Antibiotics Amoxicillin, Ampicillin and Their Mixture-Impact on Bacteria, Fungi, Ostracods and Plants.

Ampicillin (AMP) and amoxicillin (AMX) are popular antibiotics, which are penicillin derivatives, and are used in both human and veterinary medicine. In the conducted study, AMP, AMX and their mixtures did not cause major changes in the total bacterial counts in soil samples, and even an increase in the bacterial counts from 3,700,000 to 6,260,000 colony-forming units (cfu) per gram of soil dry weight (g of soil DW) was observed for minimal amounts of these drugs in the soil. The total abundance of fungi, on the other hand, increased from values ranging from 17,000 to 148,000 cfu∙g-1 of soil DW to a level of 32,000 to 131,000 cfu∙g-1 of soil DW. The tested antibiotics and their mixtures had no significant effect on the mortality and growth of H. incongruens. AMX and the AMP + AMX mixture also showed no effect on the plant fresh weight yield, plant aboveground part length and dry weight content of wheat seedlings. In contrast, AMP caused an increase in the plant fresh weight yield and wheat seedling length compared to the control. The drug also caused a slight decrease in the seedling dry weight content. Both AMP and AMX showed inhibitory effects on the plant root length at the highest concentrations of the compounds.

Antibiotics stimulates the development of persistent cells in biofilms of Candida albicans bloodstream isolates.

Candida albicans invasive candidiasis is considered a global health problem. In such cases, biofilm formation on implanted devices represents a therapeutic challenge and the presence of metabolically inactive persistent cells (PCs) in these communities increases their tolerance to fungicidal drugs. This study investigated the influence of amoxicillin, AMX; cefepime, CEF; gentamicin, GEN; amikacin, AMK; vancomycin, VAN; and ciprofloxacin, CIP; on the production of PCs in biofilms of C. albicans bloodstream isolates. 48 h-mature biofilms (n = 6) grown in RPMI-1640 supplemented with antibiotics were treated with 100 µg ml-1 amphotericin B and then evaluated for PCs. Biofilms grown in the presence of antibiotics produced more PCs, up to 10×, when exposed to AMX and CIP; 5 × to CEF; and 6 × to GEN and VAN. The results indicate that antibiotics can modulate PC production in C. albicans biofilms. This scenario may have clinical repercussions in immunocompromised patients under broad-spectrum antibiotic therapy.

Biofilms are microbial communities tolerant to antifungals. Our research showed that antibiotics stimulate the formation of persistent cells within Candida albicans biofilms. These are dormant, metabolically silent cells that resist to therapy and can be related to metastatic and recalcitrant infections.

Photodegradation of Amoxicillin in Aqueous Systems: A Review.

Amoxicillin (AMX) is utilized in the treatment of several infectious diseases, and its concentration in wastewater has increased quite significantly over the years, posing high health hazards for humans and other living organisms. Investigations are in progress globally to eliminate AMX and other related pollutants using several methods that include adsorption, photolysis, photocatalytic degradation, photoelectrocatalytic degradation, and electrochemical conversion. AMX can be eliminated efficiently from the environment using photodegradation, either by photolysis or a photocatalytic process. Several types of semiconductor NMs have been used to eliminate AMX and other related drugs present in wastewater. This review spans the photodegradation studies conducted during the years 2018-2024 to degrade and eliminate AMX in aquatic systems. Several studies have been reported to eliminate AMX from different water streams. These studies are categorized into TiO2-containing and non-TiO2-based catalysts for better comparison. A section on photolysis is also included, showing the use of UV alone or with H2O2 or PS without using any nanomaterial. A tabulated summary of both types of catalysts showing the catalysts, reaction conditions, and degradation efficiency is presented. Researchers have used a variety of reaction conditions that include radiation types (UV, solar, and visible), pH of the solution, concentration of AMX, number of nanomaterials, presence of other additives and activators such as H2O2 as oxidant, and the influence of different salts like NaCl and CaCl2 on the photodegradation efficiency. TiO2 was the best nanomaterial found that achieved the highest degradation of AMX in ultraviolet irradiation. TiO2 doped with other nanomaterials showed very good performance under visible light. WO3 was also used by several investigators and found quite effective for AMX degradation. Other metal oxides used for AMX elimination were derived from molybdenum, zinc, manganese, copper, cerium, silver, etc. Some researchers have used UV and/or visible irradiation or sunlight, without using solid catalysts, in the presence of oxidants such as H2O2. A summarized description of earlier published reviews is also presented.

