Changing patterns of antibiotic resistance of Helicobacter pylori in patients with peptic ulcer disease]

BACKGROUND/AIMS: Antibiotic resistance of Helicobacter pylori (H. pylori) is a significant clinical problem because it reduces the efficacy of eradication therapy. The aims of this study were to assess the changing patterns of antibiotic resistance of H. pylori in patients with peptic ulcer diseases and to evaluate the eradication rate in antibiotic resistant H. pylori strains. METHODS: One hundred forty four H. pylori isolates obtained from 466 patients with peptic ulcer disease between June 2001 and December 2005 were examined for antimicrobial resistance. The minimum inhibitory concentration (MIC) of metronidazole was determined by modified broth microdilution method (mBMD) and E test. MICs of clarithromycin and amoxicillin were determined by mBMD, E test, and disc diffusion test. The breakpoints for metronidazole, clarithromycin, and amoxicillin resistance were defined as >8 microg/mL, >1 microg/mL, and > or =1 microg/mL, respectively. RESULTS: Resistance to metronidazole and clarithromycin was detected in 34.7% and 16.7% of H. pylori isolates, respectively. During the recent 5-year study period, amoxicillin-resistant rate of H. pylori was 11.8%, and multi-drug resistance rate of H. pylori was 16.7%. The eradication rate of clarithromycin containing triple therapies was low (7.8%) in clarithromycin-resistant H. pylori strains. CONCLUSIONS: The proportions of clarithromycin-resistant H. pylori strains have increased significantly over the last 5-years. There is an increasing tendency for the emergence of strains with multi-drug resistance. The increase in clarithromycin-resistant strains results in a decrease in eradication rate for H. pylori. In areas with high clarithromycin resistance, new alternative first-line treatment combination should be considered.     

Clarithromycin-resistance and point mutations in the 23S rRNA gene in Helicobacter pylori isolates from Japan

BACKGROUND: Resistance of Helicobacter pylori to clarithromycin is mostly due to the point mutations in the 23S rRNA. In Japan, however, the frequency of these mutations has not been fully investigated. Furthermore, no study has used gastric biopsy specimens to detect these point mutations. METHODS: The frequency of primary clarithromycin-resistant H. pylori was examined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Eighty-two strains (42 isolated from patients with gastric cancer and 40 isolated from patients with chronic gastritis) were examined. Two biopsy specimens obtained from patients in whom eradication therapy including clarithromycin had failed were also studied. RESULTS: Either A2143G or A2144G point mutation was detected in 90% of clarithromycin-resistant H. pylori strains. Eight out of 82 strains (9.8%) had either A2143G or A2144G point mutation. Only one out of 42 strains in patients with gastric cancer had A2143G mutation, whereas five strains had A2144G and two had A2143G mutations in 40 strains isolated from control subjects. The proportion was significantly lower in patients with early gastric cancer (P < 0.05). This PCR-RFLP was also applicable for DNA samples extracted from biopsy specimens and infection of clarithromycin-resistant H. pylori was observed. CONCLUSION: The results suggest that the point mutation in the 23S rRNA gene is commonly seen in clarithromycin-resistant H. pylori and it contributes to the treatment failure in Japan. The PCR-RFLP system is a sensitive method by which to diagnose H. pylori infection as well as a simple method for detecting clarithromycin resistance without bacterial culture.     

Characterization of clarithromycin resistance in Malaysian isolates of Helicobacterpylori

AIM： To characterize the types of mutations present in the 23S rRNA genes of Malaysian isolates of clarithromycin-resistant Helicobacter pylori （H pylorl~. METHODS： Clarithromycin susceptibility of H pylori isolates was determined by E test. Analyses for point mutations in the domain V of 23S rRNA genes in clarithromycin-resistant and -sensitive strains were performed by sequence analysis of amplified polymerase chain reaction products. Restriction fragment length polymorphism was performed using Bsa I and MboI enzymes to detect restriction sites that correspond to the mutations in the clarithromycin- resistant strains. RESULTS： Of 187 isolates from 120 patients, four were resistant to clarithromycin, while 183 were sensitive. The MIC of the resistant strains ranged from 1.5 to 24 pg/mL. Two isolates had an A2142G mutation and another two had A2143G mutations. A T2182C mutation was detected in two out of four clarithromycin-resistant isolates and in 13 of 14 clarithromycin-sensitive isolates. Restriction enzyme analyses with Bsa I and Mbo I were able to detect the mutations. CONCLUSION： Clarithromycin resistance is an uncommon occurrence among Malaysian isolates of Hpylori strains and the mutations A2142G and A2143G detected were associated with low-level resistance.     

