Helicobacter最新文献_第9页

Prevalence of multidrug-resistant Campylobacter species in wastewater effluents: A menace of environmental and public health concern 废水中普遍存在耐多药弯曲杆菌：环境和公共卫生问题的威胁。

IF 4.4 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Helicobacter

Pub Date : 2024-05-26 DOI: 10.1111/hel.13095

Olufunmilayo Modupe Oluwakoya, Anthony Ifeanyi Okoh

The prevalence of multidrug-resistant Campylobacter species in wastewater effluents presents a formidable challenge at the intersection of environmental sustainability and public health. This study examined the presence of multidrug-resistant Campylobacter in wastewater effluents in the Eastern Cape Province, South Africa, and its implications for environmental ecosystems and public health. Forty-five samples from household effluent (HHE) and wastewater treatment plant effluent (WWTPE) were collected at different geographical locations within the province between April and September 2022. The counts of the presumptive Campylobacter genus ranged from 5.2 × 10³ to 6.03 × 10⁴ CFU/mL for HHE and 4.93 × 10³ to 1.04 × 10⁴ CFU/mL for WWTPE. About 42.55% of the samples were positive for Campylobacter species. Five virulence determinants including the cadF and wlaN were detected in all the isolates; however, flgR (19.23%), ciaB, and ceuE (15.38%) were less prevalent. The antibiogram profiles of confirmed Campylobacter isolates revealed high resistance (>55%) against all tested antibiotics ranging from 55.77% (nalidixic acid) to 92.30% (erythromycin), and resistance against the other antibiotics followed the order ciprofloxacin (51.92%), azithromycin (50%), and levofloxacin (48.08%). On the contrary, gentamicin was sensitive against 61.54% of the isolates, followed by imipenem (57.69%) and streptomycin (51.92%). The WWTPE's antibiotic resistance index (ARI) was 0.19, lower than the permitted Krumperman threshold of 0.2; and HHE's ARIs were higher. The isolates' respective multiple antibiotic resistance indexes (MARI) varied between 0.08 and 1.00. Among the phenotypically resistant Campylobacter isolates examined, 21 resistance determinants encoding resistance against β-lactam, carbapenems, aminoglycosides, phenicol, quinolones, tetracyclines, and macrolides were detected, which explains the phenotypic resistance observed in the study. This study concludes that the wastewaters in the study areas are important reservoirs of multidrug-resistant and potentially pathogenic Campylobacter species, suggesting the need for proper treatment of the wastewaters to eliminate the organisms in the effluents before discharge the final effluent to the receiving watershed.

污水中普遍存在的耐多药弯曲杆菌给环境可持续性和公共卫生带来了严峻的挑战。本研究考察了南非东开普省废水中存在的耐多药弯曲杆菌及其对环境生态系统和公共卫生的影响。2022 年 4 月至 9 月期间，在该省不同地点收集了 45 份家庭污水（HHE）和污水处理厂污水（WWTPE）样本。在 HHE 和 WWTPE 中，推定弯曲杆菌属的计数范围分别为 5.2 × 103 至 6.03 × 104 CFU/mL，4.93 × 103 至 1.04 × 104 CFU/mL。约 42.55% 的样本对弯曲杆菌呈阳性。所有分离物中都检测到了五种毒力决定因子，包括 cadF 和 wlaN；然而，flgR（19.23%）、ciaB 和 ceuE（15.38%）的流行率较低。确诊弯曲杆菌分离物的抗生素图谱显示，对所有测试抗生素的耐药性都很高（>55%），从 55.77%（萘啶酸）到 92.30%（红霉素）不等，对其他抗生素的耐药性依次为环丙沙星（51.92%）、阿奇霉素（50%）和左氧氟沙星（48.08%）。相反，庆大霉素对 61.54% 的分离株敏感，其次是亚胺培南（57.69%）和链霉素（51.92%）。WWTPE 的抗生素耐药性指数（ARI）为 0.19，低于克鲁姆伯曼允许的 0.2 临界值；而 HHE 的抗生素耐药性指数较高。分离物各自的多重抗生素耐药性指数（MARI）介于 0.08 和 1.00 之间。在检测的表型耐药弯曲杆菌分离物中，发现了 21 个耐药基因，分别编码对 β-内酰胺类、碳青霉烯类、氨基糖苷类、酚类、喹诺酮类、四环素类和大环内酯类的耐药性，这也解释了本研究中观察到的表型耐药性。本研究的结论是，研究地区的废水是具有多种耐药性和潜在致病性弯曲杆菌的重要贮存地，这表明有必要对废水进行适当处理，以消除废水中的生物，然后再将最终废水排放到受纳流域。

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引用次数: 0

Vonoprazan-based therapies versus PPI-based therapies in patients with H. pylori infection: Systematic review and meta-analyses of randomized controlled trials 幽门螺杆菌感染患者中基于沃诺普拉赞的疗法与基于 PPI 的疗法：随机对照试验的系统回顾和荟萃分析。

IF 4.4 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Helicobacter

Pub Date : 2024-05-24 DOI: 10.1111/hel.13094

Ligang Liu, Hekai Shi, Yufei Shi, Anlin Wang, Nuojin Guo, Fang Li, Milap C. Nahata

Background

This study aims to evaluate the efficacy and safety of vonoprazan-amoxicillin (VA), vonoprazan-amoxicillin-clarithromycin (VAC), vonoprazan-based bismuth-containing quadruple therapy (VBQT), and PPI-based triple (PAC) or quadruple therapy (PBQT) for H. pylori infection with the consideration of duration of therapy and amoxicillin dose (H: high; L: low).