National survey questionnaire on the diagnosis and treatment status of Helicobacter pylori in peptic ulcer bleeding disease.

Background and objective: The Maastricht VI/Florence Consensus and Chinese National Consensus Report provide comprehensive guidelines for treating Helicobacter pylori infection. This study aimed to assess physicians' understanding of and adherence to this consensus in different hospitals. Methods: Chinese medical staff attending gastrointestinal conferences across various regions were selected for this study. The questionnaire included: 1. the number of patients with peptic ulcer bleeding in hospitals of different levels annually and the diagnostic methods used for H. pylori; 2. whether routine H. pylori examination was conducted and the specific methods employed; and 3. Treatment plans for H. pylori eradication; 4. The mean follow-up duration after treatment 5. Plans for re-eradication in cases of H. pylori treatment failure. Results: Across all levels of Chinese hospitals, the urea breath test was the most commonly used method for detecting H. pylori infection. Most primary (81.53%), secondary (89.49%), and tertiary (91.42%) centers opted for a 14-day quadruple regimen. The preferred antibiotic regimen at all hospital levels was amoxicillin+clarithromycin, with rates of 63.69, 58.08, and 59.27% in the primary, secondary, and tertiary hospitals, respectively. The rates of H. pylori re-examination were 68.15, 87.07, and 87.46% in the primary, secondary, and tertiary hospitals. If H. pylori eradication failed, hospitals at different levels choose to replace the initial plan. Conclusion: There is a need for an enhanced understanding of and adherence to guidelines for H. pylori among physicians in hospitals at all levels.

Characterization of Metronidazole, Clarithromycin and Amoxicillin Resistance Genes in Helicobacter pylori Isolated from Gastroenteritis Patients.

BACKGROUND: Helicobacter pylori (H. pylori)is a Gram-negative, microaerophilic, and spiral shape bacterium that resides inside the human stomach. The human stomach serves as its primary reservoir. Complaints about stomach complication due to H. pylori infections are reported in the majority of populations around the globe. Chronic gastritis and intestinal metaplasia of the gastric mucosa are major complications of a long-term H. pylori infections that can lead to gastric cancer in severe cases. This study aims to characterize H. pylori isolates from gastroenteritis patients and to determine the resistance of H. pylori to various antibiotics. METHODS: In the current study, a total of (n = 80) gastric biopsy samples were randomly collected from gastroenteritis patients in brain-heart infusion broth. These were inoculated on Columbia blood agar supplemented with Helicobacter pylori selective supplement (DENT). After culturing, Microscopy and biochemical tests were performed. The susceptibility profile of H. pylori isolates was evaluated using the Kirby Bauer disk diffusion method. On the basis of the drug resistance profile, a total of (n = 20) isolates including (n = 10) from females and (n = 10) from males were selected for the detection and characterization of resistant genes. After confirmation of H. pylori using 16s rRNA, polymerase chain reaction (PCR) was done for the detection of resistance genes including Metronidazole resistance (rdxA gene), Clarithromycin resistance (23s rRNA gene) and Amoxicillin resistance (Penicillin-binding protein A1 (pbpA1) gene). RESULTS: In a total of (n = 80) samples, H. pylori was isolated from 72.5% (n = 58) samples. Among the positive patients, there were 62% (n = 36) of female positive patients while in males, its ratio was 38% (n = 22). It was more common in the age between 30-50 years 55.17% (n = 32). It has shown the highest resistance towards Metronidazole 90% (n = 52), and the lowest toward Levofloxacin 65% (n = 38). Metronidazole resistance gene (rdxA gene) was detected in (n = 13) isolates including (n = 9) isolates from females and (n = 4) from males. In the case of, the Clarithromycin resistance gene (23s rRNA) (n = 10) was positive for H. pylori including (n = 6) isolates from females and (n = 7) were positive for Amoxicillin (pbpA1 gene) including (n = 2) in female and (n = 5) from male patients. CONCLUSION: This study highlights the increasing incidence of H. pylori infections in both male and female patients. It also revealed the current status of antibiotic resistance and its resistance genes in patients facing gastrointestinal issues. Continuous surveillance of resistant clones will help in formulating strategies that can help in combating of resistant clone. It will also help clinician in proper prescription and management of H. pylori infections.

