Effect and mechanism of Qingre Huashi decoction on drug-resistant Helicobacter pylori

BACKGROUND Helicobacter pylori(HP),the most common pathogenic microorganism in stomach,can induce inflammatory reactions in the gastric mucosa,causing chronic gastritis and even gastric cancer.HP infection affects over 4.4 billion people globally,with a worldwide infection rate of up to 50%.The multidrug resistance of HP poses a serious challenge to eradication.It has been monstrated that compared to bismuth quadruple therapy,Qingre Huashi decoction(QHD)combined with triple therapy exhibits comparable eradication rates but with a lower incidence of adverse reactions;in addition,QHD directly inhibit and kill HP in vitro.METHODS In this study,12 HP strains were isolated in vitro after biopsy during gastroscopy of HP-infected patients.In vitro,the minimum inhibitory concentration(MIC)values for clinical HP strains and biofilm quantification were determined through the E-test method and crystal violet staining,respectively.The most robust biofilm-forming strain of HP was selected,and QHD was evaluated for its inhibitory and bactericidal effects on the strain with strong biofilm formation.This assessment was performed using agar dilution,E-test,killing dynamics,and transmission electron microscopy(TEM).The study also explored the impact of QHD on antibiotic resistance in these HP strains with strong biofilm formation.Crystalline violet method,scanning electron microscopy,laser confocal scanning microscopy,and(p)ppGpp chromatographic identification were employed to evaluate the effect of QHD on biofilm in strong biofilm-forming HP strains.The effect of QHD on biofilm and efflux pump-related gene expression was evaluated by quantitative polymerase chain reaction.Non-targeted metabolomics with UHPLC-MS/MS was used to identify potential metabolic pathways and biomarkers which were different between the NC and QHD groups.RESULTS HP could form biofilms of different degrees in vitro,and the intensity of formation was associated with the drug resistance of the strain.QHD had strong bacteriostatic and bactericidal effects on HP,with MICs of 32-64 mg/mL.QHD could inhibit the biofilm formation of the strong biofilm-forming HP strains,disrupt the biofilm structure,lower the accumulation of(p)ppGpp,decrease the expression of biofilm-related genes including LuxS,Spot,glup(HP1174),NapA,and CagE,and reduce the expression of efflux pump-related genes such as HP0605,HP0971,HP1327,and HP1489.Based on metabolomic analysis,QHD induced oxidative stress in HP,enhanced metabolism,and potentially inhibited relevant signaling pathways by upregulating adenosine monophosphate(AMP),thereby affecting HP growth,metabolism,and protein synthesis.CONCLUSION QHD exerts bacteriostatic and bactericidal effects on HP,and reduces HP drug resistance by inhibiting HP biofilm formation,destroying its biofilm structure,inhibiting the expression of biofilm-related genes and efflux pump-related genes,enhancing HP metabolism,and activating AMP in HP.

Research Progress of Radical Treatment of Helicobacter Pylori Based on Drug Sensitivity Test as First-Line Treatment

Helicobacter pylori (HP) infection is a global problem that affects about half of the world’s population and requires sufficient attention in clinical and scientific work. Due to differences in economic and medical conditions among countries around the world, there is currently no unified treatment plan for anti-HP. In China, empirical quadruple therapy is mainly used. With the abuse of antibiotics, many patients face the problem of secondary eradication after failure, and the resistance rate of HP is gradually increasing. After eradication failure, drug sensitivity cultivation is carried out to choose sensitive antibiotics for treatment. A new strategy is currently needed to address how to improve the eradication rate of HP during the first eradication. This article aims to discuss the first-line treatment plans and research progress for eradicating HP based on drug sensitivity testing before eradication. Compared with traditional empirical therapies, treatment based on drug sensitivity results can effectively improve the eradication rate of HP, and reduce drug resistance rates, and adverse reactions, among other benefits. .