Materials and Methods

PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched for eligible randomized controlled trials (RCTs) up to December 15, 2023. The efficacy outcome was eradication rate, and safety outcomes included the rates of adverse events and treatment discontinuation.

Results

Twenty-seven RCTs were included. The pooled eradication rates were 82.8% for VA, 89.1% for VAC, and 91.8% for VBQT, which increased with the higher amoxicillin frequency of administration and extended duration of therapy within each regimen. There were no significant differences in eradication rate when comparing 7-VA versus 7-VAC and 14-VA versus 14-VAC. VA was at least comparable to PAC. The eradication rate did not differ significantly between 10-H-VA or 14-H-VA versus 14-PBQT. 7-L-VAC demonstrated higher eradication rate versus 7-PAC and comparable rate to 14-PAC. 14-VBQT showed higher eradication rates versus 14-PBQT. The adverse events rate was 19.3% for VA, 30.6% for VAC, and 38.4% for VBQT. VA had similar risk of adverse events versus VAC and significantly fewer adverse events compared to PBQT. The treatment discontinuation rate did not differ significantly between treatments.

Conclusions

The eradication rate of VBQT was the highest at above 90% followed by VAC and VA. VA was as effective as VAC and superior to PPI-based therapies with favorable safety, highlighting the potential of VA therapy as a promising alternative to traditional PPI-based therapies. VPZ-based triple or quadruple therapies was more effective than PPI-based therapies. Further studies are needed to establish the optimal treatment regimen especially in the western countries.

研究背景本研究旨在评估冯诺普拉唑-阿莫西林（VA）、冯诺普拉唑-阿莫西林-卡里霉素（VAC）、基于冯诺普拉唑的含铋四联疗法（VBQT）以及基于PPI的三联疗法（PAC）或四联疗法（PBQT）治疗幽门螺杆菌感染的疗效和安全性，同时考虑疗程和阿莫西林剂量（H：高；L：低）：检索了 PubMed、Embase 和 Cochrane 对照试验中央注册中心截至 2023 年 12 月 15 日的符合条件的随机对照试验 (RCT)。疗效结果为根除率，安全性结果包括不良事件发生率和治疗中止率：结果：共纳入 27 项随机对照试验。VA、VAC和VBQT的总根除率分别为82.8%、89.1%和91.8%。7-VA 与 7-VAC 和 14-VA 与 14-VAC 相比，根除率没有明显差异。VA 至少与 PAC 相当。10-H-VA 或 14-H-VA 与 14-PBQT 的根除率没有明显差异。7-L-VAC的根除率高于7-PAC，与14-PAC相当。14-VBQT 的根除率高于 14-PBQT。VA的不良事件发生率为19.3%，VAC为30.6%，VBQT为38.4%。与 VAC 相比，VA 的不良事件风险相似，而与 PBQT 相比，VA 的不良事件风险要低得多。不同治疗方法的治疗中断率没有明显差异：结论：VBQT的根除率最高，超过90%，其次是VAC和VA。VA的疗效与VAC相当，优于基于PPI的疗法，且安全性良好，这凸显了VA疗法作为传统PPI疗法替代品的潜力。基于 VPZ 的三联或四联疗法比基于 PPI 的疗法更有效。需要进一步研究以确定最佳治疗方案，尤其是在西方国家。

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引用次数: 0

Helicobacter pylori infection found during upper endoscopy performed for the diagnosis of celiac, inflammatory bowel diseases, and eosinophilic esophagitis: A multicenter pediatric European study 为诊断糜烂性胃炎、炎症性肠病和嗜酸性食管炎而进行上内镜检查时发现的幽门螺杆菌感染：一项欧洲多中心儿科研究。

IF 4.4 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Helicobacter

Pub Date : 2024-05-24 DOI: 10.1111/hel.13092

Kallirroi Kotilea, Claudio Romano, Erasmo Miele, Angelika Kindermann, Yael Dolstra, Zrinjka Misak, Vaidotas Urbonas, Josef Sykora, Pedro Urruzuno, Alexander Krauthammer, Maria Rogalidou, Konstantina Dimakou, Tsili Zangen, Eleftheria Roma, Aglaia Zellos, María Luz Cilleruelo, Meline M'Rini, Patrick Bontems, Yasin Sahin, Marta Tavares, Tatevik Shahinyan, Biljana Vuletic, Nicolas Kalach, Michal Kori, the ESPGHAN H. pylori special interest group

Background

Helicobacter pylori may be found during upper gastrointestinal endoscopy (UGE) performed to diagnose celiac disease (CeD), inflammatory bowel disease (IBD), and eosinophilic esophagitis (EoE). We aimed to describe the frequency of H. pylori in children undergoing UGE for CeD, IBD, and EoE and the number of children receiving eradication treatment.

