幽门螺杆菌抗生素耐药趋势研究：2000年到2009年 中国上海

The Evolution of Helicobacter pylori Antibiotics Resistance Over 10Years in Beijing,China

Wen Gao,*,1Hong Cheng,*,1Fulian Hu,*Jiang Li,*Lihui Wang,*Guibin Yang,?Le Xu?and Xiaoli Zheng?

*Department of Gastroenterology,Peking University First Hospital,Beijing,China,?Department of Gastroenterology,Aerospace Clinical College of Peking University,Beijing,China,?Department of Gastroenterology,Beijing Hospital,Beijing,China

Helicobacter pylori is a Gram-negative?agellated spiral bacteria.Infection with H.pylori is mainly acquired in childhood.H.pylori infection is recognized as a causal factor in the pathogenesis of chronic gastritis,peptic ulcer,gastric cancer,and gastric MALT lymphoma.

H.pylori eradication treatment is indicated in patients with peptic ulcer disease,MALToma,atrophic gastritis, post-gastric cancer resection,or patients who are?rst-degree relatives of patients with gastric cancer[1]. Among numerous eradication regimens,a proton pump inhibitor and combination of two antibiotics(amoxicil-lin,clarithromycin,and metronidazole)are considered to be the most effective and?rst-line therapy regimens recommended by Maastricht III Consensus and in China[1,2].However,antibiotic resistance of H.pylori, especially to clarithromycin and metronidazole, strongly undermined the ef?cacy of eradication treat-ment.The reported frequencies of resistance to anti-biotics varied widely between geographic regions.A European study involving17countries and1274H.pylori isolates showed a mean resistance rate(deter-mined by E-test)to amoxicillin0.8%;to clarithromycin 9.9%;and to metronidazole33.1%[3].Another recent study from French examined530H.pylori strains iso-lates from2004to2007,among those,26%(138?530) strains were resistant to clarithromycin,61% (324?530)to metronidazole,and13.2%(70?530)to cipro?oxacin,whereas no resistance against amoxicillin and tetracycline was observed[4].As culture-based antimicrobial susceptibility data are not always avail-able and the H.pylori eradication regimen especially antibiotics involved should be chosen based on local resistant epidemiologic data and an empirical basis,it is important to understand the regional antibiotics resis-tance status and trend of this bacterium.The aim of this study was to assess the prevalence of antibiotics (amoxicillin,clarithromycin,metronidazole,tetracy-cline,levo?oxacin,and moxi?oxacin)resistance of H.pylori strains isolated from Beijing in recent 10years.

Keywords

Helicobacter pylori,antibiotic resistance, amoxicillin,clarithromycin,metronidazole, tetracycline,levo?oxacin,moxi?oxacin.

Reprint requests to:Fulian Hu,Professor, Department of Gastroenterology,Peking University First Hospital,Beijing100034, China.E-mail:hufulian@https://www.wendangku.net/doc/9b12789439.html,

1These authors contributed equally to the study.

Supported by Beijing Medicine Research and Development Fund(No.2005-1008).Abstract

Objectives:To evaluate Helicobacter pylori antibiotics resistance evolution from2000to2009to amoxicillin,clarithromycin,metronidazole,tetra-cycline,levo?oxacin and moxi?oxacin in Beijing,China.

Methods:A total of374H.pylori strains isolated from374subjects who had undergone upper gastrointestinal endoscopy from2000to2009were collected and examined by E-test method for antibiotics susceptibility. Results:The average antibiotics resistance rates were0.3%(amoxicillin), 37.2%(clarithromycin),63.9%(metronidazole),1.2%(tetracycline),50.3% (levo?oxacin)and61.9%(moxi?oxacin).Overall resistance to clarithro-mycin,metronidazole,and?uoroquinolone increased annually(from14.8 to65.4%,38.9to78.8%,and27.1to63.5%,in2000or2006–2007to 2009,respectively).The secondary resistance rates were much higher than primary rates to these antibiotics,which also increased annually in recent 10years.

Conclusions:The trend of clarithromycin,metronidazole,and?uoroquino-lone resistance of H.pylori increased over time and the resistance to amoxi-cillin and tetracycline was infrequent and stable in Beijing.Clarithromycin, metronidazole,and?uoroquinolone should be used with caution for H.pylori eradication treatment.

Helicobacter ISSN1523-5378

Materials and Methods

Patients and Isolation of H.pylori Strains Demographic and endoscopic data were recorded in each case.All patients were asked about previous H.pylori eradication therapy and antibiotics use for other infections.Patients who did not remember their previous antibiotics use or lacked prescription records were regarded as previously untreated group.

Three biopsy specimens were taken from gastric antrum from each patient,one for rapid urease test, one for histopathologically examination.One of the gastric mucosal biopsy specimen obtained from gastric antrum was grinded,planted,and primarily cultured on 8%de?brinated sheep blood with3.9%agar medium (Columbia Agar Base;Oxoid LTD,Basingstoke,Hamp-shire,UK)with0.5%trimethoprim,0.3%vancomycin, and0.2%amphotericin at37°C under microaerophilic conditions(5%O2,10%CO2,85%N2).Plates were incubated for at least3days,up to7days prior to passage.The bacterial strains obtained from primary culture were identi?ed as H.pylori strains by colony morphology,Gram’s stain,urease reaction,oxidase reaction,and catalase reaction.All strains were stored at)80°C in brain heart infusion broth(BHI;Difco Laboratory,Detroit,MI,USA)supplemented with30% glycerol.Before the antibiotics E-test,H.pylori strains were cultured for1–2passages on8%sheep blood with 3.9%agar medium at37°C under microaerophilic conditions.

A total of374H.pylori strains isolated from374 patients who had undergone upper gastrointestinal endoscopy in GI department of Peking University First Hospital,Aerospace Clinical College of Peking University and Beijing Hospital from2000to2009were collected and involved in antimicrobial susceptibility test.Determination of MIC for E-test

Although agar or broth dilution methods are estab-lished for standard susceptibility test for H.pylori,they are dif?cult to perform routinely and E-test has been widely performed and yielded reliable results equivalent to agar dilution method[5].In this study,all374 isolated H.pylori strains were cultured and performed E-test to identify the minimal inhibitory concentration (MIC)value to metronidazole,amoxicillin,clarithro-mycin,tetracycline,levo?oxacin,and moxi?oxacin (E-test strips from AB Biodisk,Solna,Sweden).

The H.pylori strains were considered amoxicillin, clarithromycin,metronidazole,tetracycline,levo?oxa-cin and moxi?oxacin resistant with MICs?1,?1,?8,?1,?1,?1mg?L,respectively[6].

Results

The374patients consisted of213(57.0%)men and 161(43.0%)women,median age49years(range13–83years).Of the374subjects,290(77.5%)patients never received H.pylori eradication treatment before, while84(22.5%)patients failed in their previous anti-H.pylori treatment once or more times.Endoscopic diagnosis showed that162patients had chronic gastri-tis,160had duodenal ulcer,36had gastric ulcer,8had both gastric and duodenal ulcer,7had gastric cancer, and1had gastric MALToma(Table1).