New mutation points in 23S rRNA gene associated with Helicobacter pylori resistance to clarithromycin in northeast China

AIM: To investigate the resistance rate of Helicobacter pylori (H pylori ) to clarithromycin, metronidazole, amoxicillin and tetracycline to guide clinical practice, and to study the mechanism of H pylori resistant to clarithromycin. METHODS: Thirty H pylori strains were isolated from the mucosa of peptic ulcer, gastric tumor and chronic gastritis patients, then the minimal inhibitory concentration (MIC) to clarithromycin, metronidazole, amoxicillin and tetracycline was evaluated by E-test method. The sequence analysis of PCR fragments was conducted in 23S rRNA gene of H pylori resistant to clarithromycin to get the resistance mechanism of the bacteria. RESULTS: Among 30 H pylori strains, 7 cases were resistant to clarithromycin, 12 to metronidazole, 2 to tetracycline and no strain was found to be resistant to amoxicillin. The resistance rates were 23.3%, 40%, 6.7% and 0%, respectively. Three new mutation points were found to be related to the clarithromycin resistance in H pylori isolates, which were G2224A, C2245T and T2289C. CONCLUSION: In northeast China, H pylori shows high resistance to metronidazole, while sensitive to amoxicillin. The mechanism of resistance to clarithromycin may be related to the mutation of G2224A, C2245T and T2289C in the 23S rRNA gene.     

幽门螺杆菌对克拉霉素耐药的分子机制研究

目的：研究幽门螺杆菌（Hp)对克拉霉素耐的分子机制。方法：用E－test进行克拉霉素药敏试验,选取治疗前敏感、治疗后耐药的配对菌株及原发耐药Hp菌株进行研究;应用随机扩增多态性DNA（RAPD）分析,确定治疗前后菌株的同一性;用PCR－限制性片段长度多态性（RFLP）分析探讨克拉霉素耐药机制。结果9株克拉霉素耐药菌23SrRNA基因功能区V PCR扩增片段,8株被BsaI酶切,9株均未被BbsI酶切,提示8株在2144位点有A→G突变。结论上海地区大多数克拉霉素耐药Hp菌株存在23SrRNA基因功能区V2144位点A→G突变。     

Antibiotic resistance of Helicobacter pylori isolated from Korean patients]

The distribution of minimal inhibitory concentrations (MIC) for amoxicillin, clarithromycin, metronidazole, tetracycline, azithromycin, and fluoroquinolone (ciprofloxacin, levofloxacin, and moxifloxacin) have shifted to higher concentrations from 1987 to 2003 in Helicobacter pylori (H. pylori) strains isolated from Korean patients. MIC values of secondary isolates were higher than those of primary isolates. Of treatment-failure patients, 16.4% showed mixed infections with both antibiotic-susceptible and -resistant H. pylori strains. A total of 89.6% of patients with treatment failure and 52.3% of patients without antibiotic treatment had H. pylori strains resistant to two or more antimicrobial agents (multi-drug resistance, MDR). The most common antibiotics showing MDR were clarithromycin, metronidazole, and azithromycin. The resistance rates to both amoxicillin and clarithromycin were 34.3% in secondary isolates and 6.2% in primary isolates. The resistance rates to both clarithromycin and metronidazole were 73.1% in secondary isolates and 7.7% in primary isolates. In addition, there was a significant difference in antibiotic resistance between two institutions located at Seoul and Gyeonggi provinces. To provide adequate informations about susceptible antibiotics to clinicians, continuous surveillance of antibiotic susceptibilities is needed in Korea.     