Appropriateness of antibiotic prescribing in paediatrics: retrospective controlled study assessing a multifaceted intervention in Northern Italy in a 7-year period.

BACKGROUND: Academic detailing, audit and feedback, and peer comparison have been advocated as effective ways to promote appropriateness of prescribing and antimicrobial stewardship (AMS). This study explored the effectiveness of a multifaceted intervention aimed at supporting the appropriateness of antibiotic prescribing in paediatrics. METHODS: Over the course of 7 years, all 89 paediatricians of the Local Health Authority (LHA) of Reggio Emilia (530 000 residents) were provided with scientific literature focused on antimicrobial resistance and the appropriateness of use of specific antibiotics, together with local data on antimicrobial resistance and prescribing reports comparing each paediatrician with colleagues in the same district and with local averages. Prescribing rates of specific target antibiotics/classes of antibiotics were evaluated by comparing Reggio-Emilia with the other seven LHAs of the Emilia-Romagna Region (control area), adjusting for prescriptions during a 2-year baseline period. RESULTS: A significant increase in the rate of amoxicillin prescriptions (91 more per 1000 children/year) was observed in the intervention area compared with the control area along with a significant reduction in the rate of amoxicillin+clavulanate prescriptions (70 fewer per 1000 children/year) and a significant increase in the ratio of their prescription rates. No differences were observed in cephalosporin and macrolide prescription rates and overall antibiotic prescriptions. CONCLUSIONS: Improvements in prescribing appropriateness were observed. This study confirms the importance of an audit and feedback approach through small group meetings supported by scientific literature, local resistance data and prescribing reports. Such approach should always be considered as part of multifaceted interventions to promote AMS.

Vonoprazan Dual or Triple Therapy Versus Bismuth-Quadruple Therapy as First-Line Therapy for Helicobacter pylori Infection: A Three-Arm, Randomized Clinical Trial.

BACKGROUND: We compared efficacy of vonoprazan-dual or triple therapies and bismuth-quadruple therapy for treatment-naive Helicobacter pylori (HP) infection in Southern China, where primary resistance rates of clarithromycin and levofloxacin are >30%. METHODS: This was an investigator-initiated, three-arm, randomized clinical trial in Southern China. Between March 2022 and August 2023, treatment-naïve HP-infected adults were randomly assigned to receive one of three 14-day regimens (1:1:1 ratio): vonoprazan-dual (VA-dual; vonoprazan 20 mg twice daily and amoxicillin 1 g thrice daily), vonoprazan-triple (VAC-triple; vonoprazan 20 mg/amoxicillin 1 g/clarithromycin 500 mg twice daily), or bismuth-quadruple therapy containing bismuth, esomeprazole, tetracycline, and metronidazole. Primary outcome was noninferiority in HP eradication, evaluated by UBT 4-6 weeks post-treatment by intention-to-treat (ITT) and per-protocol (PP) analysis (based on subjects who completed 14-day treatment and rechecked UBT). Bonferroni-adjusted p-value of <0.017 was used to determine statistical significance. RESULTS: A total of 298 subjects (mean age: 35.7 ± 8.4 years; male: 134 [45.0%]; VC-dual: 100, VAC-triple: 98, bismuth-quadruple: 100) were enrolled, and 292 (98.0%) had UBT rechecked. ITT analysis showed that both VA-dual (eradication rate of 96.0%) and VAC-triple therapies (95.9%) were noninferior to bismuth-quadruple therapy (92.0%) (difference: 4.0%, 95% CI: -2.9% to 11.5%, p < 0.001; and 3.9%, 95% CI: -3.1% to 11.5%, p < 0.001, respectively). PP analysis also revealed noninferiority (96.7% or 96.7% vs. 97.4%, with difference: -2.9% and -2.9%, p = 0.009 and 0.010, respectively). The frequency of adverse events was 39.0%, 56.1%, and 71.0% in VA-dual, VAC-triple, and bismuth-quadruple therapies, respectively. CONCLUSIONS: VA-dual and VA-triple therapies are highly effective and noninferior to bismuth-quadruple therapy in Southern China. Given the lower adverse effects and fewer antibiotic use, VA-dual therapy is the preferred first-line treatment for HP infection. TRIAL REGISTRATION: Chinese Clinical Trial Registry (No. ChiCTR2200056375). Registered on February 4, 2022, https://www.chictr.org.cn/showproj.aspx?proj=14131.

