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Background: Helicobacter pylori ( H. pylori )is a Gram-negative, microaerophilic, and spiral shape bacterium that resides inside the human stomach. The human stomach serves as its primary reservoir. Complaints about stomach complication due to H. pylori infections are reported in the majority of populations around the globe. Chronic gastritis and intestinal metaplasia of the gastric mucosa are major complications of a long-term H. pylori infections that can lead to gastric cancer in severe cases. This study aims to characterize H. pylori isolates from gastroenteritis patients and to determine the resistance of H. pylori to various antibiotics., Methods: In the current study, a total of (n = 80) gastric biopsy samples were randomly collected from gastroenteritis patients in brain-heart infusion broth. These were inoculated on Columbia blood agar supplemented with Helicobacter pylori selective supplement (DENT). After culturing, Microscopy and biochemical tests were performed. The susceptibility profile of H. pylori isolates was evaluated using the Kirby Bauer disk diffusion method. On the basis of the drug resistance profile, a total of (n = 20) isolates including (n = 10) from females and (n = 10) from males were selected for the detection and characterization of resistant genes. After confirmation of H. pylori using 16s rRNA , polymerase chain reaction (PCR) was done for the detection of resistance genes including Metronidazole resistance ( rdxA gene), Clarithromycin resistance ( 23s rRNA gene) and Amoxicillin resistance (Penicillin-binding protein A1 ( pbpA1 ) gene)., Results: In a total of (n = 80) samples, H. pylori was isolated from 72.5% (n = 58) samples. Among the positive patients, there were 62% (n = 36) of female positive patients while in males, its ratio was 38% (n = 22). It was more common in the age between 30-50 years 55.17% (n = 32). It has shown the highest resistance towards Metronidazole 90% (n = 52), and the lowest toward Levofloxacin 65% (n = 38). Metronidazole resistance gene ( rdxA gene) was detected in (n = 13) isolates including (n = 9) isolates from females and (n = 4) from males. In the case of, the Clarithromycin resistance gene ( 23s rRNA ) (n = 10) was positive for H. pylori including (n = 6) isolates from females and (n = 7) were positive for Amoxicillin ( pbpA1 gene) including (n = 2) in female and (n = 5) from male patients., Conclusion: This study highlights the increasing incidence of H. pylori infections in both male and female patients. It also revealed the current status of antibiotic resistance and its resistance genes in patients facing gastrointestinal issues. Continuous surveillance of resistant clones will help in formulating strategies that can help in combating of resistant clone. It will also help clinician in proper prescription and management of H. pylori infections.

The aim of the present study was first to isolate Helicobacter pylori from gastric biopsy specimens and to test their antibiotic susceptibility. Second, it was to evaluate the efficacy of the standard triple therapy from patients of the west central region of Colombia. H. pylori positive patients received standard triple therapy with proton pump inhibitor (PPI) (40 mg b.i.d.), clarithromycin (500 mg b.i.d.), and amoxicillin (1 g b.i.d.) for 14 days. Thereafter, antibiotic susceptibility of the isolates was assessed by E-Test. From 94 patients enrolled, 67 were positive for H. pylori by histology or culture. Overall resistance to metronidazole, levofloxacin, rifampicin, clarithromycin, and amoxicillin was 81%, 26.2%, 23.9%, 19%, and 9.5%, respectively. No resistance was found for tetracycline. A total of 54 patients received standard triple therapy, 48 attended follow-ups testing, and of them, 30 had resistance test reports. Overall eradication rate was 81.2%. Second-line treatment was given to eight patients, four of whom were followed up with a 13C urea breath test (UBT) and remained positive for H. pylori . Eradication was significantly higher in patients with clarithromycin susceptible than in resistant strains (95.6% vs 42.8% P = 0.001). The updated percentages of resistance to clarithromycin in this geographical area had increased, so this value must be considered when choosing the treatment regimen.IMPORTANCEAntibiotic resistance in Helicobacter pylori has increased worldwide, as has resistance to multiple antimicrobials (MDRs), which seriously hampers the successful eradication of the infection. The ideal success rate in eradicating H. pylori infection (≥90%) was not achieved in this study (81.2%). This is the first time that MDR is reported (14.3%) in the region; the resistance to clarithromycin increased over time (3.8%-19%), and levofloxacin (26.2%) and rifampicin (23%) resistant isolates were detected for the first time. With these results, strain susceptibility testing is increasingly important, and the selection of treatment regimen should be based on local antibiotic resistance patterns., Competing Interests: The authors declare no conflict of interest.

Heterogeneity of Helicobacter pylori communities contributes to its pathogenicity and diverse clinical outcomes. We conducted drug-susceptibility tests using four antibiotics, clarithromycin (CLR), amoxicillin (AMX), metronidazole and sitafloxacin, to examine H. pylori population diversity. We also analyzed genes associated with resistance to CLR and AMX. We examined multiple isolates from 42 Japanese patients, including 28 patients in whom primary eradication with CLR and AMX had failed, and 14 treatment-naïve patients. We identified some patients with coexistence of drug resistant- and sensitive-isolates (drug-heteroR/S-patients). More than 60% of patients were drug-heteroR/S to all four drugs, indicating extensive heterogeneity. For the four drugs except AMX, the rates of drug-heteroR/S-patients were higher in treatment-naïve patients than in primary eradication-failure patients. In primary eradication-failure patients, isolates multi-resistant to all four drugs existed among other isolates. In primary eradication-failure drug-heteroR/S-patients, CLR- and AMX-resistant isolates were preferentially distributed to the corpus and antrum with different minimum inhibitory concentrations, respectively. We found two mutations in PBP1A, G591K and A480V, and analyzed these in recombinants to directly demonstrate their association with AMX resistance. Assessment of multiple isolates from different stomach regions will improve accurate assessment of H. pylori colonization status in the stomach., (© 2024. The Author(s).)