BanXiaXieXin decoction treating gastritis mice with drug-resistant Helicobacter pylori and its mechanism

BACKGROUND Helicobacter pylori(H.pylori)is the main pathogen that causes a variety of upper digestive diseases.The drug resistance rate of H.pylori is increasingly higher,and the eradication rate is increasingly lower.The antimicrobial resistance of H.pylori is an urgent global problem.It has been confirmed that Banxia Xiexin decoction(BXXXT)demonstrates the effects of treating gastrointestinal diseases,inhibiting H.pylori and protecting gastric mucosa.The purpose of the present study is to further explore the therapeutic effects of BXXXT on drug-resistant H.pylori.AIM To confirm that BXXXT demonstrates therapeutical effects in vivo and in vitro on gastritis mice with drug-resistant H.pylori and explain its mechanism to provide an experimental basis for promoting the application of BXXXT.METHODS The aqueous extract of BXXXT was gained by water decocting method.The inhibitory effect of the aqueous extract on H.pylori was detected by dilution in vitro;drug-resistant H.pylori cells were used to build an acute gastritis model in vivo.Thereafter,the model mice were treated with the aqueous extract of BXXXT.The amount of H.pylori colonization,the repair of gastric mucosal damage,changes of inflammatory factors,apoptosis,etc.,were assessed.In terms of mechanism exploration,the main medicinal compositions of BXXXT aqueous extract and the synergistic bacteriostatic effects they had demonstrated were analyzed using mass spectrometry;the immune function of peripheral blood cells such as CD3+T and CD4+T of mice with gastritis before and after treatment with BXXXT aqueous extract was detected using a flow cytometry;the H.pylori transcriptome and proteome after treatment with BXXXT aqueous extract were detected.Differently expressed genes were screened and verification was performed thereon with knockout expression.RESULTS The minimum inhibitory concentration of BXXXT aqueous extract against H.pylori was 256-512μg/mL.A dose of 28 mg/kg BXXXT aqueous extract treatment produced better therapeutical effects than the standard triple therapy did;the BXXXT aqueous extract have at least 11 ingredients inhibiting H.pylori,including berberine,quercetin,baicalin,luteolin,gallic acid,rosmarinic acid,aloe emodin,etc.,of which berberine,aloe emodin,luteolin and gallic acid have a synergistic effect;BXXXT aqueous extract was found to stimulate the expressions of CD3+T and CD4+T and increase the number of CD4+T/CD8+T in gastritis mice;the detection of transcriptome and proteome,quantitative polymerase chain reaction,Western blotting and knockout verification revealed that the main targets of BXXXT aqueous extract are CFAs related to urea enzymes,and CagA,VacA,etc.CONCLUSION BXXXT aqueous extract could demonstrate good therapeutic effects on drug-resistance H.pylori in vitro and in vivo and its mechanism comes down to the synergistic or additional antibacterial effects of berberine,emodin and luteolin,the main components of the extract;the extract could activate the immune function and enhance bactericidal effects;BXXXT aqueous extract,with main targets of BXXXT aqueous extract related to urease,virulence factors,etc.,could reduce the urease and virulence of H.pylori,weaken its colonization,and reduce its inflammatory damage to the gastric mucosa.

Helicobacter pylori,esophageal precancerous lesions,and proton pump inhibitor overuse

This article reviews the cohort study published in the World Journal of Gastroenterology,which reported low rates of Helicobacter pylori(H.pylori)infection among esophageal cancer(EC)patients,coupled with proton pump inhibitor(PPI)overuse.These findings suggest a potential protective role of H.pylori against EC and indicate a possible association between PPI use and increased cancer risk.In light of these findings,our article examines the complex relationship between H.pylori and esophageal precancerous lesions,exploring the potential underlying mechanisms.We also address growing concerns regarding PPI overuse,including its potential effects on cancer therapy efficacy and the risk of drug interactions.Ultimately,this article highlights the urgent need for further research to evaluate the safety and efficacy of PPIs in cancer patients and to better understand their broader implications.

Helicobacter pylori infection and drugs malabsorption

Drug absorption represents an important factor affecting the efficacy of oral drug treatment.Gastric secretion and motility seem to be critical for drug absorption.A causal relationship between impaired absorption of orally administered drugs and Helicobacter pylori(H.pylori)infection has been proposed.Associations have been reported between poor bioavailability of l-thyroxine and l-dopa and H.pylori infection.According to the Maastricht Florence Consensus Report on the management of H.pylori infection,H.pylori treatment improves the bioavailability of both these drugs,whereas the direct clinical benefits to patients still await to be established.Less strong seems the association between H.pylori infection and other drugs malabsorption,such as delavirdine and ketoconazole.The exact mechanisms forming the basis of the relationship between H.pylori infection and impaired drugs absorption and/or bioavailability are not fully elucidated.H.pylori infection may trigger a chronic inflammation of the gastric mucosa,and impaired gastric acid secretion often follows.The reduction of acid secretion closely relates with the wideness and the severity of the damage and may affect drug absorption.This minireview focuses on the evidence of H.pylori infection associated with impaired drug absorption.