Annual prevalence rates of overall,primary and secondary antibiotic resistance rates of H.pylori strains to amoxicillin,clarithromycin,and metronidazole were showed in Table2,resistant rates to tetracycline, levo?oxacin and moxi?oxacin were shown in Table3. The resistance status to tetracycline,levo?oxacin and moxi?oxacin was not examined until the year of2006–2007and2008.The trend of resistance prevalence to

Table1General data of the374subjects

Year Total Gender Treatment Diagnosis

N Male Female Untreated Treated G DU GU DU+GU Ga MALT

200054351947715343110 200171442763835278010 2002–2003271892257128000 2004–20052719824312105000 2006–200780423871936377631 2008633330392434225110 2009522230242833180010 Total374213(57%)161(43%)290(77.5%)84(22.5%)162(43.3%)160(42.8%)36(9.6%)8(2.1%)7(1.9%)1(0.3%)

M,male;F,female;G,gastritis;DU,duodenal ulcer;GU,gastric ulcer;DU+GU,duodenal ulcer+gastric ulcer;Ca,gastric cancer;MALT,gastric mucosa-associated lymphoid tissue lymphoma.

Gao et al.Evolution of H.pylori Antibiotics Resistance

clarithromycin,metronidazole and levo?oxacin was shown in Figs 1–3.

H.pylori resistance to amoxicillin was found in only one case in all 374strains (MIC =1mg ?L,0.27%),which was isolated from an untreated patient in the

year of 2000.This H.pylori strain was actually triply resistant to amoxicillin,clarithromycin and metronidazole.

The overall resistance rate to clarithromycin rose from 14.8%in 2000to 65.4%in 2009(Fig.1),while the primary resistance rate to clarithromycin was 12.8%in the year of 2000,rose to its peak of 38.5%in the year of 2006–2007and 2008,then decreased to 25%in 2009(Fig.2).Compared with primary resis-tance status,the secondary resistance rate dramatically increased from 28.6%(2?7)in 2000to 100%(28?28)in 2009(Fig.3).

Metronidazole resistance rate was relatively high with an average value of 63.9%(239?374),ranged from 38.9%in 2000to 78.8%in 2009,with a highest rate of 83.6%in 2007(Table 2,Fig.1).When it came to primary and secondary resistance rate,the latter was even higher.The peak primary resistance rate was 83.1%in 2006–2007,and then decreased a little to 66.7%in 2008and 2009(Fig.2).The secondary metro-nidazole resistance rate arrived 100%in the year of 2004–2005and 2008,with an average rate of 89.3%(Table 2,Fig.3).

Table 3Annual prevalence of antibiotic resistance of Helicobacter pylori strains to tetracycline,levo?oxacin,and moxi?oxacin from 2006to 2009

Primary Secondary Overall T

Le

Mx

T Le

Mx

T

Le

Mx

2006–20070?41(0)10?40(25.0)N ?C

1?8(12.5)3?8(37.5)N ?C

1?49(2.0)13?48(27.1)N ?C

20080?39(0)18?39(46.2)11?27(40.7)0?24(0)18?24(75.0)16?18(88.9)0?63(0)36?63(57.1)27?45(60.0)20091?24(4.2)10?24(41.7)10?24(41.7)0?28(0)23?28(82.1)23?28(82.1)1?52(1.9)33?52(63.5)33?52(63.5)Overall

1?104(1.0)

38?103(36.9)

21?51(41.2)

1?60(1.7)

44?60(73.3)

39?46(84.8)

2?164(1.2)

82?163(50.3)

60?97(61.9)

Values given in parentheses are percentages.T,tetracycline;Le,levo?oxacin;Mx,moxi?oxacin.

Table 2Annual prevalence of antibiotic resistance of Helicobacter pylori strains to amoxicillin,clarithromycin,and metronidazole from 2000to 2009

Primary Secondary Overall A

C

Mz

A C

Mz

A

C

Mz

20001?47(2.1)6?47(12.8)16?47(12.8)0?7(0)2?7(28.6)5?7(71.4)1?54(1.9)8?54(14.8)21?54(38.9)2001

0?63(0)8?63(12.7)20?63(12.7)0?8(0)4?8(50.0)6?8(75.0)0?71(0)12?71(16.9)26?71(36.6)2002–20030?22(0)2?22(9.1)12?22(9.1)0?5(0)4?5(80.0)4?5(80.0)0?27(0)6?27(22.2)16?27(59.3)2004–20050?24(0)5?24(20.8)17?24(20.8)0?3(0)3?3(100.0)3?3(100.0)0?27(0)8?27(29.6)20?27(74.1)2006–20070?71(0)27?71(38.0)57?71(38.0)0?9(0)8?9(88.9)8?9(88.9)0?80(0)35?80(43.8)65?80(81.3)20080?39(0)15?39(38.5)26?39(38.5)0?24(0)21?24(87.5)24?24(100.0)0?63(0)36?63(57.1)50?63(79.4)20090?24(0)6?24(25.0)16?24(25.0)0?24(0)28?28(100.0)25?28(89.3)0?52(0)34?52(65.4)41?52(78.8)Overall

1?290(0.3)

69?290(23.8)

164?290(56.6)

0?84(0)

70?84(83.3)

75?84(89.3)

1?374(0.3)

139?374(37.2)

239?374(63.9)

Values given in parentheses are percentages.

A,amoxicillin;C,clarithromycin;Mz,metronidazole.

Evolution of H.pylori Antibiotics Resistance Gao et al.

The resistance to tetracycline was infrequent.It hap-pened in one of forty-nine(2.0%)in2006–2007,zero of sixty-three in2008,and one of?fty-two(1.9%)in 2009(Table3).

It was reported that there was cross-resistance between levo?oxacin and moxi?oxacin.Although not all H.pylori strains that received levo?oxacin suscepti-bility test(n=163)were screened by moxi?oxacin (n=97),all97H.pylori strains whose resistance status to the two antibiotics were examined simultaneously were resistant to both of them,with an average rate of50.3and61.9%,respectively(Table3).The second-ary resistance rate was much higher than primary rate.The primary resistance rate to levo?oxacin and moxi?oxacin was36.9and41.2%,respectively (Table3),while the secondary rate was73.3and 84.8%,respectively(Table3).The primary levo?oxa-cin resistance rate rose from25%in2006–2007to 41.7%in2009(Fig.2),while the secondary resistance rate rose from37.5%in2006–2007to82.1%in2009 (Table3,Fig.3).

Discussion

The European multicenter study con?rmed that the E-test showed excellent intra-and interlaboratory cor-relation with agar dilution for amoxicillin and clarithro-mycin[7,8].It was performed in the present study for at least twice for each isolated H.pylori strain to get sta-ble and reliable results.