This clinical trial was conducted to evaluate the pharmacokinetics and pharmacodynamics of tegoprazan when coadministered with amoxicillin/clarithromycin in healthy subjects. Cohort 1 was an open-label, randomized multiple-dose study to evaluate the mutual interaction of tegoprazan and amoxicillin/clarithromycin on the disposition of 3 tested drugs including tegoprazan M1 metabolite and 14-hydroxyclarithromycin (14-OH-clarithromycin). Cohort 2 was an open-label, randomized, active-controlled, parallel multiple-dose study to compare the intragastric pH profile after multiple oral doses of 50 or 100 mg tegoprazan coadministered with amoxicillin/clarithromycin 1000/500 mg for 7 days and pantoprazole-based triple therapy as the comparator arm. The coadministration of tegoprazan with amoxicillin/clarithromycin increased C ss,max (2.2-fold) and AUC τ (2.7-fold) of tegoprazan and M1 (2.1- and 2.2-fold for C ss,max and AUC τ , respectively) compared with administration of tegoprazan alone. The C ss,max and AUC τ of 14-OH-clarithromycin increased by 1.7- and 1.8-fold, respectively; the disposition of amoxicillin and clarithromycin were not significantly changed. On days 1 and 7 of treatment, tegoprazan-based therapies (both 50- and 100-mg therapies) maintained pH above 6 for more than 88% of the 24-hour period, which was significantly longer compared with pantoprazole-based therapy. Tegoprazan either alone or in combination with amoxicillin/clarithromycin was well tolerated in healthy subjects. In conclusion, the exposure of tegoprazan was increased after coadministration of amoxicillin/clarithromycin, which led to increase pharmacodynamic response measured by intragastric pH compared with tegoprazan alone. Therefore, tegoprazan-based triple therapy would be effective therapeutic regimen to manage intragastric pH in terms of gastric or duodenal ulcers healing, treatment of gastroesophageal reflux disease, and Helicobacter pylori eradication., (© 2020, The American College of Clinical Pharmacology.)

Objective: While the global prevalence of antibiotic-resistant Helicobacter pylori (H. pylori) is increasing, there is much regional variation, and local data are required to guide eradication therapy. We performed a systematic review and meta-analysis to determine rates of H. pylori antibiotic resistance in Australia and New Zealand., Study Design: Random effects meta-analysis of data from 15 published studies and three published abstracts reporting prevalence of primary or secondary H. pylori antibiotic resistance in Australasia., Data Sources: PubMed, EMBASE, MEDLINE, PROSPERO, and the Cochrane Library were searched until August, 2020., Data Synthesis: Fifteen published studies and three published abstracts were identified; one study was excluded due to high risk of bias. Seventeen studies conducted between 1996 and 2013 were included in the final analysis, 12 reporting primary and five reporting secondary antibiotic resistance. Prevalence of primary resistance was clarithromycin 7.4% (95% confidence interval [CI], 5.3-9.7%), metronidazole 50.0% (95%CI, 23.9-56.1%), fluoroquinolones 3.7% (95%CI, 0.004-14.8%), and both amoxicillin and tetracycline <0.5%. Subgroup analysis (last 20 years) showed doubling of clarithromycin resistance to 16.1% (95%CI 11.2-21.7%) with other resistance stable. Prevalence of secondary resistance was high for all antibiotics, particularly clarithromycin 78.7% (95%CI, 64.1-90.1%) and metronidazole 68.3% (95%CI, 59.9-76.1%)., Conclusions: The outcomes reveal an increase in primary H. pylori clarithromycin resistance since the year 2000, while metronidazole resistance has remained stable and primary resistance to amoxicillin, tetracycline, and fluoroquinolones is low. Rates of secondary resistance to metronidazole and clarithromycin are high. The results highlight the need for contemporary local data on antibiotic resistance in Australia and New Zealand., (© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Amoxicillin and proton pump inhibitor dual Helicobacter pylori therapy has proved not to be reliably highly effective primarily because of traditional proton pump inhibitors' inability to maintain a high intragastric pH. Clarithromycin and proton pump inhibitor H. pylori dual therapy failed in part because clarithromycin resistance emerged during therapy causing treatment failures. The combination of amoxicillin, clarithromycin, and proton pump inhibitor was subsequently undermined by increasing clarithromycin resistance. Although vonoprazan appeared to restore the effectiveness of triple therapy, the improvement was almost entirely to improved effectiveness of amoxicillin dual therapy component and resulted in the majority (>85% currently in Japan) of those receiving vonoprazan-amoxicillin plus a second antibiotic (e.g. clarithromycin, metronidazole, fluoroquinolone, or rifabutin) receiving no benefit from the second antibiotic. The results in somewhere between 2800 and 5600 kg of unnecessary clarithromycin per one million H. pylori treatment courses per year in Japan. The only contribution of the second antibiotic is to increase global antimicrobial resistance. There are now sufficient data to prove that optimized vonoprazan-amoxicillin dual therapy can reliably achieve cure rates ≥95%. This manuscript discusses use of the principles of antimicrobial stewardship to develop potassium-competitive acid blocker-containing H. pylori therapies that will reliably achieve high H. pylori cure rates with minimal or no use of excess antibiotics. Such therapies are urgently needed so that use of vonoprazan triple therapies can be curtailed while also improving overall H. pylori cure rates., (© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Symptom resolution is the most common clinical practice during assessment and evaluation of helicobacter pylori infected patients after employing eradication therapy., Objective: Prediction of eradication of H. pylori with symptom resolution and assess factors affecting symptom resolution., Method: Facility based follow up study was done on consented H. pylori positive adult patients who received standard triple therapy consisting of a proton pump inhibitor, amoxicillin, and clarithromycin from May 2016 to April 2018 at Bahir Dar city in Ethiopia. Sociodemographic and clinical data was collected before and after eradication therapy by using pre-developed structured questionnaire. Both positive and negative predictive values were calculated. SPSS version 23 was used to conduct bivariate and backward stepwise multivariate logistic regression to analyze data. P-value < 0.05 at 95%CI was considered as significant., Result: The study involved a total of 421 patients who completed follow up. Patients' mean age and body weight (±SD) were 30.63 (± 10.74) years and 56.71 (± 10.19) kg, respectively. Complete symptom resolution was achieved in 84.3% of the patients and eradication of H. pylori was successful in 90% of patients. Positive predictive value of complete symptom resolution for H. pylori eradication was 98.9% (351/355) and whereas negative predictive value was 57.6%(38/66). Factors associated with complete symptom resolution were regimen completion (AOR: 2.77 95%CI (1.12-6.86), p = 0.028) and no use of traditional homemade supplements prepared from Fenugreek or Flaxseed (AOR: 2.09 95%CI (1.22-3.58), p = 0.007)., Conclusion: Complete symptom resolution is a powerful predictor of success of H. pylori eradication and can be used to assess H. pylori status after eradication therapy. Assessment of complete symptom resolution should consider regimen completion and traditional practice of using homemade supplements prepared from Fenugreek or Flaxseed., Competing Interests: The authors have declared that no competing interests exist.

