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1.
Helicobacter ; 29(1): e13052, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38332683

RESUMEN

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.


Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Adulto , Humanos , Amoxicilina , Antibacterianos , Chile , Claritromicina/uso terapéutico , Quimioterapia Combinada/efectos adversos , Esomeprazol/uso terapéutico , Infecciones por Helicobacter/tratamiento farmacológico , Hospitales , Estudios Prospectivos , Inhibidores de la Bomba de Protones , Resultado del Tratamiento
2.
Ann Med Surg (Lond) ; 86(1): 522-524, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38222713

RESUMEN

Introduction: Bullous erythema multiforme (BEM), an immune-mediated, acute condition, frequently includes erosion affecting the oral, genital, and/or ocular mucosa in addition to discrete target-like lesions on the skin. BEM has been linked to various factors, including infections, medications, malignancy, autoimmune disease, immunization, and radiation. Case presentation: Here, we report a case of a 38-year-old married woman who presented with symptoms of reddish-raised, fluid-filled and painful, nonpruritic lesions along with the swelling of bilateral hand and feet. This patient had a history of taking some unrecorded ayurvedic medication for bloating and abdominal pain in a background of antibiotic use before exhibiting the dermatological symptoms of BEM 2 days later. She was successfully managed with ampicillin and cloxacillin, acyclovir and prednisolone. Clinical discussion: A few incidence of BEM after the administration of amoxicillin has been reported, which precipitated only after consuming ayurvedic medication. BEM has a clinical diagnosis with biopsy rarely required. Here, the hypersensitivity reaction induced by the antibiotic itself or by altering the immune response to the concomitant consumed herbal medicine could explain the BEM. Conclusion: Physicians should note that amoxicillin can trigger BEM, regardless of its use with ayurvedic drugs. Antibiotics should be used with caution, especially in patients with a history of BEM.

3.
United European Gastroenterol J ; 12(1): 122-138, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38050339

RESUMEN

BACKGROUND: Management of Helicobacter pylori (H. pylori) infection requires co-treatment with proton pump inhibitors (PPIs) and the use of antibiotics to achieve successful eradication. AIM: To evaluate the role of dosage of PPIs and the duration of therapy in the effectiveness of H. pylori eradication treatments based on the 'European Registry on Helicobacter pylori management' (Hp-EuReg). METHODS: Hp-EuReg is a multicentre, prospective, non-interventionist, international registry on the routine clinical practice of H. pylori management by European gastroenterologists. All infected adult patients were systematically registered from 2013 to 2022. RESULTS: Overall, 36,579 patients from five countries with more than 1000 patients were analysed. Optimal (≥90%) first-line-modified intention-to-treat effectiveness was achieved with the following treatments: (1) 14-day therapies with clarithromycin-amoxicillin-bismuth and metronidazole-tetracycline-bismuth, both independently of the PPI dose prescribed; (2) All 10-day (except 10-day standard triple therapy) and 14-day therapies with high-dose PPIs; and (3) 10-day quadruple therapies with clarithromycin-amoxicillin-bismuth, metronidazole-tetracycline-bismuth, and clarithromycin-amoxicillin-metronidazole (sequential), all with standard-dose PPIs. In first-line treatment, optimal effectiveness was obtained with high-dose PPIs in all 14-day treatments, in 10- and 14-day bismuth quadruple therapies and in 10-day sequential with standard-dose PPIs. Optimal second-line effectiveness was achieved with (1) metronidazole-tetracycline-bismuth quadruple therapy for 14- and 10 days with standard and high-dose PPIs, respectively; and (2) levofloxacin-amoxicillin triple therapy for 14 days with high-dose PPIs. None of the 7-day therapies in both treatment lines achieved optimal effectiveness. CONCLUSIONS: We recommend, in first-line treatment, the use of high-dose PPIs in 14-day triple therapy and in 10-or 14-day quadruple concomitant therapy in first-line treatment, while standard-dose PPIs would be sufficient in 10-day bismuth quadruple therapies. On the other hand, in second-line treatment, high-dose PPIs would be more beneficial in 14-day triple therapy with levofloxacin and amoxicillin or in 10-day bismuth quadruple therapy either as a three-in-one single capsule or in the traditional scheme.


Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Adulto , Humanos , Inhibidores de la Bomba de Protones/uso terapéutico , Metronidazol , Claritromicina/uso terapéutico , Levofloxacino/uso terapéutico , Bismuto , Estudios Prospectivos , Quimioterapia Combinada , Antibacterianos/uso terapéutico , Infecciones por Helicobacter/tratamiento farmacológico , Amoxicilina/uso terapéutico , Tetraciclina , Sistema de Registros
4.
Therap Adv Gastroenterol ; 16: 17562848231192750, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37675247

RESUMEN

A standard bismuth quadruple therapy, a fluoroquinolone-containing triple (or quadruple) therapy or a proton pump inhibitor (PPI)-amoxicillin high-dose dual therapy has been recommended as a second-line treatment for Helicobacter pylori infection by the Maastricht VI/Florence Consensus Report. The major shortcoming of levofloxacin-amoxicillin triple therapy is low cure rate for eradicating levofloxacin-resistant strains. With the rising prevalence of levofloxacin-resistant strains, levofloxacin-amoxicillin triple therapy cannot reliably achieve a high eradication rate for second-line treatment of H. pylori infection in most countries now. The present article aims to review current second-line eradication regimens with a per-protocol eradication rate exceeding 85% in most geographic areas. Recently, a novel tetracycline-levofloxacin quadruple therapy consisting of a PPI, bismuth, tetracycline, and levofloxacin for rescue treatment of H. pylori infection has been developed. The new therapy achieved a higher per-protocol eradication rate than levofloxacin-amoxicillin triple treatment in a randomized controlled trial (98% versus 69%). Additionally, the tetracycline-levofloxacin quadruple therapy also exhibits a higher eradication rate than amoxicillin-levofloxacin quadruple therapy. High-dose dual PPI-amoxicillin therapy is another novel second-line treatment for H. pylori infection. The new therapy can achieve an eradication rate of 89% by per-protocol analysis for the second-line treatment in Taiwan. Recently, levofloxacin-based sequential quadruple therapy and potassium-competitive acid blocker have also been applied in the second-line treatment of H. pylori infection. A meta-analysis revealed that a vonoprazan-based regimen has significant superiority over a PPI-based regimen for second-line H. pylori eradication therapy. In conclusion, the eradication rate of levofloxacin-amoxicillin triple therapy is suboptimal in the second-line treatment of H. pylori infection now. Currently, a standard bismuth quadruple therapy (tetracycline-metronidazole quadruple therapy), a tetracycline-levofloxacin quadruple therapy, an amoxicillin-levofloxacin quadruple therapy, a levofloxacin-based sequential quadruple therapy or a high-dose PPI-amoxicillin dual therapy is recommended for the second-line treatment of H. pylori infection.

5.
Int J Pharm ; 645: 123435, 2023 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-37741560

RESUMEN

A recommended first-line acute bacterial rhinosinusitis (ABR) treatment regimen includes a high dose of orally administered amoxicillin, despite its frequent systemic adverse reactions coupled with poor oral bioavailability. Therefore, to overcome these issues, nasal administration of amoxicillin might become a potential approach for treating ABR locally. The present study aimed to develop a suitable carrier system for improved local nasal delivery of amoxicillin employing the combination of albumin nanoparticles and gellan gum, an ionic-sensitive polymer, under the Quality by Design methodology framework. The application of albumin nanocarrier for local nasal antibiotic therapy means a novel approach by hindering the nasal absorption of the drug through embedding into an in situ gelling matrix, further prolonging the drug release in the nasal cavity. The developed formulations were characterized, including mucoadhesive properties, in vitro drug release and antibacterial activities. Based on the results, 0.3 % w/v gellan gum concentration was selected as the optimal in situ gelling matrix. Essentially, each formulation adequately inhibited the growth of five common nasal pathogens in ABR. In conclusion, the preparation of albumin-based nanoparticles integrated with in situ ionic-sensitive polymer provides promising ability as nanocarrier systems for delivering amoxicillin intranasally for local antibiotic therapy.


Asunto(s)
Amoxicilina , Nanopartículas , Albúmina Sérica Bovina , Administración Intranasal , Mucosa Nasal , Antibacterianos , Polímeros , Geles , Sistemas de Liberación de Medicamentos , Polisacáridos Bacterianos
6.
BMC Vet Res ; 19(1): 164, 2023 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-37726783

RESUMEN

BACKGROUND: A new antibacterial compound powder of amoxicillin (AMO)/Radix Scutellaria extract (RSE) was developed, and its pharmacokinetics were determined in pigs following oral administration. RESULTS: The MIC ranges of AMO against Escherichia coli, Staphylococcus aureus and Streptococcus were 1-8 µg/mL, 0.5-4 µg/mL and 0.5-64 µg/mL, respectively. The MIC ranges of RSE against E. coli, S. aureus, and Streptococcus were greater than 2.5 mg/mL, 0.156-2.5 mg/mL, and greater than 2.5 mg/mL, respectively. For S. aureus, the combined drug susceptibility test showed that AMO and RSE had an additive or synergistic effect. The results of compatibility test, the excipient screening test and the drug quality control test showed that the formulation had stable quality and uniform properties under the test conditions. Two studies were conducted to investigate the pharmacokinetics of the compound product in pigs. First, the pharmacokinetics of the AMO-RSE powder were compared with those of their respective single products. The results showed no significant change in the main pharmacokinetic parameters when either component was removed from the compound formulation; thus, AMO and RSE have no pharmacokinetic interaction in pigs. Second, pigs were orally administered three different doses of AMO-RSE powder. The Cmax and AUC increased proportionally with increasing p.o. dose; thus, the λz, t1/2λ, MRT, and Tmax were unchanged for the doses of 10, 20, and 30 mg/kg AMO and the doses of 5, 10, and 15 mg/kg BCL, showing that AMO/baicalin in AMO-RSE powder showed linear pharmacokinetic characteristics in pigs. CONCLUSIONS: The combined drug sensitivity test of AMO and RSE against S. aureus showed that the combination was additive or synergistic. Pharmacokinetic studies indicated that AMO and BCL do not interfere with each other in pigs when used in a compound formulation. The pharmacokinetic parameters remained unchanged regardless of the dose for p.o. administration, indicating linear pharmacokinetic properties over the tested dose range. The quality of the AMO-RSE powder was good and stable, providing a foundation for its clinical application in veterinary medicine. Further bioavailability, PK/PD and clinical trials are still needed to determine the final dosage regimen.