Reports of amoxicillin resistance are infrequent.The loss of the penicillin-binding protein was found associ-ated with resistance to it[9].Resistance to amoxicillin has been estimated to be<1%in most studies[10,11], but also at a high rate(8.8%)in Japan[12].In the present study,there was one H.pylori strain resistant to it,with a prevalence rate of0.3%(1?374).Hence,the amoxicillin resistance’s role in clinical practice may even be marginalized[13],which means this antibiotic could be chosen to be prescribed in most suitable cases in clinical practice.Although very high resistance rates to amoxicillin(71.9%)have been reported in some studies[14],however,these results must be interpreted with caution until the strains have been explored in depth[10].

The prevalence of H.pylori resistance to metronida-zole varies from20to40%in Europe and the USA to 50–80%in developing countries[10].A previous study performed in China showed a resistance rate of77.8% (119?153)to metronidazole.In the present study,the overall metronidazole resistance rate was63.9% (239?374),which was higher than that in Europe and similar to that in China.The primary and secondary resistance rate was56.6%(164?290)and89.3% (75?84),respectively.As the Maastricht III Consensus Report stated that the PPI-clarithromycin-metronidazole regimen is preferable in populations with<40%metro-nidazole resistance[1],a regimen including metronida-zole is not suitable and should not be chosen at least as ?rst-line treatment therapy in Beijing,China. Resistance to macrolides(clarithromycin is most widely used)is produced by a mutation in the2143 and2144position in the V domain of the rRNA23S [15].Resistance to clarithromycin is considered to be caused by the previous consumption of macrolides.The resistance of this antibiotic seriously affected the eradi-cation rate of H.pylori infection as PPI-clarithromycin-amoxicillin regimen was recommended as?rst-line therapy in most countries[1].

Gao et al.Evolution of H.pylori Antibiotics Resistance

The clarithromycin resistance status varied a lot in different regions of the world.Before the year2000,it was estimated to be<4%in Canada[16],which has already reached10–15%in the USA based on data from clinical trials[10,17].A survey from Japan observed an average resistance rate of16.4% (577?3521)from1996to2008and it has increased gradually to approximately30%from1996through 2004,remained unchanged since2004[11].A survey from Taiwan reported a10.6%resistance rate to this antibiotic,the resistance rate elevated signi?cantly after

a failed clarithromycin-based triple therapy(78.7vs

10.6%,p<.001)[18].Compared with the resistance status in developed countries and regions in Asia,the resistance rate in Beijing was pretty high,especially in strains isolated from previous treatment failure patients. In our present study,the overall resistance to clarithro-mycin increased from14.8%in2000to65.4%in2009, while the increase in primary resistance rate to clari-thromycin was12.8%in the year of2000,rose to its peak of38.5%in the year of2006–2007and2008, decreased to25%in2009.Clarithromycin was intro-duced to clinical practice in China in1995and then was largely used for the treatment of respiratory diseases,which may be a factor in the emergence of macrolide-resistant strains[19].

Compared with primary resistance status,the second-ary resistance rate to clarithromycin dramatically increased from28.6%(2?7)in2000to100%(28?28) in2009,with an average rate of83.3%(70?84).From the year of2000to2009,the trend of secondary resis-tance rate was keeping increasing,even the actual number of H.pylori strains involved was little.It was thought that the clarithromycin resistance is easily acquired,and H.pylori strains often became resistant to it after previous treatment with this antibiotic[20].The Maastricht III Consensus Report stated that the thresh-old of clarithromycin resistance at which antibiotic should not be used or a clarithromycin susceptibility test should be performed is15–20%[1].According to the consensus and the resistance characteristics of the antibiotic,the regimen that comprised clarithromycin should be chosen cautiously.To patients who had failed in previous clarithromycin containing treatment,this antibiotic should not be chosen or readministered, except with the support from antimicrobial susceptibil-ity test.However,in some regions of China,it was common that clarithromycin was readministered to cure H.pylori infection again and again even after mul-tiple times of failure in eradication treatment without susceptibility test,which might be an important reason of refractory H.pylori infection and the severe resistance status of this antibiotic.

The tetracycline resistance mechanism has been described as a change in three contiguous nucleotides in the16S rRNA gene(AGA926-928RTTC)[21].Resis-tance to tetracycline is very low,or even absent,in most countries[4,10].There were also high resistance rate reports in Korea(5.3%)[22]and Bulgaria(primary resistance 4.4%and secondary resistance13.3%), which might be because of the high consumption of tetracycline in previous years[23].

Tetracycline is rarely prescribed in China recently, especially in cities such as Beijing.In the present study, there were two H.pylori strains resistant to tetracycline, with a resistance prevalence rate of1.2%(2?164).It would be an option after failure in?rst-or second-line therapy treatment.

Fluoroquinolones(levo?oxacin)-based triple therapy achieved good eradication rates(90–94%)in Italy[24] and in Germany(86.7%)[25].High eradication rate (82.4%)was also reported in China recently[26].As other bacteria,resistance of H.pylori to?uoroquinol-ones is because of point mutations in the quinolone resistance determining regions of gyrA[27].Resistance to?uoroquinolones also mirrors the use of these kinds of drugs.The?uoroquinolone resistance rate was relatively low in European and American coun-tries.It was reported that the resistance rate was 3.9%(cipro?oxacin)in eastern European countries in 1998[28],11.5%(levo?oxacin)in Hong Kong[29]. In the present study,the levo?oxacin and moxi?oxa-cin resistance tests were performed on H.pylori strains isolated in2006–2009,with an average rate of50.3 and61.9%,respectively.The average primary resistance rate to levo?oxacin was36.9%,while the average secondary resistance rate increased to73.3%, suggesting the easy-to-acquired resistance characteris-tics.In our hospital,the prescription of?uoroquino-lone topped other antibiotics in recent years,which might be an important cause of its high resistance rates.

The relatively high?uoroquinolone resistance rate observed in our study contrasted with the pretty high eradication rate of more than80%of levo?oxacin-or moxi?oxacin-based triple regimen[26,30],indicating that the susceptibility or resistance status in vitro did not always predict treatment success or failure,at least as?uoroquinolone was mentioned.