Helicobacter pylori infection is a WHO class 1 carcinogenic factor of gastric adenocarcinoma. In the past decades, many studies have demonstrated the increasing trend of antibiotic resistance and pointed out the necessity of new effective treatment. This study was aimed at identifying phytochemicals that can inhibit H. pylori and possibly serve as adjuvant treatments. Here, in silico molecular docking and drug-like properties analyses were performed to identify potential inhibitors of urease, shikimate kinase and aspartate-semialdehyde dehydrogenase. These three enzymes are targets of the treatment of H. pylori . Susceptibility and synergistic testing were performed on the selected phytochemicals and the positive control antibiotic, amoxicillin. The in-silico study revealed that oroxindin, rosmarinic acid and verbascoside are inhibitors of urease, shikimate kinase and aspartate-semialdehyde dehydrogenase, respectively, in which, oroxindin has the highest potency against H. pylori , indicated by a minimum inhibitory concentration (MIC) value of 50 μg/mL. A combination of oroxindin and amoxicillin demonstrated additive effects against H. pylori , as indicated by a fractional inhibitory concentration (FIC) value of 0.75. This study identified phytochemicals that deserve further investigation for the development of adjuvant therapeutic agents to current antibiotics against H. pylori .

Most patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma are infected with Helicobacter pylori, and eradication therapy is the first-line treatment for localized disease with H pylori infection. However, there were several reports showing effectiveness of eradication therapy in even H pylori negative cases. Gastric MALT lymphomas are endoscopically classified into three common types: superficial, ulcerative, and elevated types. For the past 20 years, we have encountered 200 cases of localized gastric MALT lymphoma. Among them, only 4 cases (2%) showed similar macroscopic findings to those of nodular gastritis (gastric MALT lymphoma with nodular gastritis-like appearance; M-NGA). Here, we compared clinicopathological characteristics and prevalence of non-H pylori Helicobacter (NHPH) infection between M-NGA and other common types of gastric MALT lymphoma. To examine the prevalence of NHPH infection, DNA was extracted from formalin-fixed paraffin-embedded biopsy tissues from four cases of M-NGA, 20 cases of common endoscopic types of gastric MALT lymphoma, and 10 cases of nodular gastritis. We used a highly sensitive polymerase chain reaction assay to detect the presence of five species of NHPH (Helicobacter suis, H felis, H bizzozeronii, H salomonis, and H heilmannii). H suis infection was detected in 4, 2, and 0 of the 4, 20, and 10 cases of M-NGA, other types of gastric MALT lymphoma, and nodular gastritis, respectively. Other NHPH species were not detected in any cases. Complete response rate by eradication therapy was 4/4 in M-NGA cases. Therefore, nodular gastritis-like MALT lymphoma, which shows a very rare phenotype, is closely associated with NHPH infection, and eradication therapy may be the first-choice treatment., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

