Oral ß-Lactam Pairs for the Treatment of Mycobacterium avium Complex Pulmonary Disease.

Cure rates for pulmonary disease caused by the Mycobacterium avium complex (MAC) are poor. While ß-lactam are front line antibiotics against Mycobacterium abscessus pulmonary disease, they have not been used or recommended to treat MAC lung infections. Through a comprehensive screen of oral ß-lactams, we have discovered that selected pairs combining either a penem/carbapenem or penicillin with a cephalosporin are strongly bactericidal at clinically achieved concentrations. These dual ß-lactam combinations include tebipenem and sulopenem, both in phase 3, and Food and Drug Administration-approved amoxicillin and cefuroxime. They could therefore immediately enter clinical trials or clinical practice.

Amoxicillin-Clavulanate Breakpoints Against Enterobacterales: Rationale for Revision by the Clinical and Laboratory Standards Institute.

Amoxicillin-clavulanate (AMC) is among the most frequently prescribed antibiotics globally. It has broad antibacterial activity against gram-positive, gram-negative, and anaerobic bacteria and has been used to treat infections caused by a broad range of pathogens. AMC breakpoints against Enterobacterales were initially set in the 1980s. However, since that time, increases in antibiotic resistance, advances in pharmacokinetic/pharmacodynamic analyses, and publication of additional clinical data prompted a reassessment by the Clinical and Laboratory Standards Institute (CLSI) Subcommittee on Antimicrobial Susceptibility Testing. Based on this contemporary reappraisal, the CLSI retained the Enterobacterales breakpoints but revised comments regarding dosing associated with use of the AMC breakpoints in the 2022 supplement of M100. This viewpoint provides insight into the CLSI breakpoint reevaluation process and summarizes the data and rationale used to support these revisions to the AMC Enterobacterales breakpoint.

Amoxicillin crystalluria and Amoxicillin-induced crystal nephropathy: a narrative review.

Amoxicillin crystalluria (AC) refers to the precipitation of amoxicillin in the urine as amoxicillin trihydrate crystals. Amoxicillin-induced crystal nephropathy (AICN) refers to the obstruction of kidney tubules by amoxicillin trihydrate crystals, resulting in acute kidney injury (AKI). Usually considered rare and not serious, AC and AICN would be more frequent in patients receiving high-dose intravenous amoxicillin (HDIVA ≥150 mg/kg per day) than previously reported. AC prevalence ranges from 24% to 41%. AICN prevalence remains unclear. AC is generally asymptomatic, but sudden macroscopic hematuria with cloudy urine suggests the diagnosis. AC is diagnosed by detecting amoxicillin trihydrate crystals in urine. AC is a risk factor for AKI. Diagnosing AICN is more challenging in the absence of non-invasive diagnostic tools. It is suspected in HDIVA-treated patients who develop AKI and AC, and after excluding other causes of AKI (mainly sepsis and acute interstitial nephritis). When testing for AC is unavailable, the presence of demonstrated (high blood amoxicillin levels, low urinary pH) or suspected (rapid intravenous amoxicillin administration, hypovolemia) risk factors for AC suggests its diagnosis. AICN management includes discontinuation/reduction of amoxicillin doses and volume resuscitation to improve tubular flow and urine output and decrease amoxicillin supersaturation. Patients generally recover normal kidney function rapidly after stopping amoxicillin, but renal replacement therapy is required in 10%-40% of patients. No deaths have been directly attributed to AICN. Future studies are needed to assess the exact prevalence of AC/AICN and to define optimal therapeutic options.

A pairwise approach to revitalize ß-lactams for the treatment of TB.

The dual ß-lactam approach has been successfully applied to overcome target redundancy in nontuberculous mycobacteria. Surprisingly, this approach has not been leveraged for Mycobacterium tuberculosis, despite the high conservation of peptidoglycan synthesis. Through a comprehensive screen of oral ß-lactam pairs, we have discovered that cefuroxime strongly potentiates the bactericidal activity of tebipenem and sulopenem-advanced clinical candidates-and amoxicillin, at concentrations achieved clinically. ß-lactam pairs thus have the potential to reduce TB treatment duration.

