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Journal of Korean Medical Science Sep 2023The lack of well-established operational definitions is a major limitation of eradication studies that use secondary databases. We aimed to develop and validate...
BACKGROUND
The lack of well-established operational definitions is a major limitation of eradication studies that use secondary databases. We aimed to develop and validate operational definitions related to eradication therapy.
METHODS
Operational definitions were developed by analyzing a nationwide eradication registry and validated using real-world data from hospital medical records. The primary endpoint was the sensitivity of the operational definitions in identifying individuals who received eradication therapy. The secondary endpoint was the sensitivity and specificity of the operational definition in identifying successful eradication therapy.
RESULTS
eradication therapy was defined as a prescription for one of the following combinations: 1) proton pump inhibitor (PPI) + amoxicillin + clarithromycin, 2) PPI + amoxicillin + metronidazole, 3) PPI + metronidazole + tetracycline, 4) PPI + amoxicillin + levofloxacin, 5) PPI + amoxicillin + moxifloxacin, or 6) PPI + amoxicillin + rifabutin. In the validation set, the sensitivity of the operational definition for identifying individuals who received eradication therapy was 99.7% and 99.8% for the first- and second-line therapies, respectively. Operational definition to determine success or failure of the eradication therapy was developed based on a confirmatory test and the prescription of rescue therapy. The sensitivity and specificity of the operational definition for predicting successful eradication were 97.6% and 91.4%, respectively, in first-line therapy and 98.6% and 54.8%, respectively, in second-line therapy.
CONCLUSION
We developed and validated operational definitions related to eradication therapy. These definitions will help researchers perform various eradication-related studies using secondary databases.
Topics: Humans; Helicobacter pylori; Metronidazole; Research Design; Anti-Bacterial Agents; Amoxicillin; Proton Pump Inhibitors
PubMed: 37667583
DOI: 10.3346/jkms.2023.38.e278 -
The Journal of Allergy and Clinical... Nov 2022Amoxicillin-associated reactions (AARs) in children presenting as rashes are common, and recent data suggest that >90% tolerate amoxicillin on re-exposure. However,...
BACKGROUND
Amoxicillin-associated reactions (AARs) in children presenting as rashes are common, and recent data suggest that >90% tolerate amoxicillin on re-exposure. However, additional data would help pediatricians and allergists gain confidence in referring and testing children who experienced systemic symptoms perceived as "worrisome," thus leading to urgent medical evaluations. By characterizing the entire spectrum of AAR symptoms in pediatric patients presenting to emergency department (ED)/urgent care (UC) settings, we sought to increase our diagnostic acumen to guide subsequent allergy evaluations.
OBJECTIVE
To fully characterize clinical features of rash and systemic symptoms in children presenting to the ED/UC with AARs.
METHODS
A retrospective chart review of children seen in the ED/UC from July 1, 2015, to June 30, 2017, was conducted. Clinical features, chronology, and seasonality were detailed, and cases were classified into 3 previously described AAR phenotypes: maculopapular exanthem (MPE), urticaria, and serum sickness-like reactions (SSLRs), if they experienced joint symptoms.
RESULTS
Children (n = 668; median age: 1.8 years) presented to the ED/UC with urticaria (44%), MPE (36%), and SSLRs (11%) typically on days 7 to 10 of amoxicillin. Although children with SSLRs were more frequently treated with corticosteroids (28%, P < .0001) and exhibited higher rates of "worrisome" features (fever, angioedema, or gastrointestinal symptoms; 73%, P < .0001), delayed-onset systemic symptoms were identified frequently in all 3 groups. ED/UC reutilization was unexpectedly high with 66 children (10%) returning to the ED/UC for re-evaluation.
CONCLUSION
"Worrisome" symptoms are common in children presenting to the ED/UC with AARs. Future studies are needed to determine the impact on subsequent referral and allergy testing.