The human gastric pathogen Helicobacter pylori forms biofilms in vitro and in vivo. We previously demonstrated that H. pylori biofilm formation in vitro decreased its susceptibility to clarithromycin (CAM). The aim of this study was to evaluate the effects of biofilm formation on amoxicillin (AMPC) and metronidazole (MNZ) susceptibility. In addition, we assessed the influence of biofilms of CAM resistant H. pylori on CAM susceptibility. It was shown that high levels of efflux pump gene transcripts were detected in biofilm cells of all H. pylori strains used in this study. H. pylori biofilm biomass was significantly decreased compared to initial biomass after treatment with the minimum inhibitory concentration (MIC) of AMPC. Similarly, the biofilm biomass of H. pylori decreased after treatment with MIC of MNZ, although the difference was not statistically significant. However, minimum bactericidal concentrations (MBCs) of AMPC or MNZ to biofilm cells were higher than those of planktonic cells. The biofilm biomasses of all of the CAM resistant strains were significantly decreased compared to initial biomass after treatment with 2x MIC of CAM. However, the viability of the CAM treated biofilm cells with 2x MIC of CAM was not significantly reduced compared to initial cell numbers with the exception of one strain. The viability of biofilm cells of all strains was higher than that of planktonic cells after treatment with various concentrations of CAM. These results indicate that biofilm cells were more resistant to these antibiotics than planktonic cells and that the assessment of the ability to form biofilms in H. pylori is important for eradication of this microorganism., (Copyright © 2019. Published by Elsevier Ltd.)

The efficacy and safety of polaprezinc combined with triple therapy was compared with triple therapy alone in the eradication of Helicobacter pylori. A randomized, parallel-group, open-label, controlled, prospective multicenter study was conducted in 11 cities in China. Treatment-naive patients with H. pylori-associated gastritis were randomly assigned to one of three arms for a 14-day treatment: Arm A triple therapy (omeprazole 20 mg, amoxicillin 1 g, and clarithromycin 500 mg, each twice daily) plus polaprezinc 75 mg twice daily; Arm B triple therapy plus polaprezinc 150 mg twice daily, or Arm C triple therapy alone. The rate of H. pylori eradication was the primary endpoint. Secondary endpoints were symptom improvement and lower incidence of adverse events. 303 patients completed the study- 106, 96, and 101 patients in Arms A, B, and C, respectively. Intention-to-treat (ITT) analysis showed that the rate of H. pylori eradication was significantly higher for Arms A (77.0%) and B (75.9%) compared to Arm C (58.6%) (P < 0.01), whereas there was no difference between Arms A and B (P = 0.90). Per-protocol (PP) analysis showed that the rate of H. pylori eradication was significantly higher for Arms A (81.1%) and B (83.3%) compared to Arm C (61.4%) (P < 0.01), whereas there was no significant difference between Arms A and B (P = 0.62). All three groups reported significant symptom improvement at 7, 14, and 28 days after treatment, compared to baseline (P < 0.0001). The adverse event rate for Arm B (5.1%) was higher than for Arms A (2.8%) (P = 0.04) and C (1.9%) (P = 0.02). There were no serious adverse events in any group. It appears that standard dose polaprezinc combined with triple therapy can significantly improve the H. pylori eradication rate, without an increase in toxicity.

Domain V of 23S rRNA, gyrA and gyrB Quinolones Resistance-Determining Region (QRDR), and pbp-1A gene point mutations were investigated in Helicobacter pylori-resistant isolates from three centres of Buenos Aires. Minimal inhibitory concentrations (MICs) were performed in 197 isolates from 52 H. pylori-positive naive patients by agar dilution method. Point mutations were achieved by amplification and sequencing of the target genes, and their association with resistance was determined by natural transformation assays. Resistance rates were as follows: metronidazole 28.8%, clarithromycin (CLA) 26.9%, levofloxacin (LEV) 32.7%, and amoxicillin (AMX) 7.6%. Nearly one-third of patients carried multidrug-resistant isolates. A2143G or A2142G in domain V of 23S-rRNA was found in all isolates showing high level of resistance to CLA (MIC >2 mg/L), accounting for 76.0% (38/50) of those with the resistant phenotype. The mutations A2267G or T1861C carried by 8/12 isolates with MIC 1-2 mg/L (low level) did not confer resistance by transformation. Substitutions at GyrA position 87 or 91, mainly N87K and D91G, were found in 92.8% (52/56) of the LEV-resistant isolates: 48 isolates with MIC 4-64 mg/L and 4/8 isolates with MIC 2 mg/L. The remaining four harboured K133N, also present in susceptible isolates. None of the substitutions in GyrB demonstrated to confer resistance. Transformation proved that PBP-1A N562Y and/or T556S substitutions confer the AMX resistance in our isolates, showing an additive effect. In conclusion, the usually reported mutations related to CLA, LEV, and AMX resistance were found in our isolates. However, low-level CLA resistance seems not to be due to mutations in Domain V of 23S rRNA gene.

