the intestinal flora. A combination of OPZ, AMX, CLA, and 8 could further decrease the bacteria load (2.8-log reduction). More importantly, the mono-therapy of 8 exhibited comparable eradication to both triple-therapy (OPZ + AMX + CLA) and quadruple-therapy (OPZ + AMX + CLA + bismuth citrate) groups. SecA and BamD, playing a major role in outer membrane protein (OMP) transport and assembling, were identified and verified as the direct targets of 8 by employing the chemoproteomics technique. In summary, by targeting the relatively conserved OMPs transport and assembling system, 8 has the potential to be developed as a novel anti-H. pylori candidate, especially for the eradication of drug-resistant strains.


Subject(s)
Anti-Bacterial Agents , Berberine , Deep Learning , Helicobacter pylori , Helicobacter pylori/drug effects , Berberine/pharmacology , Berberine/chemistry , Berberine/pharmacokinetics , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Humans , Helicobacter Infections/drug therapy , Helicobacter Infections/microbiology , Microbial Sensitivity Tests , Drug Resistance, Multiple, Bacterial/drug effects , Drug Resistance, Multiple, Bacterial/genetics , Animals , Omeprazole/pharmacology , Clarithromycin/pharmacology , Amoxicillin/pharmacology
6.
Pharmacotherapy ; 44(7): 558-569, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38922947

ABSTRACT

IMPORTANCE: Trimethoprim-sulfamethoxazole (TMP-SMX) may increase digoxin concentration, a medication with a narrow therapeutic index. Small changes in digoxin concentration could predispose individuals to the risk of toxicity. OBJECTIVE: To characterize the risk of digoxin toxicity in older adults taking digoxin following co-prescription of TMP-SMX compared with co-prescription of amoxicillin. DESIGN, SETTINGS, AND PARTICIPANTS: Retrospective population-based cohort study in Ontario, Canada (2002-2020) using linked health care data. Participants comprised 47,961 older adults taking digoxin (58% women; median age 80 years [interquartile range 74-86]) who were newly treated with TMP-SMX (n = 10,273) compared with those newly treated with amoxicillin (n = 37,688). EXPOSURE: Co-prescription of TMP-SMX versus amoxicillin in older adults concurrently taking digoxin. MAIN OUTCOME AND MEASURE: The primary outcome was a hospital encounter (i.e., hospital admission or emergency department visit) with digoxin toxicity within 30 days of the antibiotic prescription. Inverse probability of treatment weighting on the propensity score was used to balance comparison groups on indicators of baseline health. Weighted risk ratios (RR) were obtained using modified Poisson regression and weighted risk differences (RD) using binomial regression. The number needed to harm (NNH) was calculated as 1/RD. RESULTS: A hospital encounter with digoxin toxicity occurred in 49/10,273 (0.48%) patients treated with TMP-SMX versus 32/37,688 (0.08%) in those treated with amoxicillin (weighted RR, 5.71 [95% confidence interval (CI), 3.19 to 10.24]; weighted RD, 0.39% [95% CI, 0.25% to 0.53%]; NNH 256 [95% CI, 233 to 400]). CONCLUSION AND RELEVANCE: In older adults taking digoxin, the 30-day risk of a hospital encounter with digoxin toxicity was nearly 6 times higher in those co-prescribed TMP-SMX versus amoxicillin, although the absolute risk difference was low (0.4%). Physicians should prescribe an alternative antibiotic when clinically appropriate. If TMP-SMX must be co-prescribed with digoxin (if the benefit is believed to outweigh the risk), digoxin should be dose-reduced on an individual basis.


Subject(s)
Amoxicillin , Anti-Bacterial Agents , Digoxin , Trimethoprim, Sulfamethoxazole Drug Combination , Humans , Digoxin/adverse effects , Digoxin/administration & dosage , Aged , Female , Male , Aged, 80 and over , Retrospective Studies , Amoxicillin/adverse effects , Amoxicillin/administration & dosage , Trimethoprim, Sulfamethoxazole Drug Combination/adverse effects , Trimethoprim, Sulfamethoxazole Drug Combination/administration & dosage , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/administration & dosage , Cohort Studies , Drug Interactions , Ontario/epidemiology , Cardiotonic Agents/adverse effects , Cardiotonic Agents/therapeutic use , Cardiotonic Agents/administration & dosage
7.
Nat Commun ; 15(1): 5498, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38944647

