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.     

Resistance to metronidazole, clarithromycin and levofloxacin of Helicobacter pylori before and after clarithromycin-based therapy in Taiwan

Background and Aim:  Clarithromycin-based triple therapy has been commonly applied as the first-line therapy for Helicobacter pylori eradication. Levofloxacin could serve as an alternative in either first-line or second-line regimens. This study surveyed the prevalence of levofloxacin resistance of H. pylori isolates in naive patients and in patients with a failed clarithromycin-based triple therapy.
Methods:  The study collected the H. pylori isolates from 180 naive patients and 47 patients with a failed clarithromycin-based triple therapy. Their in vitro antimicrobial resistance was determined by E -test.
Results:  The naive H. pylori isolates had resistance rates for amoxicillin, levofloxacin, clarithromycin and metronidazole of 0%, 9.4%, 10.6% and 26.7%, respectively. An evolutional increase of the primary levofloxacin resistance was observed in isolates collected after 2004, as compared to isolates collected before 2004 (16.3% vs 3.2%, P  = 0.003). There was no evolutional increment of the primary clarithromycin resistance. The clarithromycin resistance elevated significantly after a failed clarithromycin-based triple therapy (78.7% vs 10.6%, P  < 0.001). The post-treatment isolates remained to have a levofloxacin resistance rate of near 17%, but the levofloxacin-resistant isolates were correlated with a higher incidence of metronidazole resistance ( P  = 0.023). No strain was found to be resistant to amoxicillin even after eradication failure.
Conclusion:  The levofloxacin resistance of naive H. pylori remains less than 10% in Taiwan. With relatively lower resistance to levofloxacin than to metronidazole of the H. pylori isolates collected after a failed clarithromycin-based therapy, proton pump inhibitor–levofloxacin–amoxicillin may be an alternative choice to serve as the second-line therapy.     

Antibiotic treatment for Helicobacter pylori : Is the end coming?

Infection with the Gram-negative pathogen Helicobacter pylori(H. pylori) has been associated with gastroduodenal disease and the importance of H. pylori eradication is underscored by its designation as a groupI carcinogen. The standard triple therapy consists of a proton pump inhibitor, amoxicillin and clarithromycin, although many other regimens are used, including quadruple, sequential and concomitant therapy regimens supplemented with metronidazole, clarithromycin and levofloxacin. Despite these efforts, current therapeutic regimens lack efficacy in eradication due to antibiotic resistance, drug compliance and antibiotic degradation by the acidic stomach environment. Antibiotic resistance to clarithromycin and metronidazole is particularly problematic and several approaches have been proposed to overcome this issue, such as complementary probiotic therapy with Lactobacil us. Other studies have identified novel molecules with an anti-H. pylori effect, as well as tailored therapy and nanotechnology as viable alternative eradication strategies. This review discusses current antibiotic therapy for H. pylori infections, limitations of this type of therapy and predicts the availability of newly developed therapies for H. pylori eradication.     

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.     

Patterns of Helicobacter pylori isolate resistance to fluoroquinolones, amoxicillin, clarithromycin and metronidazoles

Helicobacter pylori eradication using the three antibiotic regimen of amoxicillin, clarithromycin and metronidazole often fails, making it imperative to find substitutes. The following study made use of 72 H. pylori isolates derived from pyloric antrum mucosa biopsies of gastritis and chronic dyspepsia patients treated at the Cipto Mangunkusumo National General Hospital and three private hospitals in Jakarta. Testing for H. pylori sensitivity to various antimicrobials was conducted using the disk diffusion method (Kirby Bauer) and procedures determined by the Clinical and Laboratory Standards Intitute (CLSI)/NCCLS. The resistance rates of the isolates were 100% for metronodazole, 27.8% for clarithromycin, 19.4% for amoxicillin, 6.9% for ciprofloxacin, norfloxacin and ofloxacin, 2.8% for sparfloxacin and gatifloxacin, and 1.4% for levofloxacin and moxifloxacin. Fluoroquinolons have the lowest resistance compared to amoxicillin, clarithromycin and metronidazole.     

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.     

Treatment of Helicobacter pylori

Triple therapy, consisting of two antibiotics, clarithomycin and amoxicillin or metronidazole in combination with a proton pump inhibitor (PPI) has become the first-line option for infection with Helicobacter pylori and has been recommended at several consensus conferences. In clinical practice, approximately 20% of patients will fail to obtain H. pylori eradication with the recommended treatment regimens. Major causes of treatment failure are insufficient patient compliance and antibiotic resistance. Because of antibiotic resistance, bismuth-based quadruple therapy has also become a first-line regimen in areas with exceedingly high rates of clarithromycin and metronidazole resistance, and is the preferred second-line option otherwise. Triple therapies based on levofloxacin and/or rifabutin mainly with combination of amoxicillin are options if multiple eradication failure occurs. However, following therapy failure beyond a second treatment attempt requires antibiotic resistance testing. New drugs and adjuvant agents have been reported but their efficacy needs further evaluation.     