Efficacy and Safety of Vonoprazan-Amoxicillin Dual Regimen With Varying Dose and Duration for Helicobacter pylori Eradication: A Multicenter, Prospective, Randomized Study.

BACKGROUND & AIMS: Previous studies confirm vonoprazan-amoxicillin effectiveness for Helicobacter pylori. This study aims to investigate vonoprazan with varying amoxicillin dose and duration. METHODS: This multicenter, prospective, randomized controlled, noninferiority trial enrolled patients with treatment naive H pylori infection from 5 clinical centers. Eligible participants were randomly assigned to H-VA-10 (vonoprazan 20 mg twice a day (b.i.d.) + amoxicillin 750 mg 4 times a day, 10 days), L-VA-10 (vonoprazan 20 mg b.i.d. + amoxicillin 1000 mg b.i.d, 10 days), and H-VA-14 (vonoprazan 20 mg b.i.d + amoxicillin 750 mg 4 times a day, 14 days) in a 1:1:1 ratio. The eradication rate was assessed using the 13C-urea breath test at least 28 days after treatment. RESULTS: Of the 623 eligible patients, 516 patients were randomized. In both the intention-to-treat and per-protocol analyses, eradication rates were comparable between H-VA-10 and H-VA-14 groups (86.6% vs 89.5% and 90.9% vs 94.5%, P = .021 and .013 for noninferiority, respectively). However, eradication rates were significantly lower in the L-VA-10 group than the H-VA-14 group (79.7% vs 89.5% and 82.0% vs 94.5%, P = .488 and .759, respectively). Rates of study withdrawal, loss to follow-up, and adverse events were similar across study groups. CONCLUSIONS: H-VA-10 and H-VA-14 regimens provide satisfactory efficacy for H pylori infection, and the L-VA-10 regimen was inferior. CLINICALTRIALS: gov number: NCT05719831.

Identification of Reduced ERAP2 Expression and a Novel HLA Allele as Components of a Risk Score for Susceptibility to Liver Injury Due to Amoxicillin-Clavulanate.

BACKGROUND & AIMS: Drug-induced liver injury (DILI) due to amoxicillin-clavulanate (AC) has been associated with HLA-A∗02:01, HLA-DRB1∗15:01, and rs2476601, a missense variant in PTPN22. The aim of this study was to identify novel risk factors for AC-DILI and to construct a genetic risk score (GRS). METHODS: Transcriptome-wide association study and genome-wide association study analyses were performed on 444 AC-DILI cases and 10,397 population-based controls of European descent. Associations were confirmed in a validation cohort (n = 133 cases and 17,836 population-based controls). Discovery and validation AC-DILI cases were also compared with 1358 and 403 non-AC-DILI cases. RESULTS: Transcriptome-wide association study revealed a significant association of AC-DILI risk with reduced liver expression of ERAP2 (P = 3.7 × 10-7), coding for an aminopeptidase involved in antigen presentation. The lead eQTL single nucleotide polymorphism, rs1363907 (G), was associated with AC-DILI risk in the discovery (odds ratio [OR], 1.68; 95% CI, 1.23-1.66; P = 1.7 × 10-7) and validation cohorts (OR, 1.2; 95% CI, 1.04-2.05; P = .03), following a recessive model. We also identified HLA-B∗15:18 as a novel AC-DILI risk factor in both discovery (OR, 4.19; 95% CI, 2.09-8.36; P = 4.9 × 10-5) and validation (OR, 7.78; 95% CI, 2.75-21.99; P = .0001) cohorts. GRS, incorporating rs1363907, rs2476601, HLA-B∗15:18, HLA-A∗02:01, and HLA-DRB1∗15:01, was highly predictive of AC-DILI risk when cases were analyzed against both general population and non-AC-DILI control cohorts. GRS was the most significant predictor in a regression model containing known AC-DILI clinical risk characteristics and significantly improved the predictive model. CONCLUSIONS: We identified novel associations of AC-DILI risk with ERAP2 low expression and with HLA-B∗15:18. GRS based on the 5 risk variants may assist AC-DILI causality assessment and risk management.