Materials and Methods

A retrospective multicenter study from 14 countries included pediatric patients diagnosed with CeD, IBD, and EoE between January 2019 and December 2021. Data collected: age, gender, hematologic parameters, endoscopic, histologic, and H. pylori culture results, and information on eradication treatment.

Results

H. pylori was identified in 349/3890 (9%) children [167 (48%) male, median 12 years (interquartile range 8.1–14.6)]. H. pylori was present in 10% (173/1733) CeD, 8.5% (110/1292) IBD and 7.6% (66/865) EoE patients (p = NS). The prevalence differed significantly between Europe (Eastern 5.2% (28/536), Southern 3.8% (78/2032), Western 5.6% (28/513)) and the Middle East 26.6% (215/809) [odds ratio (OR) 7.96 95% confidence interval (CI) (6.31–10.1) p < 0.0001]. Eradication treatment was prescribed in 131/349 (37.5%) patients, 34.6% CeD, 35.8% IBD, and 56.1% EoE. Predictors for recommending treatment included erosions/ulcers [OR 6.45 95% CI 3.62–11.47, p < 0.0001] and nodular gastritis [OR 2.25 95% CI 1.33–3.81, p 0.003]. Treatment rates were higher in centers with a low H. pylori prevalence (<20%) [OR 3.36 95% CI 1.47–7.66 p 0.004].

Conclusions

Identifying H. pylori incidentally during UGE performed for the most common gastrointestinal diseases varies significantly among regions but not among diseases. The indications for recommending treatment are not well defined, and less than 40% of children received treatment.

背景：为诊断糜烂性胃炎（CeD）、炎症性肠病（IBD）和嗜酸性食管炎（EoE）而进行的上消化道内窥镜检查（UGE）可能会发现幽门螺杆菌。我们旨在描述因糜烂性胃炎、炎症性肠病和嗜酸性食管炎而接受 UGE 检查的儿童中幽门螺杆菌的感染频率以及接受根除治疗的儿童人数：一项来自14个国家的回顾性多中心研究纳入了2019年1月至2021年12月期间被诊断为CeD、IBD和EoE的儿童患者，收集的数据包括：年龄、性别、血液学参数、内镜、组织学和幽门螺杆菌培养结果以及根除治疗信息：结果：349/3890（9%）名儿童中发现了幽门螺杆菌[167（48%）名男性，中位数为 12 岁（四分位数间距为 8.1-14.6）]。10%（173/1733）CeD、8.5%（110/1292）IBD 和 7.6%（66/865）EoE 患者体内存在幽门螺杆菌（p = NS）。欧洲（东部 5.2% (28/536)、南部 3.8% (78/2032)、西部 5.6% (28/513)）和中东 26.6% (215/809)之间的患病率存在显著差异[比值比 (OR) 7.96 95% 置信区间 (CI) (6.31-10.1) p 结论：在对最常见的胃肠道疾病进行胃镜检查时偶然发现幽门螺杆菌，不同地区之间存在显著差异，但不同疾病之间的差异不大。建议治疗的适应症没有明确界定，只有不到 40% 的儿童接受了治疗。

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引用次数: 0

Nationwide survey of Helicobacter pylori seropositivity and gastric atrophy in Zambia 赞比亚全国幽门螺杆菌血清阳性和胃萎缩调查。

IF 4.4 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Helicobacter

Pub Date : 2024-05-24 DOI: 10.1111/hel.13096

Violet Kayamba, Husna Munshi, Mutinta Nyama Hankolwe, Ciluvya Kaluba Kavimba, Gershom Chongwe, Viktoria Knaze, Jin Young Park, Paul Kelly

Background

Helicobacter pylori (H. pylori) is a common bacterial infection which predominately drives upper gastrointestinal pathology. We carried out a nationwide serological survey in response to the deficiency of robust African data on H. pylori prevalence, age of acquisition, socio-geographic determinants, and impact on gastric physiology.

Materials and Methods

This was a cross-sectional study of archival plasma samples collected during the Zambia Population-based HIV impact Assessment (ZAMPHIA) 2016 survey. ZAMPHIA used a two-stage door-to-door stratified cluster sample approach to collect samples from adults and children from age 0 to 59 years (n = 24,266). We randomly retrieved one fifth of these samples from each of Zambia's 10 provinces and used ELISA to test for H. pylori IgG antibodies, pepsinogen 1 and 2 and gastrin-17. A pepsinogen 1:2 ratio of <3 was used to define gastric atrophy.

