Success of susceptibility-guided eradication of Helicobacter pylori in a region with high secondary clarithromycin and levofloxacin resistance rates

BACKGROUND Resistance to clarithromycin(CLA)and levofloxacin(LFX)of Helicobacter pylori(H.pylori)is increasing in severity,and successful eradication is essential.Presently,the eradication success rate has greatly declined,leaving a large number of patients with previous treatment histories.AIM To investigate secondary resistance rates,explore risk factors for antibiotic resistance,and assess the efficacy of susceptibility-guided therapy.METHODS We recruited 154 subjects positive for Urea Breath Test who attended The First Affiliated Hospital of China Medical University between July 2022 and April 2023.Participants underwent a string test after an overnight fast.The gastric juice was obtained and transferred to vials containing storage solution.Subsequently,DNA extraction and the specific DNA amplification were performed using quantitative polymerase chain reaction(qPCR).Demographic information was also analyzed as part of the study.Based on these results,the participants were administered susceptibility-guided treatment.Efficacy was compared with that of the empiric treatment group.RESULTS A total of 132 individuals tested positive for the H.pylori ureA gene by qPCR technique.CLA resistance rate reached a high level of 82.6%(n=109),LFX resistance rate was 69.7%(n=92)and dual resistance was 62.1%(n=82).Gastric symptoms[odds ratio(OR)=2.782;95%confidence interval(95%CI):1.076-7.194;P=0.035]and rural residence(OR=5.152;95%CI:1.407-18.861;P=0.013)were independent risk factors for secondary resistance to CLA and LFX,respectively.A total of 102 and 100 individuals received susceptibility-guided therapies and empiric treatment,respectively.The antibiotic susceptibility-guided treatment and empiric treatment groups achieved successful eradication rates of 75.5%(77/102)and 59.0%(59/411)by the intention-to-treat(ITT)analysis and 90.6%(77/85)and 70.2%(59/84)by the per-protocol(PP)analysis,respectively.The eradication rates of these two treatment strategies were significantly different in both ITT(P=0.001)and PP(P=0.012)analyses.CONCLUSION H.pylori presented high secondary resistance rates to CLA and LFX.For patients with previous treatment failures,treatments should be guided by antibiotic susceptibility tests or regional antibiotic resistance profile.

Optimizing clarithromycin-containing therapy for Helicobacter pylori in the era of antibiotic resistance

The efficacy of triple therapy for Helicobacter pylori infection has dramatically declined over the last decade,largely related to increasing clarithromycin resistance rates.From a microbiological standpoint,bismuth quadruple therapy is the ideal replacement since it combines drugs for which resistance does not impair its efficacy.Nonetheless,several obstacles such as availability,complexity or tolerance prevent a general implementation of bismuth quadruple therapy,so nonbismuth quadruple regimens remain the best firstline treatment in clinical practice in many geographical areas.We review the rationale and efficacy of several optimization tools(increasing the length of duration,high-dose acid suppression,probiotics),which have been largely evaluated over the last 5 years to increase the effectiveness of standard triple therapy.Then,we update available evidence on the effectiveness of several non-bismuth quadruple therapies(sequential,concomitant,hybrid,miscellaneous therapy),which have gained interest lately.We also revise evidence on the efficacy of the aforementioned optimization tools for non-bismuth quadruples schemes and,finally we provide a novel regionalized therapeutic algorithm,based on novel formulas recently developed for predicting the outcome of non-bismuth quadruple regimens,upon local antibiotic resistance rates.

Mechanisms of Helicobacter pylori antibiotic resistance:An updated appraisal

Helicobacter pylori(H. pylori) antibiotic resistance is the main factor affecting the efficacy of the current eradicating therapies. The aim of this editorial is to report on the recent information about the mechanisms accounting for the resistance to the different antibiotics currently utilized in H. pylori eradicating treatments. Different mechanisms of resistance to clarithromycin,metronidazole,quinolones,amoxicillin and tetracycline are accurately detailed(point mutations,redox intracellular potential,pump efflux systems,membrane permeability) on the basis of the most recent data available from the literature. The next hope for the future is that by improving the knowledge of resistance mechanisms,the elaboration of rational and efficacious associations for the treatment of the infection will be possible. Another auspicious progress might be the possibility of a cheap,feasible and reliable laboratory test to predict the outcome of a therapeutic scheme.