Modified allele-specific primer-polymerase chain reaction method for analysis of susceptibility of Helicobacter pylori strains to clarithromycin

BACKGROUND AND AIM: Most clarithromycin-resistant strains of Helicobacter pylori have a mutation from adenine (A) to guanine (G) at position 2142 or 2143 of the 23S rRNA gene. Our aim in this study was to develop a polymerase chain reaction (PCR)-based assay that could determine these mutations in a single reaction tube. METHODS: We designed the forward primer FP2143G and the reverse primer RP2142G, which specifically anneal with the 2143G- and 2142G-mutated sequences, respectively, of the 23S rRNA gene of H. pylori. We also designed the forward primer FP-1 and reverse primer RP-1 upstream and downstream from the positions 2142 and 2143, respectively, to distinguish the wild-type A2142G and A2143G mutations from each other by amplicon sizes. DNA was extracted from 292 gastric tissue samples positive for rapid urease test, and the DNA underwent the PCR reaction. The results were compared with minimum inhibitory concentrations (MIC) for clarithromycin. RESULTS: Helicobacter pylori strains with A2142G, A2143G and wild type could be distinguished by amplicon sizes by a single PCR reaction. The genotyping results were correlated well with the MIC values for clarithromycin. The median MIC for clarithromycin of the wild-type strains was <0.015 microg/mL. Those of strains with 2142G or 2143G were > or =1.0 microg/mL. CONCLUSION: Our new PCR-based assay for 23S rRNA mutations of H. pylori is a useful method for detecting clarithromycin-resistant strains of H. pylori easily.     

Resistance rate to antibiotics of Helicobacter pylori isolates in eastern Taiwan

BACKGROUND AND AIM: Prevalence of Helicobacter pylori (H. pylori) strains resistant to metronidazole, clarithromycin and amoxicillin is increasing worldwide. The aim of this study was to determine the antibiotic susceptibility patterns in H. pylori strains isolated from eastern Taiwan. METHODS: One strain each of H. pylori was isolated from 133 symptomatic patients and subjected to determination of the minimal inhibitory concentration (MIC) by the Epsilometer test (E-test) for four antibiotics commonly used in the treatment of H. pylori infections. RESULTS: None of the strains were resistant to tetracycline. Resistance to metronidazole (8 microg/mL), clarithromycin (1 microg/mL) and amoxicillin (8 microg/mL) was found in 51.9%, 13.5% and 36.1% of the isolates, respectively. Metronidazole-resistant strains were isolated more frequently from women (49/78; 62.8%) than from men (20/55; 36.4%). Resistance to at least two antimicrobial agents was detected in 33.8% of the isolates. There was a high rate of resistance to both metronidazole and amoxicillin (18.1%). CONCLUSIONS: Clarithromycin and tetracycline may provide useful components of treatment regimens in eastern Taiwan. In addition, pretreatment microbial susceptibility testing rather than empiric therapy is highly recommended for eradication of H. pylori infection.     

Prevalences of metronidazole‐ and clarithromycin‐resistant Helicobacter pylori isolates in Shanghai and molecular mechanism of resistance to clarithromycin

OBJECTIVE : To investigate the prevalences of metronidazole‐ and clarithromycin‐resistant Helicobacter pylori over the period from 1995 to 1999 in Shanghai, and the molecular mechanism of resistance to clarithromycin. METHODS : A total of 150 H. pylori strains were randomly selected from the isolates collected in 1995, 1997 and 1999, and tested for sensitivity against metronidazole and clarithromycin by using the E‐test. The mechanism of resistance was studied by polymerase chain reaction (PCR)–restriction fragment length polymorphism (RFLP). RESULTS : It was found that 42% (21/50), 57% (27/50) and 70% (35/50) of the tested strains were resistant to metronidazole among the isolates collected in 1995, 1997 and 1999, respectively. In 1995, there was no strain (0/50) resistant to clarithromycin, of which the prevalence rose to 2% (1/50) in 1997, and to 10% (5/50) in 1999. The prevalences of metronidazole‐ and clarithromycin‐resistant H. pylori in 1999 were significantly higher than those in 1995 (P < 0.05). Of nine clarithromycin‐resistant H. pylori strains, eight were found to have an A→G mutation at position 2144 of domain V of the 23S rRNA. CONCLUSIONS : These results suggest a significant increase in the prevalences of metronidazole‐ and clarithromycin‐resistant H. pylori in Shanghai during the 1995–1999 period. The majority (88.8%) of clarithromycin‐resistant H. pylori isolates have an A2144G mutation in domain V of the 23S rRNA.     