Results

The analysis of 4050 plasma samples (30% <16 years, 53% females) revealed an overall H. pylori seroprevalence of 79%. By the age of 10 years, more than 75% of the children had H. pylori. Urban residence was associated with increased odds (OR 1.8, 95% CI 1.5–2.2, p < 0.001) and HIV infection was associated with reduced odds (OR 0.7, 95% CI 0.5–0.9, p = 0.02) of H. pylori seropositivity. Gastric atrophy was detected in 6% of H. pylori seropositive adults below 45 years of age and 9% in those between 45 and 59 years.

Conclusions

We have confirmed a high prevalence of H. pylori seropositivity in Zambia, predominantly in urban settings. The prevalence of gastric atrophy is broadly consistent with other populations around the globe, but our sample did not include adults over 60 years.

背景：幽门螺杆菌（H. pylori）是一种常见的细菌感染，主要导致上消化道病变。由于非洲缺乏有关幽门螺杆菌感染率、感染年龄、社会地理决定因素以及对胃生理影响的可靠数据，因此我们在全国范围内开展了血清学调查：这是一项横断面研究，研究对象是在 2016 年赞比亚人口艾滋病影响评估（ZAMPHIA）调查期间收集的档案血浆样本。ZAMPHIA 采用两阶段逐户分层群组抽样方法，从 0 至 59 岁的成人和儿童中收集样本（n = 24266）。我们从赞比亚 10 个省的每个省随机抽取其中五分之一的样本，并使用 ELISA 检测幽门螺杆菌 IgG 抗体、胃蛋白酶原 1 和 2 以及胃泌素-17。结果显示，胃蛋白酶原 1:2 的比例为 1:2：对 4050 份血浆样本（30%）进行了分析：我们证实了幽门螺杆菌血清阳性在赞比亚的高流行率，主要是在城市环境中。胃萎缩的发病率与全球其他人群基本一致，但我们的样本不包括 60 岁以上的成年人。

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引用次数: 0

Treatment failure is a key factor in the development of Helicobacter pylori resistance 治疗失败是幽门螺旋杆菌产生抗药性的一个关键因素。

IF 4.4 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Helicobacter

Pub Date : 2024-05-23 DOI: 10.1111/hel.13091

Jinliang Xie, Jianxiang Peng, Dingwei Liu, Rong Zeng, Jiayu Qiu, Liting Shen, Xiaomin Gong, Dongsheng Liu, Yong Xie

Background

Helicobacter pylori eradication failure influences its antibiotic resistance.

Aims

This study aimed to evaluate the effect of previous treatment failures on it, including the changes in the antibiotic resistance rates, minimal inhibitory concentration (MIC) distributions, and resistance patterns.

Materials and Methods

This single-center retrospective study included 860 primary isolates and 247 secondary isolates. Antibiotic susceptibility testing was performed for amoxicillin, metronidazole, clarithromycin, levofloxacin, furazolidone, tetracycline, and rifampicin. The demographic data and detailed regimens were collected.

Results

The primary resistance rates to amoxicillin, metronidazole, clarithromycin, levofloxacin, tetracycline, rifampin, and furazolidone were 5.93%, 83.84%, 28.82%, 26.28%, 0.35%, 1.16%, and 0%, while secondary were 25.10%, 92.31%, 79.76%, 63.16%, 1.06%, 3.19%, and 0%, respectively. The resistance rates to amoxicillin, metronidazole, clarithromycin, and levofloxacin increased significantly with the number of treatment failures accumulated, and showed a linear trend. The proportion of primary and secondary multidrug-resistant (MDR) isolates were 17.79% and 63.16%, respectively. The MIC values of amoxicillin, clarithromycin, and levofloxacin were elevated significantly with medication courses increased.

Conclusion

The prevalence of amoxicillin, clarithromycin, levofloxacin, and metronidazole resistance would increase rapidly following first-line treatment failure, as well as the MIC values of them. Clinicians should pay great attention to the first-line treatment to cure H. pylori infection successfully.

背景：幽门螺杆菌根除失败会影响其抗生素耐药性：目的：本研究旨在评估以往治疗失败对幽门螺杆菌的影响，包括抗生素耐药率、最小抑菌浓度（MIC）分布和耐药模式的变化：这项单中心回顾性研究包括 860 例初次分离株和 247 例二次分离株。对阿莫西林、甲硝唑、克拉霉素、左氧氟沙星、呋喃唑酮、四环素和利福平进行了抗生素药敏试验。收集了人口统计学数据和详细的治疗方案：阿莫西林、甲硝唑、克拉霉素、左氧氟沙星、四环素、利福平和呋喃唑酮的一级耐药率分别为5.93%、83.84%、28.82%、26.28%、0.35%、1.16%和0%，二级耐药率分别为25.10%、92.31%、79.76%、63.16%、1.06%、3.19%和0%。随着治疗失败次数的累积，阿莫西林、甲硝唑、克拉霉素和左氧氟沙星的耐药率显著增加，并呈线性趋势。原发性和继发性多重耐药（MDR）分离株的比例分别为 17.79% 和 63.16%。随着疗程的增加，阿莫西林、克拉霉素和左氧氟沙星的 MIC 值明显升高：结论：阿莫西林、克拉霉素、左氧氟沙星和甲硝唑的耐药性在一线治疗失败后会迅速增加，其 MIC 值也会增加。临床医生应高度重视一线治疗，以成功治愈幽门螺杆菌感染。