Interaction between Helicobacter pylori infection, nonsteroidal anti-inflammatory drugs and/or low-dose aspirin use: Old question new insights

Previous reports clearly demonstrated that Helicobacter pylori(H.pylori)infection,nonsteroidal anti-inflammatory drugs(NSAID)or low dose aspirin(ASA)use significantly and independently increased the risk for the development of peptic ulcer disease.Today,the presence of H.pylori infection associated with low dose ASA and/or NSAID use in the same patient is becoming more frequent and therefore the potential interaction between these factors and the consequences of it has important implications.Whether NSAID intake in the presence of H.pylori infection may further increase the risk of peptic ulcer carried by the presence of only one risk factor is still a matter of debate.Studies on the interaction between the two risk factors yielded conflicting data and no consensus has been reached in the last years.In addition,the interaction between H.pylori infection and low-dose ASA remains even more controversial.In real clinical practice,we can find different clinical scenarios involving these three factors associated with the presence of different gastrointestinal and cardiovascular risk factors.These huge variety of possible combinations greatly hinder the decision making process of physicians.

Helicobacter pylori-negative,non-steroidal anti-inflammatory drug:Negative idiopathic ulcers in Asia

Since the discovery of Helicobacter pylori(H.pylori)infection in the stomach,the bacteria infection and non-steroidal anti-inflammatory drugs(NSAIDs)use had been considered to be the 2 main causes of peptic ulcers.However,there have been recent reports of an increase in the proportion of peptic ulcers without these known risk factors;these are termed idiopathic peptic ulcers.Such trend was firstly indicated in 1990s from some reports in North America.In Asia,numerous studies reported that idiopathic ulcers accounted for a small percentage of all ulcers in the 1990s,but in the2000s,multiple studies reported that the proportion of idiopathic ulcers had reached 10%-30%,indicating that the incidence of idiopathic ulcers in Asia has also been rising in recent years.While a decline in H.pylori infection rates of general population in Asia is seen as the main reason for the increased incidence of idiopathic ulcers,it is also possible that the absolute number of idiopathic ulcer cases has increased.Advanced age,serious systemic complication,and psychological stress are considered to be the potential risk factors for idiopathic ulcers.Management of idiopathic ulcers is challenging,at present,because there is no effective preventative measure against recurrence in contrast with cases of H.pylori-positive ulcers and NSAIDs-induced ulcers.As it is expected that H.pylori infection rates in Asia will decline further in the future,measures to treat idiopathic ulcers will also likely become more important.

Helicobacter pylori infection in bleeding peptic ulcer patients after non-steroidal antiinflammatory drug consumption

AIM： TO establish the prevalence of He/icobacterpy/on （H. pylori） infection in patients with a bleeding peptic ulcer after consumption of non-steroidal antiinflammatory drugs （NSAIDs）.METHODS： A very early upper endoscopy was performed to find the source of upper gastrointestinal bleeding and to take biopsy specimens for analysis of H. pylori infection by the rapid urease （CLO） test, his- tological examination, and bacterial culture. TgG anti- CagA were also sought. The gold standard for identifying H. pylori infection was positive culture of biopsy specimens or contemporary positivity of the CLO test and the presence of H. pylori on tissue sections.RESULTS： Eighty patients, 61 males （76.3%）, mean age 61.2 ~ 15.9 years, were consecutively enrolled. Forty-seven （58.8%） patients occasionally consumed NSAIDs, while 33 （41.3%） were on chronic treatment with low-dose aspirin （LD ASA）. Forty-four （55.0%） patients were considered infected by H. pylori. The infection rate was not different between patients who occasionally or chronically consumed NSAIDs. The culture of biopsy specimens had a sensitivity of 86.4% and a specificity of 100%; corresponding figures for histological analysis were 65.9% and 77.8%, for the CLO test were 68.2% and 75%, for the combined use of histology and the CLO test were 56.8% and 100%, and for IgG anti-CagA were 90% and 98%. The high- est accuracy （92.5%） was obtained with the culture of biopsy specimens.CONCLUSION： Patients with a bleeding peptic ulcer after NSAID/LD ASA consumption frequently have H. pylori infection. Biopsy specimen culture after an early upper gastrointestinal tract endoscopy seems the most efficient test to detect this infection.