Helicobacter pylori isolates from ethnic minority patients in Guangxi:Resistance rates,mechanisms,and genotype

AIM:To investigate the rate of Helicobacter pylori(H.pylori)resistance to clarithromycin among ethnic minority patients in Guangxi,explore the underlyingmechanisms,and analyze factors influencing genotype distribution of H.pylori isolates.METHODS:H.pylori strains were isolated,cultured and subjected to drug sensitivity testing.The 23S rRNA gene of H.pylori isolates was amplified by PCR and analyzed by PCR-RFLP and direct sequencing to detect point mutations.REP-PCR was used for genotyping of H.pylori isolates,and NTsys_2 software was used for clustering analysis based on REP-PCR DNA fingerprints.Factors potentially influencing genotype distribution of H.pylori isolates were analyzed.RESULTS:The rate of clarithromycin resistance was31.3%.A2143G and A2144G mutations were detected in the 23S rRNA gene of all clarithromycin-resistant H.pylori isolates.At a genetic distance of 78%,clarithromycin-resistant H.pylori isolates could be divided into six groups.Significant clustering was noted among H.pylori isolates from patients with peptic ulcer or gastritis.CONCLUSION:The rate of clarithromycin resistance is relatively high in ethnic minority patients in Guangxi.Main mechanisms of clarithromycin resistance are A2143G and A2144G mutations in the 23S rRNA gene.Clarithromycin-resistant H.pylori isolates can be divided into six groups based on REP-PCR DNA fingerprints.Several factors such as disease type may influence the genotype distribution of H.pylori isolates.

Molecular detection of Helicobacter pylori antibiotic resistance in stool vs biopsy samples

AIM To compare(1) demographics in urea breath test(UBT) vs endoscopy patients; and(2) the molecular detection of antibiotic resistance in stool vs biopsy samples.METHODS Six hundred and sixteen adult patients undergoing endoscopy or a UBT were prospectively recruited to the study. The Geno Type Helico DR assay was used to detect Helicobacter pylori(H. pylori) and antibiotic resistance using biopsy and/or stool samples from CLOpositive endoscopy patients and stool samples from UBT-positive patients. RESULTS Infection rates were significantly higher in patients referred for a UBT than endoscopy(overall rates: 33% vs 19%; treatment-na?ve patients: 33% vs 14.7%, respectively). H. pylori-infected UBT patients were younger than H. pylori-infected endoscopy patients(41.4 vs 48.4 years, respectively, P < 0.005), with a higher percentage of H. pylori-infected males in the endoscopy-compared to the UBT-cohort(52.6% vs 33.3%, P = 0.03). The Geno Type Helico DR assay was more accurate at detecting H. pylori infection using biopsy samples than stool samples [98.2%(n = 54/55) vs 80.3%(n =53/66), P < 0.005]. Subset analysis using stool and biopsy samples from CLO-positive endoscopy patients revealed a higher detection rate ofresistance-associated mutations using stool samples compared to biopsies. The concordance rates between stool and biopsy samples for the detection of H. pylori DNA, clarithromycin and fluoroquinolone resistance were just 85%, 53% and 35%, respectively. CONCLUSION Differences between endoscopy and UBT patients provide a rationale for non-invasive detection of H. pylori antibiotic resistance. However, the Geno Type Helico DR assay is an unsuitable approach.