Asunto(s)
Amoxicilina , Scutellaria , Animales , Porcinos , Escherichia coli , Polvos , Staphylococcus aureus , Extractos Vegetales/farmacología
7.
Bioengineered ; 14(1): 2252207, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37712693

RESUMEN

Residual antibiotics have become emerging contaminants of concern for their adverse impact on the ecosystem. Additionally, their accumulation in the environment is increasing antibiotic resistance among pathogens. This study assessed the impact of intensification of biochar, nutrients, aeration, and bacteria (BNAB) on the remediation potential of floating treatment wetlands (FTWs) to treat amoxicillin (AMX)-contaminated water. The FTWs were developed with saplings of Vetiveria zizanioides and intensified with biochar (1.5%), nutrients (25 mgL-1 N, 25 mgL-1 P, 20 mg L1 K), aeration (7 mg L-1), and AMX-degrading bacteria. The results showed that all the amendments enhanced the AMX degradation, while the maximum reduction in COD (89%), BOD (88%), TOC (87%), and AMX (97%) was shown by the combined application of all the amendments. The combined application also enhanced plant growth and persistence of the inoculated bacteria in the water, roots, and shoots. This approach can be employed for the low-cost, environment-friendly treatment, and recycling of antibiotic-contaminated wastewater, where BNAB intensification can further improve the bioremediation efficiency of FTWs in the case of heavily polluted waters.


Vetiver grass floating treatment wetlands (FTWs) removed 83% amoxicillin.Intensification of floating treatment wetlands enhanced amoxicillin removal to 97%.Intensified-FTW removed COD, BOD, and TOC by 89%, 88%, and 87%, respectively.Potential of Intensified-FTW for bioremediation of highly polluted water is shown.


Asunto(s)
Amoxicilina , Antibacterianos , Humedales , Ecosistema , Anticuerpos ampliamente neutralizantes , Nutrientes , Bacterias , Agua
8.
Antimicrob Resist Infect Control ; 12(1): 73, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37528415

RESUMEN

BACKGROUND: Higher resistance rates of > 20% have been noted in Enterobacteriaceae urinary isolates towards ciprofloxacin and co-trimoxazole (C + C) in Singapore, compared with amoxicillin-clavulanate and nitrofurantoin (AC + N). This study examined if treatment failure varied between different antibiotics, given different resistant rates, for uncomplicated urinary tract infections (UTIs) managed in primary care. We also aimed to identify gaps for improvement in diagnosis, investigations, and management. METHODS: A retrospective cohort study was conducted from 2019 to 2021 on female patients aged 18-50 with uncomplicated UTIs at 6 primary care clinics in Singapore. ORENUC classification was used to exclude complicated UTIs. Patients with uncomplicated UTIs empirically treated with amoxicillin-clavulanate, nitrofurantoin, ciprofloxacin or co-trimoxazole were followed-up for 28 days. Treatment failure was defined as re-attendance for symptoms and antibiotic re-prescription, or hospitalisation for UTI complications. After 2:1 propensity score matching in each group, modified Poisson regression and Cox proportional hazard regression accounting for matched data were used to determine risk and time to treatment failure. RESULTS: 3194 of 4253 (75.1%) UTIs seen were uncomplicated, of which only 26% were diagnosed clinically. Urine cultures were conducted for 1094 (34.3%) uncomplicated UTIs, of which only 410 (37.5%) had bacterial growth. The most common organism found to cause uncomplicated UTIs was Escherichia coli (64.6%), with 92.6% and 99.4% of isolates sensitive to amoxicillin-clavulanate and nitrofurantoin respectively. Treatment failure occurred in 146 patients (4.57%). Among 1894 patients treated with AC + N matched to 947 patients treated with C + C, patients treated with C + C were 50% more likely to fail treatment (RR 1.49, 95% CI 1.10-2.01), with significantly higher risk of experiencing shorter time to failure (HR 1.61, 95% CI 1.12-2.33), compared to patients treated with AC + N. CONCLUSION: Treatment failure rate was lower for antibiotics with lower reported resistance rates (AC + N). We recommend treating uncomplicated UTIs in Singapore with amoxicillin-clavulanate or nitrofurantoin, based on current local antibiograms. Diagnosis, investigations and management of UTIs remained sub-optimal. Future studies should be based on updating antibiograms, highlighting its importance in guideline development.