However,in our study,the number of strains per year for secondary antibiotic resistance status analysis was low,so only a trend can be considered,and this trend was toward an increased prevalence over time. However,with a so high rate of resistance,it should be necessary to test the antimicrobial susceptibility of the H.pylori strains,using either the culture or the

Evolution of H.pylori Antibiotics Resistance Gao et al.

available molecular methods,particularly in case of secondary resistance(but not only perhaps). Conclusion

The high prevalence of clarithromycin,metronidazole, and?uoroquinolone resistance of H.pylori strains particularly in cases of secondary resistance highlighted that the management of the treatment of H.pylori infection is becoming a problem.Even knowing the susceptibility of H.pylori,eradication rates do not achieve100%,as the results observed in vivo by following in vitro susceptibility to anti-H.pylori antibi-otics are often disappointing[31].More than20%of patients will fail to eradicate H.pylori infection even with the current most effective treatment regimens. Antibiotic resistance to clarithromycin has been identi-?ed as one of the major factors affecting the eradication rate of H.pylori infection,as PPI-amoxicillin-clarithro-mycin regimen is recommended as?rst-line treatment in most countries.The resistance rate to clarithromycin seemed to be relatively high and increasing in China annually.Alternative antibiotics should be considered as a choice of?rst-line or rescue therapy.Amoxicillin and tetracycline might be a good option as their resis-tance rates were very low.However,levo?oxacin or moxi?oxacin-based?rst-line or rescue therapy may constitute an encouraging strategy,as in vitro antimicrobial susceptibility does not necessarily lead to eradication in vivo.

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Evolution of H.pylori Antibiotics Resistance Gao et al.

不用抗生素就消灭幽门螺杆菌

不用抗生素就消灭幽门螺杆菌,远离胃病 幽门螺杆菌是什么？它是一种导致胃部疾病的细菌，即使是在胃酸的环境下也能生存。据调查数据表明，我国成人幽门螺杆菌的感染率大约为65%左右，有近7亿人受到感染，是比较惊人的。 一般正常情况下，发现体内存在少量幽门螺杆菌是没有必要进行杀菌的。而当人体内存在大量幽门螺杆菌就需要重视了，很有可能会给胃部健康带来威胁，例如会引起慢性胃炎、胃溃疡、胃癌等疾病。所以当发现检测发现幽门螺杆菌数量超标比较严重，甚至已经出现胃痛、反酸、胀气等胃部不适症状，就应该重视起来并及时杀菌了。 教你1招，不用抗生素就可消灭幽门螺杆菌，胃病不打扰 传统的二联、三联、四联疗法都是比较常见的用于清除幽门螺杆菌的方法。不过无论是哪一种疗法，都无法能达到百分百根除幽门螺杆菌的目的，这样长期使用抗生素治疗，很容易导致幽门螺杆菌的耐药性增加，而且还会出现身体其他副作用。 所以一般采用抗生素治疗，不建议太长时间使用，一般使用一个疗程，也就是10天或14天。然后再从饮食去配合调理，这样两方面做好，通常幽门螺杆菌的清除率可达90%以上。 猴头菇有非常不错的杀菌养胃效果，能够保护并修复胃黏膜，提高胃的消化和吸收功能，还对伤害胃健康的幽门螺杆菌有较好的克制，经常吃一点高浓度猴头菇和丁香的食用液，对改善胃炎、胃溃疡、胃部不适等幽门螺杆菌感染的病症很有帮助，如果经常有胃部不适、胃功能不好的情况，可以试试这样助胃病好转。 虽然幽门螺杆菌感染十分普遍，而且带来的后果也比较严重，但幸运的是，通过经过正规耐心的治疗和调理，90%以上的幽门螺杆菌都可以被根除。所以就算感染幽门螺杆菌，也不必过于担心和惊慌。

幽门螺杆菌及根治

幽门螺杆菌及根治方案 在二十世纪八十年代中期及以前的一段时间里，民间流传着用“痢特灵”治疗“顽固性、难治性”胃痛的“偏方”。该方确实有效，但人们却不知道它为何有效。胡医生也曾经治疗过一位慢性浅表性胃炎的患者，中西药服了不少，但效果不理想。后来他在胃痛时自己服用“土霉素”，胃痛却神奇般地消失了。他问我为什么，我无法回答他。 1983年，澳大利亚两位科学家，从慢性胃炎的胃粘膜中取样，在微需氧的条件下，培养出幽门螺杆菌（Hp），并指出这种菌与慢性胃炎的直接关系以来，引起了全世界医学界人们的广泛研究和证实，并在活动性慢性胃炎及消化性溃疡病灶中，查出幽门螺杆菌，检出率为98%和100%。此菌被公认为慢性胃炎及消化性溃疡的致病菌。此后的研究表明，痢特灵和土霉素均有抗幽门螺杆菌的作用，至此，它们治疗“顽固性、难治性”胃痛的神秘面纱才被揭了下来。（虽然痢特灵和土霉素均有抗幽门螺杆菌的作用，但由于其副作用和幽门螺杆菌的抗药性，不提倡使用。）幽门螺杆菌的致病机理： 幽门螺杆菌的致病机理目前还不十分清楚。受幽门螺杆菌感染的人有的发病，有的不发病，发病也各不同；有的人发生慢性胃炎，而有的人发生消化性溃疡。有关研究还在进行之中。幽门螺杆菌的传播途径： 一般认为幽门螺杆菌仅寄居于人类，人是唯一的传染源。幽门螺杆菌多系口－口传染，因为在牙菌斑中可以培养出幽门螺杆菌。而粪－口传染途径尚未得到证实。知道了幽门螺杆菌是怎样相互传染的，大家就应该预防为主，讲究个人卫生，常洗手，勤刷牙，勿食被污染的食品，实行分餐制等等。幽门螺杆菌相关性胃病： 下面介绍几种与幽门螺杆菌感染最为密切的几种疾病； 1. 慢性胃炎 慢性胃炎发病率很高。有上腹不适患者的检出率可达80％以上，但过去对其病因却一直不清楚。自从澳大利亚两位科学家发现幽门螺杆菌以后，对幽门螺杆菌的研究成为全世界医学研究的热点。研究证实幽门螺杆菌是慢性胃炎的主要病因。我国也于1985年首次分离出幽门螺杆菌，并对幽门螺杆菌进行了大量的基础和临床研究，发现慢性活动性胃炎病人中幽门螺杆菌感染率为95％，幽门螺杆菌阳性的胃炎多为活动性胃炎，杀灭幽门螺杆菌后则变为非活动性胃炎。慢性活动性浅表性胃炎逐渐发展可以转变为慢性萎缩性胃炎，继而加重萎缩性胃炎并发生肠上皮化生及异型增生，成为癌前病变。萎缩性胃炎被认为是胃的癌前疾病，因此萎缩性胃炎患者每1－2年需胃镜复查一次，以便及时发现早期癌变。 2. 消化性溃疡 消化性溃疡比较常见，其胃镜检出率为16.5％－28.9％。过去认为“无酸（pH)则无溃疡”，抑酸可愈合溃疡。虽然抑酸愈合溃疡不难，但一年内复发率高达60％－90％。幽门螺杆菌的发现和相关研究显示，消化性溃疡与幽门螺杆菌的感染密切相关。我国胃溃疡的幽门螺杆菌检出率约为70％，十二指肠溃疡的幽门螺杆菌检出率约为90％，而根除幽门螺杆菌之后经过长期随访观察，溃疡复发率明显下降至10％以下。因此有人提出了“无Hp（幽门螺杆菌）则无溃疡”的说法。 3. 胃癌 根据流行病学资料，幽门螺杆菌与胃癌的发生有十分密切的关系，幽门螺杆菌被认为是胃癌的一个高危致病因素。实验研究显示幽门螺杆菌可引起细胞过度增殖，使DNA易受损伤；幽门螺杆菌还可引起原癌基因激活，抑癌基因失活，癌基因过度表达及基因突变等因此认为幽门螺杆菌是胃癌的一个启动因子。幽门螺杆菌的治疗： 幽门螺杆菌感染，是导致消化性溃疡和慢性胃炎发生和反复发作的重要因素。幽门螺杆菌感染的途径目前是：口－口、胃－口（还有人认为粪－口也是一个传染途径），我国的感染率达60%。幽门螺杆菌常常寄生于胃黏膜，它通过引起胃黏膜自我保护的屏障作用下