主要 clarithromycin 抵抗到 Helicobacter pylori : 这是为三倍的治疗失败的主要原因？

Conventional triple therapies for Helicobacter pylori (H. pylori ) eradication have recently shown a disappointing reduction in effectiveness in many countries. The main reason for failure was found to be bacterial resistance to one of the most commonly used antibiotics, clarithromycin. An additional problem for conventional triple therapy is the high rate of resistance to metronidazole found in Europe, America and Asia. In Italy, in the last 15 years a 2-fold increase in resistance has occurred. A recent study of the whole of Italy included about 20 patients from each region at the first endoscopic diagnosis of H. pylori infection. The most surprising result was the patchy distribution of resistance, which was almost absent in two regions (one northern and one southern), although the highest prevalence was found in some regions of the South. In the paediatricpopulation we found a 25% prevalence of resistance in a sample of H. pylori positive children observed between 2002 and 2007, mirroring data obtained in southern European countries. Clarithromycin resistance assessment is currently based on phenotypic detection performed after culture the agar dilution method or E-test, and genotypic methods based on polymerase chain reaction (PCR). In a recent comparative study we found a 71.2% agreement between the two methods. Culture-free techniques are highly accurate in finding even minimal traces of genotypically resistant strains. Moreover, PCR-based tools are accurate in detecting a heteroresistant status, defined as the co-existence of some strains that are susceptible and some resistant to the same antibiotic in an individual patient. Three point mutations, namely A2143G , A2142G and A2142C , are responsible for 90% of cases of primary clarithromycin resistance in H. pylori strains isolated in Western countries, although we previously demonstrated that the presence of the A2143G mutation, but not A2142G or A2142C , significantly lowered the H. pylori eradication rate. Treatment failure has considerable cost/benefit implications because of 'waste' of National Health System and patient resources, in terms of drugs, further diagnostic tests and medical examination expenses. Therefore, in future it would be very useful to be able to test for clarithromycin resistance before starting conventional triple therapy. Hopefully, fast, effective noninvasive tests may soon be devised to determine this condition.

Resistance of Helicobacter pylori to antibiotics from 2000 to 2009 in Shanghai

AIM: To investigate the resistance of Helicobacter pylori (H. pylori ) to 6 commonly used antibiotics from 2000 to 2009 in Shanghai. METHODS: A total of 293 H. pylori strains were collected from 2000 to 2009 in Shanghai and tested for their susceptibility to metronidazole, clarithromycin, amoxicillin, furazolidone, levofloxacin and tetracycline using agar dilution. RESULTS: The resistant rates of H. pylori to clarithromycin (8.6%, 9.0% and 20.7%) and levofloxacin (10.3%, 24.0% and 32.5%) increased from 2000 to 2009 in Shanghai. The resistant rate of H. pylori to metronidazole remained stable (40%-50%). Only one strain of H. pylori isolated in 2005 was resistant to tetracycline. All strains were sensitive to amoxicillin and furazolidone.The resistant rate of H. pylori to antibiotics was not related with the sex, age and clinical outcome of patients. CONCLUSION: Resistance of H. pylori to antibiotics plays an important role in making treatment strategies against H. pylori -associated diseases.

Antibiotic resistance and cagA gene correlation:A looming crisis of Helicobacter pylori

AIM:To determine antibiotic resistance of Helicobacter pylori(H.pylori) in Pakistan and its correlation with host and pathogen associated factors.METHODS:A total of 178 strains of H.pylori were isolated from gastric biopsies of dyspeptic patients.Susceptibility patterns against first and second-line antibiotics were determined and trends of resistance were analyzed in relation to the sampling period,gastric conditions and cagA gene carriage.The effect of cagA gene on the acquisition of resistance was investigated by mutant selection assay.RESULTS:The observations showed that monoresistant strains were prevalent with rates of 89% for metronidazole,36% for clarithromycin,37% for amoxicillin,18.5% for ofloxacin and 12% for tetracycline.Furthermore,clarithromycin resistance was on the rise from 2005 to 2008(32% vs 38%,P = 0.004) and it is significantly observed in non ulcerative dyspeptic patients compared to gastritis,gastric ulcer and duodenal ulcer cases(53% vs 20%,18% and 19%,P = 0.000).On the contrary,metronidazole and ofloxacin resistance were more common in gastritis and gastric ulcer cases.Distribution analysis and frequencies of resistant mutants in vitro correlated with the absence of cagA gene with metronidazole and ofloxacin resistance.CONCLUSION:The study confirms the alarming levels of antibiotic resistance associated with the degree of gastric inflammation and cagA gene carriage in H.pylori strains.