Coptis,Pinellia,and Scutellaria as a promising new drug combination for treatment of Helicobacter pylori infection

BACKGROUND Helicobacter pylori(H.pylori)is the most important infectious agent and plays an important role in the progression of chronic gastritis and the development of gastric cancer.AIM To identify efficient therapeutic agents or strategies that can treat H.pylori infection.METHODS We performed literature analysis,experimental validation,and network pharmacology.First,traditional Chinese medicine(TCM)prescriptions for the treatment of H.pylori infection were obtained from the China National Knowledge Infrastructure,China Biology Medicine,China Science and Technology Journal Database,and WanFang databases.In addition,we conducted a relevant search by Reference Citation Analysis(RCA)(https://www.referencecitationanalysis.com).Next,we used TCM Inheritance Support System V2.5 to identify core drug combinations in the TCM prescriptions.Then,an H.pylori-associated chronic mouse model of gastritis was established.The antibacterial properties and antiinflammatory potential of the core drug combination were evaluated by the rapid urease test,modified Warthin-Starry silver staining,histopathological analysis,and enzyme linked immunosorbent assay.Finally,the active compounds,hub targets,and potential signaling pathways associated with the core drug combination were analyzed by network pharmacology.RESULTS The TCM treatment of H.pylori was mainly based on reinforcing the healthy Qi and eliminating pathogenic factors by simultaneously applying pungent dispersing,bitter descending,cold and warm drugs.The combination of Coptis,Pinellia,and Scutellaria(CPS)was identified as the core drug combination from 207 prescriptions and 168 herbs.This drug combination eradicated H.pylori,alleviated the gastric pathology induced by H.pylori infection,and reduced the expression levels of tumor necrosis factor-α(P=0.024)and interleukin-1β(P=0.001).Moreover,a total of 35 compounds and 2807 targets of CPS were identified using online databases.Nine key compounds(tenaxin I,neobaicalein,norwogonin,skullcapflavone II,baicalein,5,8,2'-trihydroxy-7-methoxyflavone,acacetin,panicolin,and wogonin)and nine hub target proteins(EGFR,PTGS2,STAT3,MAPK3,MAPK8,HSP90AA1,MAPK1,MMP9,and MTOR)were further explored.Seventy-seven signaling pathways were correlated with H.pylori-induced inflammation and carcinogenesis.CONCLUSION In summary,we showed that CPS is the core drug combination for treating H.pylori infection.Animal experiments demonstrated that CPS has bacteriostatic properties and can reduce the release of inflammatory cytokines in the gastric mucosa.Network pharmacology predictions further revealed that CPS showed complex chemical compositions with multi-target and multipathway regulatory mechanisms.Although the results derived from network pharmacology are not necessarily comprehensive,they still expand our understanding of CPS for treating H.pylori infection.

Clinical characteristics of Helicobacter pylori-negative drugnegative peptic ulcer bleeding

AIM:To investigate the clinical characteristics and outcomes of idiopathic Helicobacter pylori(H.pylori)-negative and drug-negative]peptic ulcer bleeding(PUB).METHODS:A consecutive series of patients who experienced PUB between 2006 and 2012 was retrospectively analyzed.A total of 232 patients were enrolled in this study.The patients were divided into four groups according to the etiologies of PUB:idiopathic,H.pylori-associated,drug-induced and combined(H.pylori-associated and drug-induced)types.We compared the clinical characteristics and outcomes between the groups.When the silver stain or rapid urease tests were H.pylori-negative,we obtained an additional biopsy specimen by endoscopic re-examination and performed an H.pylori antibody test 6-8 wk after the initial endoscopic examination.For a diagnosis of idiopathic PUB,a negative result of an H.pylori antibody test was confirmed.In all cases,re-bleeding was confirmed by endoscopic examination.For the risk assessment,the Blatchford and the Rockall scores were calculated for all patients.RESULTS:For PUB,the frequency of H.pylori infection was 59.5%(138/232),whereas the frequency of idiopathic cases was 8.6%(20/232).When idiopathic PUB was compared to H.pylori-associated PUB,the idiopathic PUB group showed a higher rate of rebleeding after initial hemostasis during the hospital stay(30%vs 7.4%,P = 0.02).When idiopathic PUB was compared to drug-induced PUB,the patients in the idiopathic PUB group showed a higher rate of rebleeding after initial hemostasis upon admission(30%vs 2.7%,P < 0.01).When drug-induced PUB was compared to H.pylori-associated PUB,the patients in the drug-induced PUB were older(68.49 ± 14.76 years vs 47.83 ± 15.15 years,P< 0.01) and showed a higher proportion of gastric ulcer(77%vs 49%,P < 0.01).However,the Blatchford and the Rockall scores were not significantly different between the two groups.Among the patients who experienced drug-induced PUB,no significant differences were found with respect to clinical characteristics,irrespective of H.pylori infection.CONCLUSION:Idiopathic PUB has unique clinical characteristics such as re-bleeding after initial hemostasis upon admission.Therefore,these patients need to undergo close surveillance upon admission.

