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Background: Helicobacter pylori infection is a primary global health concern. However, the widespread use of antibiotics, particularly macrolides such as clarithromycin, has increased resistance among H. pylori strains. This study aimed to investigate the prevalence of macrolide resistance in H. pylori in different world regions. Methods: This systematic literature search was performed using the appropriate search syntax after searching PubMed, Embase, Web of Science, and Scopus databases between May 2015 and December 2023. Statistical analysis was performed using Pooled and random effects model in R and the metafor package. Results: A total of 7,768 articles were retrieved. After a thorough evaluation, 155 studies (by 178 reports) were finally eligible for inclusion in this systematic review and meta-analysis. According to the results, the majority of studies (178 reports from 43 countries) assessed clarithromycin susceptibility, with a pooled prevalence of 33.3% and high heterogeneity between studies (I 2 = 98.57%, p < 0.001). The rate of erythromycin resistance was moderate (22.8%, 10 reports), while azithromycin resistance was 34.4% (4 reports). Subgroup analysis revealed significant differences in the prevalence of resistance based on geographic location, continent, and year of publication. Clarithromycin resistance increased from 29.1% (2015–2019) to 36.5% (2020–2023). Conclusion: This study highlights the critical challenges of macrolide resistance in treating H. pylori infection. The high prevalence and geographic variation underscore the need for tailored treatment strategies based on regional resistance patterns. Furthermore, continuously monitoring resistance trends and investigating contributing factors are essential to optimize treatment. Systematic review registration: https://www.crd.york.ac.uk/prospero; CRD42024557749. [ABSTRACT FROM AUTHOR]

Pest rodents persistently undermine crop yields and food security. Fertility control could be a viable alternative for managing rodent populations. This study investigates the antifertility effects of various concentrations of clarithromycin combined with 1.0 mg/kg quinestrol on male rodents to determine an effective contraceptive dose that minimizes quinestrol usage, addressing key concerns such as potential environmental residue, which may impact ecological balance, and poor palatability, which could reduce ingestion and limit the sterilant's effectiveness. Male mice were divided into five groups and administered different doses of clarithromycin or clarithromycin and quinestrol for three consecutive days, while the control group received sunflower seed oil only. After seven days, organ weights, reproductive organ weights, sperm density, serum hormone levels, and CYP3A4 content in small intestinal and liver tissues were measured to assess persistent effects. Compared with the control group, all treatment groups had significant reductions in epididymal weight, seminal vesicle weight, and serum T and LH levels. Higher concentrations of clarithromycin (2 mg/kg and 10 mg/kg) significantly impacted reproductive metrics, including sperm density, organ weights, and serum LH and testosterone levels, though complete sterilization was not achieved, with more than 60 million cauda epididymal spermatozoa remaining. However, the combination demonstrated potential as an effective strategy for male fertility control. The combination of 2.0 mg/kg clarithromycin and quinestrol can mitigate organ enlargement seen with quinestrol alone. This combination also decreased total enzyme content, thereby diminishing quinestrol's induction of CYP3A4, which may increase the sterilization effectiveness of the treatment. [ABSTRACT FROM AUTHOR]

Background/Aims: Bismuth-based quadruple therapy (BQT) is a treatment option for clarithromycin-resistant Helicobacter pylori (HP) infection. The aim of this study was to compare the efficacy of 7-day BQT with that of 14-day BQT as first-line treatment for clarithromycin-resistant HP infection. Methods: A total of 162 treatment-naïve patients with peptic ulcer disease and clarithromycinresistant HP infection confirmed by real-time polymerase chain reaction (RT-PCR) were enrolled. The enrolled patients were prospectively randomized to receive BQT for either 7 or 14 days of treatment. Eradication of HP infection was assessed using a 13C-urea breath test. Eradication and adverse event rates of the two groups were assessed. Results: The overall eradication rates in the intention-to-treat (ITT) and per-protocol (PP) analyses were 83.0% (95% confidence interval [CI], 77.2% to 88.9%; 132/159) and 89.8% (95% CI, 84.9% to 94.7%; 132/147), respectively. The eradication rates in the ITT analysis were 79.0% (64/81) in the 7-day group and 87.2% (68/78) in the 14-day group (p=0.170). The eradication rates in the PP analysis were 86.5% (64/74) in the 7-day group and 93.2% (68/73) in the 14-day group (p=0.182). Clinically significant adverse events occurred in 18.2% of patients. There was no statistically significant difference in the rates of individual or all adverse events between the two groups. Conclusions: Both 7-day and 14-day BQT were effective and safe as first-line therapy for HP infections identified as resistant to clarithromycin by RT-PCR. For clarithromycin-resistant HP infections, 7-day BQT may be sufficient as first-line therapy. [ABSTRACT FROM AUTHOR]