Treatment of Helicobacter pylori infection]

Significant progress and new insights have been gained since Helicobacter pylori was found in 1982. Even with currently most effective treatment regimen, about 10-20% of patients will fail to obtain the eradication of H. pylori infection. This review will focus on the empirical treatment for H. pylori infection in Korea. Seven days triple therapy (proton pump inhibitor, amoxicillin and clarithromycin) has been the main first line therapy for H. pylori infection in Korea after the recommendation by Korean H. pylori study group in 1998. Such triple therapy has been the effective regimen for eradication of H. pylori infection. However, the efficacy of 7 days proton pump inhibitor-amoxicillin-clarithromycin therapy becomes lower and various eradication rates probably reflects the increase in antimicrobial resistance, recently. The recent multi-center prospective randomized study and meta-analysis showed 14 days proton pump inhibitor-amoxicillin-clarithromycin therapy is more effective than 7 days or 10 days therapy. In the case of failure, quadruple therapy (proton pump inhibitor, a bismuth salt, metronidazole and tetracycline) is a very effective second-line regimen. After the failure of two or more eradication treatments, bacterial resistance to antibiotics should be evaluated and the regimen of third-line therapy should be selected according to each antimicrobial susceptibility. The empirical third-line therapies, recommended in the cases that antimicrobial susceptibility test is unavailable, are unclear of its validity at present in Korea. The triple therapies including rifabutin, moxifloxacin, or levofloxacin or dual therapy including high dose proton pump inhibitor and amoxicillin are needed to be proven as possible candidates for the empirical third-line therapy. Multiple eradication failures should be handled on a case-by-case basis by specialists.     

Changing pattern of antimicrobial resistance of <Emphasis Type="Italic">Helicobacter pylori</Emphasis> in Korean patients with peptic ulcer diseases

BACKGROUND: Antibiotic resistance of Helicobacter pylori is problematic because it reduces the efficacy of eradication therapy. It has been suggested that the incidence of resistance is rising. In Korea, information on the antimicrobial resistance of H. pylori is rare. The aim of this study was to assess the prevalence of H. pylori antibiotic resistance at a single center in Korea, and the changes in its antimicrobial resistance, and to detect the mutation foci of clarithromycin-resistant strains. METHODS: H. pylori isolates obtained from 224 patients with peptic ulcer disease in Korea between June 1996 and March 2000 were tested for antimicrobial resistance. The minimum inhibitory concentration (MIC) for metronidazole and clarithromycin was determined by the broth microdilution method. Isolates were considered resistant when the MIC was more than 8 microg/ml for metronidazole and more than 1 microg/ml for clarithromycin. To detect H. pylori 23S rRNA mutations, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed. Sequencing was performed on the two strands of the nonrestricted amplicons. RESULTS: Overall, resistance to metronidazole and clarithromycin was detected in 41.9% and 5.4% of patients, respectively. There was no significant difference in metronidazole and clarithromycin resistance according to age group and sex. Six strains were resistant to both metronidazole and clarithromycin. Six of nine clarithromycin-resistant isolates possessed the A2144G mutation in the gene encoding 23S rRNA. Sequencing of the three non-restricted clarithromycin-resistant strains revealed a T-to-C mutation at position 2182. CONCLUSIONS: In Korea, there was no significant increase in the prevalence of metronidazole resistance, but clarithromycin-resistant H. pylori strains had increased relatively over the 5-year period. There was an increasing tendency for the emergence of strains with dual resistance to metronidazole and clarithromycin. Many of the clarithromycin-resistant strains possessed the A2144G mutation.     