ABSTRACT

IncX3 plasmids carrying the New Delhi metallo-ß-lactamase-encoding gene, blaNDM-5, are rapidly spreading globally in both humans and animals. Given that carbapenems are listed on the WHO AWaRe watch group and are prohibited for use in animals, the drivers for the successful dissemination of Carbapenem-Resistant Enterobacterales (CRE) carrying blaNDM-5-IncX3 plasmids still remain unknown. We observe that E. coli carrying blaNDM-5-IncX3 can persist in chicken intestines either under the administration of amoxicillin, one of the largest veterinary ß-lactams used in livestock, or without any antibiotic pressure. We therefore characterise the blaNDM-5-IncX3 plasmid and identify a transcription regulator, VirBR, that binds to the promoter of the regulator gene actX enhancing the transcription of Type IV secretion systems (T4SS); thereby, promoting conjugation of IncX3 plasmids, increasing pili adhesion capacity and enhancing the colonisation of blaNDM-5-IncX3 transconjugants in animal digestive tracts. Our mechanistic and in-vivo studies identify VirBR as a major factor in the successful spread of blaNDM-5-IncX3 across one-health AMR sectors. Furthermore, VirBR enhances the plasmid conjugation and T4SS expression by the presence of copper and zinc ions, thereby having profound ramifications on the use of universal animal feeds.


Subject(s)
Anti-Bacterial Agents , Chickens , Conjugation, Genetic , Escherichia coli , Plasmids , beta-Lactamases , Animals , Plasmids/genetics , beta-Lactamases/genetics , beta-Lactamases/metabolism , Chickens/microbiology , Humans , Escherichia coli/genetics , Escherichia coli/drug effects , Anti-Bacterial Agents/pharmacology , Escherichia coli Proteins/genetics , Escherichia coli Proteins/metabolism , Type IV Secretion Systems/genetics , Type IV Secretion Systems/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Amoxicillin/pharmacology , Promoter Regions, Genetic/genetics , Escherichia coli Infections/veterinary , Escherichia coli Infections/microbiology , Escherichia coli Infections/transmission , Gene Expression Regulation, Bacterial/drug effects , Intestines/microbiology
8.
Environ Monit Assess ; 196(7): 674, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38942963

ABSTRACT

Solar Fenton is an important and extensively used advanced oxidation process (AOP) to degrade pharmaceutical pollutants. The objective of this study was to evaluate the performance of simultaneous degradation of the mixed pollutants (amoxicillin, acetaminophen, and ciprofloxacin) for an aqueous solution using the solar Fenton process. Operating parameters such as pH, iron doses, H2O2 doses, pollutant concentrations, and time were studied. From the experimental results, the ideal conditions were obtained for the removal of mixed pollutants such as pH 3, Fe2+ 0.04 mM, H2O2 4 mM, the concentration of the mixed pollutants 5 mg/L, solar radiation 400 W/m2, and time 10 min, respectively. The pseudo-first-order kinetics were utilized to investigate the degradation efficacy of the mixed pollutants. The result of the study indicates that the degradation efficiency was > 99% for the mixed pollutants. A maximum of 63% mineralization was observed, and hydroxyl radical scavenger effects were studied. The best optimal conditions were applied to assess the spiked wastewater (municipal wastewater (MWW) and hospital wastewater (HWW)). The highest elimination rates for AMX, ACET, and CIP were observed as 65%, 89%, and 85% for MWW and 76%, 92%, and 80% for HWW, respectively. The degraded by-products were detected by LC-ESI-MS in the water matrix (aqueous solution and spiked wastewater), and ECOSAR analysis was performed for the transformed products. The study concluded that the solar Fenton technique is promising and effective for the removal of mixed pollutants from the water matrix.