Adverse Drug Reactions Resulting From the Use of Chiral Medicines Amoxicillin, Amoxicillin-Clavulanic Acid, and Ceftriaxone: A Mixed Prospective-Retrospective Cohort Study.

The use of chiral medicines (possessing center(s) of asymmetric carbon) may cause adverse drug reactions (ADRs). The safety assurance of these medicines is critical. We aimed to evaluate registered and commonly used anti-infective chiral medicines circulating in the Tanzanian market to establish their safety profile to protect public health. A mixed prospective-retrospective cohort study was conducted to assess the safety profile of amoxicillin, amoxicillin-clavulanic acid and ceftriaxone injection. ADRs causality assessment was conducted by using World Health Organization (WHO)-Algorithm criteria. Data were collected from 7 tertiary hospitals: Muhimbili National Hospital (MNH), Kilimanjaro Christian Medical Centre (KCMC), Bugando Medical Centre (BMC), Ligula Referral-Regional Hospital (LRRH), Kitete Referral-Regional Hospital (KRRH), Dodoma Referral-Regional Hospital (DRRH), and Mbeya Zonal-Referral Hospital (MZRH). Data were supplemented by those recorded in the WHO-Vigiflow/VigiLyze database within the same monitoring period. Data were analyzed using STATA version-15. The results were considered statistically significant when P < .05. A total of 2522 patients were enrolled in hospitals: MNH (499), KCMC (407), BMC (396), LRRH (387), KRRH (345), DRRH (249), and MZRH (239). Among those, 1197 (47.5%) were treated with ceftriaxone, 585 (23.2%) amoxicillin and 740(29.3%) amoxicillin-clavulanic acid. Out of those, 102 (4.5%) experienced adverse events (AEs), 49 (48%) were due to ceftriaxone, 37 (36.3%) amoxicillin-clavulanic acid and 16 (15.7%) amoxicillin (P-value .012). A total of 443 participants from the enrolled and WHO-Vigiflow/VigiLyze database were experienced with ADRs. The ADRs affected mainly gastro-intestinal system 234 (53%), skin and subcutaneous tissue 85 (19%), nervous system 49 (11%), respiratory thoracic 22 (5%), and general disorders 18(4%). In this study, approximately 90% of reported AEs were ADRs possible-related to the monitored medicines, with few plausible and certain. Ceftriaxone injection caused more ADRs. Amoxicillin-clavulanic acid was associated with more ADRs than amoxicillin alone. The safety profile of these medicines is still maintained; however, comprehensive monitoring of ADRs is recommended to improve patient safety and enhance overall treatment outcomes.

Development and validation of next-generation sequencing panel for personalized Helicobacter pylori eradication treatment targeting multiple species.

Introduction: The decreasing Helicobacter pylori eradication rate is primarily attributed to antibiotic resistance, and further exacerbated by uniform drug administration disregarding a host's metabolic capability. Consequently, applying personalized treatment based on antibiotic resistance-associated variants and the host's metabolic phenotype can potentially increase the eradication rate. Method: A custom next-generation sequencing panel for personalized H. pylori eradication treatment (NGS-PHET) was designed which targeted the regions for amoxicillin, clarithromycin, metronidazole, tetracycline, and levofloxacin-resistance in H. pylori and human proton-pump inhibitor (PPI) metabolism. The libraries were constructed following customized methods and sequenced simultaneously. The customized framework criteria, grounded in previously reported antibiotic resistance associated variants and the host's PPI metabolism, was applied to the NGS-PHET results and suggested a personalized treatment for each subject, which was validated through each subject's actual eradication outcome. Results: Both previously reported and novel variants were identified from H. pylori sequencing results. Concurrently, five CYP2C19 homozygous extensive metabolizers and three CYP3A4 intermediate metabolizers were identified. Among the total of 12 subjects, clarithromycin triple therapy was suggested for five subjects, bismuth quadruple therapy was suggested for six subjects, and rifabutin triple therapy was suggested for one subject by following the customized framework criteria. The treatment suggestion for nine of the 12 subjects was consistent with the treatment that each subject achieved eradication with. Discussion: Applying the methodology using the NGS-PHET and customized framework helps to perform eradication treatment quickly and effectively in most patients with antibiotic-resistant H. pylori strains, and is also useful in research to find novel antibiotic-resistance candidates.