Can bacterial virulence factors predict antibiotic resistant Helicobacter pylori infection?

AIM To evaluate the association between virulence factor status and antibiotic resistance in Helicobacter pylori(H. pylori)-infected patients in Ireland. METHODS DNA was extracted from antral and corpus biopsies obtained from 165 H. pylori-infected patients. Genotyping for clarithromycin and fluoroquinolone-mediating mutations was performed using the Genotype Helico DR assay. cag A and vac A genotypes were investigated using PCR. RESULTS Primary, secondary and overall resistance rates for clarithromycin were 50.5%(n = 53/105), 78.3%(n = 47/60) and 60.6%(n = 100/165), respectively. Primary, secondary and overall resistance rates for fluoroquinolones were 15.2%(n = 16/105) and 28.3%(n = 17/60) and 20%(n = 33/165), respectively. Resistance to both antibiotics was 12.4%(n = 13/105) in treatment-na?ve patients, 25%(n = 15/60) in those previously treated and 17%(n = 28/165) overall. A cag A-positive genotype was detected in 22.4%(n = 37/165) of patient samples. The dominant vac A genotype was S1/M2 at 44.8%(n = 74/165), followed by S2/M2 at 26.7%(n = 44/165), S1/M1 at 23.6%(n = 39/165) and S2/M1 at 4.8%(n = 8/165). Primary clarithromycin resistance was significantly lower in cag A-positive strains than in cag A-negative strains [32%(n = 8/25) vs 56.3%(n = 45/80); P = 0.03]. Similarly, in patients infected with more virulent H. pylori strains bearing the vac A s1 genotype, primary clarithromycin resistance was significantly lower than in those infected with less virulent strains bearing the vac A s2 genotype, [41%(n = 32/78) vs 77.8%(n = 21/27); P = 0.0001]. No statistically significant association was found between primary fluoroquinolone resistance and virulence factor status.CONCLUSION Genotypic H. pylori clarithromycin resistance is high and cag A-negative strains are dominant in our population. Less virulent(cag A-negative and vac A S2-containing) strains of H. pylori are associated with primary clarithromycin resistance.

He/icobacter py/ori infection in hemodialysis patients: Susceptibility to amoxicillin and clarithromycin

AIM: To evaluate susceptibility of Helicobacter pylori to amoxicillin and clarithromycin in end-stage renal disease (ESRD) patients and non-uremic controls.METHODS: The subjects with dyspeptic complaints were 33 ESRD patients and 46 age- and sex-matched nonuremic controls who exhibited H pylori on antral biopsy specimens. The two groups were age and sex matched.The H pylori strains' pattern of susceptibility to amoxicillin and clarithromycin was investigated with the agar dilution technique.RESULTS: None of the H pylori strains from either group showed resistance to amoxicillin with the agar dilution method. Twelve (36.4%) of the ESRD group strains and 7 (15.2%) of the control group strains showed resistance to clarithromycin, and this difference was statistically significant (P＜0.05).CONCLUSION: Resistance to amoxicillin does not appear to be an important problem in H pylori-infected ESRD and non-uremic patients in our region. In contrast, the rates of resistance to clarithromycin are high, particularly in the ESRD population.

108株幽门螺杆菌(Hp)菌株的耐药分析及其对Hp根除的影响

目的：了解北京地区幽门螺杆菌（Ｈｐ）的临床耐药情况以及耐药菌株对Ｈｐ根除治疗的影响。方法：对１０８例Ｈｐ阳性患者的临床分离株，采用Ｅ－ｔｅｓｔ方法测定幽门螺杆菌对甲硝唑、克拉霉素和阿莫西林的敏感性；并用７ｄ三联疗法或３ｄ四联疗法分别对其中４１位十二指肠溃疡患者予幽门螺杆菌根除治疗。结果：１０８株幽门螺杆菌菌株中，对甲硝哇耐药率为３７．０％，对克拉霉素耐药率为１３．０％，对其中１８株幽门螺杆菌菌株进行了阿莫西林的药物敏感试验，发现 １例耐药，７ｄ疗法和３ｄ疗法对幽门螺杆菌敏感株的根除率分别为９１．７％及８０．０％，耐药株的根除率分别为４０．０％及２５．０％。结论：幽门螺杆菌对甲硝唑、克拉霉素和阿莫西林均有耐药出现，其中以甲硝唑耐药率最高，克拉霉素的耐药率也呈增高趋势，耐药菌株的出现是导致幽门螺杆菌根除治疗失败的主要原因之一。