Subject(s)
Hydrogen Peroxide , Iron , Sunlight , Waste Disposal, Fluid , Water Pollutants, Chemical , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/chemistry , Hydrogen Peroxide/chemistry , Kinetics , Iron/chemistry , Waste Disposal, Fluid/methods , Wastewater/chemistry , Oxidation-Reduction , Ciprofloxacin/chemistry , Ciprofloxacin/analysis , Acetaminophen/chemistry , Acetaminophen/analysis , Amoxicillin/chemistry , Amoxicillin/analysis
9.
Sci Rep ; 14(1): 13152, 2024 06 07.
Article in English | MEDLINE | ID: mdl-38849408

ABSTRACT

To assess the effectiveness and safety of combining Saccharomyces boulardii powder with triple therapy as a primary approach for eradicating H. pylori infection, a total of 144 patients who tested positive for H. pylori and diagnosed with non-ulcer dyspepsia underwent endoscopy at two national centers between June 2017 and March 2019 were included. The patients were categorized into three groups using a subsection randomization method and received initial H. pylori eradication treatments. Microbial composition, eradication rates, symptom alleviation, and adverse reactions were monitored on the 14th and 44th days post-treatment. According to PP analysis showed the eradication rates for the SRAC group was 75%, BRAC was 93.18% and RAC was 65.2%. Group BRAC exhibited a marginally higher eradication rate compared to other groups. However, patients receiving Saccharomyces boulardii treatment exhibited an overall reduction in initial dyspepsia symptoms by the end of the treatment period. When employed as a primary strategy, the combination of Saccharomyces boulardii powder with triple therapy displayed notable efficacy and smaller gastrointestinal side effects in eradicating initial H. pylori infections among non-ulcer dyspepsia patients. Moreover, this approach demonstrated advantages in alleviating symptoms, exhibited favorable tolerance, and maintained a high level of clinical safety.


Subject(s)
Drug Therapy, Combination , Dyspepsia , Helicobacter Infections , Helicobacter pylori , Probiotics , Saccharomyces boulardii , Humans , Helicobacter Infections/therapy , Helicobacter Infections/drug therapy , Male , Female , Helicobacter pylori/drug effects , Middle Aged , Probiotics/administration & dosage , Probiotics/therapeutic use , Dyspepsia/microbiology , Dyspepsia/therapy , Adult , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/administration & dosage , Gastrointestinal Microbiome , Treatment Outcome , Proton Pump Inhibitors/therapeutic use , Proton Pump Inhibitors/administration & dosage , Aged , Amoxicillin/therapeutic use , Amoxicillin/administration & dosage
10.
Helicobacter ; 29(1): e13054, 2024.
Article in English | MEDLINE | ID: mdl-38900537

ABSTRACT

BACKGROUND: The amoxicillin dose used in dual therapy to eradicate Helicobacter pylori varies across studies and the optimal amoxicillin dose for vonoprazan-based dual therapies remains unclear. We aimed to investigate the efficacy and safety of low- and high-dose amoxicillin in vonoprazan-amoxicillin dual therapy. MATERIALS AND METHODS: A comprehensive systematic review was conducted by searching databases from inception to October 2023. All trials that evaluated the effectiveness and safety of vonoprazan-amoxicillin dual therapy for eradicating H. pylori were included. Pooled eradication rate, incidence of adverse events, relative risks, and 95% confidence intervals are presented. RESULTS: Eighteen studies with 12 low-dose amoxicillin (VLA) and 13 high-dose amoxicillin (VHA) arms were included. The pooled eradication rates were 82.4% and 86.8% for VLA therapy, and 86.0% and 90.9% for VHA therapy by the intention-to-treat and per-protocol analyses, respectively. In the subgroup analysis stratified by duration, the eradication rates achieved in 7 days, 10 days, and 14 days treatments with VLA and VHA dual therapies were 80.8%, 84.2%, 83.1%, and 67.3%, 88.8%, 87.5%, respectively. In the four randomized controlled trials that directly compared VLA and VHA dual therapies, the efficacy was not statistically different in the intention-to-treat (76.9% vs 81.4%, p = 0.337) and per-protocol (81.6% vs 84.0%, p = 0.166) analyses. Additionally, the incidence of adverse events (p = 0.965) and compliance (p = 0.994) were similar in both groups. CONCLUSION: VLA therapy demonstrated comparable efficacy and safety to VHA therapy, along with regional differences. An appropriately extended treatment duration may be critical for therapeutic optimization of vonoprazan-amoxicillin treatment.


