• 대한미생물학회지
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• 제34권6호
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• pp.543-554
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• 1999

The purpose of this study was to evaluate the existence of amoxicillin, clarithromycin, and metronidazole resistance Helicobacter pylori and to determine the in-vitro MIC of two and three kinds of antibiotic concominant administration in the isolates. The antimicrobial agents tested against 169 H. pylori included metronidazole, amoxicillin, ciprofloxacin, clarithromycin, omeprazole, josamycin, erythromycin, and tetracycline. MIC of each antimicrobial agents was determined by broth microdilution method. The 169 strains of H. pylori were isolated from biopsy specimens of patients with gastric cancer. $MIC_{50}$ of clarithromycin, amoxicillin, metronidazole, omeprazole, erythromycin, josamycin, tetracycline, and ciprofloxacin was 2.0, 1.0, 4.0, 8.0, 0.5, 0.5, and $0.5\;{\mu}g/ml$, respectively. $MIC_{90}$ of clarithromycin, amoxicillin, metronidazole, omeprazole, erythromycin, josamycin, tetracycline, and ciprofloxacin was 64.0, 64.0, 32.0, 16.0, 8.0, 2.0, and $1.0\;{\mu}g/ml$, respectively. H. pylori isolates were detected in the following resistaince rates: 34.3% to clarithromycin, 31.9% to metronidazole, 20.7% to amoxicillin, 12.4% to erythromycin, and 10.1% to josamycin. The prevalence of the antibiotic resistant strains of H. pylori were detected 18.1% for two kind of antibiotics and 9.6% for three kind of antibiotics, and 3.9% for four kind of antibiotics. The $MIC_{90}$ of clarithromycin-, metronidazole-, and amoxicillin-resistant H. pylori was decreased under the $1\;{\mu}g/ml$ by the two or three kind of antibiotic concomitant administration in-vitro. These results suggest that two or three antibiotics concomitant administration could be more effective for the treatment of clarithromycin-, amoxicillin-, metronidazole-, and josamycin-resistant H. pylori strains.

• Asian Pacific Journal of Cancer Prevention
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• 제16권10호
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• pp.4353-4356
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• 2015

Background: Levofloxacin is an effective medication for second line Helicobacter pylori (H. pylori) eradication. However, limited studies have approved its use as an effective antibiotic in first line therapy. Dexlansoprazole is a new PPI and lacks of evidence in support of a role in H. pylori eradication. This study was designed to evaluate efficacy of levofloxacin-dexlansoprazole-based quadruple therapy for H. pylori eradication in Thailand. Materials and Methods: This prospective randomized control study was performed during June 2014 to December 2014. H. pylori infected gastritis patients were randomized to receive 7- or 14-day levofloxacin-dexlansoprazole based on quadruple therapy (levofloxacin 500 mg OD, dexlansoprazole 60 mg bid, clarithromycin MR 1000 mg OD, bismuth subsalicylate 1048 mg bid). CYP2C19 genotyping and antibiotic susceptibility tests were conducted for all patients. A 13C urea breath test was performed to confirm H. pylori eradication at least 4 weeks after treatment. Results: A total of 100 patients were enrolled, comprising 44 males and 56 females (mean age of 52.6 years). Eradication rate by PP analysis was 85.7% (42/49) with the 7-day regimen and 98% (48/49) with the 14-day regimen (85.7% vs 98%; p-value=0.059). ITT analysis was 84% and 96% with 7- and 14-day regimens, respectively (84% vs 96%; p-value=0.092). Antibiotic susceptibility testing demonstrated 35.1% resistance to metronidazole, 18.3% to clarithromycin, and 13.5% to levofloxacin. CYP2C19 genotyping revealed 54.1% RM, 34.7% IM and 11.2% PM. The 14-day regimen provided 100% eradication in patients with clarithromycin or dual clarithromycin and metronidazole H. pylori resistant strains. Moreover, the eradication rate was 96.6% in patients with CYP2C19 genotype RM. Conclusions: The 14-day levofloxacin-dexlansoprazole based quadruple therapy provides high H. pylori eradication regardless of CYP2C19 genotype, clarithromycin or dual clarithromycin and metronidazole resistant strains. This regimen could be use as an alternative first line therapy for H. pylori eradication in Thailand.