幽门螺杆菌临床菌株克拉霉素耐药性及耐药基因突变位点分析

目的检测贵阳地区幽门螺杆菌(Helicobacter pylori,Hp)临床菌株对克拉霉素耐药性及相关基因突变情况。方法采用琼脂稀释法对临床分离鉴定的Hp菌株,进行体外抗生素敏感试验,选取Hp克拉霉素耐药的临床菌株10株、克拉霉素敏感的临床菌株4株和质控菌株2株,进行23SrRNA基因功能区V区片段的PCR扩增和测序,与GenBank中公布的Hp菌株相关序列进行比对分析。结果贵阳地区Hp临床分离株对克拉霉素的耐药率达30.9%(13/42)。贵阳地区10株Hp耐药菌的23SrRNA基因片段的碱基突变包括T2183C(10/10)、T2245C(9/10)、A2144G(6/10)、C2196T(1/10)、A2224G(1/10),4株敏感菌株在2183、2196、2224和2245位点也存在碱基差异,2144位点的基因突变仅存于耐药菌株中。结论贵阳地区Hp克拉霉素耐药率较高,耐药菌株23SrDNA与耐药性相关的基因突变主要为A2144G。

淮南地区幽门螺杆菌对克拉霉素耐药性及其耐药分子机制的研究

目的探讨淮南地区幽门螺杆菌(Helimbacter pylori,Hp)对克拉霉素耐药情况及其耐药分子机制。方法用E-test和琼脂稀释法进行克拉霉素药敏试验,提取Hp基因组DNA,PCR扩增Hp 23S rRNA基因,并用PCR-限制性片段长度多态性(RFLP)分析克拉霉素耐药机制。结果淮南地区克拉霉素耐药率为9.15%(27/141),克拉霉素耐药与性别、年龄无关。PCR从Hp基因组DNA中扩增出425bp的Hp 23S rRNA基因,PCR-RFLP检测,27株耐药菌株均可被Bbsl酶切成332、93bp两个片段,未检测到被BsaⅠ酶切的耐药菌株。结论淮南地区克拉霉素耐药率较高,耐药菌株存在23S rRNA基因功能区V2143位点A-G突变。

2017 IHPWG共识:爱尔兰成人幽门螺杆菌感染的诊断和治疗

目前,爱尔兰人群幽门螺杆菌(Helicobacter pylori,H.pylori)根除率不断下降,其耐药菌发生率逐年增加,这一趋势引起研究者对当前H.pylori管理策略的质疑。成立爱尔兰幽门螺杆菌工作组(Irish Helicobacter pylori Working Group,IHPWG)并评估、修订和调整现有推荐建议。邀请胃肠病学和微生物学领域专家参加IHPWG。采用PICO方法提出与诊断、一线和补救治疗相关的问题,并进行文献检索。然后,使用"证据推荐分级的评估、制订与评价"方法对有效证据的质量进行评估,并对推荐结果进行分级。IHPWG关键陈述(Statements,S)如下,S8:不再推荐持续7 d的标准三联疗法(推荐强度:强;证据质量:中等)。S9:推荐14 d克拉霉素三联疗法与大剂量质子泵抑制剂联用作为一线疗法。如果可以,14 d铋剂四联疗法可作为替代疗法(推荐强度:强;证据质量:中等)。S12:二线疗法基于一线治疗而非相同治疗。方案a:14 d左氧氟沙星为基础治疗和大剂量质子泵抑制剂联合;b:14 d克拉霉素三联疗法和大剂量质子泵抑制剂联合;c:14 d铋剂四联疗法(推荐强度:强;证据质量:中等)。S13:两种治疗方案失败后应进行H.pylori培养和药敏试验(推荐强度:弱;证据质量:低或极低)。本文推荐意见旨在为爱尔兰成人H.pylori感染管理提供最相关、最佳的实践指南。