Institutional difference of antibiotic resistance of Helicobacter pylori strains in Korea

GOALS: This study was performed to evaluate whether the prevalence rates of primary antibiotic resistance in Helicobacter pylori isolates could be different between 2 institutions, which are located in the different areas in Korea, and to evaluate the effect of antibiotic resistance on the eradication rate of H. pylori. STUDY: H. pylori were isolated from gastric mucosal biopsy specimens obtained from 113 Koreans, who did not have any eradication history. The susceptibilities of the H. pylori isolates to amoxicillin, clarithromycin, metronidazole, tetracycline, levofloxacin, and moxifloxacin were examined according to the agar dilution method by 1 technician. RESULTS: All of these patients were treated with the same regimen, proton pump inhibitor-amoxicillin-clarithromycin triple therapy. There was a statistical difference in resistance to metronidazole, levofloxacin, and moxifloxacin among 6 antibiotics between 2 institutions located in Seoul and Gyeonggi province. The rates of eradication were 94.2% for the clarithromycin and amoxicillin-susceptible strains, and 42.8% for the amoxicillin-susceptible and clarithromycin-resistant strains. In contrast, eradication rate was 100% for the amoxicillin-resistant strains. CONCLUSIONS: These results show that there is institutional difference of antibiotic resistance of H. pylori, explaining the institutional difference of eradication rate of H. pylori. The resistance to clarithromycin seems to be an important determinant for the eradication by proton pump inhibitor triple therapy but resistance to amoxicillin does not have any effect.     

山西省243株幽门螺杆菌药物敏感性及克拉霉素耐药基因突变特征分析

目的 了解山西幽门螺杆菌（Helicobacter pylori,H.pylori）对5种抗生素药物敏感性及其克拉霉素耐药相关基因突变特征.方法 收集临床分离的H.pylori243株,采用纸片扩散法检测H.pylori对5种抗菌药物的敏感性.选取所有耐克拉霉素及相当数量的敏感菌株,提取基因组DNA,PCR法扩增23SrRNA基因功能区并测序,测序结果采用DNAStar软件包分析.统计结果分析采用x2检验和Fisher精确概率法.结果 临床分离的243株H.pylori,药敏结果显示对甲硝唑,克拉霉素,阿莫西林,左氧氟沙星和呋喃唑酮5种药物的耐药率分别为：75.3％（183/243）,7.4％（18/243）,7.4％（18/243）,12.4％（30/243）,8.6％（21/243）,5种药物的耐药率有统计学意义（P＜0.05）.结论 H.pylori临床菌株对甲硝唑,左氧氟沙星,克拉霉素、阿莫西林及呋喃唑酮存在不同程度的耐药,以对甲硝唑耐药率最高.克拉霉素耐药菌株23SrRNA基因突变以A2143C为主,此突变可能与该地区H.pylori耐药性有关,此外,还发现了A2214G位点的突变.     

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

摘要：目的：了解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克拉霉素耐药相关基因突变情况,为耐药性的快速检测提供依据。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,了解贵阳地区Hp临床株对克拉霉素耐药状况。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23S rRNA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%。贵阳地区10株Hp耐药菌的23S rRNA基因片段的碱基突变包括T2183C（10/10）、T2245C（9/10）、 A2144G（6/10）、C2196G（1/10）、A2204G（1/10）,4株敏感菌株在2183、2245、2196和2204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。     

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 NTsys₂ 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.     

Metronidazole- and clarithromycin-resistant Helicobacter pylori in dyspeptic patients in western Sydney as determined by testing multiple isolates from different gastric sites

It is unknown whether antibiotic susceptibility testing of antral isolates alone is representative of Helicobacter pylori susceptibility. We aimed to determine: (i) the prevalence of metronidazole- and clarithromycin-resistant strains in infected dyspeptic patients; and (ii) whether there is consistency in the susceptibility to metronidazole and clarithromycin among isolates cultured from different gastric sites. Antral, body and fundus biopsies were taken from 242 consecutive patients and cultured on blood agar under micro-aerophilic conditions for 5–7 days. Isolates from 66 patients (13 had one, 15 had two and 38 had three isolates) were tested for susceptibility to metronidazole and clarithromycin using previously validated disc diffusion tests. Of the 66 patients, 42 (64%) had strains resistant to metronidazole while four (6.1%) had clarithromycin-resistant strains. The prevalence of metronidazole resistance was not significantly different between men and women (65% vs 60%) or across different age groups. In five (9.4%) of the 53 patients with multiple isolates, discrepant results for metronidazole susceptibility were observed: susceptible antral and body isolates but resistant fundus isolates in two cases and susceptible antral isolates but resistant body and fundus isolates in the others. Clarithromycin susceptibilities were consistent among the isolates cultured from different gastric sites in all patients. It is concluded that metronidazole-resistant strains of H. pylori are common while clarithromycin-resistant strains are rare. Metronidazole susceptibility testing of antral isolates does not appear to be representative of isolates from the body and fundus in a subset of patients.     