Subject(s)
Amoxicillin , Anti-Bacterial Agents , Drug Therapy, Combination , Helicobacter Infections , Helicobacter pylori , Pyrroles , Sulfonamides , Amoxicillin/administration & dosage , Amoxicillin/therapeutic use , Humans , Helicobacter Infections/drug therapy , Sulfonamides/administration & dosage , Sulfonamides/therapeutic use , Sulfonamides/adverse effects , Pyrroles/administration & dosage , Pyrroles/therapeutic use , Pyrroles/adverse effects , Helicobacter pylori/drug effects , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/adverse effects , Treatment Outcome , Proton Pump Inhibitors/administration & dosage , Proton Pump Inhibitors/therapeutic use , Proton Pump Inhibitors/adverse effects
11.
Sci Rep ; 14(1): 14542, 2024 06 24.
Article in English | MEDLINE | ID: mdl-38914675

ABSTRACT

Antibiotic resistance among bacteria is recognized as the primary factor contributing to the failure of treatment. In this research, our objective was to examine the prevalence of antibiotic resistance in H. pylori bacteria in Palestine. We enlisted 91 individuals suffering from dyspepsia, comprising 49 females and 42 males. These participants underwent esophagogastroduodenoscopy procedures with gastric biopsies. These biopsies were subsequently subjected to microbiological assessments and tested for their susceptibility to various antimicrobial drugs. Among the 91 patients, 38 (41.7%) exhibited the presence of H. pylori. Notably, Ciprofloxacin displayed the highest efficacy against H. pylori, followed by Levofloxacin, Moxifloxacin, and Amoxicillin, with resistance rates of 0%, 0%, 2.6%, and 18.4%, respectively. On the contrary, Metronidazole and Clarithromycin demonstrated the lowest effectiveness, with resistance percentages of 100% and 47.4%, respectively. The outcomes of this investigation emphasize that H. pylori strains within the Palestinian patient group exhibit substantial resistance to conventional first-line antibiotics like clarithromycin and metronidazole. However, alternative agents such as fluoroquinolones and amoxicillin remain efficacious choices. Consequently, we recommend favoring quinolone-based treatment regimens for H. pylori infections and adopting a more judicious approach to antibiotic usage among the Palestinian population.


Subject(s)
Anti-Bacterial Agents , Helicobacter Infections , Helicobacter pylori , Humans , Helicobacter pylori/drug effects , Helicobacter pylori/isolation & purification , Female , Male , Helicobacter Infections/drug therapy , Helicobacter Infections/microbiology , Helicobacter Infections/epidemiology , Cross-Sectional Studies , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/pharmacology , Adult , Prevalence , Middle Aged , Drug Resistance, Bacterial , Hospitals, University , Microbial Sensitivity Tests , Amoxicillin/therapeutic use , Amoxicillin/pharmacology , Clarithromycin/therapeutic use , Clarithromycin/pharmacology , Metronidazole/therapeutic use , Metronidazole/pharmacology , Levofloxacin/therapeutic use , Levofloxacin/pharmacology
12.
Microbiol Res ; 285: 127774, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38833829

ABSTRACT

Extended-spectrumß-lactam producing Escherichia coli (ESBL-EC) readily colonizes live poultry and serves as a major source of contamination in retail chicken meat, posing significant threats to public health. This study aims to investigate the impact of inappropriate antibiotic use on the dissemination and exacerbation of antibiotic resistance in ESBL-EC and explore the underlying molecular mechanisms. Through experimental analysis, we propose a hypothesis that inappropriate antibiotic use may exacerbate resistance by affecting vesicle formation and protein secretion. Experimental results demonstrate that under the influence of amoxicillin, the concentration of proteins secreted in outer membrane vehicles (OMVs) by ESBL-EC significantly increases, along with a significant upregulation in the expression of the CTX-M-55-type Extended-spectrum beta-lactamase (CTX-M-55). Proteomic analysis and differential gene knockout experiments identified the key protein YdcZ, associated with OMVs formation and protein transportation in ESBL-EC under amoxicillin treatment. Further investigations reveal direct interactions between YdcZ and other proteins (YdiH and BssR). Upon ydcz gene knockout, a significant decrease in protein concentration within OMVs is observed, accompanied by a noticeable reduction in protection against sensitive bacteria. These findings suggest a critical role of YdcZ in regulating the process of protein transportation to OMVs in ESBL-EC under the influence of amoxicillin. In summary, our research uncovers the significant role of inappropriate antibiotic use in promoting the secretion of OMVs by ESBL-EC, aiding the survival of antibiotic-sensitive bacteria in the vicinity of infection sites. These findings provide new insights into the mechanisms underlying antibiotic-induced bacterial resistance dissemination and offer novel avenues for exploring prevention and control strategies against bacterial resistance propagation.