Topics: Humans; Amoxicillin; Retrospective Studies; Emergency Service, Hospital; Drug Eruptions; Urticaria
PubMed: 35872212
DOI: 10.1016/j.jaip.2022.07.002 -
Journal of Pharmaceutical Sciences Oct 2017Literature and experimental data relevant to waiver of in vivo bioequivalence (BE) testing for the approval of immediate-release solid oral dosage forms containing... (Review)
Review
Literature and experimental data relevant to waiver of in vivo bioequivalence (BE) testing for the approval of immediate-release solid oral dosage forms containing amoxicillin trihydrate are reviewed. Solubility and permeability characteristics according to the Biopharmaceutics Classification System (BCS), therapeutic uses, therapeutic index, excipient interactions, as well as dissolution and BE and bioavailability studies were taken into consideration. Solubility and permeability studies indicate that amoxicillin doses up to 875 mg belong to BCS class I, whereas 1000 mg belongs to BCS class II and doses of more than 1000 mg belong to BCS class IV. Considering all aspects, the biowaiver procedure can be recommended for solid oral products of amoxicillin trihydrate immediate-release preparations containing amoxicillin as the single active pharmaceutical ingredient at dose strengths of 875 mg or less, provided (a) only the excipients listed in this monograph are used, and only in their usual amounts, (b) the biowaiver study is performed according to the World Health Organization-, U.S. Food and Drug Administration-, or European Medicines Agency-recommended method using the innovator as the comparator, and (c) results comply with criteria for "very rapidly dissolving" or "similarly rapidly dissolving." Products containing other excipients and those containing more than 875 mg amoxicillin per unit should be subjected to an in vivo BE study.
Topics: Administration, Oral; Amoxicillin; Animals; Biological Availability; Biopharmaceutics; Dosage Forms; Excipients; Humans; Permeability; Solubility; Therapeutic Equivalency
PubMed: 28483422
DOI: 10.1016/j.xphs.2017.04.068 -
International Journal of Molecular... Feb 2023The World Health Organization has indicated as a high-priority pathogen whose infections urgently require an update of the antibacterial treatments pipeline. Recently,...
The World Health Organization has indicated 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- 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 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 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 were found with respect to the same compounds used alone, thereby representing an innovative and promising strategy to counteract infections.
Topics: Humans; Amoxicillin; Helicobacter pylori; Anti-Bacterial Agents; Helicobacter Infections; Biofilms; Microbial Sensitivity Tests
PubMed: 36901886
DOI: 10.3390/ijms24054455 -
MBio Feb 2022Mycobacterium abscessus () infections are a growing menace to the health of many patients, especially those suffering from structural lung disease and cystic fibrosis....
Mycobacterium abscessus () infections are a growing menace to the health of many patients, especially those suffering from structural lung disease and cystic fibrosis. With multidrug resistance a common feature and a growing understanding of peptidoglycan synthesis in , it is advantageous to identify potent β-lactam and β-lactamase inhibitor combinations that can effectively disrupt cell wall synthesis. To improve existing therapeutic regimens to address serious infections, we evaluated the ability of durlobactam (DUR), a novel diazobicyclooctane β-lactamase inhibitor to restore susceptibilities in combination with β-lactams and provide a biochemical rationale for the activity of this compound. In cell-based assays, susceptibility of subsp. isolates to amoxicillin (AMOX), imipenem (IMI), and cefuroxime (CXM) was significantly enhanced with the addition of DUR. The triple drug combinations of CXM-DUR-AMOX and IMI-DUR-AMOX were most potent, with MIC ranges of ≤0.06 to 1 μg/mL and an MIC/MIC of ≤0.06/0.25 μg/mL, respectively. We propose a model by which this enhancement may occur, DUR potently inhibited the β-lactamase Bla with a relative Michaelis constant ( ) of 4 × 10 ± 0.8 × 10μM and acylation rate (/) of 1 × 10 M s. Timed mass spectrometry captured stable formation of carbamoyl-enzyme complexes between DUR and Ldt and d,d-carboxypeptidase, potentially contributing to the intrinsic activity of DUR. Molecular modeling showed unique and favorable interactions of DUR as a Bla inhibitor. Similarly, modeling showed how DUR might form stable Michaelis-Menten complexes with Ldt and d,d-carboxypeptidase. The ability of DUR combined with amoxicillin or cefuroxime and imipenem to inactivate multiple targets such as d,d-carboxypeptidase and Ldt supports new therapeutic approaches using β-lactams in eradicating . Durlobactam (DUR) is a potent inhibitor of Bla and provides protection of amoxicillin and imipenem against hydrolysis. DUR has intrinsic activity and forms stable acyl-enzyme complexes with Ldt and Ldt. The ability of DUR to protect amoxicillin and imipenem against Bla and its intrinsic activity along with the dual β-lactam target redundancy can explain the rationale behind the potent activity of this combination.