Mucoadhesive in situ nasal gel of amoxicillin trihydrate for improved local delivery: Ex vivo mucosal permeation and retention studies.

Orally administered amoxicillin is recommended as the first-line treatment of acute bacterial rhinosinusitis (ABR) and given in a high-dose regimen. However, the risk of various systemic adverse reactions and low oral bioavailability are unbearable, increasing the threat of antibiotic resistance. Therefore, nasal delivery of amoxicillin can be a potential approach for effectively treating ABR locally, as well as overcoming those drawbacks. In a way to guarantee the effectiveness for local therapy in nasal cavity, the permeation and retention properties are of significant importance considerations. Accordingly, the present work aimed to investigate the characteristics with respect to the nasal applicability of the in situ gelling amoxicillin trihydrate (AMT) and further evaluate its permeability and retention properties through human nasal mucosa. The lyophilized formulations were characterized utilizing the Differential Scanning Calorimetry (DSC) and X-ray Powder Diffraction (XRPD), and also evaluated for its polarity, reconstitution time, droplet size distribution, mucoadhesive properties, and ex vivo permeability and retention studies. The results confirmed that the in situ gelling AMT formulations possess adequate mucoadhesive behavior, especially the formulation containing 0.3 % of gellan gum. Substantially, the in situ gelling AMT formulations were able to retain the drug on the surface of nasal mucosa instead of permeating across the membrane; thus, suitable for treating nasal infections locally. Altogether, the in situ gelling systems demonstrates promising abilities as a delivery platform to enhance local application of AMT within the nasal cavity.

Synergistic effects of novel penicillin-binding protein 1A amino acid substitutions contribute to high-level amoxicillin resistance of Helicobacter pylori.

The growing resistance to amoxicillin (AMX)-one of the main antibiotics used in Helicobacter pylori eradication therapy-is an increasing health concern. Several mutations of penicillin-binding protein 1A (PBP1A) are suspected of causing AMX resistance; however, only a limited set of these mutations have been experimentally explored. This study aimed to investigate four PBP1A mutations (i.e., T558S, N562H, T593A, and G595S) carried by strain KIN76, a high-level AMX-resistant clinical H. pylori isolate with an AMX minimal inhibition concentration (MIC) of 2 µg/mL. We transformed a recipient strain 26695 with the DNA containing one to four mutation allele combinations of the pbp1 gene from strain KIN76. Transformants were subjected to genomic exploration and antimicrobial susceptibility testing. The resistance was transformable, and the presence of two to four PBP1A mutations (T558S and N562H, or T593A and G595S), rather than separate single mutations, was necessary to synergistically increase the AMX MIC up to 16-fold compared with the wild-type (WT) strain 26695. An AMX binding assay of PBP1A was performed using these strains, and binding was visualized by chasing Bocillin, a fluorescent penicillin analog. This revealed that all four-mutation allele-transformed strains exhibited decreased affinity to AMX on PBP1A than the WT. Protein structure modeling indicated that functional modifications occur as a result of these amino acid substitutions. This study highlights a new synergistic AMX resistance mechanism and establishes new markers of AMX resistance in H. pylori.IMPORTANCEThe development of resistance to antibiotics, including amoxicillin, is hampering the eradication of Helicobacter pylori infection. The identification of mechanisms driving this resistance is crucial for the development of new therapeutic strategies. We have demonstrated in vitro the synergistic role of novel mutations in the pbp1 gene of H. pylori that is suspected to drive amoxicillin resistance. Also deepening our understanding of amoxicillin resistance mechanisms, this study establishes new molecular markers of amoxicillin resistance that may be useful in molecular-based antibiotic susceptibility testing approaches for clinical practice or epidemiologic investigations.

Interkingdom biofilm of Streptococcus pyogenes and Candida albicans: establishment of an in vitro model and dose-response validation of antimicrobials.

Although Streptococcus pyogenes and Candida albicans may colonize tonsillar tissues, the interaction between them in mixed biofilms has been poorly explored. This study established an interkingdom biofilm model of S. pyogenes and C. albicans and verified the dose-response validation of antimicrobials. Biofilms were formed on microplates, in the presence or absence of a conditioning layer of human saliva, using Brain Heart Infusion (BHI) broth or artificial saliva (AS) as a culture medium, and with variations in the microorganism inoculation sequence. Biofilms grown in AS showed higher mass than those grown in BHI broth, and an opposite trend was observed for metabolism. The number of S. pyogenes colonies was lower in AS. Amoxicillin and nystatin showed dose-dependent effects. The inoculation of the two species at the same time, without prior exposure to saliva, and using BHI broth would be the model of choice for future studies assessing the effects of antimicrobials on dual S. pyogenes/C. albicans biofilms.