Asunto(s)
Antibacterianos , Infecciones Urinarias , Humanos , Femenino , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Nitrofurantoína/uso terapéutico , Combinación Trimetoprim y Sulfametoxazol , Estudios Retrospectivos , Farmacorresistencia Bacteriana , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/microbiología , Combinación Amoxicilina-Clavulanato de Potasio/uso terapéutico , Ciprofloxacina , Escherichia coli , Insuficiencia del Tratamiento , Atención Primaria de Salud
9.
Helicobacter ; 28(5): e13004, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37391943

RESUMEN

Nano-structure Cu(II) complex [Cu(AMAB)2 ]Cl2 with Schiff base (AMAB) derived from the condensation between 4-(dimethylamino)benzaldehyde and amoxicillin trihydrate was prepared. (AMAB) Schiff base and its Cu(II) complex were identified and confirmed by different physicochemical techniques. The Schiff base (AMAB) was coordinated to copper ion through carbonyl oxygen and imine nitrogen donor sites. X-ray powder diffraction shows a cubic crystal system of the Cu(II) complex. The density functional theory was used to optimize the structure geometries of the investigated compounds. The molecular docking of the active amino acids of the investigated proteins' interactions with the tested compounds was evaluated. The bactericidal or bacteriostatic effect of the compounds was screened against some bacterial strains. The activity of Cu-chelate against Gram-negative bacteria was mainly more effective than its (AMAB) ligand and vice versa in the case of Gram-positive bacteria. The biological activity of the prepared compounds with biomolecules calf thymus DNA (CT-DNA) was determined by electronic absorption spectra and DNA gel electrophoresis technique. All studies revealed that the Cu-chelate derivative exhibited better binding affinity to both CT-DNA than the AMAB and amoxicillin itself. The anti-inflammatory effect of the designed compounds was determined by testing their protein denaturation inhibitory activity spectrophotometrically. All obtained data supported that the designed nano-Cu(II) complex with Schiff base (AMAB) is a potent bactericide against H. pylori, and exhibits anti-inflammatory activity. The dual inhibition effects of the designed compound represent a modern therapeutic approach with extended spectrum of action. Therefore, it can act as good drug target in antimicrobial and anti-inflammtory therapies. Finally, H. pylori resistance to amoxicillin is absent or rare in many countries, thus amoxicillin nanoparticles may be beneficial for countries where amoxicillin resistance is reported.


Asunto(s)
Antiinfecciosos , Infecciones por Helicobacter , Helicobacter pylori , Humanos , Helicobacter pylori/metabolismo , Bases de Schiff/farmacología , Bases de Schiff/química , Cobre/farmacología , Cobre/química , Amoxicilina/farmacología , Simulación del Acoplamiento Molecular , Infecciones por Helicobacter/tratamiento farmacológico , Antiinfecciosos/farmacología , Antibacterianos/farmacología , Antibacterianos/química , ADN/química , ADN/metabolismo , Pruebas de Sensibilidad Microbiana
10.
Int J Antimicrob Agents ; 62(1): 106821, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37088439

RESUMEN

INTRODUCTION: International guidelines recommend high doses of ß-lactams for most cases of infective endocarditis (IE). Therapeutic drug monitoring (TDM) is increasingly used to adjust ß-lactam dose based on plasma concentrations, although there are no comparative studies to support this practice. The benefit of amoxicillin TDM during IE was evaluated. METHODS: An observational, retrospective, cohort study of adults treated with high-dose amoxicillin for enterococcal or streptococcal IE was conducted in two referral centers. Patients with, or without TDM were compared. The primary outcome was mean daily amoxicillin dose. RESULTS: A total of 206 cases of streptococcal (n=140, 68%) or enterococcal (n=66, 32%) IE were included. IE occurred on prosthetic valves in 77 (37%) cases, and on intracardiac devices in 28 (14%) cases. Aortic valve was involved in 136 (66%) cases. There were 154 men (75%), mean age was 70 ± 14 years, valve surgery was performed in 81/206 (39%) patients, and in-hospital mortality was 8% (17/206). All patients in the TDM group and most patients in the group without TDM received amoxicillin as continuous infusion. Amoxicillin TDM was performed for 114 patients (55.3%), with a mean of 4.7 ± 2.3 measures per patient, a mean plasma steady-state concentration of 41.2 ± 19 mg/L, most (82/114, 72%) being within the therapeutic target (20-80 mg/L). Mean amoxicillin dose was lower in patients with TDM (10.0 ± 3.3 g/day) than those without TDM (11.3 ± 2.0 g/day) (P=0.003). CONCLUSION: Amoxicillin TDM was associated with a reduction in daily doses, with no impact on adverse events and prognosis. Individualized treatment of IE through TDM may contribute to decreased use of antibiotics.