幽门螺杆菌抗生素耐药相关菌体因素的研究进展

幽门螺杆菌(Helicobacter pylori,H.pylori)感染是最广泛的慢性细菌感染,与许多疾病的发生发展密切相关.近年来,随着根除治疗的不断应用,H.pylori抗生素耐药率也不断增高,导致根除疗效不断下降.在众多导致耐药根除失败的原因中,H.pylori菌体自身的某些因素是最主要的原因.H.pylori可以通过产生灭活抗生素的灭活酶、改变药物作用的结合靶位、阻止氧化还原电位的电子传递、影响抗菌药物渗透屏障与主动外排机制、改变细菌自身代谢状态等途径耐药.明确H.pylori产生耐药的机制,有助于针对性的研发新药,从而有效地根除H.pylori.本文就目前报道与抗生素耐药有关的H.pylori菌体因素及其耐药相关分子机制的研究现状做一综述.

幽门螺杆菌耐药初探

目的:观察幽门螺杆菌(Helicobacter pylori,H.pylori)对克拉霉素、呋喃唑酮的耐药情况,初步了解克拉霉素耐药菌株为原发耐药还是继发耐药,初步探讨抗H.pylori感染失败的原因是由于原有菌株未消灭还是由于感染了新的菌株。方法:从消化性溃疡及糜烂性胃炎患者的胃黏膜中分离培养出H.pylori共21株,利用纸片法进行药物敏感试验,观察耐药情况。应用随机扩增多态性DNA分析方法,进行菌株指纹图谱分析,确定抗H.pylori治疗前后菌株的同一性。结果:(1)21株H.pylori中有8株对克拉霉素耐药,1株对呋喃唑酮耐药,耐药率分别为38.1%和4.8%。(2)3对治疗前后配对菌株中,1例为原发性耐药(持续感染),1例为继发性耐药,另有1例为新菌株感染。结论:H.pylori对克拉霉素耐药率比较高,而对呋喃唑酮高度敏感。抗H.pylori感染失败的原因与菌株对克拉霉素原发性及继发性耐药有关。

宁波地区幽门螺杆菌优势基因型及其与耐药性的关系

目的探讨宁波地区幽门螺杆菌(Hp)优势基因型及其与Hp耐药性的关系。方法选取宁波地区慢性胃炎和消化性溃疡患者的胃镜活检标本,对40株临床分离菌株,采用PCR法检测Hp的cagA、vacAm1、vacAm2、vacAs1a和babA2基因型;采用纸片扩散法作药敏试验。结果40株Hp中cagA、vacAm1、vacAm2、vacAs1a和babA2基因型的阳性率分别为100%、52.5%、85.5%、92.5%和57.5%;慢性胃炎和消化性溃疡患者中分离的Hp基因型的检出率差异均无显著性(>0.05);Hp对甲硝唑的耐药率高于阿奇霉素(<0.05),并显著高于阿莫西林和克拉霉素(<0.01);Hp的甲硝唑耐药株与敏感株之间cagA、vacA和babA2基因型分布差异无显著性(>0.05)。结论宁波地区慢性胃炎和消化性溃疡患者中分离的Hp以cagA、vacAm2、vacAs1a、babA2、vacAs1a/m2基因型为主。Hp基因亚型的确定尚不能对Hp根治疗法中抗生素的选择提供帮助。