Background: The best rescue therapy for Helicobacter pylori (H. pylori) infection following failure of non-bismuth quadruple therapy (NBQT) remains unanswered., Aims: To determine the efficacy, safety and compliance of levofloxacin, bismuth, amoxicillin and esomeprazole (LBAE) regimen following failure of NBQT., Methods: 132 patients with H. pylori infection refractory to first-line NBQT received LBAE regimen (levofloxacin 500mg once/day, bismuth potassium citrate 220mg twice/day, amoxicillin 1000mg twice/day and esomeprazole 20mg twice/day for 14 days). Gastric mucosal biopsy was obtained for H. pylori culture, antimicrobial sensitivity test and cytochrome P450 isoenzyme 2C19 polymorphism analysis., Results: LBAE therapy achieved eradication rates of 73.5% [95% confidence intervals (CI) 65.9-81.1%] in intention-to-treat and 78.5% (71.1-85.9%) in per-protocol analyses in patients with high antibiotic resistance (amoxicillin 8.3%, clarithromycin 55.6%, metronidazole 73.6% and levofloxacin 36.1%). Adverse effects were found in 19.2% and compliance in 96.1% of the treated patients. Multivariate analyses identified levofloxacin resistance [odds ratio (OR) 7.183, 95% CI 1.616-31.914, P=0.010] and history of quinolone intake (4.844, 1.174-19.983, P=0.029) as independent predictors of treatment failure. The eradication rate of patients with dual amoxicillin and levofloxacin resistance was significantly decreased (33.3%, P=0.006)., Conclusions: In populations with high levofloxacin resistance, 14-day second-line LBAE regimen resulted in an unsatisfactory efficacy in patients resistant to NBQT despite good safety and compliance., (Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Helicobacter pylori resistance to antibiotics is the main cause for eradication failures., Methods: Antibiotic resistance in 299 H. pylori strains from 233 untreated adults, 26 treated adults, and 40 untreated children was assessed by E tests and, for metronidazole, by breakpoint susceptibility testing and two breakpoint systems., Results: Using EUCAST breakpoints (EBPs) and previous breakpoints (PBPs), overall resistance rates were: amoxicillin 4.0 and 0.6%, metronidazole 33.8 and 33.8%, clarithromycin 28.1 and 27.4%, levofloxacin 19.4 and 19.4%, tetracycline 3.7 and 1.5%, respectively, and rifampin 8.3% (EBP). Multidrug resistance was detected in treated and untreated adults and an untreated child and included 17 (EBPs) and 15 strains (PBPs). Differences between susceptibility categories were found for amoxicillin (3.5% of strains), clarithromycin (0.7%), and tetracycline (2.2%). Using PBPs, from 2005-2007 to 2010-2015, overall primary clarithromycin resistance continued to increase (17.9-25.6%) as noted in our previous study. However, in 2010-2015, overall primary metronidazole (24.0-31.5%) and fluoroquinolone (7.6-18.3%) resistance rates also increased. Primary resistance rates in children and adults were comparable., Conclusions: Briefly, differences in resistance rates by the two breakpoint systems affected the results for three antibiotics. National antibiotic consumption was linked to macrolide resistance in adults. Current primary H. pylori resistance to three antibiotics increased in all untreated patients and in the untreated adults, with the sharpest rise for the fluoroquinolones. The presence of fivefold H. pylori resistance to metronidazole, clarithromycin, tetracycline, levofloxacin, and amoxicillin according to EBPs is alarming.

Objective: To compare eradication rates, safety and compliance of minocycline quadruple and tailored therapies in patients retreated for Helicobacter pylori (H.pylori) infection., Methods: Between January 2014 and June 2014, 135 patients with dyspepsia (18-70 years) and H. pylori infection after at least one previous eradication treatment at a tertiary hospital were randomly assigned to a 10-day treatment with minocycline quadruple therapy versus tailored triple regimen of PPI, amoxicillin and a third antibiotic. In the group of tailored therapy, medications were adjusted based on clarithromycin sensitivity and cytochrome P450 isoenzyme 2C19 genotype. Eradication status was assessed 4-12 weeks after treatment., Results: Although H. pylori eradication rates were higher in the minocycline therapy group than that in the tailored therapy group in intention-to-treat [84.1% (95%CI 75.0%-93.2%) vs 75.8%(95%CI 65.1%-86.5%), P=0.245] and per-protocol [88.3% (95%CI 80.3%-96.3%) vs 79.7%(95%CI 69.7%-89.7%), P=0.197] analyses, the differences between the two groups were not statistically significant.The incidence of adverse effects and compliance between the two groups were also comparable., Conclusions: The tailored therapy in this study had a poor eradication efficacy in the retreated patients with H. pylori infection.Minocycline quadruple therapy achieved a relatively satisfactory eradication efficacy and may be an alternative choice for the retreatment of H. pylori infection., Clinical Trial Registration: Chinese Clinical Trial Registry, ChiCTR-TRC-13003975.