Subject(s)
Amoxicillin , Anti-Bacterial Agents , Escherichia coli Proteins , Escherichia coli , Protein Transport , beta-Lactamases , Anti-Bacterial Agents/pharmacology , Escherichia coli/genetics , Escherichia coli/drug effects , Escherichia coli/metabolism , Escherichia coli Proteins/genetics , Escherichia coli Proteins/metabolism , beta-Lactamases/metabolism , beta-Lactamases/genetics , Amoxicillin/pharmacology , Animals , Microbial Sensitivity Tests , Proteomics , Bacterial Outer Membrane Proteins/metabolism , Bacterial Outer Membrane Proteins/genetics , Chickens/microbiology , Drug Resistance, Bacterial , Bacterial Outer Membrane/drug effects , Bacterial Outer Membrane/metabolism , Escherichia coli Infections/microbiology , Escherichia coli Infections/drug therapy
13.
J Antimicrob Chemother ; 79(7): 1677-1682, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38831599

ABSTRACT

OBJECTIVES: MRSA is a major cause of hospital-acquired and community-acquired infections. Treatment options for MRSA are limited because of the rapid development of ß-lactam resistance. Combining antibiotics offers an affordable, time-saving, viable and efficient approach for developing novel antimicrobial therapies. Both amoxicillin and cefdinir are oral ß-lactams with indications for a wide range of bacterial infections and mild side effects. This study aimed to investigate the in vitro and in vivo efficacy of combining these two ß-lactams against MRSA strains. METHODS: Fourteen representative prevalent MRSA strains with diverse sequence types (STs) were tested with a combination of amoxicillin and cefdinir, using chequerboard and time-kill assays. The Galleria mellonella larvae infection model was used to evaluate the in vivo efficacy of this dual combination against the community-acquired MRSA (CA-MRSA) strain USA300 and the hospital-acquired MRSA (HA-MRSA) strain COL. RESULTS: The chequerboard assay revealed a synergistic activity of the dual amoxicillin/cefdinir combination against all tested MRSA strains, with fractional inhibitory concentration index (FICI) values below 0.5 and at least a 4-fold reduction in the MICs of both antibiotics. Time-kill assays demonstrated synergistic bactericidal activity of this dual combination against the MRSA strain USA300 and strain COL. Moreover, in vivo studies showed that the administration of amoxicillin/cefdinir combination to G. mellonella larvae infected with MRSA strains significantly improved the survival rate up to 82%, which was comparable to the efficacy of vancomycin. CONCLUSIONS: In vitro and in vivo studies indicate that the dual combination of amoxicillin/cefdinir demonstrates a synergistic bactericidal efficacy against MRSA strains of various STs. Further research is needed to explore its potential as a treatment option for MRSA infections.


Subject(s)
Amoxicillin , Anti-Bacterial Agents , Drug Synergism , Methicillin-Resistant Staphylococcus aureus , Microbial Sensitivity Tests , Staphylococcal Infections , Methicillin-Resistant Staphylococcus aureus/drug effects , Animals , Anti-Bacterial Agents/pharmacology , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Amoxicillin/pharmacology , Cephalosporins/pharmacology , Disease Models, Animal , Cefdinir/pharmacology , Larva/microbiology , Larva/drug effects , Microbial Viability/drug effects , Humans , Moths/microbiology , Survival Analysis , Treatment Outcome , Drug Therapy, Combination , beta-Lactams/pharmacology
14.
Environ Geochem Health ; 46(7): 219, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38849667

ABSTRACT

This study investigates the removal of amoxicillin micropollutants (AM) from hospital wastewater using CoMoO4-modified graphitic carbon nitride (CMO/gCN). Consequently, CMO/gCN exhibits notable improvements in visible light absorption and electron-hole separation rates compared to unmodified gCN. Besides, CMO/gCN significantly enhances the removal efficiency of AM, attaining an impressive 96.5%, far surpassing the performance of gCN at 48.6%. Moreover, CMO/gCN showcases outstanding reusability, with AM degradation performance exceeding 70% even after undergoing six cycles of reuse. The removal mechanism of AM employing CMO/gCN involves various photoreactions of radicals (•OH, •O2-) and amoxicillin molecules under light assistance. Furthermore, CMO/gCN demonstrates a noteworthy photodegradation efficiency of AM from hospital wastewater, reaching 92.8%, with a near-complete reduction in total organic carbon levels. Detailed discussions on the practical applications of the CMO/gCN photocatalyst for removal of micropollutants from hospital wastewater are provided. These findings underline the considerable potential of CMO/gCN for effectively removing various pollutants in environmental remediation strategies.