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引用次数: 0

Antibiotic susceptibility pattern of Helicobacter pylori against eight antibiotics: A study from North India 幽门螺杆菌对八种抗生素的敏感性模式：印度北部的一项研究

IF 4.4 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Helicobacter

Pub Date : 2024-05-16 DOI: 10.1111/hel.13093

Safiya Arfi, Prateek Sharma, Mithun Kumar, Shubham Mehra, Kunal Das, Rajashree Das, Ashwini Setya

Background

The purpose of this analysis is to evaluate the antimicrobial susceptibility of eight drugs effective against Helicobacter pylori (H. pylori) strains and the genetic diversity of H. pylori virulence genes to foresee clinical outcomes in North India.

Materials and Methods

Fifty-eight H. pylori strains isolated from patients suffering from various gastrointestinal (GI) diseases were included in the study. MICs of various antibiotics were determined by the agar dilution method. The chi-squared test and Fisher exact test were used to determine the p-value, which was considered significant at p-value ≤ 0.05. RStudio 4.0 was used to for the data visualization.

Results

The prevalence of drug resistance was found to be: cefixime (CFM) (41.3%), furazolidone (FZD) (34.4%), amoxicillin (AMX) (20.7%), levofloxacin (LVFX) (70.7%), metronidazole (MTZ) (39.6%), tetracycline (TET) (20.7%), clarithromycin (CLA) (17.2%), and rifabutin (RIF) (17.2%). Out of 58 H. pylori strains, 3 were pan susceptible. There were H. pylori strains with single-drug resistance (21.8%, 12/55), dual resistance (30.9%, 17/55), triple resistance (20%, 11/55), and multidrug resistance (27.3%, 15/55). The resistance rate in MTZ, CLA and RIF were found to be significantly higher in females as compared to males (p = 0.005, p = 0.002, and p = 0.02), respectively. The resistance to TET exhibited significantly higher levels in gastritis compared to GERD, DU, and other disease groups (p = 0.04) respectively.

Conclusion

TET, AMX, CLA, and RIF were found to be more effective antibiotics against H. pylori infections, whereas more studies are required to provide evidence on increasing resistance rate of LVFX.

背景本分析的目的是评估对幽门螺旋杆菌（H. pylori）菌株有效的八种药物的抗菌敏感性以及幽门螺旋杆菌毒力基因的遗传多样性，以预测北印度的临床结果。材料和方法研究对象包括从各种胃肠道疾病患者体内分离出的 58 株幽门螺杆菌。采用琼脂稀释法测定了各种抗生素的 MICs。采用卡方检验和费舍尔精确检验来确定 p 值，当 p 值≤0.05 时视为显著。数据可视化使用 RStudio 4.0。结果发现耐药率为：头孢克肟（CFM）（41.3%）、呋喃唑酮（FZD）（34.4%）、阿莫西林（AMX）（20.7%）、左氧氟沙星（LVFX）（70.7%）、甲硝唑（MTZ）（39.6%）、四环素（TET）（20.7%）、克拉霉素（CLA）（17.2%）和利福布汀（RIF）（17.2%）。在 58 株幽门螺杆菌中，有 3 株对泛敏感。幽门螺杆菌菌株中存在单耐药（21.8%，12/55）、双耐药（30.9%，17/55）、三耐药（20%，11/55）和多耐药（27.3%，15/55）。与男性相比，女性对 MTZ、CLA 和 RIF 的耐药率明显更高（分别为 p = 0.005、p = 0.002 和 p = 0.02）。与胃食管反流病、DU 和其他疾病组相比，胃炎患者对 TET 的抵抗力明显更高（p = 0.04）。结论 TET、AMX、CLA 和 RIF 被认为是对幽门螺杆菌感染更有效的抗生素，而 LVFX 的耐药率增加还需要更多的研究来证明。

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引用次数: 0

In vitro efficacy of combinations of antibiotics used in clinical practice on clinical isolates of Helicobacter pylori 临床实践中使用的抗生素组合对幽门螺旋杆菌临床分离株的体外疗效。

IF 4.4 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Helicobacter

Pub Date : 2024-05-08 DOI: 10.1111/hel.13081

Zahyra Kaouah, Julien M. Buyck, Maxime Pichon, Christophe Burucoa, Laure Prouvensier, Jeremy Moreau, Sandrine Marchand, Julie Cremniter, Nicolas Grégoire

Background

The main antibiotics used against Helicobacter pylori have been chosen empirically over time, with few preclinical studies to provide support. The rise in resistance to some of these antibiotics is prompting a reassessment of their use. This work aimed to evaluate the in vitro efficacy of 2 × 2 combinations of the most widely used antibiotics against H. pylori.