Background and Aim: Clarithromycin-based triple therapy (TT) is the first-line treatment for Helicobacter pylori infection in Singapore. There is awareness that TT may no longer be effective due to increased clarithromycin resistance rates. Sequential therapy (ST) and concomitant therapy (CT) are alternative treatment regimens. This study aimed to compare the efficacy of 10-day TT, ST, and CT as first-line treatment for H. pylori infection., Methods: A randomized study conducted in a teaching hospital. Patients aged 21 years and older with newly diagnosed H. pylori infection were randomized to 10-day TT, ST, or CT. Treatment outcome was assessed by 13-carbon urea breath test at least 4 weeks after therapy. Intention to treat (ITT), modified ITT (MITT), and per protocol (PP) analyses of the eradication rates were performed., Results: A total of 462 patients were enrolled (ST: 154; TT 155; CT 153). Patient demographics were similar. Eradication rates for ST versus TT versus CT: ITT analysis: 84.4% versus 83.2% versus 81.7% (P = not significant [NS]); MITT analysis: 90.3% versus 92.1% versus 94.7% (P = NS); PP analysis: 94.1% versus 92.8% versus 95.4% (P = NS). Antibiotic resistance rates for amoxicillin, clarithromycin, and metronidazole were 4.7%, 17.9%, and 48.1%, respectively. Dual clarithromycin and metronidazole resistance occurred in 7.5%. Dual resistance and lack of compliance were predictors of treatment failure., Conclusions: TT, ST, and CT all achieved eradication rates above 80% on ITT and above 90% on MITT and PP analyses. Dual resistance and lack of compliance were predictors of treatment failure (clinicaltrials.gov: NCT02092506)., (© 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)

Introduction: Helicobacter pylori is a bacteria which infects half the world population and is an important cause of gastric cancer. The eradication therapy is not always effective because resistance to antimicrobials may occur. The aim of this study was to determine the susceptibility profile of H. pylori to amoxicillin, clarithromycin and ciprofloxacin in the population of Southern Brazil., Material and Methods: Fifty four samples of H. pylori were evaluated. The antibiotics susceptibility was determined according to the guidelines of the British Society for Antimicrobial Chemotherapy and the Comité de l'Antibiogramme de la Société Française de Microbiologie., Results: Six (11.1%) H. pylori isolates were resistant to clarithromycin, one (1.9%) to amoxicillin and three (5.5%) to ciprofloxacin. These indices of resistance are considered satisfactory and show that all of these antibiotics can be used in the empirical therapy., Conclusion: The antibiotics amoxicillin and clarithromycin are still a good option for first line anti-H. pylori treatment in the population of Southern Brazil.

Introduction: Helicobacter pylori resistance to antibiotics is steadily increasing and multidrug-resistant strains are common and difficult to eliminate, mainly in countries where bismuth, tetracycline, furazolidone, and rifabutin are unavailable., Aim: To evaluate the efficacy and safety of a triple therapy with proton-pump inhibitor (PPI), amoxicillin, and doxycycline in patients with multidrug-resistant H. pylori., Patients and Methods: This prospective study involved 16 patients (13 females; mean age - 50 ± 11.3 years) infected by H. pylori with known resistance to clarithromycin, metronidazole, and levofloxacin, but susceptibility to amoxicillin and tetracycline. All patients were previously submitted to upper endoscopy with gastric biopsies for H. pylori culture and susceptibility testing by Etest. Mutations in 23S rRNA and gyrA genes were determined by real-time PCR. A 10-day eradication regimen with PPI (double-standard dose b.i.d.), amoxicillin (1000 mg b.i.d.), and doxycycline (100 mg b.i.d.) was prescribed after pretreatment with PPI during 3 days. Eradication success was assessed by (13) C-urea breath test 6-10 weeks after treatment. Compliance and adverse events were determined through phone contact immediately after treatment and specific written questionnaires., Results: Only one patient did not complete treatment due to adverse events. Another four patients experienced mild side effects not affecting compliance. The control (13) C-urea breath test was positive in all patients. Per-protocol and intention-to-treat eradication rates were 0%., Conclusions: Although safe, a triple-therapy protocol with high-dose PPI, amoxicillin, and doxycycline is useless for multidrug-resistant H. pylori eradication., (© 2014 John Wiley & Sons Ltd.)

Aim: To evaluate the in vitro effect of amoxicillin and clarithromycin on the cag pathogenicity island (cag PAI)., Methods: One hundred and forty-nine clinical isolates of Helicobacter pylori (H. pylori) cultured from gastric biopsies from 206 Colombian patients with dyspeptic symptoms from a high-risk area for gastric cancer were included as study material. Antimicrobial susceptibility was determined by the agar dilution method. Resistant isolates at baseline and in amoxicillin and clarithromycin serial dilutions were subjected to genotyping (cagA, vacA alleles s and m), Glu-Pro-Ile-Tyr-Ala (EPIYA) polymerase chain reaction and random amplified polymorphic DNA (RAPD). Images of the RAPD amplicons were analyzed by Gel-Pro Analyzer 4.5 program. Cluster analyses was done using SPSS 15.0 statistical package, where each of the fingerprint bands were denoted as variables. Dendrograms were designed by following Ward's clustering method and the estimation of distances between each pair of H. pylori isolates was calculated with the squared Euclidean distance., Results: Resistance rates were 4% for amoxicillin and 2.7% for clarithromycin with 2% double resistances. Genotyping evidenced a high prevalence of the genotype cagA-positive/vacA s1m1. The 3' region of cagA gene was successfully amplified in 92.3% (12/13) of the baseline resistant isolates and in 60% (36/60) of the resistant isolates growing in antibiotic dilutions. Upon observing the distribution of the number of EPIYA repetitions in each dilution with respect to baseline isolates, it was found that in 61.5% (8/13) of the baseline isolates, a change in the number of EPIYA repetitions lowered antibiotic pressure. The gain and loss of EPIYA motifs resulted in a diversity of H. pylori subclones after bacterial adjustment to changing conditions product of antibiotic pressure. RAPD PCR evidenced the close clonal relationship between baseline isolates and isolates growing in antibiotic dilutions., Conclusion: Antibiotic pressure does not induce loss of the cag pathogenicity island, but it can lead--in most cases--to genetic rearrangements within the 3' region cagA of the founding bacteria that can affect the level of tyrosine phosphorylation impacting on its cellular effects and lead to divergence of cagA-positive subclones.