Vonoprazan-amoxicillin dual therapy for Helicobacter pylori eradication in Chinese population: A prospective, multicenter, randomized, two-stage study.

BACKGROUND: The efficacy of Vonoprazan-amoxicillin dual therapy (VAT) in the treatment of Helicobacter pylori (H. pylori) is controversial. AIM: To evaluate the efficacy of VAT in the Chinese population. METHODS: This prospective, multicenter, randomized, open-label, and two-stage study was conducted at 23 centers in Fujian, China (May 2021-April 2022). H. pylori-infected patients were randomized to bismuth quadruple therapy (BQT), BQT-Vonoprazan (BQT-V), seven-day VAT (VAT-7), ten-day VAT (VAT-10), and fourteen-day VAT (VAT-14) groups. The primary endpoint was the H. pylori eradication rate. The secondary endpoint was the frequency of adverse events. This study was registered with the Chinese Clinical Trial Registry, ChiCTR2100045778. RESULTS: In the first stage, VAT-7 and BQT-V groups were selected for early termination because less than 23 among 28 cases were eradicated. In the second stage, the eradication rates for BQT, VAT-10, and VA-14 were 80.2% [95% confidence interval (95%CI): 71.4%-86.8%], 93.2% (86.6%-96.7%), 92.2% (85.3%-96.0%) in the intention-to-treat (ITT) analysis, and 80.9% (95%CI: 71.7%-87.5%), 94.0% (87.5%-97.2%), and 93.9% (87.4%-97.2%) in the per-protocol analysis. The ITT analysis showed a higher eradication rate in the VAT-10 and VAT-14 groups than in the BQT group (P = 0.022 and P = 0.046, respectively). The incidence of adverse events in the VAT-10 and VAT-14 groups was lower than in the BQT group (25.27% and 13.73% vs 37.62%, respectively; P < 0.001). CONCLUSION: VAT with a duration of 10 or 14 days achieves a higher eradication rate than the BQT, with a more tolerable safety profile in H. pylori-infected patients in Fujian.

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.

Tetracycline Three Times Daily Versus Four Times Daily in Bismuth-Containing Quadruple Therapy as the First-Line Treatment of Helicobacter pylori Infection: A Multicenter, Noninferiority, Randomized Controlled Trial.

BACKGROUND: Current guidelines recommend bismuth-containing quadruple therapy for patients newly diagnosed with Helicobacter pylori (H. pylori) infection. We aimed to compare the efficacy and safety of tetracycline administered three times daily versus four times daily in bismuth-containing quadruple therapy for first-line treatment of H. pylori infection. METHODS: This multicenter, noninferiority, randomized controlled study, conducted in China, recruited treatment-naïve adults with H. pylori infection, randomized 1:1 into two treatment groups to receive either of the following bismuth-containing quadruple therapies: esomeprazole 20 mg twice-daily; bismuth 220 mg twice-daily; amoxicillin 1000 mg twice-daily; and tetracycline 500 mg three times daily (TET-T) versus 500 mg four times daily (TET-F). At least 6 weeks post-treatment, a 13C-urea breath test was performed to evaluate H. pylori eradication. RESULTS: In total, 406 patients were randomly assigned to the two treatment groups. Intention-to-treat eradication rates were 91.63% (186/203; 95% confidence interval [CI] 87.82%-95.44%) versus 90.15% (183/203; 95% CI 86.05%-94.25%) (p = 0.0005) and per-protocol eradication rates were 95.34% (184/193; 95% CI 92.36%-98.31%) versus 95.72% (179/187; 95% CI 92.82%-98.62%) (p = 0.0002) for the TET-T and TET-F group, respectively. TET-T-treated patients had a lower incidence of adverse effects than TET-F-treated patients (21.61% vs. 31.63%, p = 0.024), with no significant differences in compliance to treatment between the groups. CONCLUSION: As a first-line therapy for H. pylori infection, the eradication rate of the TET-T therapy was noninferior to that of the TET-F therapy while significantly reducing the incidence of adverse reactions. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05431075.