Background Effective management of drug–food interactions is crucial for enhancing antibiotics' efficacy/safety. Adhering to PRISMA guidelines, we conducted a systematic review to assess the impact of dietary interventions on the bioavailability of 15 macrolides and 10 tetracyclines. Methods We included studies examining the influence of food, beverages, antacids, and mineral supplements on the pharmacokinetic parameters of orally administered macrolides and tetracyclines. We searched Medline (via PubMed), Embase and Cochrane Library databases up to December 2022. Risk of bias was assessed using Cochrane and NIH tools. Quantitative analyses were conducted if two or more comparable food-effect studies were available; otherwise, a qualitative summary was provided. Results We included 120 studies from 97 reports. Meta-analyses were conducted for 8 macrolides and 4 tetracyclines, with qualitative synthesis for 10 and 9, respectively. About 64% of the studies were open-label, crossover designs. Our assessment found that 37% of the studies had a high risk of bias, while only 6% had low risk. Food significantly affected 10 of 13 macrolides (77%) and 6 of 7 tetracyclines (86%). High positive effects on bioavailability were seen with extended-release azithromycin and clarithromycin, and erythromycin estolate. High negative impacts were observed with erythromycin propionate and stearate, azithromycin capsules, demeclocycline and omadacycline. Antacids and mineral supplements significantly decreased tetracyclines absorption. Milk and grapefruit juice showed variable impacts on absorption. Discussion Interactions depend on antibiotics' physicochemical characteristics, intervention type, drug formulation and potential patient factors. The quality of evidence was rated low due to outdated studies, methodological diversity and unequal data availability. [ABSTRACT FROM AUTHOR]

Accurate detection of Helicobacter pylori and its antimicrobial resistance is essential for eradication of the infections. The aim of this study was to compare five different CE‐IVD marked assays in detection of H. pylori from 268 clinical stool samples. Samples were considered positive for H. pylori when at least three of the five tests were positive. Amplified IDEIA Hp StAR (Oxoid) and Premier Platinum HpSA PLUS (Meridian Bioscience Inc.) assays showed sensitivity of 100% [95% CI (confidence interval): 87–100] and LIAISON® Meridian H. pylori SA (DiaSorin) of 83.3% (95% CI: 66–93). Specificities of the assays were 94.5% (95% CI: 91–97), 95.4%; (95% CI: 92–97), and 97.1% (95% CI: 94–99) respectively. Amplidiag® H. pylori + ClariR (Mobidiag) assay showed 93.3% (95% CI: 78–99) and Allplex™ H. pylori & ClariR Assay (Seegene Inc.) 36.7% (95% CI: 22–55) sensitivity, while specificity of both was 97.9% (95% CI: 95–99). The Amplidiag® and Allplex™ assays concordantly detected clarithromycin resistance in positive for H. pylori samples. The Amplidiag® assay showed the highest accuracy, namely 97.4% (95% CI: 95–99). These data provide helpful information for planning laboratory diagnostics of H. pylori and detection of clarithromycin resistance from stool samples. [ABSTRACT FROM AUTHOR]