Helicobacter pylori antibiotic resistance in a Dutch region: trends over time

AIM: Most patients treated for H. pylori infection receive empirical therapy based on epidemiological data of antibiotic resistance. However, previous European studies indicate that resistance patterns may be changing. Therefore, the aim of this study was to investigate the prevalence of primary clarithromycin and/or metronidazole resistant H. pylori strains over a six-year period (1997-2002) in a regional hospital. METHODS: All patients visiting Slingeland Hospital in Doetinchem, the Netherlands between 1997 and 2002 with a positive H. pylori culture were included in this study. Susceptibility to metronidazole and clarithromycin was determined by disk diffusion. RESULTS: Of the 1355 patients with an H. pylori positive culture, 1127 did not have a history of H. pylori eradication, 58 did, and for 170 this information was not available. Mean rates of primary resistance to metronidazole and clarithromycin were 14.4% (162/1125) and 1.0% (11/1123), respectively. Primary metronidazole resistance was stable throughout the study period and primary clarithromycin resistance showed a decreasing trend. Patients of foreign descent and from secondary care had a higher chance of harbouring primary metronidazole-resistant H. pylori (adjusted OR (95% CI) 1.75 (1.1 to 2.8), and 1.60 (1.1 to 2.2), respectively). Patients with failed H. pylori eradication had a higher chance of harbouring metronidazole-resistant H. pylori (43 vs 14%, p<0.0001) and clarithromycin-resistantH. pylori (5.3 vs 1.0%, p=0.004) than untreated patients.CONCLUSION: Primary metronidazole resistance is stableat a low level, while primary clarithromycin resistance isvirtually absent in the eastern part of the Netherlands.Therefore, triple therapy with a proton pump inhibitor,clarithromycin and amoxicillin can remain the empiricaltreatment of choice in the Netherlands.     

The efficacy of levofloxacin based triple therapy for Helicobacter pylori eradication]

BACKGROUND/AIMS: The failure rates of first and second line therapies of Helicobacter pylori (H. pylori) eradication range from 15 to 20%. This study was aimed to evaluate the efficacy and safety of levofloxacin based triple therapy compared with standard triple or quadruple therapy for H. pylori eradication in Korea. METHODS: We enrolled two hundred and sixty seven patients with presence of H. pylori infection. One hundred and forty-one patients were treated with levofloxacin based triple therapy (LAP; levofloxacin, amoxicillin, proton pump inhibitor; PPI), and 126 patients were treated with standard triple therapy (CAP; clarithromycin, amoxicillin, PPI). We retreated the patients who had failed in H. pylori eradication with standard quadruple second-line therapy (MTPB; metronidazole, tetracycline, PPI, bismuth subcitrate) or levofloxacin based therapy (LAP or LCP; levofloxacin, clarithromycin, PPI). RESULTS: In first line therapy of H. pylori eradication, the eradication rates of levofloxacin based triple therapy and standard triple therapy were 69.8% and 74.0% respectively (p=0.52). In second-line therapy, the eradication rate of levofloxacin based triple therapy and standard quadruple therapy were 62.5% and 40.0% respectively (p=0.34). CONCLUSIONS: Levofloxacin based triple therapy is effective as standard regimen to eradicate H. pylori infection and is useful for an alternative rescue therapy as well.     

Antimicrobial susceptibility of Helicobacter pylori strains isolated from patients in Shiraz, Southern Iran

AIM: To improve our understanding of Iranian regional variation in Helicobacter pylori (H. pylori ) antibiotic resistance rates to find the best antibiotic therapy for eradication of H. pylori infections.METHODS: A total of 266 patients undergoing endoscopy in Shiraz, Southern Iran, were included in this study. H. pylori strains were isolated from antral biopsies by culture and confirmed by the rapid urease-test and gram staining. Antibiotic susceptibility of H. pylori isolates was determined by E-test.RESULTS: A total of 121 H. pylori strains were isolated, 50 from male and 71 from female patients. Data showed that 44% (n = 53), 20% (n = 24), 5% (n = 6), and 3% (n = 4) of all strains were resistant to the antibiotics metronidazole, amoxicillin, clarithromycin, and tetracycline, respectively. When the antibiotics were considered together we found 11 sensitivity patterns for the strains. Resistance to metronidazole was significantly higher in female than in male patients (P < 0.05). In about 71% of the metronidazole-resistant isolates, the minimum inhibitory concentrations (MICs) exceeded 256 μg/mL.CONCLUSION: We found a moderate rate of primary resistance to metronidazole. However, a high MIC (> 256 mg/L) which was found in 71% of the isolates is considerable. In the case of amoxicillin, an increased resistance rate of 20% is worrying. Resistance to clarithromycin and tetracycline is also emerging among the H. pylori strains in our region.     