幽门螺杆菌对抗生素的耐药机制进展研究

伴随幽门螺旋杆菌(Hp)根除治疗法的逐步推广与使用,医学界开始关注抗生素耐药性越发严重的情况,该耐药性已被发现对一些Hp治疗方法的根治率有不利影响。因此,对幽门螺旋菌耐药分子机制的钻研正成为国内外研究的热点话题。例如,硝基咪唑类(甲硝唑)的耐药机制和rdx A、Frx A基因突变有重要关系。大环内酯类(克拉霉素)的耐药机制和Hp中23Sr RNA里V区域的点突变存在密切关系。阿莫西林一类药物的耐药机制和青霉素结合蛋白存在关联。作为快速抑菌剂的四环素类的耐药机制和Hp16Sr RNA序列的突变有关联。对耐药机制的分类研究为Hp的进一步诊断及医治奠定了重要基础。

幽门螺杆菌对左氧氟沙星、克拉霉素耐药性及基因突变分析

目的分析幽门螺杆菌(Hp)对左氧氟沙星、克拉霉素的耐药表型及与耐药相关基因突变(基因型)的相关性,为临床制定Hp个体化根除治疗方案提供实验依据。方法分别选择2021年6月至12月和2018年8月至2019年3月在南京医科大学附属南京医院就诊的未经治疗的292例和350例Hp阳性患者的胃黏膜组织进行分离培养,用E-test药敏试验法检测左氧氟沙星、克拉霉素的耐药性,用卡方检验分析不同性别、年龄患者耐药表型的差异;用基因测序方法检测耐药相关基因型,并分析与耐药表型的一致性。结果在左氧氟沙星耐药性研究的292例病例中,有120例(41.10%)表型耐药,不同性别(P=0.031)、年龄(P<0.01)患者间耐药率差异均有统计学意义;耐药相关基因型中有123例(42.12%)突变,与表型的一致性很高(Kappa=0.951,P<0.01),且主要耐药基因gyrA的第87位突变与表型的一致性略高于第91位突变。在克拉霉素耐药性研究的350例病例中,有168例(48.00%)表型耐药,不同性别(P=0.165)、年龄(P=0.192)患者间耐药率差异均无统计学意义;耐药相关基因型中有182例(52.00%)突变,与表型的一致性较高(Kappa=0.795,P<0.01)。结论Hp对左氧氟沙星、克拉霉素的耐药率较高,且耐药相关基因型与表型的一致性都较高。在培养条件不够、培养失败或者要求时效性的情况下,临床医生可根据耐药相关基因型来预测表型,以制定Hp个体化根除的方案。

2020—2022年宁夏地区幽门螺杆菌对左氧氟沙星和克拉霉素耐药率和耐药基因的调查

目的探索宁夏地区幽门螺杆菌(Hp)对左氧氟沙星和克拉霉素耐药率及耐药基因的常见突变方式,评估其表型与基因型耐药的一致性。方法横断面研究。回顾性选取2020年2月至2022年5月宁夏地区14家医院确诊为Hp感染的患者。从Hp感染患者的胃活检标本中分离到Hp菌株,进行表型药敏试验和耐药基因的检测,分析宁夏地区Hp对左氧氟沙星和克拉霉素耐药率及耐药基因常见突变方式;采用符合率和Kappa系数评估表型与基因型耐药的一致性。结果共分离培养1942株Hp,感染者中,男1069例(55.0%),女873例(45.0%),年龄(50.0±12.5)岁(15~86岁)。宁夏地区Hp对左氧氟沙星和克拉霉素耐药率分别为42.1%(818/1942)和40.1%(779/1942),双重耐药率为22.8%(443/1942)。其中来自女性患者的Hp菌株对左氧氟沙星和克拉霉素耐药率均较男性高(左氧氟沙星:50.4%(440/873)比35.4%(378/1069);克拉霉素:44.4%(388/873)比36.6%(391/1069),均P<0.001)。与左氧氟沙星耐药有关的GyrA基因突变中,除了Asn87Thr外,第87和91位氨基酸突变率在耐药菌株和敏感菌株间的差异均有统计学意义(均P<0.001)。Hp菌株对左氧氟沙星(Kappa=0.834,P<0.001)和克拉霉素(Kappa=0.829,P<0.001)的耐药性在表型和基因型上具有良好的一致性。结论宁夏地区Hp对左氧氟沙星和克拉霉素的耐药严重,基因型和表型耐药具有良好的一致性。