Background: Edoxaban, the only factor Xa inhibitor with active metabolites, is metabolized by carboxylesterase-1 to its main active metabolite, M-4, which is a substrate of organic anion transporting polypeptide 1B1 (OATP1B1) and is excreted in bile and urine. Because the area under the plasma concentration–time curve ratio of M-4 to parent compound is typically less than 10% in healthy subjects, M-4 is generally considered to exhibit negligible antithrombotic activity in patients treated with edoxaban. However, we identified a case in which drug interactions and kidney impairment led to a substantive increase in plasma M-4 concentrations. Case presentation: This case report involved a 68-year-old man with pancreatic cancer who was orally administered edoxaban tablets for prevention of thrombus formation in non-valvular atrial fibrillation, in addition to rifampin and clarithromycin (CAM) for treatment of mycobacterium avium complex lung disease. These medications were temporarily discontinued for a pancreaticoduodenectomy but were resumed 8 days post-surgery (POD8). On POD9, the patient developed acute kidney injury, and the trough concentrations of edoxaban and M-4 were 131.1 ng/mL and 115.8 ng/mL, respectively (M-4 ratio: 88.3%). On POD11, the M-4 trough concentration and M-4 ratio increased to 216.2 ng/mL and 186.2%, respectively. The plasma concentration of coproporphyrin-I, an endogenous biomarker of OATP1B1 activity, increased during this period. Conclusions: This case suggests that in patients with impaired renal function taking edoxaban, co-administration of carboxylesterase-1 inducers such as rifampin and/or OATP1B1 inhibitors such as rifampin or clarithromycin may increase plasma concentrations of M-4 to clinically non-negligible levels. [ABSTRACT FROM AUTHOR]

Introduction: Helicobacter pylori causes chronic gastric diseases in nearly 50% of people around the world. It is suggested that biofilm formation has a pronounced effect on the dynamic resistance spread and recurrence of these infections. Methods: To mimic the scenario of therapeutic ineffectiveness, we investigated the impact of sub-minimal inhibitory concentrations (sub-MICs) of antibiotics on the development and parameters of biofilms produced by clinical H. pylori strains. Results: We observed that constant exposure of planktonic forms to metronidazole or levofloxacin stimulated the speed of autoaggregation and the amount of extracellular matrix, resulting in increased dimensions of the developed biofilms. Contrary to this, continuous exposure to clarithromycin negatively affected a number of biofilm-related reactions and led to the biofilm-weakening effect. Through assessing the membrane fatty acid profiles of antibiotic-exposed cells, we confirmed that metronidazole and levofloxacin induced a biofilm-like phenotype, while clarithromycin kept bacteria in a planktonic form. Discussion: Our results suggest that sub-MICs of antibiotics affect the biochemical and biophysical properties of the developing biofilm of H. pylori strains and may impact the effectiveness of antibiotic treatment. [ABSTRACT FROM AUTHOR]

Background: Warfarin and Direct Oral Anticoagulant (DOAC) users may have more frequent antibiotic prescriptions than non-users. The aim of this study was to estimate rates of common and resistant infections, and antibiotic prescribing amongst warfarin and DOAC users versus non-users. Methods: This matched retrospective cohort study used data from patients registered with General practices in England contributing to the Clinical Practice Research Datalink GOLD. We included 61,750 adults who initiated warfarin or a DOAC between 1st January 2011 and 31st December 2019, matched 1:1 to non-users. We estimated Incident Rate Ratios (IRR) and 95% Confidence Intervals for three common infections and all-cause antibiotic prescribing. We estimated hazard ratios (HRs) and 95% CIs for the risk of methicillin resistance Staphylococcus aureus (MRSA), other antibiotic-resistant organisms, or Clostridium difficile. We assessed the extent to which any of the effect of warfarin and DOAC use on antibiotic resistant infections or Clostridium difficile was mediated by antibiotic prescribing patterns. Results: 37,143 warfarin users and 24,607 DOAC users were matched 1:1 to non-users. Warfarin and DOAC users had greater relative consultation rates for respiratory, urinary, and skin infections. All-cause antibiotic prescribing was greater in warfarin and DOAC users (warfarin; adjusted IRR 1.47, 95% CI 1.45–1.50, DOAC; adjusted IRR 1.66, 95% CI 1.63–1.69). Largest effect sizes were observed for flucloxacillin (adjusted IRR 2.11, 95% CI 2.01–2.20), and erythromycin (adjusted IRR 2.32, 95% CI 2.00–2.70). Warfarin users had significantly higher risk of MRSA (adjusted HR 1.68, 95% CI 1.38–2.05) and hospital admission with antibiotic resistant infections (adjusted HR 1.91, 95% CI 1.11–3.30). DOAC users had significantly higher risk of MRSA (adjusted HR 1.57, 95% CI 1.20–2.06), hospital admission with antibiotic resistant infections (adjusted HR 2.13, 95% CI 1.61–2.82), and Clostridium difficile (adjusted HR 1.45, 95% CI 1.10–1.92). We found little evidence to suggest that the increased risks of studied outcomes were mediated by rates of antibiotic prescription. Conclusion: Warfarin and DOAC use was associated with greater rates of infection consultations, all-cause antibiotic prescribing, antibiotic resistant infections, and Clostridium difficile, but there was little evidence that antibiotic prescribing rates mediated risk of resistant infections or Clostridium difficile. [ABSTRACT FROM AUTHOR]