幽门螺杆菌感染的治疗,医生指出：这3种情况必须根治

幽门螺杆菌“生活”在胃部和十二指肠的各个区域内，不仅会引起胃黏膜发炎，还会导致胃和十二指肠溃疡，而长期的胃溃疡正是导致胃癌的因素之一。 因此世界卫生组织将幽门螺杆菌认定为可致癌物质，很多人就误以为得了幽门螺杆菌就会得癌，下面来帮助大家了解一下被幽门螺杆菌感染要不要治疗以及幽门螺杆菌和胃癌之间的关系。 有症状的幽门螺杆菌患者需要治疗，无症状的幽门螺杆菌患者不需要治疗 多数人出生起5到8个月后，都有可能被幽门螺杆菌感染，因为幽门螺杆菌的传播途径实在是简单，那就是吃，无论是不干净的餐具、生鱼片、口对口喂饭、共用水杯或是接吻，都是幽门螺杆菌的感染途径，被幽门螺杆菌感染后有以下症状： 1、胃痛。幽门螺杆菌的存在会导致胃和十二指肠粘膜的损伤并出现炎症，感染幽门螺杆菌患者会出现胃痛慢性胃炎症状。 2、反酸、恶心。幽门螺杆菌会诱发胃酸分泌，导致胃酸过多，症状表现为反酸和恶心。 3、口臭。幽门螺杆菌会在牙菌斑中生存繁殖，严重者会出现口臭的症状。 如果的确感染了幽门螺杆菌并出现以上三个症状，应该及时就医治疗，通过抗生素疗法使溃疡愈合并根除幽门螺杆菌，以防胃病发展到消化性溃疡和慢性胃炎的地步，胃癌就是由溃疡和胃炎慢慢发展而成的。 无症状的幽门螺杆菌患者则不需要治疗，因为前面也说到了，我国70%以上的居民都被感染了幽门螺杆菌，这其中可能就包括你的亲人和朋友，而幽门螺杆菌可以通过一起吃饭互相传染，即使你通过吃药把幽门螺杆菌杀光了，那你能保证自己不再和亲人朋友吃饭了吗？只要一起吃饭，就有被感染的可能，所以我认为，没有任何症状的幽门螺杆菌患者是不需要治疗的，更何况大部分幽门螺杆菌患者终生都没有任何症状，只要幽门螺杆菌没有影响到你的个人健康和肠胃状态就不需要治疗，毕竟使用抗生素杀死幽门螺杆菌实属杀敌一千自损八百的行为，会影响到自身的健康，没必要。

抗幽门螺杆菌药物的发展与临床应用近况

抗幽门螺杆菌药物的发展与临床应用近 况 (作者：__________ 单位：___________ 邮编：___________ ) 【关键词】幽门螺杆菌药物治疗胃、十二指肠炎性疾病自从1983年澳大利亚佩思皇家医院的Warren和Marshall报道从胃内成功地分离出“未鉴定的弯曲状杆菌”(unidentified curved bacilli )后[1,2],引起医学界的广泛兴趣，它的发现对消化病学、特别是胃十二指肠病学的发展起到了极大作用。因此对其进行了各方 面的深入研究。人们在研究这种细菌的生物学特性时，曾几次对其易 名，至1989年才正式将其命名为幽门螺杆菌 (Helicobacter pylori , Hp) :3]o 幽门螺杆菌被证明与慢性萎缩性胃炎(慢性胃炎患者Hp检出率在80%以上)[4]胃、十二指肠溃疡的发生有关。幽门螺杆菌容易定居于胃的粘膜层深部，它分泌高活性的尿毒酶，能将组织内的尿素分解产生氨，进而使胃粘膜的跨膜电位下降，粘液分泌减少，血流降低，结果使胃粘膜的防御机制遭受损害。新近报道，它与胃癌发生关系密切。

在活动性炎症或溃疡的粘膜中，螺杆菌阳性率多达100% 另外，药物治疗Hp的根除率与患者的牙周状况和口腔卫生状况有关，口腔Hp可能是胃再感染的病原因素［5］。Hp还可通过对胃酸度和质子泵抑制剂的抗分泌的影响而诱发或恶化胃食管反流病［6］。 在认识到Hp是致病菌后，必然要对其进行治疗。1984年就有Hp抗生素药敏试验的报道］7］。随着研究的深入，越来越多的药物试用于Hp感染的治疗。现已明确就有抗生素、抑酸剂、金属制剂及其它药物可用于Hp感染的治疗。 1抗生素类药物 抗生素类药物中有阿莫西林（B :内酰胺类），四环素、土霉素（四环素类），红霉素、克拉霉素、阿奇霉素（大环内酯类），庆大霉素（氨基糖苷类），阿柔比星、柔红霉素（蒽醌类），环丙沙星、诺氟沙星（喹喏酮类），咲喃唑酮，甲硝唑、替硝唑（硝基咪唑类），克林霉素，利福平、利布汀等药对Hp有杀菌或抑菌作用。据体外药物敏感试验，Hp对青霉素类药物最敏感；对氨基糖苷类、四环素类、头孢菌素类、氧氟沙星、环丙沙星及利福平等高度敏感；对大环内酯类、硝基咪唑类、咲喃类、诺氟沙星、氯霉素中度敏感］8］。 1. 1阿莫西林在体外对Hp的MIC90为0.12mg/L,胃内pH>7 时，其杀菌活性显著增加，基本无Hp耐药性。参与构成根除Hp的二联、四联方案，常见副作用为腹泻、恶心、皮疹，青霉素过敏者禁用。