Background: Clarithromycin (CLR) is the most commonly recommended antibiotic in Helicobacter pylori eradication regimens, but the prevalence of CLR-resistant H. pylori is increasing. CLR resistance is associated with mutations in the 23S rRNA gene. However, H. pylori eradication can still be achieved with triple therapy, and an additive effect may occur with multiple antibiotics., Methods: Twenty-six CLR-resistant strains were examined. The MIC of clarithromycin was determined by agar-dilution-testing on Columbia agar, as described elsewhere. The conserved region of the H. pylori 23S rRNA gene between nucleotide positions 1445 and 2846 [GenBank: U27270] was amplified. RFLP and sequence analysis were performed with the 1402-bp PCR product. Synergy between clarithromycin and amoxicillin was assessed using the agar dilution checkerboard technique. To confirm the correlation between mutation and synergistic effect with subinhibitory concentrations of AMX, site-directed mutagenesis was performed in four CLR-susceptible H. pylori isolates., Results: Twenty-six clarithromycin-resistant strains were examined. The conserved region of the H. pylori 23S rRNA gene was amplified, and the purified PCR product was checked for mutations by restriction fragment length polymorphism (RFLP) analysis and sequencing. A synergistic effect was found in only three of the 12 H. pylori strains (25%) with the A2142G mutation and five of the 10 H. pylori strains (50%) with the A2143G mutation (fractional inhibitory concentration: FIC < 0.5, minimal inhibitory concentration: MIC<2 mg/L) was found. Site-directed mutagenesis was performed in four CLR-susceptible H. pylori isolates.Three of these isolates harboring a mutation in position A2143G grew under selection with CLR (MIC >16 mg/L), and all three strains showed the synergistic effect (FIC<0.5). In contrast, three of the same four strains transformed with DNA fragments with a mutation in position A2142G were resistant to CLR (MIC>16 mg/L) and showed no synergism with amoxicillin (FIC>2)., Conclusions: Here we demonstrate that in 100% of the in vitro transformed strains, a mutation at position A2143G leads to a synergistic effect between clarithromycin and amoxicillin, whereas a mutation at position at A2142G had no discernible effect.

The aim of this study was to assess the pattern of evolution of resistance to antibiotics in Helicobacter pylori isolated from children who underwent upper endoscopy with antral biopsy during a 10-year period (2001-2010). We retrospectively analyzed data of all children (n = 3,008) who underwent upper endoscopy during the observed period at the Children's Hospital Zagreb, a university tertiary medical center. We calculated the rate, antibiotic susceptibility and risk factors for the H. pylori infection in our cohort. Antral biopsy was performed in 2,313 (76.89%) patients. Altogether, 382 (16.51%) children had positive biopsy for H. pylori (histology and/or culture). There was no significant difference in the incidence of H. pylori during 10 years of observation (p = 0.21). Infected children compared to non-infected group were older (p = 0.005), and had more often antral nodularity (p < 0.0001), and duodenal ulcer (p = 0.002). Altogether, 22.4% of treatment-naïve patients had strains resistant to tested antibiotics: majority to azithromycin (17.9%), followed by clarithromycin (11.9%), metronidazole (10.1%) and amoxicillin (0.6%). In the eradication failure group, 9/11 of children had strains resistant to tested antibiotics, mostly to metronidazole (7/11), followed by azithromycin (3/11) and clarithromycin (1/11). No correlation was found between age or gender and antibiotic resistance (p = 0.32, for both). In conclusion, our data strongly support current guidelines which recommend antibiotic susceptibility testing prior to eradication therapy. Based on our results we recommend the use of amoxicillin-metronidazole-based regimen as the first-line therapy in our study population.

Introduction: Infection by Helicobacter pylori is prevalent in approximately half the world´s population.However, the susceptibility of H. pylori to antimicrobial agents must be evaluated by in vitro methods in order to determine the susceptibility levels and to guide treatment regimes., Objective: The prevalence of infection and antibiotic susceptibility was evaluated in gastric biopsies containing H. pylori., Materials and Methods: The prevalence of infection and antibiotic susceptibility was investigated in 203 patients with chronic gastritis from Tumaco, Colombia. Diagnosis was confirmed by histopathological evidence (Dixon scale) and microbiological (culture on blood agar supplemented with antibiotics).The antibiotic resistance of H. pylori was measured by its response toantimicrobial amoxicillin and clarithromycin using the agar dilution method., Results: The prevalence of infection for H. pylori with histopathological and microbiological tests was88.7% and 84.7% respectively. The prevalence of resistance of H. pylori to antimicrobial amoxicillin was 20.5%, to clarithromycin 19.8%, and to both antibiotics concurrently, 10.9%., Conclusions: A high incidence of clarithromycin-resistant and amoxicillin-resistant H. pylori was discovered in patients from Tumaco with chronic gastritis. Dual drug-resistant strains of H. pylori to clarithromycin and amoxicillin were also present.