Materials and Methods

J99 reference strains and 19 clinical isolates of H. pylori with various antibiotic resistance phenotypes were used. Minimum inhibitory concentrations were carried out using the microdilution method in 96-well plates. The activity of 15 possible combinations of two antibiotics including amoxicillin, clarithromycin (CLA), levofloxacin, rifampicin, tetracycline, and metronidazole was determined for all strains by the checkerboard method. A mean fractional inhibitory concentration index (FIC_mean) was calculated for each combination and strain and the type of pharmacodynamic interaction was considered as synergic if FIC_mean ≤ 0.5, additive if 0.5 < FIC_mean ≤ 1, indifferent if 1 < FIC_mean < 4 or antagonistic if FIC_mean ≥ 4.

Results

Most of the 285 pharmacodynamic interactions tested with clinical strains were close to additivity (average FIC_mean = 0.89 [0.38–1.28]). No interaction was found to be antagonistic. When two antibiotics to which a strain was resistant were combined, the concentrations required to inhibit bacterial growth were higher than their respective breakpoints.

Conclusion

The present results have shown that in vitro, the different antibiotics used in therapeutics have additive effects. The addition of the effects of two antibiotics to which a strain was resistant was not sufficient to inhibit bacterial growth. In probabilistic treatment, the choice of antibiotics to combine should therefore be based on the local epidemiology of resistance, and on susceptibility testing in the case of CLA therapy, so that at least one antibiotic to which the strain is susceptible is used.

背景：针对幽门螺旋杆菌的主要抗生素是长期以来根据经验选择的，很少有临床前研究提供支持。其中一些抗生素耐药性的增加促使人们对其使用进行重新评估。这项工作旨在评估最广泛使用的抗生素的 2 × 2 组合对幽门螺杆菌的体外疗效：材料和方法：使用 J99 参考菌株和 19 个具有不同抗生素耐药性表型的幽门螺杆菌临床分离株。采用微量稀释法在 96 孔板中测定最小抑菌浓度。采用棋盘格法测定了所有菌株的两种抗生素（包括阿莫西林、克拉霉素（CLA）、左氧氟沙星、利福平、四环素和甲硝唑）的 15 种可能组合的活性。计算每种组合和菌株的平均分数抑制浓度指数（FICmean），如果 FICmean≤0.5 则认为药效学相互作用类型为协同作用，如果 0.5 平均值≤1 则认为药效学相互作用类型为相加作用，如果 1 平均值≥4 则认为药效学相互作用类型为无关作用：用临床菌株测试的 285 种药效学相互作用中，大多数接近相加性（平均 FICmean = 0.89 [0.38-1.28]）。没有发现任何相互作用是拮抗的。当两种对菌株耐药的抗生素联合使用时，抑制细菌生长所需的浓度高于它们各自的断点：本研究结果表明，在体外，用于治疗的不同抗生素具有相加效应。对一种菌株具有抗药性的两种抗生素的叠加效应不足以抑制细菌生长。因此，在进行概率治疗时，应根据当地的抗药性流行病学情况和 CLA 治疗时的药敏试验来选择联合使用的抗生素，以便至少使用一种菌株易感的抗生素。

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引用次数: 0

Comparison of Helicobacter pylori eradication rates between 7 and 14 days of tailored therapy according to clarithromycin resistance test: A randomized, multicenter, non-inferiority study 根据克拉霉素耐药性测试结果比较 7 天和 14 天定制疗法的幽门螺杆菌根除率：一项随机、多中心、非劣效性研究。

IF 4.4 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Helicobacter

Pub Date : 2024-05-08 DOI: 10.1111/hel.13084

Kyoungwon Jung, Sam Ryong Jee, Moon Won Lee, Myeongseok Koh, Su Jin Kim, Jin Lee, Moo In Park

Background

Recently, a simple tailored therapy based on clarithromycin resistance has been implemented as Helicobacter pylori (H. pylori) eradication therapy. Nonetheless, despite the tailored therapy and frequent adverse events, studies on treatment period are lacking. This study aimed to compare the H. pylori eradication rates of 7-day and 14-day tailored therapy regimens according to clarithromycin resistance.

Materials and Methods

This multicenter, prospective, randomized, noninferiority trial enrolled H. pylori-positive patients who were randomly assigned to 7-day and 14-day regimen groups, depending on the presence or absence of clarithromycin resistance by 23S rRNA gene point mutations. Standard triple therapy (STT) (20 mg rabeprazole, 1 g amoxicillin, and 500 mg clarithromycin twice daily) or bismuth quadruple therapy (BQT) (20 mg rabeprazole twice daily, 500 mg metronidazole thrice daily, 120 mg bismuth four times daily, and 500 mg tetracycline four times daily) was assigned by clarithromycin resistance. Eradication rates and adverse events were evaluated.