• 한국식품영양과학회:학술대회논문집
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• 한국식품영양과학회 2001년도 International Symposium on Food,Nutrition and Health for 21st Century
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• pp.161-169
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• 2001

Lactic acid producing bacteria were isolated from baby feces and characterized to be used as a probiotic with anti Helicobacter pylori functions. The selected bacteria had inhibition activity on the adherance and growth of H. pylori. These bacteria had additional beneficial characteristics for the probiotic such as antibacterial activity, antitumor activity, immunostimulation activity, resistance to antibiotic and bile salt, ability to bind to the intestinal cells, and safe for the human use.

• Journal of Microbiology and Biotechnology
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• 제9권3호
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• pp.328-333
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• 1999

Susceptibility of 61 strains of Helicobacter pylori to metronidazole was examined by both the disk diffusion method using a cut-off of 15㎜ for resistance and the E test with a cut-off of 8㎎/l. The MIC/sub 50/ and MIC/sub 90/ by the E test were 2 ㎎/l and 256㎎/l, respectively. Metronidazole resistance was found in 22 (36％) out of the 61 H. pylori strains by the E test and in three additional strains by the disk diffusion method. Amongst the latter three isolates, the MICs by the E test were 4 ㎎/l, 6㎎/l, and 6㎎/l, respectively. These figures are one log₂ or half log₂ dilution lower than the cut-off of 8㎎/l recommended as resistance for the E test. All 22 metronidazole resistant H. pylori isolates by the E test that were subjected to random amplified polymorphic DNA (RAPD) fingerprinting showed different DNA fingerprints. Interestingly, >90％ of resistant isolates possess two common DNA bands of 0.4 and 0.9 kb. This study demonstrates that the results of the disk diffusion method for testing H. pylori susceptibility to metronidazole correlates well with that of the E test. The criteria for interpretation need to be internationally standardized so that the results from different centers can be compared.

• Preventive Nutrition and Food Science
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• 제18권2호
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• pp.104-110
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• 2013

Presence of Helicobacter pylori is associated with an increased risk of developing upper gastrointestinal tract diseases. Antibiotic therapy and a combination of two or three drugs have been widely used to eradicate H. pylori infections. Due to antibiotic resistant drugs, new drug resources are needed such as plants which contain antibacterial compounds. The aim of this study was to investigate the ability of GutGard$^{TM}$ to inhibit H. pylori growth both in Mongolian gerbils and C57BL/6 mouse models. Male Mongolian gerbils were infected with the bacteria by intragastric inoculation ($2{\times}10^9$ CFU/gerbil) 3 times over 5 days and then orally treated once daily 6 times/week for 8 weeks with 15, 30 and 60 mg/kg GutGard$^{TM}$. After the final administration, biopsy samples of the gastric mucosa were assayed for bacterial identification via urease, catalase and ELISA assays as well as immunohistochemistry (IHC). In the Mongolian gerbil model, IHC and ELISA assays revealed that GutGard$^{TM}$ inhibited H. pylori colonization in gastric mucosa in a dose dependent manner. The anti-H. pylori effects of GutGard$^{TM}$ in H. pylori-infected C57BL/6 mice were also examined. We found that treatment with 25 mg/kg GutGard$^{TM}$ significantly reduced H. pylori colonization in mice gastric mucosa. Our results suggest that GutGard$^{TM}$ may be useful as an agent to prevent H. pylori infection.