39株对克拉霉素耐药的结核分枝杆菌临床分离株23SrRNA检测结果分析

目的 分析对克拉霉素耐药的结核分枝杆菌临床分离株23S rRNA的A2058位点的变化。 方法 选择我院菌株库的结核分枝杆菌临床分离株64株,其中10株为对全部抗结核药物敏感的结核分枝杆菌临床分离株;14株为单耐克拉霉素的结核分枝杆菌临床分离株;15株为耐多药,同时耐克拉霉素的结核分枝杆菌临床分离株;15株为耐多药,同时对克拉霉素敏感的结核分枝杆菌临床分离株;10株为广泛耐药菌株,同时对克拉霉素耐药的结核分枝杆菌临床分离株;此外,还有结核分枝杆菌标准株H37Rv 1株。对结核分枝杆菌23S rRNA行PCR检测和测序。 结果 经检测,H37Rv标准株没有A2058突变,只有1株广泛耐药临床分离株检测有A2058A-G的突变,其他临床分离株均没有突变,在耐克拉霉素的结核分枝杆菌临床分离株中占2.56%（1/39）,在广泛耐药结核分枝杆菌临床分离株中占1/10。 结论 结核分枝杆菌临床分离株对克拉霉素耐药的机制中, A2058突变可能不是产生对克拉霉素耐药的主要机制。结核分枝杆菌产生对克拉霉素耐药的机制有待进一步研究。     

Antibiotic resistance of Helicobacter pylori isolated from Korean patients in 2003]

BACKGROUND/AIMS: Development of antibiotic resistance is a significant clinical problem in the eradication of H. pylori. To select an appropriate regimen, systematic information on antibiotic resistance is mandatory. Thus, we investigated the distribution of minimal inhibitory concentration (MIC) and evaluated the antibiotic resistance of H. pylori isolates from Korean patients in 2003. METHODS: The susceptibility of 65 isolates obtained in 2003 to amoxicillin, clarithromycin, metronidazole, tetracycline, azithromycin, and ciprofloxacin were determined by agar dilution method. RESULTS: Resistance rates of H. pylori to amoxicillin, clarithromycin, metronidazole, tetracycline, azithromycin, and ciprofloxacin were 18.5%, 13.8%, 66.2%, 12.3%, 32.3%, and 33.8%, respectively. Multi-drug resistance rate of H. pylori was 47.7%. Especially, 6.2% of the H. pylori isolates were resistant to both amoxicillin and clarithromycin. In addition, resistance to amoxicillin and clarithromycin resulted in decreasing tendency of the eradication efficacy for H. pylori. CONCLUSIONS: These results indicate that the antibiotics used for H. pylori eradication show high resistance rates in Korea. Furthermore, continuous surveillance of antibiotic susceptibilities should be needed and further increases in antibiotic resistance would require susceptibility testing before treatment to maximize the efficacy of H. pylori treatment.     

Simultaneous colonisation of Helicobacter pylori with and without mutations in the 23S rRNA gene in patients with no history of clarithromycin exposure

BACKGROUND: It was recently reported that A to G transition mutations at positions 2143 and 2144 in the 23S rRNA gene are associated with clarithromycin resistance in Helicobacter pylori. AIMS: To study the incidence and mechanism of development of clarithromycin resistance by analysing these mutations. SUBJECTS: Eighty two H pylori positive patients who had an endoscopic examination and no history of treatment with macrolide antibiotics. METHODS: Clarithromycin resistance was screened for by polymerase chain reaction-restriction fragment length polymorphism of the 23S rRNA gene coupled with antibiotic susceptibility testing. In clinical isolates with mutations or resistance, mutations in individual colonies were analysed by direct sequencing. RESULTS: Of the 79 amplicons (DNA fragments amplified by polymerase chain reaction), Alw26I and MboII digestion disclosed the mutation in four (5%) and one (1%) respectively. However, the Alw26I cleavage was incomplete in two of the four amplicons, as was the MboII cleavage. Individual colony analysis of the isolates with incomplete cleavage patterns showed the presence of both wild type and mutated strains in the 23S rRNA genes. CONCLUSIONS: Both clarithromycin sensitive and resistant strains colonised in some patients with no history of exposure to macrolides. The results suggest that resistant strains may not be formed but selected by clarithromycin administration.     