Incidence of secondary Helicobacter pylori resistance to antibiotics in treatment failures after 1-week proton pump inhibitor-based triple therapies: a prospective study

BACKGROUND: Antibiotic-resistant Helicobacter pylori strains are becoming increasingly prevalent, although it is not clear to what extent the new resistant organisms will spread. AIM: To evaluate the incidence of secondary Helicobacter pylori resistance to metronidazole, clarithromycin and/or amoxycillin after one-week proton pump inhibitor based triple therapy failure in patients who were, before therapy infected with Helicobacter pylori strains susceptible to these antibiotics. PATIENTS AND METHODS: Enrolled in the study were 97 consecutive Helicobacter pylori-positive subjects infected by Helicobacter pylori strains susceptible to metronidazole, clarithromycin and amoxycillin. Activity of tested antibiotics was determined by means of the E-test. Patients were treated for seven days with a proton pump inhibitor, omeprazole 20 mg twice daily or pantoprazole 40 mg once daily, plus clarithromycin 250 mg twice daily and metronidazole 250 mg four times daily; or with a proton pump inhibitor plus amoxycillin 1 g twice daily and clarithromycin 500 mg twice daily. Two months after completion of therapy, endoscopy and gastric biopsies for histology, rapid urease test and culture were repeated. RESULTS: Four patients were dropped from the study Overall Helicobacter pylori cure rates expressed as both intention-to-treat and per-protocol analyses, were, respectively 80% (40/50) and 81.6% (40/49) with proton pump inhibitor, clarithromycin and metronidazole and 76.6% (36/47) and 81.8% (36/44) with proton pump inhibitor amoxycillin and clarithromycin. No significant differences were observed between the two treatments. Subjects in whom treatment failed were significantly younger and had less active ulcer than cured patients. Of treatment failures, 70.6% (12 out of 17 subjects) de veloped a secondary resistance to metronidazole (35.33% and/or clarithromycin (64.7%). Secondary antibiotic resistance occurred in 77. 8% of treatment failures treated with proton pump inhibitor, clarithromycin and metronidazole and in 62.5% of those treated with proton pump inhibitor, amoxycillin and clarithromycin. Considering all patients treated, the overall incidence of secondary metronidazole and/or clarithromycin resistance after therapy was reported in 12.9% of subjects (12 out of 93 treated patients). CONCLUSIONS: Secondary Helicobacter pylori resistances to metronidazole and/or clarithromycin occurred in large percentages in patients with treatment failure after the one-week proton pump inhibitor-based triple therapies, proton pump inhibitor, clarithromycin and metronidazole and proton pump inhibitor, amoxycillin and clarithromycin. It is likely that new antibiotics or treatment strategies will be needed in the near future to successfully treat Helicobacter pylori infection.     

Helicobacter pylori eradication therapy in Korea

Helicobacter pylori (H. pylori) is known to be associated with many gastrointestinal diseases including peptic ulcer. In Korea, eradication of H. pylori is recommended for peptic ulcer disease, low grade gastric mucosa-associated lymphoid tissue lymphoma, and early gastric cancer. Standard triple therapy using proton pump inhibitor, clarithromycin, and amoxicillin and bismuth-containing quadruple therapy have been the main first-line and second-line therapy for H. pylori in Korea. Although eradication rate of second-line quadruple therapy remains similar to that of the past, the success rate of eradication with triple therapy has decreased with increasing antimicrobial resistance to H. pylori. There is no standard third-line therapy, and some regimens that incorporate levofloxacin, moxifloxacin, and rifabutin can be used. New regimens such as sequential or concomitant therapy are suggested as alternative treatment for H. pylori. We need more well designed randomized controlled studies to choose proper treatment for H. pylori infection.     

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.     

Five-year sequential changes in secondary antibiotic resistance of Helicobacter pylori in Taiwan

AIM: To determine changes in the antibiotic resistance of Helicobacter pylori(H. pylori) in southern Taiwan after failure of first-line standard triple therapy.METHODS: We analyzed 137 H. pylori-infected isolates from patients who experienced eradication failure after standard first-line triple therapy from January2010 to December 2014. The H. pylori strains were tested for susceptibility to amoxicillin, clarithromycin,levofloxacin, metronidazole and tetracycline using the E-test method. The minimal inhibitory concentration(MIC) was determined by the agar dilution test.MIC values of ≥ 0.5, ≥ 1, ≥ 1, ≥ 4 and ≥ 8 mg/L were considered to be the resistance breakpoints for amoxicillin, clarithromycin, levofloxacin, tetracycline and metronidazole, respectively.RESULTS: A high resistance rate was found for clarithromycin(65%-75%) and metronidazole(30%-40%)among patients who failed first-line standard therapy.The resistance levels to amoxicillin and tetracycline remained very low; however, levofloxacin resistance was as high as 37.5% in 2010 but did not increase any further during the past 5 years. The rates of resistance to these antibiotics did not show a statistically significant upward or downward trend.CONCLUSION: Antibiotic resistance of H. pylori remains a problem for the effective eradication of this pathogen and its associated diseases in Taiwan. High clarithromycin resistance indicated that this antibiotic should not be prescribed as a second-line H. pylori eradication therapy. Moreover, levofloxacin-based second-line therapy should be used cautiously, and the local resistance rates should be carefully monitored.     