Background: The issue of Helicobacter pylori (H. pylori) resistance to clarithromycin (CLR) has consistently posed challenges for clinical treatment. Hence, a rapid susceptibility testing (AST) method urgently needs to be developed. Methods: In the present study, 35 isolates of H. pylori were isolated from 203 gastritis patients of the Guangzhou cohort, and the antimicrobial resistance phenotypes were associated with their genomes to analyze the relevant mutations. Based on these mutations, a rapid detection system utilizing high-resolution melting (HRM) curve analysis was designed and verified by the Shenzhen cohort, which consisted of 38 H. pylori strains. Results: Genomic analysis identified the mutation of the 2143 allele from A to G (A2143G) of 23S rRNA as the most relevant mutation with CLR resistance (p < 0.01). In the HRM system, the wild-type H. pylori showed a melting temperature (Tm) of 79.28 ± 0.01 °C, while the mutant type exhibited a Tm of 79.96 ± 0.01 °C. These differences enabled a rapid distinction between two types of H. pylori (p < 0.01). Verification examinations showed that this system could detect target DNA as low as 0.005 ng/μL in samples without being affected by other gastric microorganisms. The method also showed a good performance in the Shenzhen validation cohort, with 81.58% accuracy, and 100% specificity. Conclusions: We have developed an HRM system that can accurately and quickly detect CLR resistance in H. pylori. This method can be directly used for the detection of gastric microbiota samples and provides a new benchmark for the simple detection of H. pylori resistance. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to compare the efficacy and tolerability of azithromycin and clarithromycin in pediatric Campylobacter enterocolitis. Methods: A prospective, randomized, controlled trial was conducted at a single center. Patients with confirmed Campylobacter enterocolitis were randomly assigned to receive either a 3-day course of azithromycin or a 5-day course of clarithromycin. Symptoms were monitored daily, and changes in laboratory markers (WBC counts, CRP levels, and stool calprotectin) were compared. Results: A total of 29 pediatric patients were included, with 14 patients in the azithromycin group and 15 patients in the clarithromycin group. The median age of patients in the azithromycin group was 10.0 years (interquartile range [IQR]: 5.0–13.0), and in the clarithromycin group, the median age was 9.0 years (IQR: 7.0–13.0) (p = 0.793). The median time to clinical resolution was 3.0 days (IQR: 2.0–3.0) in the azithromycin group and 2.0 days (IQR: 2.0–3.0) in the clarithromycin group (p = 0.132). There were no significant differences in the duration of individual symptoms, including fever, vomiting, and abdominal pain. The length of hospital stay was also similar, with a median stay of 4 days (IQR: 3.0–5.0) in both groups (p = 0.394). Both antibiotics were well-tolerated, with no significant adverse events or treatment discontinuation reported. Conclusions: Clarithromycin was found to be as effective as azithromycin in treating pediatric Campylobacter enterocolitis, with similar clinical outcomes and improvements in laboratory markers. [ABSTRACT FROM AUTHOR]

Background/Objectives: Stomach infections by Helicobacter pylori can cause acute or chronic gastritis, peptic ulcers, and gastric cancer. The rise in antibiotic resistance is a significant health issue highlighted by the World Health Organization. The increasing number of treatment failures underscores the necessity for antibiotic susceptibility testing (AST). The study aimed to investigate the current prevalence and resistance to fluoroquinolones and clarithromycin with their detected mutations. Methods: Stomach biopsies from symptomatic patients were subjected to molecular testing by GenoType Helico DR kit (Hain Lifescience GmbH, Nehren, Germany). Results: Positive findings on the presence of H. pylori were detected in 42.4% of symptomatic patients, with the significant majority of patients (69%) having previously failed treatments. The resistance rates to fluoroquinolones and clarithromycin were 53.9% and 58.5%, respectively, with significantly higher rates in secondary resistant strains. The main resistance markers in fluoroquinolones and clarithromycin were N87K (27.4%) and A2147G (78.6%), respectively. Hetero-resistance or mixed genotypes were detected in over 20% of tested patients. During the study period, a significant increase in trends in both fluoroquinolones and clarithromycin resistance rates was observed. Conclusions: Results indicate the need for the implementation of the latest Maastricht VI Consensus recommendations for both AST whenever possible and the use of tailored guided therapy options due to high resistance rates and possible treatment failures. The GenoType Helico DR kit is a useful tool for AST, especially in cases of mixed H. pylori genotypes. [ABSTRACT FROM AUTHOR]