Subject(s)
Amoxicillin , Graphite , Oxidation-Reduction , Wastewater , Water Pollutants, Chemical , Amoxicillin/chemistry , Wastewater/chemistry , Graphite/chemistry , Water Pollutants, Chemical/chemistry , Photolysis , Hospitals , Nitrogen Compounds/chemistry , Catalysis , Water Purification/methods
15.
Dent Med Probl ; 61(3): 439-446, 2024.
Article in English | MEDLINE | ID: mdl-38916079

ABSTRACT

Periodontal mechanical debridement is the most common therapy for the treatment of periodontitis. However, depending on the severity of the disease, mechanical debridement has been recommended in combination with systemic antibiotics. In this study, we performed an overview of systematic reviews using the Friendly Summaries of Body of Evidence using Epistemonikos (FRISBEE) methodology on the effectiveness and safety of mechanical debridement combined with amoxicillin and metronidazole compared to mechanical debridement alone for the treatment of chronic periodontitis. We conducted a systematic search of the Epistemonikos database, extracted data from 10 systematic reviews and re-analyzed data from 23 primary studies to generate a summary of findings (SoF) table. We used RevMan 5.3 and GRADEpro for data analysis and data presentation. The following outcomes were analyzed: probing depth (mean difference (MD): 0.07 mm); clinical attachment level (MD: 0.04 mm); bleeding on probing (MD: 5.06%); and suppuration (MD: 0.31%). There was no evidence of a clinically relevant benefit of periodontal mechanical debridement therapy combined with amoxicillin and metronidazole compared to periodontal mechanical debridement therapy alone for the treatment of chronic periodontitis in the studied periodontal outcomes.


Subject(s)
Amoxicillin , Anti-Bacterial Agents , Chronic Periodontitis , Metronidazole , Periodontal Debridement , Humans , Amoxicillin/therapeutic use , Amoxicillin/administration & dosage , Anti-Bacterial Agents/therapeutic use , Chronic Periodontitis/therapy , Chronic Periodontitis/drug therapy , Combined Modality Therapy , Metronidazole/therapeutic use , Metronidazole/administration & dosage , Periodontal Debridement/methods
16.
BMC Infect Dis ; 24(1): 647, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38937679

ABSTRACT

BACKGROUND: Refractory Helicobacter pylori (H. pylori) infection inevitably increase the difficulty of drug selection. Here, we described our experience with the use of a novel tetravalent IgY against H. pylori for the treatment of patients with refractory H. pylori infection. METHODS: Patients were randomly assigned to receive the standard quadruple therapy (amoxicillin, clarithromycin, omeprazole and bismuth potassium citrate ) for 2 weeks or 250 mg of avian polyclonal IgY orally twice a day for 4 weeks. The binding efficacy of IgY to H. pylori antigens was detected by western blotting13. C-urea breath test was performed to evaluate the eradication therap's efficacy. The side effects of IgY were evaluated via various routine tests. The questionnaire was used to gather clinical symptoms and adverse reactions. RESULTS: Western blot analysis showed that tetravalent IgY simultaneously bind to VacA, HpaA, CagA and UreB of H. pylori. Tetravalent IgY had an eradication rate of 50.74% in patients with refractory H. pylori and an inhibition rate of 50.04% against DOB (delta over baseline) of 13C-urea. The symptom relief rate was 61.76% in thirty-four patients with clinical symptoms, and no adverse reactions were observed during tetravalent IgY treatment period. CONCLUSIONS: Polyclonal avian tetravalent IgY reduced H. pylori infection, and showed good efficacy and safety in the treatment of refractory H. pylori infection patients, which represented an effective therapeutic option of choice for patients with refractory H. pylori infection.