Asunto(s)
Endocarditis Bacteriana , Endocarditis , Adulto , Masculino , Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Amoxicilina/uso terapéutico , Estudios de Cohortes , Estudios Retrospectivos , Monitoreo de Drogas , Antibacterianos/uso terapéutico , Endocarditis/tratamiento farmacológico , Endocarditis Bacteriana/tratamiento farmacológico , Streptococcus , beta-Lactamas/uso terapéutico , Enterococcus
11.
Int J Antimicrob Agents ; 61(6): 106800, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37004756

RESUMEN

Aminopenicillins (APs) achieve urinary concentrations that exceed typical minimum inhibitory concentrations for enterococcal lower urinary tract infection (UTI). The local clinical microbiology laboratory discontinued routine susceptibilities on enterococcal urine isolates, and reports that 'APs are predictably reliable for uncomplicated enterococcal UTI'. The objective of this study was to compare outcomes of APs with non-APs (NAPs) for enterococcal lower UTIs. This was an institutional-review-board-approved, retrospective cohort of adults hospitalized with symptomatic enterococcal lower UTIs from 2013 to 2021. The primary endpoint was composite clinical success at 14 days, defined as resolution of symptoms without new symptoms and no repeat culture growth of the index organism. A non-inferiority analysis was utilized with a 15% margin, and logistic regression evaluated characteristics associated with 14-day failure. In total, 178 subjects were included: 89 AP patients and 89 NAP patients. Vancomycin-resistant enterococci (VRE) were identified in 73 (82%) AP patients and 76 (85%) NAP patients (P=0.54); in total, 34 (38.2%) AP patients and 66 (74.2%) NAP patients had confirmed Enterococcus faecium (P<0.001). Amoxicillin (n=36, 40.5%) and ampicillin (n=36, 40.5%) were the most commonly used APs, and linezolid (n=41, 46%) and fosfomycin (n=30, 34%) were the most commonly used NAPs. Fourteen-day clinical success rates for APs and NAPs were 83.1% and 82.0%, respectively [1.1% difference, 97.5% confidence interval (CI) -0.117 to 0.139]. Among the E. faecium subgroup, 14-day clinical success was observed in 27/34 (79.4%) AP patients and 53/66 (80.3%) NAP patients (P=0.916). On logistic regression, APs were not associated with 14-day clinical failure (adjusted odds ratio 0.84, 95% CI 0.38-1.86). APs were non-inferior to NAPs for treating enterococcal lower UTIs, and may be considered irrespective of susceptibility results.


Asunto(s)
Enterococcus faecium , Infecciones por Bacterias Grampositivas , Infecciones Urinarias , Adulto , Humanos , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Estudios Retrospectivos , Infecciones por Bacterias Grampositivas/microbiología , Enterococcus , Ampicilina/uso terapéutico , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/microbiología , Pruebas de Sensibilidad Microbiana
12.
Int J Mol Sci ; 24(5)2023 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-36901886

RESUMEN

The World Health Organization has indicated Helicobacter pylori as a high-priority pathogen whose infections urgently require an update of the antibacterial treatments pipeline. Recently, bacterial ureases and carbonic anhydrases (CAs) were found to represent valuable pharmacological targets to inhibit bacterial growth. Hence, we explored the underexploited possibility of developing a multiple-targeted anti-H. pylori therapy by assessing the antimicrobial and antibiofilm activities of a CA inhibitor, carvacrol (CAR), amoxicillin (AMX) and a urease inhibitor (SHA), alone and in combination. Minimal Inhibitory (MIC) and Minimal Bactericidal (MBC) Concentrations of their different combinations were evaluated by checkerboard assay and three different methods were employed to assess their capability to eradicate H. pylori biofilm. Through Transmission Electron Microscopy (TEM) analysis, the mechanism of action of the three compounds alone and together was determined. Interestingly, most combinations were found to strongly inhibit H. pylori growth, resulting in an additive FIC index for both CAR-AMX and CAR-SHA associations, while an indifferent value was recorded for the AMX-SHA association. Greater antimicrobial and antibiofilm efficacy of the combinations CAR-AMX, SHA-AMX and CAR-SHA against H. pylori were found with respect to the same compounds used alone, thereby representing an innovative and promising strategy to counteract H. pylori infections.


Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Humanos , Amoxicilina/farmacología , Antibacterianos/farmacología , Infecciones por Helicobacter/microbiología , Biopelículas , Pruebas de Sensibilidad Microbiana
13.
Helicobacter ; 28(3): e12962, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36828647

RESUMEN

BACKGROUND: Currently, bismuth quadruple therapy (BQT) is indicated as a first-line treatment for Helicobacter pylori eradication in areas with high dual metronidazole and clarithromycin resistance, with its use being limited by its low tolerability and significant cost. A novel regimen with high-dose amoxicillin dual therapy (HDADT) has emerged as an alternative. The aim of this study was to compare the results of these two treatments on HP eradication. MATERIALS AND METHODS: Prospective randomized study including 100 consecutive patients undergoing H. pylori eradication. Each patient was randomized (in a 1:1 ratio) to one group of treatment: BQT (bismuth 140 mg + metronidazole 125 mg + tetracycline 125 mg, four times a day, for 10 days) or HDADT (amoxicillin 1000 mg alternating with amoxicillin 500 mg, four times a day, for 14 days), both associated with esomeprazole 40 mg twice a day. The primary aim was to compare treatments' efficacies. Secondary aims were to assess symptoms persistence and tolerability. RESULTS: A total of 100 patients were included, 54% women, with a mean age of 55 ± 14 years. From these, five were lost to follow-up. Effective eradication proven by negative stool antigen test was significantly higher in patients randomized to HDADT when compared to BQT for both intention-to-treat (ITT) (96.2% vs. 81.4%; p = .022) and per-protocol (PP) (95.9% vs. 81%; p = .025) analysis. These differences were even more pronounced when only considering second line treatment (100% vs. 62.5%; p = .028). Side effects did not differ significantly between BQT and HDADT groups for both ITT (7.0% vs. 2.0%; p = .254) and PP (4.8% vs. 0%; p = .210) analysis. CONCLUSIONS: When compared to BQT, treatment with HDADT presented higher and near 100% efficacy in eradicating H. pylori, without differences in reported side effects or compliance. This treatment represents an important alternative for populations with increasing incidences of resistance to the currently recommended antibiotic regimens.


Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Humanos , Femenino , Adulto , Persona de Mediana Edad , Anciano , Masculino , Amoxicilina , Bismuto , Metronidazol/uso terapéutico , Metronidazol/farmacología , Infecciones por Helicobacter/tratamiento farmacológico , Estudios Prospectivos , Quimioterapia Combinada , Antibacterianos , Resultado del Tratamiento
14.
Br J Clin Pharmacol ; 89(1): 232-241, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-35947524

RESUMEN

AIMS: We aimed to assess the eradication efficacy and factors that influencing it of high-dose dual therapy (HDDT) in Gansu region, Northwest China. METHODS: A total of 216 treatment-naive patients with Helicobacter pylori infection were randomly assigned to two groups for the 14-day eradication treatment: the HDDT group (amoxicillin 750 mg q.i.d. and esomeprazole 40 mg t.i.d.) and the amoxicillin and clarithromycin-containing bismuth quadruple therapy group (ACBQT: esomeprazole 20 mg, bismuth potassium citrate 2 g, amoxicillin 1 g, and clarithromycin 500 mg; b.i.d.). The eradication rates, adverse effects and patient compliance of these two groups were compared. Eradication efficacy was determined by 13 C urea breath test (13 C UBT) 4-8 weeks after finishing treatment. Antibiotic resistance was determined by the Epsilometer testing (E-test) method. RESULTS: The eradication rates for the HDDT and ACBQT groups were 71.0% and 74.7% (P = .552) by per-protocol analysis, and 65.7% and 68.5% (P = .664) by intention-to-treat analysis. The overall adverse event rates in the HDDT and ACBQT groups were 2.0% and 43.4% (P < .001), respectively. The resistance rates to amoxicillin, clarithromycin, tetracycline, levofloxacin and metronidazole were 15.2%, 42.0%, 5.4%, 35.7% and 83.0%, respectively. Amoxicillin resistance and delta over baseline (DOB) of 13 C UBT ≥ 20 before treatment significantly reduced the eradication rate in 112 participants with H. pylori cultured. CONCLUSION: The HDDT as first-line treatment for H. pylori was unsatisfactory in Gansu. Amoxicillin resistance and DOB of 13 C UBT ≥ 20 before treatment were significantly correlated with H. pylori eradication failure.


Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Humanos , Infecciones por Helicobacter/inducido químicamente , Infecciones por Helicobacter/tratamiento farmacológico , Amoxicilina , Inhibidores de la Bomba de Protones/efectos adversos , Claritromicina/farmacología , Esomeprazol , Bismuto/farmacología , Bismuto/uso terapéutico , Estudios Prospectivos , Quimioterapia Combinada , Antibacterianos , China , Resultado del Tratamiento
15.
Neuropharmacology ; 223: 109331, 2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-36396078