Comparison of three methods for generating the coccoid form of Helicobacter pylori and proteomic analysis.

BACKGROUND: Helicobacter pylori changes from spiral to coccoid depending on the host state, environmental factors, and surrounding microbial communities. The coccoid form of H. pylori still maintains its complete cellular structure, retains virulence genes, and thus plays a role in pathogenicity. To understand the coccoid form, it is crucial to establish the in vitro generation of the coccoid H. pylori. Although some conditions have been studied for the generation of the coccoid form, few studies have compared these conditions for coccoid generation. Here, we generated coccoid forms via three methods and compared the differences in morphology, viability, culturability, and protein expression. RESULTS: The coccoid H. pylori was generated in vitro via three methods: a starvation method, a method using amoxicillin, and a method using the culture supernatant of Streptococcus mitis. The morphology and viability of the cells were examined by fluorescence microscopy after staining with SYTO9 and propidium iodide. The culturability of H. pylori was examined by counting colony-forming units on chocolate agar plates. In the starvation group, no colonies formed after 7 days, but viable coccoids were continuously observed. In the amoxicillin-treated group, the culturability decreased rapidly after 12 h, and showed a viable but non culturable (VBNC) state after the third day. Most cells treated with S. mitis supernatant changed to coccoid forms after 7 days, but colonies were continuously formed, probably due to living spiral forms. We performed proteomics to analyse the differences in protein profiles between the spiral and coccoid forms and protein profiles among the coccoid forms generated by the three methods. CONCLUSION: Amoxicillin treatment changed H. pylori to VBNC cells faster than starvation. Treatment with the S. mitis supernatant prolonged the culturability of H. pylori, suggesting that the S. mitis supernatant may contain substances that support spiral form maintenance. Proteomic analysis revealed that the expression of proteins differed between the spiral form and coccoid form of H. pylori, and this variation was observed among the coccoid forms produced via three different methods. The proteins in the coccoid forms produced by the three methods differed from each other, but common proteins were also observed among them.

A comparative analysis of univariate versus multivariate eco-friendly spectrophotometric manipulations for resolving severely overlapped spectra of vonoprazan and amoxicillin new combination.

Vonoprazan and amoxicillin are pharmacological combinations that demonstrate synergistic effects in treating Helicobacter pylori (H. pylori), a global public health concern associated with peptic ulcer disease and gastric cancer. Four spectrophotometric methods were developed, including two univariate techniques (Fourier self-deconvolution and ratio difference) and two multivariate chemometric approaches (partial least squares and principal component regression). These methods provide innovative solutions for effectively resolving and accurately quantifying the overlapping spectra of vonoprazan and amoxicillin. The concentration ranges covered were 3-60 µg ml-1 for vonoprazan and 5-140 µg ml-1 for amoxicillin. To assess the environmental sustainability of the methodologies, various measures such as the Green Analytical Procedure Index (GAPI), National Environmental Method Index (NEMI), Analytical GREEnness Calculator, and Analytical Eco-scale, as well as RGB12 and hexagon toll were implemented. The validation of the developed techniques was carried out in compliance with ICH standards. The present study is highly significant because it is the first time that the mixture has been determined using the current approaches. The comparative analysis demonstrated no significant difference in terms of accuracy and precision compared to reference HPLC method (p = 0.05). The established spectrophotometric methods offer a straightforward, rapid, and cost-effective alternative to complex analytical techniques for determining the vonoprazan and amoxicillin mixture. They show potential for routine analysis in research laboratories and pharmaceutical industries.

Optimizing ß-lactam-containing antibiotic combination therapy for the treatment of Buruli ulcer.