非抗生素治疗幽门螺旋杆菌60例疗效观察

非抗生素治疗幽门螺旋杆菌60例疗效观察 邓国发;孙玉娟 【期刊名称】《医学信息》 【年(卷),期】2015(000)029 【摘要】Objective To investigate the method of non antibiotic treatment for Helicobacter pylori.Methods Selection of antibiotics in the treatment of helicobacter pylori in nearly 60 cases of typical cases of retrospective analysis, combined with the literature in this paper.Results The total ef ective rate reached 90%, HP Yin turn rate is 75%, less adverse reaction.Conclusion The antibiotics in the treatment of helicobacter pylori in patient adherence to treatment ef ect than classical treatment has certain advantages and characteristic.%目的探讨非抗生素治疗幽门螺旋杆菌的方法。方法选取我院近2年60例非抗生素治疗幽门螺旋杆菌典型病例进行回顾分析，结合文献进行论述。结果总有效率达到90%，HP阴转率75%，不良反应少。结论非抗生素治疗幽门螺旋杆菌在患者依从性治疗效果上比经典治疗有一定的优势与特点。 【总页数】1页(38-38) 【关键词】非抗生素治疗;幽门螺旋杆菌;疗效 【作者】邓国发;孙玉娟 【作者单位】成都市金堂县第三人民医院，四川成都610406;成都市金堂县第三人民医院，四川成都 610406 【正文语种】中文

2019幽门螺杆菌感染基层诊疗指南(实践版)

2019幽门螺杆菌感染基层诊疗指南（实践版） 一、定义 幽门螺杆菌（Helicobacter pylori，Hp）是一种革兰染色阴性螺 旋状细菌，主要通过口-口途径在人与人之间传播。Hp从口腔进 入人体后特异地定植于胃型上皮（gastric type epithelium）， 定植后机体难以自发清除，从而造成持久或终生感染。Hp感染几 乎均可引起胃黏膜活动性炎症，在慢性炎症活动的基础上，部分患 者还可发生消化性溃疡和胃癌等一系列疾病。 Hp感染是慢性胃炎最主要的病因，世界范围内Hp感染率超过50%[1]。《幽门螺杆菌胃炎京都全球共识》（以下简称京都共识）报告指出，Hp感染是一种感染性疾病，几乎所有的Hp感染患者 均有慢性活动性胃炎[2]。Hp感染者中，约15%~20%发生消化性 溃疡，5%~10%发生Hp相关消化不良，约1%发生胃癌和胃黏膜 相关淋巴组织（MALT）淋巴瘤[3]。 二、病理生理过程 Hp感染后机体难以自发清除，如不治疗，往往造成终生感染，即 长期存在慢性活动性胃炎。慢性活动性胃炎可导致部分患者产生消 化不良症状；以胃窦胃炎为主者部分可发生十二指肠溃疡；在Hp 毒力因素、遗传因素和环境因素共同作用下，部分患者可发生胃黏 膜萎缩/肠化生，此基础上，少部分患者发生胃溃疡，极少部分

（<1%）患者发生胃癌[4]。此外，感染者中极少部分患者还会发生胃MALT淋巴瘤。 Hp胃炎的胃内分布部位（胃窦为主胃炎、胃体为主胃炎和全胃炎）在很大程度上决定了Hp感染后胃酸分泌的变化，胃酸分泌的高低则影响了Hp胃炎的结局。例如，胃窦感染为主者多数胃酸分泌增加，这些患者十二指肠溃疡发生的风险增加（十二指肠溃疡表型胃炎），而胃癌发生风险则降低。而胃体感染为主者多数胃酸分泌降低，这些患者发生胃癌的风险增加（胃癌表型胃炎），而发生十二指肠溃疡的风险则降低。多数轻度全胃炎患者胃酸分泌无明显改变（单纯慢性胃炎表型）。 三、诊断与鉴别诊断 （一）诊断1．临床表现：Hp感染是人类最常见的慢性感染，可导致不同结局，从无症状的慢性活动性胃炎、消化不良（约10%）、消化性溃疡（约10%~15%）直至胃恶性肿瘤（约1%）[3,5]，并产生相应临床表现。 Hp感染也与一些胃肠外的疾病发生有关，如不明原因缺铁性贫血、特发性血小板减少性紫癜等[3,6,7]。 2．诊断方法[3,6,7]：（1）侵入性方法：包括组织学检测、快速尿素酶试验（RUT）、Hp培养和聚合酶链反应（PCR）检测。胃镜检查如需活检，若患者无活检禁忌，临床上推荐RUT检测Hp，

专家提示：不用抗生素,胃炎才能不反复

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一线治疗。 四联治疗的确能够克服幽门螺杆菌治疗当中抗生素耐药的问题，提高根除率，但同时也带来了一些问题。铋剂四联或非铋剂四联疗法含有2～3种抗生素，可能会导致患者耐药性增加；其次，有研究报道四联疗法的不良事件发生率更高。 2、什么是高剂量二联疗法？ （1）高剂量二联疗法 1989年有研究首次报道了二联方案，如标准剂量的质子泵抑制剂和阿莫西林或者单独增加阿莫西林或质子泵抑制剂的剂量和给药频率，但此后的研究发现这两种方案临床效果不佳。在对二联方案的不断摸索中，高剂量二联疗法横空出世。 所谓高剂量二联疗法，第一是大剂量质子泵抑制剂，它的目标在于维持胃内pH≥6；第二是大剂量阿莫西林，即阿莫西林3g/d。 （2）大剂量质子泵抑制剂 为什么在高剂量二联疗法中要提高质子泵抑制剂的使用呢？提高质子泵抑制剂的使用，主要是为了提高胃内pH至6-8，使幽门螺杆菌处于生长活跃期，这时候使用抗生素更易杀菌。大多数幽门螺杆菌存在于人体胃黏膜层，严格来说处于体外，在任何时间下，相当大比例幽门螺杆菌处于不复制状态或复制非常缓慢。对于需要依靠微生物复制机制杀死病菌的抗生素（如阿莫西林和克拉霉素）来说是一个挑战。这是因为阿莫西林和克拉霉素仅在pH值升高到6-8，幽门螺杆菌进入分割增殖时

目前根治幽门螺杆菌常用以下几种方案

目前根治幽门螺杆菌常用以下几种方案： 1.质子泵抑制剂(英文缩写“ppi”，市上有售的如奥美拉唑、兰索拉唑等)+两种抗生素: ppi标准计量+阿莫西林1.0g+克拉霉素0.5g,均一日两次，1周为一个疗程;ppi标准计量+阿莫西林1.0g+甲硝唑0.4g,均一日两次，1周为一个疗程; ppi标准计量+甲硝唑0.4g克拉霉素0.25g, 均一日两次，1周为一个疗程。 2. 铋剂：丽珠胃三联：由铋剂（丽珠得乐）＋两种抗生素组成，是目前根治幽门螺杆菌的一种十分有效的药物，一个疗程连服七天，根治率达90%以上；铋剂+两种抗生素:铋剂（推荐用丽珠得乐）标准剂量+阿莫西林0.5g+甲硝唑0.4g, 均一日两次，2周为一个疗程;铋剂（推荐用丽珠得乐）标准剂量+四环素0.5g+甲硝唑0.4g, 均一日两次，2周为一个疗程; 铋剂（推荐用丽珠得乐）标准剂量+克拉霉素0.25g+甲硝唑0.4g, 均一日两次，2周为一个疗程。 3.其他方案：雷尼替丁枸橼酸铋（rbc）0.4g替代推荐方案1中的ppi。h2-受体拮抗剂h2-ra）或ppi+推荐方案2组成四联疗法，疗程一周。方案中的甲硝唑0.4g可用替硝唑0. 5g替代。 预防幽门螺杆菌感染是十分必要的。要注意个人卫生：如每餐后的漱口、分食制、蔬菜水果清洗净等，尽量减少其感染机会。 丽珠得乐(枸橼酸铋钾) 【作用与用途】 本品在胃内能迅速崩解，在胃酸作用下水溶性胶体铋与溃疡面或炎症部位的蛋白质形成不溶性含铋沉淀，牢固地粘附于糜烂面上形成保护屏障，抵制胃酸与胃蛋白酶对粘膜面的侵蚀，并能刺激内源性前列腺素释放，促进胃粘液分泌，加速粘膜上皮修复，此外还有清除幽门螺旋杆菌的作用，临床用于治疗胃溃疡，十二指肠溃疡及红斑渗出性胃炎糜烂性胃炎。