RESUMEN

BACKGROUND: Amoxicillin has been widely used to treat infectious diseases during pregnancy. Current studies suggest that amoxicillin exposure during pregnancy could lead to developmental disorders in the offspring and increase the incidence of long-term complications such as asthma and kidney damage in adulthood. However, the adverse effects of prenatal amoxicillin exposure (PAmE) including administration stage, doses and courses on fetal hippocampal neurodevelopment and its function in the offspring have not been elucidated. In this study, we intend to investigate the effects of PAmE on fetal hippocampal development and its possible mechanisms. METHOD: Pregnant Kunming mice were given intragastric administration with amoxicillin at different administration stage, doses and courses, and GD (gestational day) 18 offspring hippocampus was collected for morphological and development-related functional assays, and the molecular mechanisms were explored. RESULTS: PAmE induced hippocampal hypoplasia in the offspring with suppressed hippocampal neuronal cell proliferation and impaired neuronal synaptic plasticity comparatively; hippocampal astrocyte and microglia were damaged to varying degrees. The developmental toxicity of PAmE in fetal mices varies by time, dose, and course of treatment. The most severe damage was observed in the late gestation, high dose, and multi-course dosing groups. The significant reduction either in SOX2, an essential gene in regulating neural progenitor cell proliferation, and reduction of genes related to the Wnt/ß-catenin pathway may suggest that the key role of SOX2/Wnt/ß-catenin pathway in impaired hippocampal development in the offspring due to PAmE. CONCLUSION: In this study, PAmE was found to be developmentally toxic to the hippocampus thus to induce developmental damage to various hippocampal cells; Even with current clinically safe doses, potential hippocampal damage to offspring may still present; This study provides a theoretical and experimental basis for guiding the rational usage of drugs during pregnancy and giving effectively assessment of the risk on fetal hippocampal developmental toxicity.


Asunto(s)
Efectos Tardíos de la Exposición Prenatal , beta Catenina , Ratones , Animales , Femenino , Humanos , Embarazo , beta Catenina/metabolismo , Efectos Tardíos de la Exposición Prenatal/metabolismo , Amoxicilina/toxicidad , Amoxicilina/metabolismo , Hipocampo
16.
J Hazard Mater ; 443(Pt B): 130326, 2023 02 05.
Artículo en Inglés | MEDLINE | ID: mdl-36444054

RESUMEN

Reasonable regulation of the micro-morphology of material can significantly enhance the related performance. Herein, bismuth tungstate (Bi2WO6, simplified as BWO) porous hollow spheres with flower-like surface were prepared successfully, and this unique morphology endowed BWO with improved photocatalytic performance by reflecting and absorbing the light multiple times inside the cavity. To inhibit the rapid recombination of photogenerated e--h+ pairs within BWO itself, black phosphorous quantum dots (BPQDs) were anchored onto the nanosheets of BWO sphere closely by a facile self-assembly process, which will not shade the pores of BWO owing to the small size of BPQDs, but the BP nanosheets have the chance to do that. The band gap of BPQDs expanded much after exfoliation due to the quantum confinement effects, which matched the energy band of BWO well to form S-scheme heterojunction, achieving more efficient separation of photogenerated charges. As a result, the BPQDs/BWO exhibited attractive photocatalytic performance in the degradation of amoxicillin (AMX) and other antibiotics. Besides, the operation conditions were optimized, specifically, 94.5 % of AMX (20 mg/L, 200 mL) can be removed in 60 min when 50 mg of 2BPQDs/BWO was used as catalyst with solution pH = 11. Moreover, a possible degradation pathway of AMX was proposed based on the detected intermediates.


Asunto(s)
Amoxicilina , Puntos Cuánticos , Fósforo , Porosidad , Luz
17.
Inflammopharmacology ; 30(6): 2153-2165, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36318434

RESUMEN

Acute diverticulitis disease is associated with inflammation and infection in the colon diverticula and may lead to severe morbidity. This study aimed to evaluate and compare the protective effects of amoxicillin antibiotic, either alone or in combination with probiotics (Lactobacillus acidophilus and Bifidobacterium lactis), in a rat model of acute diverticulitis disease. Acute diverticulitis was induced, in albino rats, by adding 3% weight/volume of dextran sulfate sodium (DSS) to the rats' drinking water; daily for 7 days, in addition to injecting lipopolysaccharide (LPS) enema (4 mg/kg). The impact of treatments was assessed by measuring the physiological and immunological parameters and evaluating colon macroscopic and microscopic lesions. The results showed that both treatments (especially probiotics with amoxicillin) alleviated the adverse effects of DSS and LPS. This was obvious through the modulation of the rats' body weight and the colon weight-to-length ratio. Also, there was a significant (p < 0.001) decrease in the colon macroscopic lesion score. The pro-inflammatory cytokines [(TNF)-α, (IL)-1ß, (IFN)-γ, and (IL)-18]; in the colon tissue; were significantly (p < 0.001) decreased. Also, both treatments significantly ameliorated the elevation of myeloperoxidase activity and C-reactive protein levels, in addition to improving the histopathological alterations in the colon tissue. In conclusion, amoxicillin and probiotics-amoxicillin were effective in preventing the development of experimentally induced acute diverticulitis, through their anti-inflammatory and immunomodulatory effects. Furthermore, this study has explored the role of probiotics in preventing DSS/LPS-induced acute diverticulitis, so it can be applied as a promising treatment option for acute diverticulitis disease.