AIMS: The current treatment for Buruli ulcer is based on empirical evidence of efficacy. However, there is an opportunity for shortening its duration and improving response rates. Evolving understanding of the pharmacokinetic-pharmacodynamic relationships provides the basis for a stronger dose rationale for antibiotics. In conjunction with modelling and simulation, it is possible to identify dosing regimens with the highest probability of target attainment (PTA). This investigation aims to: (i) assess the dose rationale for a new combination therapy including amoxicillin/clavulanic acid (AMX/CLV) currently in clinical trials; and (ii) compare its performance with alternative dosing regimens including rifampicin, clarithromycin and AMX/CLV. METHODS: In vitro estimates of the minimum inhibitory (MIC) concentration were selected as a measure of the antibacterial activity of different drug combinations. Clinical trial simulations were used to characterize the concentration vs. time profiles of rifampicin, clarithromycin and amoxicillin in a virtual cohort of adult and paediatric patients, considering the effect of baseline covariates on disposition parameters and interindividual variability in exposure. The PTA of each regimen was then assessed using different thresholds of the time above MIC. RESULTS: A weight-banded dosing regimen including 150-600 mg rifampicin once daily, 250-1000 mg clarithromycin and AMX/CLV 22.5 mg/kg /1000 mg twice daily ensures higher PTA than the standard of care with AMX/CLV 45 mg/kg/2000 mg once daily. CONCLUSION: The higher PTA values support the proposed 4-drug combination (rifampicin, clarithromycin, AMX/CLV) currently under clinical investigation. Our findings also suggest that higher rifampicin doses might contribute to enhanced treatment efficacy.

Low-dose or high-dose amoxicillin in vonoprazan-based dual therapy for Helicobacter pylori eradication? A systematic review and meta-analysis.

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.

Vonoprazan-Amoxicillin Dual Therapy With Different Amoxicillin Administration Regimens for Helicobacter pylori Treatment: A Randomized Controlled Trial.

BACKGROUND: The effect of preprandial or postprandial administration of amoxicillin on the efficacy of vonoprazan-amoxicillin dual therapy (VA-dual therapy) for Helicobacter pylori treatment has not been studied. It is also unclear whether amoxicillin dosing four times daily is more effective than three times daily. We aimed to investigate the effect of different amoxicillin administration regimens on the efficacy of VA-dual therapy. MATERIALS AND METHODS: H. pylori-infected subjects were randomly assigned to three groups in a 1:1:1 ratio to receive a 14-day dual therapy consisting of vonoprazan 20 mg twice daily + amoxicillin 1000 mg three times daily before meals (BM-TID) or 1000 mg three times daily after meals (AM-TID) or 750 mg four times daily after meals (AM-QID). H. pylori eradication rates, adverse events rates, compliance, and antibiotic resistance were compared. RESULTS: Between May 2021 to April 2023, 327 subjects were enrolled. The eradication rates of BM-TID, AM-TID, and AM-QID dual therapy were 88.1%, 89.9%, and 93.6% in intention-to-treat (ITT) analysis, 90.6%, 94.2%, and 99.0% in modified ITT (MITT) analysis, and 90.4%, 94.1%, and 99.0% in per-protocol (PP) analysis. Although there was non-inferiority between BM-TID and AM-TID, as well as between AM-TID and AM-QID, AM-QID was significantly more effective than BM-TID. There were no significant differences in adverse event rates, compliance, and antibiotic resistance among the three groups. CONCLUSIONS: Postprandial administration and the increased frequency of administration of amoxicillin may contribute to a better efficacy of VA-dual therapy, especially for rescue therapy. All VA-dual therapy in our study could achieve good efficacy for first-line treatment. TRIAL REGISTRATION: clinicaltrials.gov: NCT05901051.