Topics: Humans; beta-Lactams; beta-Lactamase Inhibitors; Anti-Bacterial Agents; Mycobacterium abscessus; Cefuroxime; Microbial Sensitivity Tests; Imipenem; Amoxicillin; beta-Lactamases
PubMed: 35073757
DOI: 10.1128/mbio.03529-21 -
British Journal of Nursing (Mark Allen... Jul 2020Chronic obstructive pulmonary disease (COPD) is widely established as a health challenge, with predictions that it will be the third leading cause of global mortality...
Chronic obstructive pulmonary disease (COPD) is widely established as a health challenge, with predictions that it will be the third leading cause of global mortality and reduced health status within the next 10 years. Exacerbations of COPD are now the second largest cause of emergency hospitalisation in the UK. The respiratory clinical nurse specialist has an active role in the acute management of COPD exacerbations in the hospital setting, and it is essential that prescribing decisions are made based on the best available evidence. This article critically evaluates the pharmacotherapeutics and evidence base for the use of two medications, salbutamol and amoxicillin, in treating unstable COPD, and discusses implications for clinical practice.
Topics: Albuterol; Amoxicillin; Disease Progression; Humans; Pulmonary Disease, Chronic Obstructive
PubMed: 32649242
DOI: 10.12968/bjon.2020.29.13.738 -
European Journal of Pharmaceutical... Oct 2023This study aimed to assess the pharmacokinetic (PK) interactions of anaprazole, clarithromycin, and amoxicillin using physiologically based pharmacokinetic (PBPK) models.
Physiologically based pharmacokinetic modeling to assess the drug-drug interactions of anaprazole with clarithromycin and amoxicillin in patients undergoing eradication therapy of H. pylori infection.
OBJECTIVE
This study aimed to assess the pharmacokinetic (PK) interactions of anaprazole, clarithromycin, and amoxicillin using physiologically based pharmacokinetic (PBPK) models.
METHODS
The PBPK models for anaprazole, clarithromycin, and amoxicillin were constructed using the GastroPlus™ software (Version 9.7) based on the physicochemical data and PK parameters obtained from literature, then were optimized and validated in healthy subjects to predict the plasma concentration-time profiles of these three drugs and assess the predictive performance of each model. According to the analysis of the properties of each drug, the developed and validated models were applied to evaluate potential drug-drug interactions (DDIs) of anaprazole, clarithromycin, and amoxicillin.
RESULTS
The developed PBPK models properly described the pharmacokinetics of anaprazole, clarithromycin, and amoxicillin well, and all predicted PK parameters (C, AUC ratios were within 2.0-fold of the observed values. Furthermore, the application of these models to predict the anaprazole-clarithromycin and anaprazole-amoxicillin DDIs demonstrates their good performance, with the predicted DDI C ratios and DDI AUC ratios within 1.25-fold of the observed values, and all predicted DDI C, and AUC ratios within 2.0-fold. The simulated results show no need to adjust the dosage when co-administered with anaprazole in patients undergoing eradication therapy of H. pylori infection since the dose remained in the therapeutic range.
CONCLUSION
The whole-body PBPK models of anaprazole, clarithromycin, and amoxicillin were built and qualified, which can predict DDIs that are mediated by gastric pH change and inhibition of metabolic enzymes, providing a mechanistic understanding of the DDIs observed in the clinic of clarithromycin, amoxicillin with anaprazole.
Topics: Humans; Clarithromycin; Amoxicillin; Helicobacter pylori; Helicobacter Infections; Drug Interactions; Models, Biological
PubMed: 37480962
DOI: 10.1016/j.ejps.2023.106534 -
Journal of Animal Breeding and Genetics... Jan 2020Enterotoxigenic Escherichia coli (ETEC) is the aetiological agent of postweaning diarrhoea (PWD) in piglets. The SNPs located on the Mucine 4 (MUC4) and...