Evaluation of three different proton pump inhibitors with amoxicillin and metronidazole in retreatment for Helicobacter pylori infection

GOALS: We compared the eradication results of retreatment of eradication with proton pump inhibitor (PPI) plus amoxicillin and metronidazole for patients with Helicobacter pylori infection not eradicated by initial treatment with PPI plus amoxicillin and clarithromycin. BACKGROUND: In Japan, the guideline proposes that the use of metronidazole in a triple therapy containing PPI, PPI plus amoxicillin and metronidazole is desirable in retreatment. However, there are no reports comparing various retreatment using different PPIs. METHODS: After initial treatment failure with a PPI plus amoxicillin and clarithromycin, 169 patients were randomized to a PPI (rabeprazole, lansoprazole, or omeprazole) plus amoxicillin and metronidazole given b.i.d. for 7 days. RESULTS: Pretreatment susceptibility testing showed a high level of clarithromycin resistance (78%). The over all eradication rates were similar with the 3 PPIs, 91.1% range 90.1 to 91.4 with intention-to-treat analysis. The presence of metronidazole resistance reduced the eradication rate by approximately 40% (from 96.6% to 57.1%, P<0.05). CONCLUSIONS: In Japan, the combination of a PPI plus amoxicillin and metronidazole provide excellent eradication rates after initial treatment failure with a PPI plus amoxicillin and clarithromycin. The results with metronidazole resistant strains are less satisfactory and pretreatment susceptibility testing may become needed if the prevalence of metronidazole resistant H. pylori increase.     

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.     

Antibiotic susceptibility of Helicobacter pylori in the Chinese population

AIM: To assess antibiotic susceptibility of Helicobacter pylori (H. pylori) strains to metronidazole, clarithromycin and tetracycline in the Chinese population, and to test the stability of antibiotic resistance in H. pylori 1 year after storage at -80 degrees C. METHODS: Fifty H. pylori strains isolated from patients with peptic ulcer disease were recovered from storage at -80 degrees C. Susceptibility of these strains to metronidazole, clarithromycin and tetracycline was determined by using validated disk diffusion tests, which was repeated 1 year after storage at -80 degrees C. The DNA profiles of each strain were determined by using the polymerase chain reaction-based-random amplified polymorphic DNA fingerprinting technique (PCR-RAPD). This was repeated if any change in antibiotic susceptibility pattern was noticed. RESULTS: The resistance rate was 50% to metronidazole and 8% to clarithromycin. None of the strains was resistant to tetracycline. A dual resistance to metronidazole and clarithromycin was demonstrated in three H. pylori strains. The antibiotic susceptibility test reproduced itself in 92% (36 of 39) of the strains 1 year later; the three strains with dual resistance exhibited susceptibility to both antibiotics. Variation in antibiotic susceptibility pattern in the three H. pylori strains was associated with change in the RAPD fingerprint. CONCLUSION: The prevalence of resistance in H. pylori is high to metronidazole but low to clarithromycin in the Chinese population. The disk diffusion test appears to be a simple and reliable test, while antibiotic resistance in some H. pylori strains may disappear after long-term storage at -80 degrees C.     

Pharmacologic aspects of eradication therapy for Helicobacter pylori Infection

The commonly used regimens for the eradication of Helicobacter pylori infection consist of administration of proton pump inhibitors (PPIs) and 1 to 3 antimicrobial agents, such as amoxicillin, clarithromycin, metronidazole, fluoroquinolone, or tetracycline. Each agent has its own pharmacologic characteristics. PPIs are metabolized by cytochrome P450 2C19 (CYP2C19), which is polymorphic. CYP2C19 genotypic differences in the pharmacokinetics and pharmacodynamics of PPIs influence the eradication rates of H pylori infection by PPI-containing regimens. Amoxicillin is a time-dependent antibiotic, whereas clarithromycin, metronidazole, tetracycline, and fluoroquinolone are not. The plasma half-life of antimicrobial agents also differs among these antibiotics. To achieve consistently high eradication rates, the eradication regimens must be designed based on a good understanding of the resistance patterns of the bacteria and the pharmacologic characteristics of the agents used for H pylori eradication therapy.