Vonoprazan-amoxicillin dual therapy versus bismuth-containing quadruple therapy for Helicobacter pylori eradication: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Recently, vonoprazan-amoxicillin (VA) dual therapy has been reported as a promising approach for Helicobacter pylori (H. pylori) eradication. However, the effects of VA therapy versus bismuth-containing quadruple therapy (BQT) on H. pylori eradication remains unclear. The objective of this meta-analysis was to compare the effects of VA dual therapy with BQT for H. pylori eradication. METHODS: A comprehensive search of the literature was conducted from the beginning to September 2023, utilizing PubMed, Embase, the Cochrane Library and Web of Science database. A random-effects model was used to perform a meta-analysis to determine the pooled relative risk (RR) with 95% confidence intervals (CIs). Moreover, trial sequential analysis (TSA) was conducted to evaluate the conclusiveness of the H. pylori eradication rate. RESULTS: Six randomized controlled trials (RCTs) with 1233 patients were included. The VA therapy has similar eradication rate (ITT analysis: 87% vs. 85.7%, RR = 1.01, 95% CI: 0.93-1.09, p = 0.84; PP analysis: 92.5% vs. 93.2%, RR = 1.00, 95% CI: 0.94-1.06, p = 0.97) and compliance (RR = 1.01, 95% CI: 0.99-1.03, p = 0.32) compared to BQT. The VA therapy group had a significantly lower incidence of total adverse events than the BQT group (16.3% vs. 40.0%, RR = 0.45, 95% CI: 0.37-0.55, p < 0.00001). The TSA result showed that the effect was conclusive. CONCLUSIONS: Current evidence indicated that VA therapy is just as successful as BQT in eliminating H. pylori, yet it has fewer adverse events and similar compliance.

Vonoprazan and amoxicillin dual therapy as the first-line treatment of Helicobacter pylori infection: A systematic review and meta-analysis.

BACKGROUND: Recent clinical trials have evaluated the efficacy of vonoprazan-amoxicillin (VA) dual therapy as the first-line treatment for Helicobacter pylori infection in different regions with inconsistent results reported. In this systematic review and meta-analysis, we aimed to evaluate the efficacy of VA dual therapy compared to the currently recommended therapy for eradicating H. pylori. MATERIALS AND METHODS: A comprehensive search of the PubMed, Cochrane, and Embase databases was performed using the following search terms: ("Helicobacter" OR "H. pylori" OR "Hp") AND ("vonoprazan" OR "potassium-competitive acid blocker" OR "P-CAB") AND ("amoxicillin" OR "penicillin") AND ("dual"). The primary outcome was to evaluate the eradication rate according to intention-to-treat and per-protocol analysis. The secondary outcomes were adverse events and compliance. RESULTS: A total of 15 studies involving 4, 568 patients were included. The pooled eradication rate of VA dual therapy was 85.0% and 90.0% by intention-to-treat and per-protocol analysis, respectively. The adverse events rate and compliance of VA dual therapy were 17.5% and 96%, respectively. The efficacy of VA dual therapy was superior to proton pump inhibitors-based triple therapy (82.0% vs. 71.4%, p < 0.01) but lower than vonoprazan-containing quadruple therapy (83.1% vs. 93.3%, p = 0.02). 7-day VA dual therapy showed lower eradication rates than 10-day (χ2 = 24.09, p < 0.01) and 14-day VA dual therapy (χ2 = 11.87, p < 0.01). The adverse events rate of VA dual therapy was lower than vonoprazan triple therapy (24.6% vs. 30.9%, p = 0.01) and bismuth-containing quadruple therapy (20.5% vs. 47.9%, p < 0.01). No significant difference of compliance was observed between VA dual therapy and each subgroup. CONCLUSION: VA dual therapy, a novel regimen, showed high efficacy as the first-line treatment for H. pylori eradication, which should be optimized before application in different regions.

Vonoprazan and amoxicillin dual therapy for 14 days as the first-line treatment of Helicobacter pylori infection: A non-inferiority, randomized clinical trial.