Seven-Day Vonoprazan-Based Triple Therapy as First-Line Helicobacter pylori Treatment in Comparison With Extended Sequential Therapy: A Randomized Controlled Trial.

BACKGROUND: Vonoprazan, a potassium-competitive acid blocker, has demonstrated greater potency and a longer duration of acid suppression when compared to the proton pump inhibitors. However, data regarding the comparison between vonoprazan-based triple therapy with standard treatment for first-line Helicobacter pylori treatment are limited. This study aimed to compare the efficacy between 7-day vonoprazan-based triple therapy with high-dose amoxicillin (VAC-7) and 14-day extended sequential therapy (S-14). MATERIALS AND METHODS: This was a single-center prospective randomized controlled trial following a noninferiority design. Subjects over 20 years old with confirmed H. pylori infection were enrolled prospectively from Fu Jen Catholic University Hospital. They were randomly assigned to the VAC-7 or S-14 group. The primary endpoint was the eradication rate in first-line treatment, evaluated by urea breath test, with noninferiority determined using the Farrington-Manning method. The secondary outcome included adverse effect rates and compliance, assessed through self-administered questionnaires. RESULTS: Between December 2021 and June 2023, a total of 628 patients were recruited. The eradication rates by per-protocol analysis and intention-to-treat analysis were 88.6%/81.8% for VAC-7 and 90.3%/81.4% for S-14, respectively. The VAC-7 was non-inferior to S-14 in terms of ITT analysis. Subjects experienced fewer incidences of nausea, anorexia, dizziness, fatigue, and any severe adverse events in the VAC-7 group. Compliance was higher in the VAC-7 group, with 94% taking all the pills correctly. CONCLUSIONS: Our findings supported the use of 7-day vonoprazan triple therapy with high-dose amoxicillin as the standard first-line treatment for H. pylori infection. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05371249.

Empirical Therapy Versus Tailored Therapy of Helicobacter pylori in Korea: Results of the K-CREATE Study.

BACKGROUND: The optimal duration of regimens for tailored therapy based on genotypic resistance for clarithromycin has yet to be established. AIM: This study was a nationwide, multicenter, randomized trial comparing empirical therapy with tailored therapy based on genotypic resistance for first-line eradication of Helicobacter pylori. We also compared the eradication rates of 7- and 14-day regimens for each group. PATIENTS AND METHODS: Patients with H. pylori infection were first randomized to receive empirical or tailored therapy. Patients in each group were further randomized into 7- or 14-day regimens. Empirical therapy consisted of a triple therapy (TT) regimen (twice-daily doses of pantoprazole 40 mg, amoxicillin 1 g, and clarithromycin 500 mg) for 7 or 14 days. Tailored therapy consisted of TT of 7 or 14 days in patients without genotypic resistance. Patients with genotypic resistance were treated with bismuth quadruple therapy (BQT) regimens (twice-daily doses of pantoprazole 40 mg, three daily doses of metronidazole 500 mg, and four times daily doses of bismuth 300 mg and tetracycline 500 mg) for 7 or 14 days. A 13C-urea breath test assessed eradication rates. The primary outcome was eradication rates of each group. RESULTS: A total of 593 patients were included in the study. The eradication rates were 65.7% (201/306) in the empirical therapy group and 81.9% (235/287) in the tailored therapy group for intention-to-treat analysis (p < 0.001). In the per-protocol analysis, the eradication rates of the empirical therapy and tailored groups were 70.3% (201/286) and 85.5% (235/274) (p < 0.001), respectively. There was no difference in compliance between the two groups. The rate of adverse events was higher in the tailored group compared to the empirical group (p < 0.001). DISCUSSION: Our study confirmed that tailored therapy based on genotypic resistance was more effective than empirical therapy for H. pylori eradication in Korea. However, no significant difference was found between 7- and 14-day regimens for each group. Future studies are needed to determine the optimal duration of therapy for empirical and tailored therapy regimens.

Leftover of Amoxicillin Suspension After Use by Children in the Netherlands.