Asunto(s)
Colitis , Diverticulitis , Probióticos , Animales , Amoxicilina/efectos adversos , Amoxicilina/metabolismo , Colitis/inducido químicamente , Colon , Citocinas/metabolismo , Sulfato de Dextran/farmacología , Modelos Animales de Enfermedad , Diverticulitis/metabolismo , Diverticulitis/patología , Lipopolisacáridos/farmacología , Modelos Teóricos , Probióticos/farmacología , Factor de Necrosis Tumoral alfa/metabolismo , Ratas
18.
Heliyon ; 8(10): e11199, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36339986

RESUMEN

A one step facile synthesis of the novel diaquabis(1,10-phenanthroline)copper(II)chloride (A2P2CuC) complex is demonstrated. Cyclic voltammetric and electrochemical impedance spectroscopic results revealed potentiodynamic deposition of a conductive electroactive poly(A2P2CuC) film on the glassy carbon electrode surface increasing its effective surface area. In contrast to the unmodified glassy carbon electrode, appearance of an oxidative peak at a reduced potential with over two fold current for amoxicillin at poly(A2P2CuC)/GCE demonstrated its electrocatalytic property attributed to reduce charge transfer resistance and the improved surface area of the electrode surface. Better correlation of the oxidative peak current with square root of scan rate (R2 = 0.99779) than with scan rate (R2 = 0.96953) supplemented by slope of 0.58 for log(current) versus log(scan rate) confirmed diffusion controlled irreversible oxidation of amoxicillin. At optimized solution and SWV parameters, current response of poly(A2P2CuC)/GCE showed linear dependence on concentration of amoxicillin (2.0-100.0 µM) with LoD 0.0115 µM. While no amoxicillin was detected in the human blood serum sample, an amount 89.40-100.55% of the nominal level was detected in the analyzed eight tablet brands. Spike recovery in tablet samples (98.90-101.95%) and blood serum sample (102.20-101.37%); interference with an error (%RSD) of 0.00-4.51% in tablet and 0.00-2.10% in serum samples; excellent stability and reproducible results, added with the wide dynamic range and low LoD validated the method for amoxicillin determination in pharmaceutical formulations and human urine samples.

19.
Artículo en Inglés | MEDLINE | ID: mdl-36281981

RESUMEN

The goal of this study was to assess the efficiency of antibiotic degradation applying different chemical treatment methods and their combinations. Thus, improvement in the efficiency of these methods when combined was quantified. The methods tested to degrade/mineralize the antibiotics amoxicillin (AMX) and ciprofloxacin (CIP) under different pH conditions (4, 7 and 10) were ultra-violet irradiation (UV254 nm), ultrasound (US), hydrogen peroxide (H2O2) and ozone (O3) alone and in combination. The results showed that individual methods were only partially efficient in the degradation/mineralization of antibiotics, except for ozonation at alkaline pH. In the combined methods, the best performance was obtained with US/UV/H2O2/O3 (pH 10, 20-min treatment), where the degradation rates for the antibiotics were 99.8% for CIP and 99.9% for AMX. For the mineralization efficiency the values obtained were 71.3% for CIP and 79.2% for AMX. The results of this study could contribute to the development and improvement of wastewater treatment aimed at avoiding the presence of residual antibiotics in the environment.


Asunto(s)
Ozono , Contaminantes Químicos del Agua , Purificación del Agua , Peróxido de Hidrógeno/química , Contaminantes Químicos del Agua/análisis , Oxidación-Reducción , Amoxicilina , Ciprofloxacina/química , Antibacterianos/química
20.
Antimicrob Agents Chemother ; 66(9): e0079022, 2022 09 20.
Artículo en Inglés | MEDLINE | ID: mdl-36047786

RESUMEN

Bioactive forms of oral ß-lactams were screened in vitro against Mycobacterium abscessus with and without the bioactive form of the oral ß-lactamase inhibitor avibactam ARX1796. Sulopenem was equally active without avibactam, while tebipenem, cefuroxime, and amoxicillin required avibactam for optimal activity. Systematic pairwise combination of the four ß-lactams revealed strong bactericidal synergy for each of sulopenem, tebipenem, and cefuroxime combined with amoxicillin in the presence of avibactam. These all-oral ß-lactam combinations warrant clinical evaluation.


Asunto(s)
Enfermedades Pulmonares , Mycobacterium abscessus , Amoxicilina/farmacología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Compuestos de Azabiciclo/farmacología , Carbapenémicos , Cefuroxima , Humanos , Lactamas , Enfermedades Pulmonares/tratamiento farmacológico , Pruebas de Sensibilidad Microbiana , Inhibidores de beta-Lactamasas/farmacología , Inhibidores de beta-Lactamasas/uso terapéutico , beta-Lactamasas , beta-Lactamas/farmacología
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