BACKGROUND: We previously optimized the duration and dose of vonoprazan and amoxicillin dual therapy in China. The efficacy of vonoprazan with b.i.d. amoxicillin in comparison with vonoprazan-containing quadruple therapy as the first-line treatment of Helicobacter pylori infection has not been adequately evaluated. METHODS: In a non-inferiority, randomized clinical trial, H. pylori infected and treatment-naïve patients were randomly assigned to receive 14 days of either vonoprazan dual (vonoprazan 20 mg and amoxicillin 1 g twice daily) or quadruple therapy (vonoprazan 20 mg + amoxicillin 1 g + furazolidone 100 mg + bismuth potassium citrate 600 mg twice daily). H. pylori status was confirmed using 13C-urea breath tests or fecal antigen test. The primary outcome was the H. pylori eradication rate following vonoprazan dual and quadruple therapy at 4-12 weeks. We also compared drug compliance to either regimen and documented their side effect. RESULTS: A total of 190 subjects were randomized. The eradication rate of vonoprazan dual and quadruple therapy were 87.4% and 92.6% (p = 0.23) by intention-to-treat analysis, respectively, and 96.5% and 97.7% (p = 0.63) by per-protocol analysis, respectively. The efficacy of vonoprazan dual therapy was non-inferior to vonoprazan-containing quadruple therapy in per-protocol analysis (p < 0.001; difference: -1.2%; 90% confidence interval: -5.4% to 3.0%). CONCLUSION: Vonoprazan with b.i.d. amoxicillin for 14 days provided similar satisfactory efficacy with vonoprazan-containing quadruple therapy as a first-line H. pylori treatment in China.

Vonoprazan-based therapies versus PPI-based therapies in patients with H. pylori infection: Systematic review and meta-analyses of randomized controlled trials.

BACKGROUND: This study aims to evaluate the efficacy and safety of vonoprazan-amoxicillin (VA), vonoprazan-amoxicillin-clarithromycin (VAC), vonoprazan-based bismuth-containing quadruple therapy (VBQT), and PPI-based triple (PAC) or quadruple therapy (PBQT) for H. pylori infection with the consideration of duration of therapy and amoxicillin dose (H: high; L: low). MATERIALS AND METHODS: PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched for eligible randomized controlled trials (RCTs) up to December 15, 2023. The efficacy outcome was eradication rate, and safety outcomes included the rates of adverse events and treatment discontinuation. RESULTS: Twenty-seven RCTs were included. The pooled eradication rates were 82.8% for VA, 89.1% for VAC, and 91.8% for VBQT, which increased with the higher amoxicillin frequency of administration and extended duration of therapy within each regimen. There were no significant differences in eradication rate when comparing 7-VA versus 7-VAC and 14-VA versus 14-VAC. VA was at least comparable to PAC. The eradication rate did not differ significantly between 10-H-VA or 14-H-VA versus 14-PBQT. 7-L-VAC demonstrated higher eradication rate versus 7-PAC and comparable rate to 14-PAC. 14-VBQT showed higher eradication rates versus 14-PBQT. The adverse events rate was 19.3% for VA, 30.6% for VAC, and 38.4% for VBQT. VA had similar risk of adverse events versus VAC and significantly fewer adverse events compared to PBQT. The treatment discontinuation rate did not differ significantly between treatments. CONCLUSIONS: The eradication rate of VBQT was the highest at above 90% followed by VAC and VA. VA was as effective as VAC and superior to PPI-based therapies with favorable safety, highlighting the potential of VA therapy as a promising alternative to traditional PPI-based therapies. VPZ-based triple or quadruple therapies was more effective than PPI-based therapies. Further studies are needed to establish the optimal treatment regimen especially in the western countries.

Eradication rate and adherence with high-dose amoxicillin and proton pump inhibitor as first-line treatment for Helicobacter pylori infection: Experience from University Hospital in Chile.