Enterotoxigenic Escherichia coli (ETEC) is the aetiological agent of postweaning diarrhoea (PWD) in piglets. The SNPs located on the Mucine 4 (MUC4) and Fucosyltransferase 1 (FUT1) genes have been associated with the susceptibility to ETEC F4 and ETEC F18, respectively. The interplay between the MUC4 and FUT1 genotypes to ETEC infection and the use of amoxicillin in modifying the intestinal microbiota during a natural infection by multiresistant ETEC strains have never been investigated. The aim of this study was to evaluate the effects of the MUC4 and FUT1 genotypes and the administration of amoxicillin through different routes on the presence of diarrhoea and the faecal microbiota composition in piglets naturally infected with ETEC. Seventy-one piglets were divided into three groups: two groups differing by amoxicillin administration routes-parenteral (P) or oral (O) and a control group without antibiotics (C). Faecal scores, body weight, presence of ETEC F4 and F18 were investigated 4 days after the arrival in the facility (T0), at the end of the amoxicillin administration (T1) and after the withdrawal period (T2). The faecal bacteria composition was assessed by sequencing the 16S rRNA gene. We described that MUC4 and FUT1 genotypes were associated with the presence of ETEC F4 and ETEC F18. The faecal microbiota was influenced by the MUC4 genotypes at T0. We found the oral administration to be associated with the presence of diarrhoea at T1 and T2. Furthermore, the exposure to amoxicillin resulted in significant alterations of the faecal microbiota. Overall, MUC4 and FUT1 were confirmed as genetic markers for the susceptibility to ETEC infections in pigs. Moreover, our data highlight that group amoxicillin treatment may produce adverse outcomes on pig health in course of multiresistant ETEC infection. Therefore, alternative control measures able to maintain a healthy faecal microbiota in weaners are recommended.
Topics: Amoxicillin; Animals; DNA, Bacterial; Diarrhea; Enterotoxigenic Escherichia coli; Escherichia coli Infections; Feces; Genotype; Microbiota; Polymorphism, Single Nucleotide; Swine; Weaning
PubMed: 31482656
DOI: 10.1111/jbg.12432 -
Bioelectrochemistry (Amsterdam,... Feb 2021Amoxicillin (AMX) is among the most successful antibiotics used for human therapy. It is used extensively to prevent or treat bacterial infections in humans and animals.... (Review)
Review
Amoxicillin (AMX) is among the most successful antibiotics used for human therapy. It is used extensively to prevent or treat bacterial infections in humans and animals. However, the widespread distribution and excess utilization of AMX can be an environmental and health risk due to the hazardous potential associated to its pharmaceutical industries effluents. Besides, their extensive use in food animal production may result in some undesirable residues in food, e.g. meat, eggs and milk. Consequently, at high enough concentrations in biological fluids, AMX may be responsible of various diseases such as nausea, vomiting, rashes, and antibiotic-associated colitis. For this reason, the detection and quantification of amoxicillin in pharmaceuticals, biological fluids, environmental samples and foodstuffs require new electroanalytical techniques with sensitive and rapid measurement abilities. This review discusses recent advances in the development of electrochemical sensors and bio-sensors for AMX analysis in complex matrices such as pharmaceuticals, biological fluids, environmental water and foodstuffs. The main electrochemical sensors used are based on chemically modified electrodes involving carbon materials and nanomaterials, nanoparticles, polymers and biological recognition molecules.
Topics: Amoxicillin; Animals; Anti-Bacterial Agents; Electrochemical Techniques; Environmental Pollutants; Food Contamination; Humans; Limit of Detection; Pharmaceutical Preparations
PubMed: 33160182
DOI: 10.1016/j.bioelechem.2020.107687 -
European Journal of Internal Medicine Aug 2022
Topics: Amoxicillin; Anti-Bacterial Agents; Exanthema; Humans; Infectious Mononucleosis
PubMed: 35577680
DOI: 10.1016/j.ejim.2022.05.012