Subject(s)
Anti-Bacterial Agents , Helicobacter Infections , Helicobacter pylori , Immunoglobulins , Humans , Helicobacter Infections/drug therapy , Male , Female , Helicobacter pylori/drug effects , Middle Aged , Immunoglobulins/therapeutic use , Immunoglobulins/administration & dosage , Adult , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/adverse effects , Treatment Outcome , Aged , Drug Therapy, Combination , Clarithromycin/therapeutic use , Amoxicillin/therapeutic use , Amoxicillin/administration & dosage , Young Adult , Antibodies, Bacterial/therapeutic use
17.
Chemosphere ; 361: 142548, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38852637

ABSTRACT

This study evaluated the effectiveness of using nanocomposite (NCs) of xanthan gum grafted polyacrylamide crosslinked Borax - iron oxide nanoparticle (XG-g-pAAm-CL-Borax-IONP) to remove the amoxicillin antibiotic (AMX) from an aquatic environment. To confirm the structural characteristics of the prepared XG-g-pAAm-CL-Borax-IONP NCs, unique characterization methods (XRD, FT-IR, FE-SEM, EDX, BET, TGA, Zeta, and VSM) were used. Adsorption experimental setups were performed with the influence of solution pH (4-9), the effect of adsorbent dose (0.003-0.02 g), the effect of contact time (5-45 min), and the effect of initial AMX concentration (50-400 mg/L) to achieve the most efficient adsorption conditions. Based on the Freundlich isotherm model, XG-g-pAAm-CL-Borax-IONP NCs provided the maximum AMX adsorption capacity of 1183.639 mg/g. This research on adsorption kinetics also established that the pseudo-second-order model (R2 = 0.991) is outstanding compatibility with the experimental results. AMX adsorption on the NCs may occur through intermolecular hydrogen bonding, diffusion, and trapping into the polymer network. Even after five cycles, these NCs still displayed the best performance. Based on these results, XG-g-pAAm-CL-Borax-IONP NCs may be a viable material for the purification of AMX from contaminated water.


Subject(s)
Acrylic Resins , Amoxicillin , Borates , Nanocomposites , Polysaccharides, Bacterial , Water Pollutants, Chemical , Nanocomposites/chemistry , Water Pollutants, Chemical/chemistry , Acrylic Resins/chemistry , Amoxicillin/chemistry , Polysaccharides, Bacterial/chemistry , Adsorption , Borates/chemistry , Kinetics , Anti-Bacterial Agents/chemistry , Water Purification/methods , Hydrogen-Ion Concentration
18.
Stomatologiia (Mosk) ; 103(3): 5-10, 2024.
Article in Russian | MEDLINE | ID: mdl-38904552

ABSTRACT

THE AIM OF THE STUDY: Was to determine the presence of an amoxicillin-based antibiotic in bone implant biopsies by Raman spectroscopy in an experiment. MATERIALS AND METHODS: Experimental animals (n=10, a miniature pig of the Svetlogorsk breed) were divided into 2 groups of 5 animals. Groups 1 and 2 were injected with amoxicillin 2 ml per 20 kg of body weight 30 minutes before dental implantation surgery, then group 2 was additionally injected with 1 ml per 20 kg of body weight for 5 days. Each animal has 6 implants installed. On the 1st, 3rd, 7th, 14th day, an implant-bone biopsy was removed from each animal, micro-preparations were made and Raman spectroscopy was performed to assess the peak matching of the Raman spectrum. RESULTS: In animals of the 1st and 2nd groups, the main peak of the Raman spectrum, which is closest to the values of the antibiotic spectrum of interest to us, is located closer to 1448 cm-1 and 1446 cm-1, respectively. At the same time, in both observations, the peaks relate to the spectrum of bone tissue, which cannot indicate the content of an antibiotic in the drug. CONCLUSION: No scattering spectra corresponding to the antibiotic molecule were found in any animal from both groups, regardless of the mode of administration and dosage of amoxicillin. The detected peaks corresponded to bone tissue without an antibiotic.