Results

A total of 314 and 278 patients were included in the intention-to-treat (ITT) and per-protocol (PP) analyses, respectively; however, 31 patients were lost to follow-up, whereas five patients violated the protocol. Both the 7-day and 14-day regimens showed similar eradication rates in the ITT (7-day vs. 14-day: 78.3% vs. 78.3%, p > 0.99) and PP (87.9% vs. 89.1%, p = 0.851) analyses. Non-inferiority was confirmed (p < 0.025). A subgroup analysis according to clarithromycin resistance (clarithromycin resistance rate: 28.7%) revealed no significant difference in eradication rates between the 7-day and 14-day STT (90.0% vs. 90.1%, p > 0.99) and BQT (82.5% vs. 86.5%, p = 0.757). Furthermore, adverse events did not significantly differ between the two groups.

Conclusions

The 7-day triple and quadruple therapy according to clarithromycin resistance showed similar eradication rates, as compared to the 14-day therapy.

背景：最近，一种基于克拉霉素耐药性的简单定制疗法已被作为根除幽门螺旋杆菌（H. pylori）的疗法。然而，尽管这种定制疗法不良反应频发，但却缺乏对治疗周期的研究。本研究旨在根据克拉霉素耐药性，比较7天和14天定制治疗方案的幽门螺杆菌根除率：这项多中心、前瞻性、随机、非劣效性试验招募了幽门螺杆菌阳性患者，根据他们是否因 23S rRNA 基因点突变而对克拉霉素产生耐药性，将他们随机分配到 7 天和 14 天治疗方案组。根据克拉霉素耐药性分配标准三联疗法（STT）（20 毫克雷贝拉唑、1 克阿莫西林和 500 毫克克拉霉素，每天两次）或铋剂四联疗法（BQT）（20 毫克雷贝拉唑，每天两次；500 毫克甲硝唑，每天三次；120 毫克铋剂，每天四次；500 毫克四环素，每天四次）。对根除率和不良反应进行了评估：共有314名和278名患者分别被纳入意向治疗（ITT）和按协议（PP）分析；但有31名患者失去了随访机会，另有5名患者违反了协议。在 ITT（7 天与 14 天：78.3% 与 78.3%，p > 0.99）和 PP（87.9% 与 89.1%，p = 0.851）分析中，7 天和 14 天疗法的根除率相似。非劣效性得到证实（p 0.99），BQT（82.5% 对 86.5%，p = 0.757）。此外，两组的不良反应没有明显差异：结论：与 14 天疗法相比，根据克拉霉素耐药性采用的 7 天三联和四联疗法显示出相似的根除率。

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引用次数: 0

Helicobacter pylori with trx1 high expression promotes gastric diseases via upregulating the IL23A/NF-κB/IL8 pathway 高表达 trx1 的幽门螺杆菌通过上调 IL23A/NF-κB/IL8 通路诱发胃病

IF 4.4 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Helicobacter

Pub Date : 2024-04-30 DOI: 10.1111/hel.13072

Xin Guan, Jing Ning, Weiwei Fu, Ye Wang, Jing Zhang, Shigang Ding

Background

Helicobacter pylori infection is one of the main causes of gastric cancer. thioredoxin-1 (Trx1) and arginase (RocF) expressed by H. pylori were found to be closely related to its pathogenicity. However, whether Trx1 and RocF can be used in clinical screening of highly pathogenic H. pylori and the pathogenesis of trx1 high expressing H. pylori remain still unknown.

Materials and Methods

We investigated the expression level of H. pylori trx1 and H. pylori rocF in human gastric antrum tissues using reverse transcription and quantitative real-time PCR (RT-qPCR) and clarified the clinical application value of trx1 and rocF for screening highly pathogenic H. pylori. The pathogenic mechanism of Trx1 were further explored by RNA-seq of GES-1 cells co-cultured with trx1 high or low expressing H. pylori. Differentially expressed genes and signaling pathways were validated by RT-qPCR, Enzyme-linked immunosorbent assay (ELISA), western blot, immunohistochemistry and immunofluorescence. We also assessed the adherence of trx1 high and low expressing H. pylori to GES-1 cells.

Results

We found that H. pylori trx1 and H. pylori rocF were more significantly expressed in the gastric cancer and peptic ulcer group than that in the gastritis group and the parallel diagnosis of H. pylori trx1 and H. pylori rocF had high sensitivity. The trx1 high expressing H. pylori had stronger adhesion ability to GES-1 cells and upregulated the interleukin (IL) 23A/nuclear factor κappaB (NF-κB)/IL17A, IL6, IL8 pathway.

Conclusions

H. pylori trx1 and H. pylori rocF can be used in clinical screening of highly pathogenic H. pylori and predicting the outcome of H. pylori infection. The trx1 high expressing H. pylori has stronger adhesion capacity and promotes the development of gastric diseases by upregulating the activation of NF-κB signaling pathway.