中国北京地区幽门螺杆菌抗生素耐药十年变迁

Gao W,Cheng H,Hu F,Li J,Wang L,Yang G,et al.The evolution of Helicobacter pylori antibiotics resistance over10years in Beijing,China. Helicobacter2010;15(5):460–6. The Evolution of Helicobacter pylori Antibiotics Resistance Over10Years in Beijing,China 中国北京地区幽门螺杆菌抗生素耐药十年变迁 OBJECTIVES: To evaluate Helicobacter pylori antibiotics resistance evolution from2000to 2009to amoxicillin,clarithromycin,metronidazole,tetracycline,levofloxacin and moxifloxacin in Beijing,China. 评价幽门螺杆菌对如下几种抗生素的耐药性在中国北京从2000年到2009年十年间的变化情况，抗生素的种类包括阿莫西林,克拉霉素,甲硝唑、四环素、左氧氟沙星和莫西沙星。 METHODS: A total of374H.pylori strains isolated from374subjects who had undergone upper gastrointestinal endoscopy from2000to2009were collected and examined by E-test method for antibiotics susceptibility. 从2000年到2009年十年间共收集了374株幽门螺杆菌菌株，这些菌株是从经历了上消化道内窥镜检查的374名受试者内镜活检标本中分离得到的，并采用E 实验的方法对其抗生素的敏感性进行了检测。 RESULTS: The average antibiotics resistance rates were0.3%(amoxicillin),37.2% (clarithromycin),63.9%(metronidazole),1.2%(tetracycline),50.3% (levofloxacin)and61.9%(moxifloxacin).Overall resistance to clarithromycin, metronidazole,and fluoroquinolone increased annually(from14.8to65.4%, 38.9to78.8%,and27.1to63.5%,in2000or2006-2007to2009,respectively). The secondary resistance rates were much higher than primary rates to these antibiotics,which also increased annually in recent10years. 这些菌株的平均抗生素耐药率分别是0.3%(阿莫西林),37.2%(克拉霉 素),63.9%(甲硝唑),1.2%(四环素),50.3%(左氧氟沙星)和61.9%(莫西沙星)。克拉霉素、甲硝唑和氟喹诺酮类抗生素的耐药率整体上呈逐年增加的趋势(在2000年或2006-2007年至2009年间,这些菌株对这三种抗生素的耐药率分别从14.8%上升至65.4%,从38.9%上升至65.4%,从27.1%上升至63.5%)。细菌对这些抗生素继发耐药率远高于原发耐药率,近10年也呈逐年增加的趋势。

幽门螺杆菌(Hp)感染与胃癌的临床关系探讨

幽门螺杆菌(Hp)感染与胃癌的临床关系探讨 发表时间：2018-06-04T14:21:39.783Z 来源：《医药前沿》2018年5月第15期作者：欧君娣 [导读] Hp感染对胃癌的发生与发展及预后有一定的影响，可作为评估胃癌发生与预后的潜在指标。 （上海普陀区利群医院上海 200063） 【摘要】目的：探讨幽门螺杆菌（Hp）感染与胃癌的临床关系。方法：选取2013年1月—2014年1月期间在我院治疗的胃癌患者80例，作为A组，另选取同期我院收治的慢性胃炎患者80为B组，并从同期来院体检的健康人群中选取80例为C组，使用碳14呼气试验和血清抗Hp-IgG检测三组的Hp阳性率，A组患者均随访3年，对比Hp阳性与Hp阴性患者的生存率。结果：三组的Hp阳性率比较有统计学差异（P＜0.05），其A组的Hp阳性率高于B、C两组（P＜0.05），B组的Hp阳性率高于C组（P＜0.05）；A组中Hp阴性患者的3年生存率大于Hp阳性患者（P＜0.05）。结论：Hp感染对胃癌的发生与发展及预后有一定的影响，可作为评估胃癌发生与预后的潜在指标。 【关键词】幽门螺杆菌感染；胃癌；碳14呼气试验 【中图分类号】R735.2 【文献标识码】A 【文章编号】2095-1752（2018）15-0208-01 胃癌是我国各类恶性肿瘤中发病率居于首位的消化道肿瘤，胃癌在发病早期及癌前病变时的症状较为隐匿，且无明显的临床特异性，当症状比较明显时已经进入晚期，此时的预后较差，因此如何做好胃癌早期的诊疗具有非常重要的意义[1]。幽门螺杆菌（Hp）感染已被世界卫生组织列为胃癌的一类致癌因子，但Hp感染与胃癌的相关性目前存在较大争议，本次的研究中主要对Hp感染与胃癌的临床关系进行分析，探讨Hp感染在胃癌中的作用，报道如下。 1.资料与方法 1.1 临床资料 本研究选取2013年1月—2014年1月我院收治的80例胃癌患者，作为A组，另从同期收治的慢性胃炎患者和来院体检的健康人群中各选取80例为B组和C组。A组男45例，女35例，年龄38～82岁，平均（58.3±4.5）岁。B组男43例，女37例，年龄35～80岁，平均（56.2±5.0）岁。C组中男44例，女36例，年龄36～78岁，平均（56.5±5.2）岁。三组的以上资料比较无明显的差异性（P＞0.05）。 1.2 方法 使用碳14呼气试验（14C-UBT）检测三组的Hp感染情况。 14C-UBT法：三组受试者均在空腹状态下口服14C胶囊1粒，保持安静状态25min，指导患者向CO2集气瓶内吹气，待瓶中液体由紫红色转为透明时则停止吹气，若吹气时间＞3min则瓶内颜色未完全褪色则停止吹气，之后向瓶内加稀释的闪烁液4.5mL，放入Hp测试仪（重庆九升医疗器械有限公司）中，以14C-UBT≥100dpmm/molCO2%为阳性。 80例胃癌患者中有46例行胃癌根治术；21例行姑息性切除术；5例患者行胃空肠吻合术；6例联合脏器切除，包括4例联合胰体尾及脾切除，2例联合脾脏切除。所有患者均实施同步放化疗以控制病情进展，同时给予药物基本治疗，如预防感染、稳定水电解质平衡，改善机体免疫功能等。 1.3 观察指标 对比三组的Hp阳性率，A组患者均随访3年，对比A组中Hp阳性和阴性患者的生存率。 1.4 统计学分析 本研究统计学分析工具为SPSS19.0，计数以（%）表示，比较为χ2检验，P＜0.05可认为差异有统计学意义。 2.结果 2.1 三组的Hp阳性率比较 三组间的Hp阳性率比较有显著的统计学差异（P＜0.05），其A组的Hp阳性率高于B组、C组（P＜0.05），B组的Hp阳性率高于C组（P＜0.05），见表。 2.2 生存率比较 A组患者中50例Hp阳性患者的3年生存率为42.00%（21/50），30例Hp阴性患者的3年生存率为66.67%（20/30），Hp阴性患者的3年生存率显著高于Hp阳性者（χ2=4.566，P=0.033）。 3.讨论 胃癌的发生是多种因素相互作用的复杂结果，其具体的病因和发病机制尚不明确，随着临床研究的深入发现，Hp感染、吸烟、慢性胃炎及胃溃疡迁延不愈等因素均是导致胃癌发生的相关因素，而Hp感染被共认为是胃癌形成的致病因素和制动因子之一。 本次的研究结果中显示三组的Hp阳性率比较有明显的统计学差异（P＜0.05），A组Hp阳性率显著高于B组和C组（P＜0.05），B、C 两组间的Hp感染阳性率比较B组更高（P＜0.05），且A组中与Hp阳性者比较Hp阴性患者的3年生存率更高（P＜0.05），提示Hp感染可能与胃癌的发生及预后有一定的关系。Hp能够通过侵袭胃组织，造成胃粘膜的炎症，发展成为慢性胃炎，造成胃粘膜肠上皮化增生和异性增生，导致胃部的癌变，而慢性胃炎也被认为为癌前病变，因此Hp感染与胃癌癌病之间的关系是微生物感染引起宿主的慢性炎症反应，继而导致癌变的一个过程。有研究表明Hp感染可削弱正常组织细胞的粘附性[3]，破坏正常组织细胞与癌细胞之间的屏障，加速癌细胞向深部组织的转移，增加癌变组织的治疗难度，从影响患者的预后。 综上所述，Hp感染是胃癌发生与发展过程中影响因素，并对胃癌预后有一定的影响，可将其作为胃癌发生与预后的潜在评估指标。