• Asian Pacific Journal of Cancer Prevention
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• 제17권1호
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• pp.285-287
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• 2016

Background: The efficacy of standard treatment of Helicobacter pylori (H. pylori) is declining because of antibiotic resistance. Clarithromycin resistance is also increasing in many Asian countries. The aim of this study was to determine the antibiotic susceptibility patterns of H. pylori infection and clinical association in Laos. Materials and Methods: A total of 329 Lao dyspeptic patients who underwent gastroscopy at Mahosot Hospital, Vientiane, Laos during December 2010-March 2012 were enrolled in this study. During gastroscopy, 4 biopsies were collected (2 each from the antrum and body) for CLO-test and histopathology. Only the positive CLO-test gastric tissues was stored at $-80^{\circ}C$ in a freezer until DNA was extracted and a GenoType$^{(R)}$HelicoDR test was conducted for detecting mutations in the rrl gene encoding 23S rRNA (clarithromycin resistance) and mutations in gyrA gene (fluoroquinolone resistance). Results: Of the total, 119 Lao patients (36.2%) were infected with H. pylori including 59 males (49.6%) and 60 females (50.4%) with a mean age of 46 years. Clarithromycin and fluoroquinolone resistance of H. pylori infection was demonstrated in 15 (12.6%) and 16 strains (13.4%) respectively. In clarithromycin resistance, the number of patients who had education above primary school and $BMI{\geq}25kg/m^2$ were significantly higher than those who had education below primary school and BMI<$25kg/m^2$ (23.1% vs 7.5%, P-value= 0.036 and 20.5% vs 8%, P-value= 0.048, respectively). In fluoroquinolone resistance, the number of lowland Lao was significantly higher than those of non-lowland (highland and midland) Lao ethnic groups (16.7% vs 0%, P-value= 0.039). Conclusions: H. pylori infections remain common in Laos. Clarithromycin and fluoroquinolone resistance with H. pylori infection are growing problems. Education above primary school and $BMI{\geq}25kg/m^2$ might be predictors for clarithromycin resistance and lowland Lao ethnicity might be predictors for fluoroquinolone resistance with H. pylori infection in Laos.

• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.1903-1907
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• 2016

Background: Studies of effects of IL-1 polymorphisms, CYP2C19 genotype together with antibiotic resistance for H. pylori eradication are rare worldwide. The present study was designed to evaluate efficacy of 10-day sequential therapy (SQT) and 14-day standard triple therapy (STT) with four- times-daily dosing of amoxicillin for H. pylori eradication related to these important host and bacterial factors in Thailand. Materials and Methods: This prospective randomized study was performed during March 2015 to January 2016. H. pylori infected gastritis patients were randomized to receive 10-day sequential therapy and 14-day standard triple therapy. CYP2C19 genotyping, IL1 polymorphism (IL-1B and IL-1RN genotypes) and antibiotic susceptibility tests were performed in all patients. 13C-UBT was conducted to confirm H. pylori eradication at least 4 weeks after treatment. Results: A total of 100 patients (33 males and 67 females, mean age=51.1 years) were enrolled. Eradication rate by PP analysis was 97.9% (47/48) with the 10-day SQT regimen and 87.8% (43/49) with 14-day STT regimen (97.9% vs 87.8%; p-value=0.053). Antibiotic susceptibility testing demonstrated 45% resistance to metronidazole, 14.8% to clarithromycin, and 24.1% to levofloxacin. CYP2C19 genotyping revealed 44.9% RM, 49% IM and 6.1% PM. IL-1B and IL-1RN genotypes were demonstrated as 21.4% for CC, 48.1% for TC, 36.8% for TT, 72.7% for 1/1, and 21.2% for 1/2 genotypes, respectively. The 10-day SQT regimen provided 100% eradication in patients with clarithromycin or dual clarithromycin and levofloxacin H. pylori resistant strains. Moreover, the 10-day SQT regimen resulted in a 100% eradication rate in all patients with CYP2C19 genotype RM and almost type of IL-1B (TC and TT) and IL1-RN genotypes ( 1/2 and other). Conclusions: Treatment with 10-day sequential therapy is highly effective for H. pylori eradication regardless of the effects of clarithromycin resistance, dual clarithromycin and levofloxacin resistance, CYP2C19 genotype, IL-1B and IL1-RN genetic polymorphisms and can be used as effective first line therapy in Thailand.