中蒙药对幽门螺杆菌的体外抑菌作用研究

目的筛选对幽门螺杆菌(H.pylori)具有抑菌作用的中蒙单药,构建新型抑菌方剂,探索中蒙药对H.pylori的治疗价值。方法取H.pylori标准菌株,常规体外培养;临床分离并培养H.pylori现症感染患者的H.pylori菌株,采用生化反应、H.pylori特异性基因检测进行鉴定。选取黄连、黄芩、大黄、丁香、鱼腥草、黄芪、茯苓、三七、生姜、苦参、诃子、蒲公英分别对H.pylori标准和临床菌株进行药敏试验,采用十字测量法测量抑菌圈直径,直径15~20 mm为高敏、直径10~14 mm为中敏。根据上述药敏试验,选取敏感药物构建新型组方,然后采用药敏试验、浓度梯度试验、尿素酶浓度测定试验评估新型组方的抑菌作用。选取阿莫西林、克拉霉素、甲硝唑、左氧氟沙星、利福平、四环素、庆大霉素、呋喃唑酮对H.pylori临床菌株进行药敏试验,分析耐药情况及耐药患者H.pylori菌株对新型组方的敏感性。结果H.pylori标准菌株对蒲公英、诃子高敏,对丁香、大黄中敏;H.pylori临床菌株对蒲公英高敏,对鱼腥草、三七、苦参、黄芩、黄连、黄芪、诃子、丁香、大黄、生姜中敏。其中蒲公英、诃子、丁香、大黄对H.pylori标准和临床菌株均具有较好抑菌作用,且蒲公英作用最强。构建的新型组方命名为半夏益胃颗粒,包括清半夏15 g、黄连6 g、黄芩10 g、干姜10 g、党参10 g、炙甘草6 g、大枣15 g、诃子10 g、丁香6 g、三七粉6 g、蒲公英30 g、百合30 g、乌药10 g、鱼腥草10 g、海螵蛸15 g。有6例H.pylori临床菌株对半夏益胃颗粒高敏,3例H.pylori临床菌株及标准菌株对半夏益胃颗粒中敏。半夏益胃颗粒最小抑菌浓度为0.5 g/mL,此浓度半夏益胃颗粒应用后,H.pylori标准和临床菌株分泌的尿素酶浓度较应用前明显降低(P均<0.05)。H.pylori临床菌株抗生素耐药情况:甲硝唑7例、左氧氟沙星4例、克拉霉素3例、呋喃唑酮1例、阿莫西林1例;半夏益胃颗粒对甲硝唑、左氧氟沙星耐药H.pylori临床菌株的药敏试验均为高敏。结论蒲公英、诃子、丁香、大黄对H.pylori标准和临床菌株均具有较好抑制作用;新组方半夏益胃颗粒对H.pylori标准和临床菌株抑制作用明显,对有些抗生素耐药的H.pylori临床菌株也有抑制作用,有望成为根除H.pylori的辅助药物。

黄连素+四联疗法治疗幽门螺杆菌阳性消化性溃疡的临床效果分析

目的探究黄连素(别称:盐酸小檗碱)与四联疗法联合用药方案治疗幽门螺杆菌(Hp)阳性消化性溃疡的临床效果,为临床医师选择合理用药方案提供参考。方法204例Hp阳性消化性溃疡患者为研究对象,采用随机数字表法分为对照组和观察组,每组102例。对照组患者接受常规四联疗法治疗,观察组采用黄连素与四联疗法联合治疗。比较两组患者症状改善时间、Hp清除率及复发率、临床治疗效果、不良反应发生率。结果观察组患者反酸、嗳气、腹痛消失时间与溃疡愈合时间分别为(2.95±0.51)、(3.85±0.44)、(5.65±0.88)、(8.74±0.85)d,较对照组的(4.35±0.85)、(6.85±0.61)、(7.51±1.38)、(12.45±1.28)d短(P<0.05)。观察组患者Hp清除率及复发率分别为96.1%、3.9%,对照组患者分别为80.4%、17.6%,两组比较,观察组患者Hp清除率高,复发率低(P<0.05)。观察组患者治疗总有效率为98.0%,对照组为90.2%,两组比较,观察组较高(P<0.05)。观察组患者不良反应发生率为2.0%(2/102),与对照组的3.9%(4/102)比较无差异(P>0.05)。结论对Hp阳性消化性溃疡患者实施四联疗法治疗时联合黄连素可以快速改善临床症状,提升治疗效果,同时还能提高Hp清除率,降低复发率,值得推广。