INTRODUCTION: In Chile, more than 70% of adults are infected by Helicobacter pylori. Clarithromycin should not be used in any regimen if there is >15% resistance to this antibiotic, being greater than 26% in our population. In this scenario, the effectiveness of triple therapy (proton pump inhibitor [PPI], clarithromycin, amoxicillin) was only 63.8%. AIM: To evaluate the eradication rate and safety of dual therapy (esomeprazole and amoxicillin) in high doses, through a prospective, observational, and descriptive study. METHODS: Patients with a positive urease test obtained in an upper digestive endoscopy were included. Any other previous H. pylori eradication regimen were excluded. All patients were treated with esomeprazole 40 mg three times a day and amoxicillin 750 mg four times a day for 14 days. The eradication rate of the dual therapy was evaluated with the H. pylori stool antigen test (the Pylori-Strip® test used) 6 weeks after completing the eradication treatment and with at least 14 days without PPI, being a negative result, confirmation of the effectiveness of this regimen. RESULTS: Of 122 patients, 106 had a negative H. pylori antigen in stool; The intention-to-treat and per protocol analysis, the eradication rates were 91.8% [95% CI: 87%-97%] and 94% [95% CI: 90%-98%], respectively. Four patients discontinued treatment due to adverse effects. Smoking and adherence to treatment were associated with eradication rate. CONCLUSIONS: In this cohort of patients with H. pylori infection, high-dose dual therapy has a high eradication rate and good adherence, raising the possibility that it could be used as first-line therapy in our country. Studies with a larger number of patients should confirm these results.

Eradication rate and safety of vonoprazan-amoxicillin dual therapy for helicobacter pylori eradication: a randomized controlled trial.

BACKGROUND: Helicobacter pylori (H. pylori), prevalent in developing regions, is a key factor in gastrointestinal diseases. Despite the common use of bismuth-based quadruple therapy, its drawbacks have prompted the search for alternatives. Recently, vonoprazan, a novel acid suppressant, has shown promise in combination with antibiotics as a dual therapy for H. pylori eradication. This study aimed to assess the therapeutic outcomes and adverse events of vonoprazan-amoxicillin dual therapy compared to quadruple therapy. METHODS: A randomized controlled trial (RCT) enrolled H. pylori-infected patients at Zhejiang Hospital. Participants were randomly assigned to dual and quadruple therapy groups. The primary endpoints were H. pylori eradication and adverse events. RESULTS: Of the 400 patients studied from April 2022 to June 2023, In the intention-to-treat (ITT) analysis, the eradication rates of H. pylori in vonoprazan-amoxicillin dual therapy group and quadruple therapy group were 94.0% and 87.0%, respectively, p = 0.017. In the per-protocol (PP) analysis were 97.9% and 93.0%, p = 0.022. Additionally, the dual therapy group had a significantly lower incidence of adverse events (19%) compared to the quadruple therapy group (53%) (p < 0.001). CONCLUSION: Vonoprazan-amoxicillin dual therapy demonstrates superior eradication efficacy and reduced adverse events compared to quadruple therapy in H. pylori-infected patients, suggesting its potential for clinical application and promotion.

Effects of amoxicillin and metronidazole as an adjunct to scaling and root planing on glycemic control in patients with periodontitis and type 2 diabetes: A short-term randomized controlled trial.