The primary goal of this study was to develop and test Clarithromycin and Curcumin-loaded floating microspheres for sustained medication delivery. Microspheres were formed utilizing a modified solvent evaporation process using Eudragit S-100 and Ethyl Cellulose (18-22 cps) as regulating polymers. The formulation was optimized using 32 factorial design factorial Design-Expert® 13 trial version software. The Drug-to-Polymer Ratio (X1) and the Polymer-to-Polymer (EC to ES-100) Ratio (X2) were chosen as independent factors, whereas % Buoyancy (Y1), Percentage Yield (Y2), and% Drug Entrapment Efficiency (%DEE) (Y3) were chosen as dependent variables. The evaluations covered micromeritic characteristics, particle size, PDI, zeta potential, entrapment efficiency, floating capacity, surface morphology (FESEM), in vitro drug release, kinetics, DSC and FTIR compatibility investigations. Microspheres exhibited good flow, with particle sizes of 31.52 µm to 40.64 µm (optical) and 33.42 µm (PCS), PDI 0.374, practical yields of 75.14±0.24% to 95.14±0.38% and buoyancy of 76.12±1.2% to 84.79±0.87%. Drug entrapment efficiencies were 78.92±0.61% to 89.42±0.71% for Clarithromycin and 74.26±0.54% to 89.56% for Curcumin, with drug loading efficiencies of 12.90±0.27% to 21.19±0.49% and 10.30±0.67% to 21.1±0.78%, respectively. For the provided formulas, the ANOVA revealed a p value of less than 0.0500. In pH 0.1N HCl, Batch F6 demonstrated superior drug release for both Clarithromycin and Curcumin, with respective values of 99.67±1.5% and 99.52±2.1%. This data aligns with the Higuchi model of the Non-Fickian release kinetics mechanism. Stability experiments verified formulation F6's effectiveness and stability, indicating its potential for targeted, prolonged release in gastrointestinal settings. [ABSTRACT FROM AUTHOR]

This is the first registered intervention study for vonoprazan, high-dose amoxicillin, clarithromycin, and metronidazole 14-day concomitant therapy based on a susceptibility test of Helicobacter pylori. We conducted this study as a fourth-line rescue regimen in Japan. Methods: Twenty patients who underwent three rounds of eradication therapies (first- or second-line 7-day triple therapy consisting of amoxicillin and clarithromycin, or metronidazole- and sitafloxacin-based third-line therapy) and had failed eradication based on a urea breath test or fecal antigen test were recruited. All patients underwent endoscopic examination and culture tests before starting eradication therapy. The intervention was concomitant therapy consisting of vonoprazan 20 mg bid, amoxicillin 500 mg qid, clarithromycin 400 mg bid, and metronidazole 250 mg bid for 14 days, which were modified based on the susceptibility test, and the resistant drugs were removed from the regimen. Patients with negative culture results were treated with quadruple therapy. The primary outcome was the eradication rate (UMIN000025765, jRCTs 031180208). Results: The eradication rate of susceptibility-testing-based fourth-line eradication therapy was 63.2% (95%CI: 38.4–83.7%) in intent-to-treat analysis and 70.6% (95%CI: 44.0–89.7%) in per-protocol analysis. Thirteen patients received quadruple therapy, with eradication rates of 61.5% and 75.0%, respectively. No serious adverse events were reported. Conclusions: This vonoprazan-based concomitant therapy modified by the susceptibility test is a potential option as fourth-line eradication after first-line clarithromycin-based 7-day triple, second-line metronidazole-based 7-day triple, and third-line sitafloxacin-based 7-day triple therapy failure. [ABSTRACT FROM AUTHOR]