克拉霉素致急性短暂性抑郁症不良反应1例分析

目的分析使用克拉霉素致急性短暂性抑郁的不良反应,为临床使用提出预警并及早处置提供参考。方法对1例29岁女性患者应用四联方案(阿莫西林、克拉霉素、泮托拉唑、枸橼酸铋钾)根治幽门螺杆菌感染引起急性短暂性抑郁症进行分析。结果考虑是四联抗幽门螺杆菌感染药物导致的急性短暂性抑郁症,循证学证据表明克拉霉素可能是最易引起急性短暂性抑郁的药物。结论在使用根治幽门螺杆菌感染药物时,医务人员需密切关注患者的情绪变化,若发生急性短暂性抑郁症及时停药,防止患者症状进一步加重。

非甾体类抗炎药对慢性萎缩性胃炎的影响及应对策略

目的探讨非甾体类抗炎药(NSAIDs)对慢性萎缩性胃炎(CAG)患者胃黏膜损伤的影响,并评估针对该影响的应对策略的有效性。方法自2019年至2024年2月,纳入了120名经胃镜及病理确诊为慢性萎缩性胃炎的患者,随机分为对照组(n=60)和试验组(n=60)。对照组仅接受常规治疗,而试验组则在常规治疗基础上继续服用NSAIDs。主要观察指标包括胃黏膜萎缩程度、幽门螺杆菌根除率、症状积分及生活质量评估。随访期为12个月,定期记录上述指标变化。结果经过12个月治疗,对照组胃黏膜萎缩评分显著降低至1.34±0.26(P<0.001),而试验组评分仅轻微下降至2.21±0.39(P>0.05),组间差异显著(P<0.05)。对照组幽门螺杆菌根除率为83.33%(50/60),试验组为66.67%(40/60),差异具有统计学意义(x^(2)=4.23,P<0.05)。对照组症状积分从基线时的6.52±1.28降至2.15±0.87(P<0.05),试验组则从6.48±1.32降至4.27±1.14(P<0.05),组间差异显著(P<0.05)。对照组SF-36量表评分从62.45±7.89提升至85.67±6.43(P<0.05),试验组从63.12±8.04提升至74.32±7.56(P>0.05),组间差异同样显著(P<0.05)。结论本研究表明,长期使用NSAIDs显著加剧了CAG患者的胃黏膜萎缩程度,降低了幽门螺杆菌根除率,并影响了症状缓解及生活质量的改善。