Subject(s)
Amoxicillin , Anti-Bacterial Agents , Dental Implants , Spectrum Analysis, Raman , Spectrum Analysis, Raman/methods , Animals , Amoxicillin/analysis , Amoxicillin/administration & dosage , Swine , Anti-Bacterial Agents/analysis , Anti-Bacterial Agents/administration & dosage , Biopsy , Swine, Miniature , Bone and Bones/chemistry , Bone and Bones/drug effects , Bone and Bones/pathology , Dental Implantation/methods
19.
J Environ Manage ; 364: 121435, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38889646

ABSTRACT

The abuse and uncontrolled discharge of antibiotics present a severe threat to environment and human health, necessitating the development of efficient and sustainable treatment technology. In this work, we employ a facile one-step electrodeposition method to prepare polyaniline/graphite oxide (PANI/GO) and samarium (Sm) co-modified Ti/PbO2 (Ti/PbO2-PANI/GO-Sm) electrode for the degradation of amoxicillin (AMX). Compared with traditional Ti/PbO2 electrode, Ti/PbO2-PANI/GO-Sm electrode exhibits more excellent oxygen evolution potential (2.63 V) and longer service life (56 h). In degradation experiment, under optimized conditions (50 mg L-1 AMX, 20 mA cm-2, pH 3, 0.050 M Na2SO4, 25 °C), Ti/PbO2-PANI/GO-Sm electrode achieves remarkable removal efficiencies of 88.76% for AMX and 79.92% for chemical oxygen demand at 90 min. In addition, trapping experiment confirms that ·OH plays a major role in the degradation process. Based on theoretical calculation and liquid chromatography-mass spectrometer results, the heterocyclic portion of AMX molecule is more susceptible to ·OH attacks. Thus, this novel electrode offers a sustainable and efficient solution to address environmental challenges posed by antibiotic-contaminated wastewater.


Subject(s)
Amoxicillin , Electrodes , Amoxicillin/chemistry , Titanium/chemistry , Water Pollutants, Chemical/chemistry , Samarium/chemistry
20.
Helicobacter ; 29(3): e13098, 2024.
Article in English | MEDLINE | ID: mdl-38853394

ABSTRACT

BACKGROUND: Potassium-competitive acid blockers have demonstrated enormous potential in the eradication treatment of Helicobacter pylori infection, with tegoprazan being one of the representatives. The available data on the safety and efficacy of tegoprazan in dual therapy are limited. MATERIALS AND METHODS: The multicenter, noninferiority, randomized-controlled trial was conducted from May 2023 to March 2024. Treatment-naive subjects were randomly assigned (1:1) to enter either the tegoprazan-amoxicillin (TA) group (tegoprazan 50 mg twice daily and amoxicillin 750 mg four times daily) or the esomeprazole-amoxicillin (EA) group (esomeprazole 20 mg and amoxicillin 750 mg all four times daily), with a duration for 14 days. The primary outcome was eradication rate as determined by 13C-urea breath test, including per-protocol (PP) analysis and intention-to-treat (ITT) analysis. Secondary outcomes were adverse events and compliance. RESULTS: A total of 368 individuals were included in the randomization. The eradication rates in the EA group and the TA group were 84.2% and 85.8%, respectively, according to an ITT analysis (p = 0.77), and 88.5% and 88.2%, respectively, according to PP analysis (p = 1.00). The eradication rates for the TA group were not inferior to those of the EA group in both PP (p = 0.0023) and ITT analyses (p = 0.0009). There were no significant statistical differences in the incidence of adverse events and compliance between the two groups. The multivariate logistic regression analysis revealed that poor compliance increased the risk of eradication failure (p < 0.001). CONCLUSIONS: Dual therapy containing tegoprazan is safe and effective to be considered as a clinical first-line treatment option, but further optimization involving antimicrobial susceptibility testing and adjustments in dosage and frequency is warranted. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT05870683.


Subject(s)
Amoxicillin , Anti-Bacterial Agents , Drug Therapy, Combination , Helicobacter Infections , Helicobacter pylori , Humans , Helicobacter Infections/drug therapy , Male , Female , Amoxicillin/therapeutic use , Amoxicillin/administration & dosage , Middle Aged , Helicobacter pylori/drug effects , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/adverse effects , Adult , Treatment Outcome , Proton Pump Inhibitors/therapeutic use , Proton Pump Inhibitors/administration & dosage , Proton Pump Inhibitors/adverse effects , Aged , Breath Tests , Esomeprazole/therapeutic use , Esomeprazole/administration & dosage , Pyrroles , Sulfonamides
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