OBJECTIVE: To assess the effects of amoxicillin and metronidazole with scaling and root planing (SRP) on periodontal parameters and glycemic control in patients with severe periodontitis and diabetes mellitus. BACKGROUND: Adjunctive antibiotics use is advantageous for treating periodontitis in patients with severe periodontitis and diabetes. However, the effects of adjunctive antibiotic use on hemoglobin A1c (HbA1c) levels remain unclear. METHODS: This short-term, randomized controlled trial enrolled patients with severe periodontitis and type 2 diabetes. The patients were randomly allocated to SPR only (i.e., control) or SPR + antibiotics (500 mg of amoxicillin and 200 mg of metronidazole, three times daily for 7 days) groups. Periodontal and hematological parameters were assessed at baseline and 3 months after treatment. Inter- and intra-group analyses were performed using Student's t-tests, Mann-Whitney U tests, and the binary logistic regression models. p-values of <.05 were considered statistically significant. RESULTS: This study enrolled 49 patients, with 23 and 26 patients in the SRP-only and SRP + antibiotics groups, respectively. The periodontal parameters improved significantly and similarly in both groups after treatment (p < .05). The SRP + antibiotics group had more sites of improvement than the SRP-only group when the initial probing depth was >6 mm. (698 [78.96%] vs. 545 [73.35%], p = .008). The HbA1c levels decreased in the SRP-only and SRP + antibiotics groups after treatment (0.39% and 0.53%, respectively). The multivariable binary logistic regression model demonstrated that antibiotics administration and a high baseline HbA1c level were associated with a greater reduction in the HbA1c level (odds ratio = 4.551, 95% confidence interval: 1.012-20.463; odds ratio = 7.162, 95% confidence interval: 1.359-37.753, respectively). CONCLUSIONS: SRP and SRP plus systemic antibiotics were beneficial for glycemic control. Adjunctive antibiotic use slightly improved the outcome for patients with severe periodontitis and poorly controlled diabetes.

Fluorescence Entrenched Probe for Onsite Detection of Amoxicillin Residue in Bovine Milk.

A novel fluorescent probe (E)-3-(4-hydroxyphenyl)-2-((pyrene-1-ylmethylene) amino)propanoic acid (PyT) was developed for the 'turn-on' detection of amoxicillin(AM), residues. The PyT molecule was developed by a simple condensation reaction between a biologically important tyrosine amino acid and pyrene carboxaldehyde. The small fluorophore molecule has spectacular photoluminescence properties such as large stock shift, high photostability, selectivity and sensitivity toward the analytes. The PyT upon dispersion in the liquid phase becomes highly luminescent possessing the restricted intramolecular rotation (RIR) and excited stated intramolecular proton transfer (ESIPT) properties which are the major criteria for aggregation induced emission enhancement (AIEE) mechanism prevailing the aggregation caused quenching (ACQ). PyT molecule shows a binding constant of 3.285 × 104 L mol-1 for amoxicillin (AM). The limit of detection (LOD) values are found to be 1.67µM. Consuming bovine milk with antibiotic residues exceeding the maximum residue limit (MRL) can lead to food toxicity and life threatening diseases in humans. The milk sample with AM antibiotic residue in presence of PyT probe shows a distinct blue colour which infers the selectivity and sensitivity of the probe towards the analyte. The fluorescence probe adheres with merits like on site and visual examination by naked eye without aid of any instruments.

Simultaneous monitoring of amoxicillin and paracetamol in synthetic biological fluids using a 3D printed disposable electrode with a lab-made conductive filament.

In this work, we are pleased to present for the first time a 3D-printed electrochemical device using a lab-made conductive filament based on graphite (Gr) and polylactic acid (PLA) polymer matrix for the simultaneous detection of amoxicillin (AMX) and paracetamol (PAR). The sensor was properly characterized by scanning electron microscopy (SEM), electrochemical impedance spectroscopy (EIS), and cyclic voltammetry (CV). Compared to the commercial glassy carbon electrode (GCE), the superior performance of the 3D-Gr/PLA electrode was verified with a 3.8-fold more favored charge transfer. A differential pulse voltammetry (DPV) method was proposed providing a linear working range of 4 to 12 µmol L-1 for both analytes and a limit of detection (LOD) of 0.80 and 0.51 µmol L-1 for AMX and PAR, respectively. Additionally, repeatability studies (n = 5, RSD < 5.7%) indicated excellent precision, and recovery percentages ranging from 89 to 109% when applied to synthetic human urine, saliva, and plasma samples, attested to the accuracy of the method. The studies also indicate that the sensor does not suffer significant interference from common substances (antibiotics and biomarkers) present in the biological fluids, which makes it a promising analytical tool considering its low-cost, ease of manufacturing, robustness, and electrochemical performance.