宿主因素对幽门螺杆菌感染患者菌株耐药性的影响

目的分析影响幽门螺杆菌(Helicobacter pylori,Hp)耐药性的宿主因素。方法连续招募2021年11月—2023年10月于南京医科大学附属苏州医院就诊的Hp感染患者为研究对象。取内镜活检标本进行病理诊断、Hp菌株培养和药敏检测,并通过电子病历及问卷收集、纳入19项涉及患者基本资料、生活方式、饮食习惯、健康状况的指标,采用Logistic回归法评估宿主因素与Hp菌株对克拉霉素、左氧氟沙星、阿莫西林、呋喃唑酮、四环素、甲硝唑6种抗菌药物耐药性的相关性。结果共入选符合纳入与排除标准的Hp感染患者115例(Hp菌株115株)。其中男性53例(46.09%)、女性62例(53.91%),平均年龄(45.16±13.39)岁。胃镜病理:浅表性胃炎86例(74.78%),萎缩性胃炎6例(5.22%),肠上皮化生14例(12.17%),低级别上皮内瘤变6例(5.22%),高级别上皮内瘤变/胃癌3例(2.61%)。Hp菌株对抗菌药物的耐药率由高至低分别为甲硝唑(91.30%,105/115)、左氧氟沙星(53.04%,61/115)、克拉霉素(51.30%,59/115),未发现对阿莫西林、呋喃唑酮、四环素耐药菌株。双重耐药:左氧氟沙星+甲硝唑双重耐药率为50.43%(58/115),克拉霉素+甲硝唑双重耐药率为47.83%(55/115),克拉霉素+左氧氟沙星双重耐药率为36.52%(42/115)。多重耐药:克拉霉素+左氧氟沙星+甲硝唑三重耐药率为34.78%(40/115)。多因素Logistic回归分析结果显示(由于无对甲硝唑敏感毒株,多因素分析未纳入该药物),既往Hp根除史(OR=74.782,95%CI:10.377~538.886,P<0.001)、家庭饮用水来源为自来水(OR=4.919,95%CI:1.160~20.859,P=0.031)可增加菌株对克拉霉素的耐药风险,年龄≥50岁可增加菌株对左氧氟沙星的耐药风险(OR=4.261,95%CI:1.420~12.785,P=0.010),既往Hp根除史(OR=5.855,95%CI:2.209~15.517,P<0.001)、年龄40~59岁(OR=3.269,95%CI:1.254~8.520,P=0.015)可增加菌株对克拉霉素+左氧氟沙星双重耐药的风险。结论南京医科大学附属苏州医院Hp感染患者分离培养的菌株对甲硝唑、左氧氟沙星、克拉霉素的耐药率较高,且双重耐药、多重耐药现象突出。年龄、既往Hp根除史、家庭饮用水来源可能与克拉霉素、左氧氟沙星单药或双重耐药具有相关性。临床在进行Hp根除时,应综合考量,合理选择抗菌药物,个体化制订治疗方案。

西藏自治区人民医院实施国家重点监控药品干预成效分析

目的:评价西藏自治区人民医院对重点监控药品进行重点干预的成效,为优化重点监控药品干预策略、促进临床合理用药提供参考。方法:西藏自治区人民医院于2020年制订《西藏自治区人民医院重点监控药品管理规定》,建立《西藏自治区人民医院重点监控药品目录》,同时开展重点监控药品处方及医嘱专项点评、采取点评结果公示及绩效考核挂钩等目标性干预措施,对比西藏自治区人民医院2019年4月-2020年3月(干预前)与2020年4月-2021年3月(干预后第一年)及2021年4月-2022年3月(干预后第二年)重点监控药品临床使用数据变化,评价重点干预措施对该类药品的管理成效及临床使用的影响。结果:该院干预后第一年及第二年的重点监控药品销售金额分别为1427.01万元、1388.12万元,低于干预前的2004.29万元;干预后重点监控药品销售金额占药品总销售金额比例分别为8.33%、7.47%,低于干预前的10.11%。重点监控药品各品种的DDC普遍较高,患者的经济负担较重。结论:西藏自治区人民医院重点监控药品的干预取得了一定成效,但医院应在此基础上采取有力措施,提高重点监控药品合理使用,进一步减轻患者经济负担。

黄连素在抑制幽门螺杆菌多重耐药中的作用研究

目的 研究黄连素抑制幽门螺杆菌(Hp)多重耐药(MDR)株对常用抗菌药物耐药性的作用。方法 采用E-test法检测临床分离Hp菌株的耐药性,从中筛选出双重耐药(DR)株和MDR株;通过抗菌药物浓度两倍递增法对DR株进行体外诱导耐药;采用倍比稀释法检测黄连素对MDR株的最小抑菌浓度(MIC);在黄连素1/2 MIC浓度下连续传代培养MDR菌株,分别在培养1代和5代后检测对应抗菌药物的MIC值变化。结果 (1)共成功分离出128株Hp菌株,根据药敏试验筛选出DR株30株,MDR株12株,阿莫西林(AMX)、左氧氟沙星(LEV)、克拉霉素(CLR)、甲硝唑(MTZ)的耐药率分别为4.7%、26.6%、32.0%、64.8%,分离株中的MDR率为9.4%。(2)体外成功诱导MDR株24株,AMX诱导失败,其中MTZ诱导株的耐药水平最高,CLR次之,LEV最低;(3)黄连素对36株MDR株有明显的抑菌作用,MIC值范围为8~128μg/mL,大部分集中在32μg/mL;(4)选取的27株高水平耐药MDR株,经黄连素作用后共有17株的MIC值降低4倍及以上或逆转为敏感株,其中分别有9株、11株、5株对应CLR、LEV、MTZ的MIC值有阳性变化。在3种抗菌药物的阳性株中,MTZ组的MIC值下降倍数最高,CLR组居中,LEV组最低,3组比较差异有统计学意义(P<0.05)。结论 黄连素可有效逆转部分MDR株对常用抗菌药物的耐药性,且逆转程度与作用时间、抗菌药物种类有关。