PURPOSE: In clinical practice, a discrepancy may exist between the prescribed amount of a drug and the commercially available pack sizes in the pharmacy, potentially contributing to drug waste. This study aimed-as an example of this phenomena-to quantify leftover of amoxicillin suspension prescribed to children, due to discrepancies between physician-prescribed and pharmacy-dispensed amounts. METHODS: We performed a retrospective cohort study including amoxicillin suspension dispensations for patients aged 0-12 years between 2017 and 2019 utilizing the Dutch PHARMO database. Leftover amount of amoxicillin was estimated by assessing the discrepancy between the prescribed and dispensed amounts. Extrapolated amoxicillin weight and economic spillage estimates for the Netherlands were determined. The impact of two theoretical interventions on leftover amount was assessed: (1) introducing vials with half the volume of the current 100 and 30 mL vials and (2) a combination of the first intervention with a maximum of 10% round-down by the dispensing pharmacy of the prescribed dose. RESULTS: We included 79 512 amoxicillin suspension dispensations for 62 252 patients. The mean leftover amount of amoxicillin suspension per dispensing was 27%. The yearly amount of amoxicillin leftover was 49.8 kg in the study cohort, equivalent to yearly 633 kg and €621 000 when extrapolated to the Netherlands. Employing the first theoretical intervention reduced the mean leftover per dispensing to 20%, reducing the yearly leftover to 31.6 kg amoxicillin in the study cohort, and to 400 kg and €400 000 extrapolated. The second theoretical intervention further reduced leftover to 17%, reducing the yearly leftover to 24.3 kg amoxicillin in the study cohort, and to 300 kg and €300 000 extrapolated. CONCLUSION: Approximately a quarter of amoxicillin suspension remains as leftover per dispensing. Applying different theoretical intervention shows the potential for a significant reduction of amoxicillin leftover.

Highly sensitive and selective detection of amoxicillin using molecularly imprinted ratiometric fluorescent nanosensor based on quantum dots.

A dual-emission ratiometric fluorescence sensor (CDs@CdTe@MIP) with a self-calibration function was successfully constructed for AMO detection. In the CDs@CdTe@MIP system, non-imprinted polymer-coated CDs and molecule-imprinted polymer-coated CdTe quantum dots were used as the reference signal and response elements, respectively. The added AMO quenched the fluorescence of the CdTe quantum dots, whereas the fluorescence intensity of the CDs remained almost unchanged. The AMO concentration was monitored using the fluorescence intensity ratio (log(I647/I465)0/(I647/I465)) to reduce interference from the testing environment. The sensor with a low detection limit of 0.15 µg/L enabled detection of the AMO concentration within 6 min. The ratiometric fluorescence sensor was used to detect AMO in spiked pork samples; it exhibited a high recovery efficiency and relative standard deviation (RSD) of 97.94-103.70% and 3.77-4.37%, respectively. The proposed highly sensitive and selective platform opens avenues for sensitive, reliable, and rapid determination of pharmaceuticals in the environment and food safety monitoring using ratiometric sensors.

Pharmacokinetics, optimal dosages and withdrawal time of amoxicillin in Nile tilapia (Oreochromis niloticus) reared at 25 and 30 °C.

Knowledge of amoxicillin (AMX) pharmacokinetics (PK) and tissue residues in fish, which is necessary for prudent drug use, remains limited. The study aimed to explore the PK characteristics of AMX in Nile tilapia (Oreochromis niloticus) reared at 25 and 30 °C as well as to determine optimal dosages and drug withdrawal time (WDT). In the PK investigation, the fish received a single dose of 40 mg/kg AMX via oral gavage, and the optimal dosage was determined by the pharmacokinetic-pharmacodynamic approach. In the tissue residue study, the fish were orally gavaged with 40 mg/kg/day AMX once daily for 5 days and the WDT was established by the linear regression analysis. The results revealed the temperature-dependent drug elimination; the clearance relative to bioavailability (CL/F) and elimination half-life at 30 °C (0.180 L/kg/h and 6.06 h, respectively) were about twice those at 25 °C (0.090 L/kg/h and 10.49 h, respectively). The optimal dosages at the minimum inhibitory concentration (MIC) of 2 µg/mL were 10.97 (25 °C) and 41.03 (30 °C) mg/kg/day, respectively. Finally, following the multiple oral administration, the muscle/skin residue of AMX on day 1 after the last dosing at 25 and 30 °C were 548 and 264 ng/g, respectively. The average tissue residues were depleted below the maximum residue limits (MRL) of 50 µg/kg on day 5 (25 °C) and 3 (30 °C), respectively, and the WDT were 6 and 4 days when rearing at 25 and 30 °C, respectively. This knowledge serves as a practical guideline for responsible use of AMX in treating bacterial diseases in Nile tilapia aquaculture.