• Asian Pacific Journal of Cancer Prevention
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• 제16권14호
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• pp.6089-6092
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• 2015

Background: The prevalence of metronidazole-resistant H. pylori is almost 50% in Thailand which severely limits the use of this drug for eradication therapy. The aims of this study were to evaluate the efficacy and safety profiles of 7-day bismuth-based quadruple therapy including metronidazole as an initial treatment for H. pylori infection in a high metronidazole resistance area. Materials and Methods: This study was performed at Thammasat University Hospital and King Chulalongkorn Memorial Hospital during January 2009 to October 2010. Patients with non-ulcer dyspepsia (NUD) with active H. pylori infection were assigned to receive seven days of quadruple therapy (pantoprazole 40 mg bid, bismuth subsalicylate 1,048 mg bid, amoxicillin 1 gm bid and metronidazole 400 mg tid). H. pylori infection was defined as positive H. pylori culture or two positive tests (rapid urease test and histology). Antibiotic susceptibility test for metronidazole by Epsilometer test (E-test) was performed in all positive cultures. At least four weeks after treatment, $^{13}C$ urea breath test ($^{13}C-UBT$) was performed to confirm H. pylori eradication. Results: A total of 114 patients were enrolled in this study, 50 males and 64 females with a mean age of 49.8 years. All 114 patients had a diagnosis of NUD. Overall eradication as confirmed by negative $^{13}C-UBT$ was achieved in 94 out of 114 patients (82.5%). 44 patients had positive cultures and success for E-test. In vitro metronidazole resistance was observed in 22/44 (50%) patients. Eradication rate in patients with metronidazole resistant strains was 16/22 (72.7%) and 20/22 (90.1%) with metronidazole sensitive strains (72.7% vs 90.1%, p-value=0.12; OR=3.75 [95%CI=0.6-31.5]). Minor adverse reactions included nausea, bitter taste, diarrhea and black stools but none of the patients dropped out from the study. Conclusions: Initial treatment with 7-day bismuth-based quadruple therapy including metronidazole, amoxycillin and pantoprazole is highly effective and well tolerated for metronidazole-sensitive H. pylori infections. However, the efficacy markedly decline with metronidazole resistance. Longer duration of this regimen might be required to improve the eradication rate and larger multi-center studies are needed to confirm this hypothesis.

• Asian Pacific Journal of Cancer Prevention
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• 제15권20호
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• pp.8883-8886
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• 2014

Background: Tetracycline is an antibiotic widely used for the treatment of Helicobacter pylori infection, but its effectiveness is decreasing due to increasing bacterial resistance. The aim of this study was to investigate the occurrence of 16S rRNA mutations associated with resistance or reduced susceptibility to tetracycline ofHelicobacter pylori by real-time PCR (RT-PCR) assays from culture. Materials and Methods: Tetracycline susceptibility and minimal inhibition concentration (MIC) was determined by the Epsilometer test (Etest) method. A LightCycler assay developed to detect these mutations was applied to DNA extracted from culture. The 16S rRNA of these isolates was sequenced and resistance-associated mutations were identified. From 104 isolates of H. pylori examined, 11 showed resistance to tetracycline. Results: LightCycler assay was applied to DNA extracted from 11 tetracycline-susceptible and 11 tetracycline resistance H. pylori isolates. In our study the sequencing of the H. pylori wild types in 16 s rRNA gene were AGA 926-928 with MIC (0.016 to $0.5{\mu}g/ml$), while the sequencing and MIC for resistant were GGA and AGC, (0.75 to $1.5{\mu}g/ml$), respectively. Also we found a novel mutation in 2 strains with $84^{\circ}C$ as their melting temperatures and exhibition of an A939C mutation. Conclusions: We conclude that real-time PCR is an excellent method for determination of H. pylori tetracycline resistance related mutations that could be used directly on biopsy specimens.