幽门螺杆菌与胃肠微生物群相互作用及关系的研究进展

幽门螺杆菌(Hp)是慢性萎缩性胃炎、消化性溃疡、胃癌等消化道疾病的重要病因之一。Hp感染可以通过影响胃微环境及宿主免疫进而改变胃肠微生态的多样性及结构,而根除Hp的治疗可造成胃肠微生态短期紊乱,且不同的Hp根除治疗方案对肠道微生态的影响各不相同。本文仅就Hp与胃肠微生态的相互作用进行综述,以便为防治Hp感染提供参考。

脂质体亚麻酸LipoLLA对幽门螺杆菌的体外抑菌作用研究

目的本研究旨在探索脂质体亚麻酸(LipoLLA)对幽门螺杆菌(HP)的抑菌作用,为LipoLLA治疗幽门螺杆菌感染的临床应用提供理论依据。方法本研究收集了50例幽门螺杆菌菌株,通过微量肉汤稀释法检测LipoLLA和阿莫西林(AMX)、甲硝唑(MTZ)、左氧氟沙星(LVFX)、克拉霉素(CAM)4种抗生素单独使用或联合使用对幽门螺杆菌的最低抑制浓度(MIC)。通过抑菌曲线评估LipoLLA在不同浓度、时间和pH值条件下的抑菌活性。检测LipoLLA处理后培养基上清液中的天冬氨酸转氨酶(AST)、葡萄糖(GLU)和三磷酸腺苷(ATP)水平,以探究其抑菌作用机制。结果LipoLLA的MIC范围为3.750~15.000μg/mL,并与4种抗生素(AMX、MTZ、LVFX和CAM)联合使用时呈现协同抑菌效果。LipoLLA的抑菌效果受浓度、时间和pH值的影响。LipoLLA处理后幽门螺杆菌外膜屏障被破坏,培养基中AST、GLU和ATP水平的上升。结论LipoLLA通过破坏幽门螺杆菌外膜屏障杀灭细菌,具有较好的抑菌作用,并且能与传统抗生素联合使用,提高对幽门螺杆菌的抑菌效果。

超细胃镜结合京都胃炎分类在幽门螺杆菌感染中的应用及其药敏结果分析

目的分析白光内镜下各种胃黏膜形态改变,评价其在我国H.pylori相关性胃炎人群中的诊断及应用价值。方法纳入同时行超细胃镜检查、^(14)C尿素呼气试验、组织病理学检查、H.pylori抗体患者共232例,采用京都胃炎分类的诊断标准,计算患者京都胃炎评分,分析内镜下胃黏膜表现诊断H.pylori的准确性及诊断效能,并进行药敏试验。结果京都胃炎评分≥2分预测H.pylori感染准确率为90.09%,灵敏度为94.54%,特异度为73.47%。其中皱襞增宽肿大蛇行灵敏度较高,特异度较低;弥漫性发红、白浊黏液、点状发红灵敏度、特异度均较高;萎缩、黏膜水肿灵敏度、特异度均较低。萎缩、皱襞增宽肿大蛇行、结节、弥漫性发红、白色浑浊黏液、点状发红、黏膜水肿在H.pylori感染患者中占比显著高于未感染H.pylori患者(P<0.05)。萎缩、皱襞增宽肿大蛇行、结节、弥漫性发红、白色浑浊黏液、点状发红、黏膜水肿是H.pylori感染的危险因素(P<0.05)。在H.pylori培养阳性的110例标本中,阿莫西林、克拉霉素、甲硝唑、左氧氟沙星、四环素、呋喃唑酮的药物耐药率分别为9.09%、66.36%、81.82%、60.91%、0.91%、0。胃镜表现有萎缩、皱襞增宽肿大蛇行、结节、弥漫性发红、白色浑浊黏液、点状发红的患者出现甲硝锉耐药显著高于未出现以上胃镜表现患者(P<0.05)。结论超细胃镜结合京都胃炎分类可提高H.pylori检出率,治疗上可优先选择耐药率低的阿莫西林、呋喃唑酮、四环素可提高H.pylori根除率,超细胃镜结合京都胃炎分类可有效及时发现H.pylori耐药性。