背景幽门螺杆菌感染是导致胃癌的主要原因之一。研究发现，幽门螺杆菌表达的硫氧还蛋白-1（Trx1）和精氨酸酶（RocF）与其致病性密切相关。然而，Trx1和RocF是否可用于临床筛查高致病性幽门螺杆菌以及高表达Trx1幽门螺杆菌的致病机理仍是未知数。材料与方法我们采用逆转录和实时定量 PCR（RT-qPCR）技术研究了人胃窦组织中幽门螺杆菌 trx1 和幽门螺杆菌 rocF 的表达水平，并明确了 trx1 和 rocF 在筛选高致病性幽门螺杆菌中的临床应用价值。通过对与高表达或低表达 trx1 幽门螺杆菌共培养的 GES-1 细胞进行 RNA 序列分析，进一步探讨了 Trx1 的致病机制。通过 RT-qPCR、酶联免疫吸附试验（ELISA）、Western 印迹、免疫组织化学和免疫荧光验证了不同表达的基因和信号通路。我们还评估了高表达和低表达 trx1 幽门螺杆菌对 GES-1 细胞的粘附性。结果我们发现，幽门螺杆菌 trx1 和幽门螺杆菌 rocF 在胃癌和消化性溃疡组中的表达量明显高于胃炎组，幽门螺杆菌 trx1 和幽门螺杆菌 rocF 的平行诊断灵敏度很高。trx1高表达幽门螺杆菌对GES-1细胞有更强的粘附能力，并上调白细胞介素（IL）23A/核因子κκB（NF-κB）/IL17A、IL6、IL8通路。结论幽门螺杆菌 trx1 和幽门螺杆菌 rocF 可用于临床筛查高致病性幽门螺杆菌和预测幽门螺杆菌感染的结果。高表达的幽门螺杆菌 trx1 具有更强的粘附能力，并通过上调 NF-κB 信号通路的活化促进胃病的发展。

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引用次数: 0

Dynamic changes in the gut microbiota after bismuth quadruple therapy and high-dose dual therapy for Helicobacter pylori eradication 根除幽门螺旋杆菌的四联铋疗法和大剂量双重疗法后肠道微生物群的动态变化

IF 4.4 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Helicobacter

Pub Date : 2024-04-29 DOI: 10.1111/hel.13077

Jing Chen, Yan Zhang, Hanchen Min, Junli Zhi, Shuyun Ma, Hongxia Dong, Jingshuang Yan, Xiaoyan Chi, Xiaomei Zhang, Yunsheng Yang

Background

A novel regimen with high-dose dual therapy (HDDT) has emerged, but its impact on the gut microbiota is not well understood. This study aimed to evaluate the impact of HDDT on the gut microbiota and compare it with that of bismuth quadruple therapy (BQT).

Methods

We enrolled outpatients (18–70 years) diagnosed with Helicobacter pylori infection by either histology or a positive ¹³C-urea breath test (¹³C-UBT) and randomly assigned to either the BQT or HDDT group. Subjects consented to provide fecal samples which were collected at baseline, Week 2, and Week 14. Amplification of the V1 and V9 regions of the 16S rRNA was conducted followed by high-throughput sequencing.

Results

Ultimately, 78 patients (41 patients in the HDDT group and 37 in the BQT group) were enrolled in this study. Eradication therapy significantly altered the diversity of the gut microbiota. However, the alpha diversity rebounded only in the HDDT group at 12 weeks post-eradication. Immediately following eradication, the predominance of Proteobacteria, replacing commensal Firmicutes and Bacteroidetes, did not recover after 12 weeks. Species-level analysis showed that the relative abundances of Klebsiella pneumoniae and Escherichia fergusonii significantly increased in both groups at Week 2. Enterococcus faecium and Enterococcus faecalis significantly increased in the BQT group, with no significant difference observed in the HDDT group. After 12 weeks of treatment, the relative abundance of more species in the HDDT group returned to baseline levels.

Conclusion

Eradication of H. pylori can lead to an imbalance in gut microbiota. Compared to BQT, the HDDT is a regimen with milder impact on gut microbiota.

背景一种新型的高剂量双重疗法（HDDT）已经出现，但其对肠道微生物群的影响还不甚了解。本研究旨在评估 HDDT 对肠道微生物群的影响，并将其与四联铋剂疗法（BQT）进行比较。方法我们招募了通过组织学检查或 13C-urea 呼气试验（13C-UBT）阳性确诊为幽门螺杆菌感染的门诊患者（18-70 岁），并将其随机分配到 BQT 组或 HDDT 组。受试者同意在基线、第 2 周和第 14 周提供粪便样本。对 16S rRNA 的 V1 和 V9 区域进行扩增，然后进行高通量测序。结果最终，78 名患者（HDDT 组 41 人，BQT 组 37 人）参与了这项研究。根除疗法明显改变了肠道微生物群的多样性。然而，只有 HDDT 组的阿尔法多样性在根除后 12 周内有所恢复。根除后，变形菌立即占据主导地位，取代了共生的固有菌和类杆菌，但在 12 周后并未恢复。物种水平分析表明，在第 2 周时，两组中肺炎克雷伯菌和弗氏埃希氏菌的相对丰度都显著增加。粪肠球菌和粪肠球菌在 BQT 组明显增加，而在 HDDT 组未观察到明显差异。治疗 12 周后，HDDT 组中更多物种的相对丰度恢复到基线水平。结论根除幽门螺杆菌会导致肠道微生物群失衡。与 BQT 相比，HDDT 对肠道微生物群的影响较小。

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