Prevalence of Helicobacter pylori resistance to clarithromycin and metronidazole determined by 23S ribosomal RNA and rdxA gene analyses in Hiroshima,Japan

BACKGROUND AND AIMS: Resistance to antibiotics in Helicobacter pylori is increasing and becoming a serious problem in eradication treatment of H. pylori. The prevalence of H. pylori infections that are resistant to clarithromycin, metronidazole, or both were determined in H. pylori isolates in Hiroshima, Japan. METHODS: Sixty Japanese patients with H. pylori infection were collected between 1999 and 2000. To detect the resistance to clarithromycin and metronidazole, mutations of the 23S ribosomal RNA (rRNA) and rdxA genes that are responsible for resistance in H. pylori, were examined by direct sequencing analysis. RESULTS: Resistance to clarithromycin and metronidazole was detected in 12 (20.0%) and nine (15.0%) of the patients, respectively. Dual resistance to clarithromycin and metronidazole was detected in five (8.3%) patients. CONCLUSION: These results indicate that the relatively high prevalence of the dual resistance in H. pylori isolates may need special attention and new therapeutic approaches in Japan.     

Clarithromycin-resistant helicobacter pylori in patients with duodenal ulcer in the united states

Background: Clarithromycin is a key component of several antimicrobial treatment regimens for Helicobacter pylori . Cure rates with clarithromycin-containing regimens are significantly decreased when resistance is present. Resistance develops by a point mutation in the ribosomal RNA of some organisms exposed to clarithromycin. We studied the prevalence of clarithromycin-resistant organisms in patients with duodenal ulcer in the United States from 1993–96.
Methods: Patients with endoscopic evidence of a duodenal ulcer were studied. Gastric biopsies were cultured for H. pylori and antimicrobial sensitivity was determined by the E-test (epsilometer agar diffusion gradient).
Results: In 1993–94, three of 78 patients (4%) had clarithromycin-resistant strains of H. pylori . In 1995–96, 44 of 348 patients (12.6%; p = 0.025 ) had resistant strains of H. pylori . Patients who had previously failed antimicrobial treatment for H. pylori accounted for much of the increase in resistant strains (25%).
Conclusions: Failed therapy with clarithromycin-based regimens is a growing cause of antimicrobial resistance in H. pylori in the United States. Whereas the overall rates of primary resistance are low, the increase in secondary resistance over a short period of time is worrisome. New treatments that prevent the emergence of resistance may be important in the future.     

幽门螺杆菌对克拉霉素的耐药性与23S rRNA基因突变相关性分析

[目的]研究本地区幽门螺杆菌（Helicobacter pylori,HP）的克拉霉素耐药与23S rRNA基因位点突变的关系,为临床根除HP治疗提供依据.[方法]入选消化性溃疡患者180例,在胃窦小弯侧距幽门2～3cm范围内取1块胃黏膜组织行常规病理检查,在胃窦小弯侧、十二指肠球部、胃体大弯侧各取1块黏膜行HP培养,对HP阳性分离菌株进行药敏实验.选取其中克拉霉素耐药菌株35例及敏感菌株30例,对23S rRNA基因PCR扩增后进行全基因测序对比分析.[结果] 180例中HP阳性率占76.11％,活检组织培养HP阳性率占73.89％.药敏检查结果克拉霉素耐药率为33.08％.HP23S rRNA测序结果显示存在多位点突变,耐药组及非耐药组中T2182C普遍存在,A2143G、A2142G和A2097G在耐药组中多见,A2097C、A2097T仅在敏感组中发现,差异有统计学意义.[结论]本地区HP对克拉霉素耐药率高,克拉霉素耐药菌株A2143G、A2142G和A2097G位点突变高于敏感组,建议根据药敏试验指导根除HP方案.