幽门螺杆菌抗生素耐药趋势研究：2000年到2009年 中国上海

The Evolution of Helicobacter pylori Antibiotics Resistance Over 10Years in Beijing,China Wen Gao,*,1Hong Cheng,*,1Fulian Hu,*Jiang Li,*Lihui Wang,*Guibin Yang,?Le Xu?and Xiaoli Zheng? *Department of Gastroenterology,Peking University First Hospital,Beijing,China,?Department of Gastroenterology,Aerospace Clinical College of Peking University,Beijing,China,?Department of Gastroenterology,Beijing Hospital,Beijing,China Helicobacter pylori is a Gram-negative?agellated spiral bacteria.Infection with H.pylori is mainly acquired in childhood.H.pylori infection is recognized as a causal factor in the pathogenesis of chronic gastritis,peptic ulcer,gastric cancer,and gastric MALT lymphoma. H.pylori eradication treatment is indicated in patients with peptic ulcer disease,MALToma,atrophic gastritis, post-gastric cancer resection,or patients who are?rst-degree relatives of patients with gastric cancer[1]. Among numerous eradication regimens,a proton pump inhibitor and combination of two antibiotics(amoxicil-lin,clarithromycin,and metronidazole)are considered to be the most effective and?rst-line therapy regimens recommended by Maastricht III Consensus and in China[1,2].However,antibiotic resistance of H.pylori, especially to clarithromycin and metronidazole, strongly undermined the ef?cacy of eradication treat-ment.The reported frequencies of resistance to anti-biotics varied widely between geographic regions.A European study involving17countries and1274H.pylori isolates showed a mean resistance rate(deter-mined by E-test)to amoxicillin0.8%;to clarithromycin 9.9%;and to metronidazole33.1%[3].Another recent study from French examined530H.pylori strains iso-lates from2004to2007,among those,26%(138?530) strains were resistant to clarithromycin,61% (324?530)to metronidazole,and13.2%(70?530)to cipro?oxacin,whereas no resistance against amoxicillin and tetracycline was observed[4].As culture-based antimicrobial susceptibility data are not always avail-able and the H.pylori eradication regimen especially antibiotics involved should be chosen based on local resistant epidemiologic data and an empirical basis,it is important to understand the regional antibiotics resis-tance status and trend of this bacterium.The aim of this study was to assess the prevalence of antibiotics (amoxicillin,clarithromycin,metronidazole,tetracy-cline,levo?oxacin,and moxi?oxacin)resistance of H.pylori strains isolated from Beijing in recent 10years. Keywords Helicobacter pylori,antibiotic resistance, amoxicillin,clarithromycin,metronidazole, tetracycline,levo?oxacin,moxi?oxacin. Reprint requests to:Fulian Hu,Professor, Department of Gastroenterology,Peking University First Hospital,Beijing100034, China.E-mail:hufulian@https://www.wendangku.net/doc/9b12789439.html, 1These authors contributed equally to the study. Supported by Beijing Medicine Research and Development Fund(No.2005-1008).Abstract Objectives:To evaluate Helicobacter pylori antibiotics resistance evolution from2000to2009to amoxicillin,clarithromycin,metronidazole,tetra-cycline,levo?oxacin and moxi?oxacin in Beijing,China. Methods:A total of374H.pylori strains isolated from374subjects who had undergone upper gastrointestinal endoscopy from2000to2009were collected and examined by E-test method for antibiotics susceptibility. Results:The average antibiotics resistance rates were0.3%(amoxicillin), 37.2%(clarithromycin),63.9%(metronidazole),1.2%(tetracycline),50.3% (levo?oxacin)and61.9%(moxi?oxacin).Overall resistance to clarithro-mycin,metronidazole,and?uoroquinolone increased annually(from14.8 to65.4%,38.9to78.8%,and27.1to63.5%,in2000or2006–2007to 2009,respectively).The secondary resistance rates were much higher than primary rates to these antibiotics,which also increased annually in recent 10years. Conclusions:The trend of clarithromycin,metronidazole,and?uoroquino-lone resistance of H.pylori increased over time and the resistance to amoxi-cillin and tetracycline was infrequent and stable in Beijing.Clarithromycin, metronidazole,and?uoroquinolone should be used with caution for H.pylori eradication treatment. Helicobacter ISSN1523-5378