Background: The optimal therapeutic regimen for Helicobacter pylori (H. pylori) infection has not been established in end-stage renal disease (ESRD) patients receiving hemodialysis. We investigated the efficacy and safety of a 7-day omeprazole-based triple therapy with low doses of amoxicillin and clarithromycin (OAC) for eradication of H. pylori infection in ESRD patients receiving hemodialysis., Methods: Thirty-three hemodialysis patients and 55 patients with normal renal function underwent upper gastrointestinal endoscopy. For eradication of H. pylori infection, a 7-day triple therapy with low-dose OAC (omeprazole 40 mg daily, amoxicillin 500 mg daily, and clarithromycin 500 mg daily) regimen was used. Four weeks after the completion of the OAC regimen, the success of the H. pylori eradication therapy was determined by histological examination and rapid urease test., Results: The prevalence of H. pylori infection was 36.4% in hemodialysis patients and 65.5% in non-uremic patients (p = 0.0150). The mean duration of hemodialysis in H. pylori-positive and -negative patients was 56.8 ± 26.9 versus 66.4 ± 26.1 months, respectively (p = 0.3196). Eradication was successful in 83.4% of hemodialysis patients and 81.0% of non-uremic patients (p = 1.000). All patients completed the eradication therapy without any serious adverse effects., Conclusion: A 7-day triple therapy with a low-dose OAC regimen was effective and safe for eradication of H. pylori infection in hemodialysis patients.

Background: The success rate of currently recommended 7-day triple therapy with a PPI plus amoxicillin and clarithromycin has fallen into the unacceptable range. It is urgent to look for a new strategy to treat the infection of Helicobacter pylori., Aims: To observe the efficacy of triple therapy-based, bismuth-containing quadruple therapy for H. pylori treatment., Methods: A total of 160 patients with functional dyspepsia who were Hp+ were randomly assigned into two groups. Regimen: Omeprazole 20 mg, Amoxicillin 1.0 g, Clarithromycin 500 mg and Bismuth Potassium Citrate 220 mg, twice a day. Eighty patients received 7-day quadruple therapy and 80 patients received the same therapy for 14 days. Six weeks after treatment, H. pylori eradication was assessed by (13)C-urea breath test. Minimal inhibitory concentrations of metronidazole, clarithromycin and amoxicillin of clinical isolates were determined by the twofold agar dilution method., Results: Fourteen-day therapy led to a significant increase of H. pylori eradication success when compared to 7-day therapy in the intention-to-treat analysis (93.7 vs 80.0%; p = .01), and the per-protocol analysis (97.4 vs 82.0%; p = .0016). The H. pylori resistance rates to metronidazole, clarithromycin and amoxicillin were 42.1, 18.0 and 0%. Fourteen-day therapy was significantly more effective in patients with clarithromycin-resistant strains. Incidences of adverse events were comparable., Conclusions: Addition bismuth and prolonging treatment duration can overcome H. pylori resistance to clarithromycin and decrease the bacterial load. Fourteen-day triple therapy-based, bismuth-containing quadruple therapy achieved ITT success rate 93% and could be recommended as the first line eradication regimen.

Background: Antimicrobial resistance of Helicobacter pylori is a growing problem in clinical practice, particularly clarithromycin resistance. The aim of the present study was therefore to investigate the prevalence of H. pylori resistance to antimicrobial agents in Japanese children., Methods: A total of 61 H. pylori strains isolated from children (mean age, 12.6 years; range, 4-18 years) between 1999 and 2007 were studied for primary antimicrobial resistance, using a microdilution method. In addition, the eradication rate with lansoprazole-based triple regimens was determined., Results: The overall resistance rate of clarithromycin, amoxicillin and metronidazole was 36.1%, 0% and 14.8%, respectively. Resistance to both clarithromycin and metronidazole was detected in 6.6% of the strains. The rate of clarithromycin-resistant strains was 32.4% from 1999 to 2002 and 40.7% from 2003 to 2007, and clarithromycin minimum inhibitory concentration at which 90% of the isolates were inhibited (MIC(90)) increased fourfold from 1999-2002 to 2003-2007, with all clarithromycin-resistant strains showing low-level resistance. Metronidazole resistance rates were not different between these two study periods. Regimens involving amoxicillin and clarithromycin (n= 49) had a higher eradication rate in clarithromycin-susceptible strains (97.1%) than in the resistant strains (57.1%; P < 0.001). There was no difference in the eradication rate between 7 day and 10 or 14 day courses of the regimens (P= 0.53). The regimen with amoxicillin and metronidazole produced successful eradication in all nine patients with clarithromycin-resistant strains., Conclusions: Clarithromycin resistance of H. pylori is high, and triple regimen treatment containing clarithromycin should be decided based on susceptibility to the agent.

The main aim of drug targeting was to increase the selectivity and efficacy of drugs at the infected site and to reduce the toxicity of biotechnological entities on other parts of the body. In the present study, we selected the triple therapy (amoxicillin, clarithromycin and omeprazole) due to its synergic and additive effects, which could drastically reduce the effective dose required for the complete eradication of Helicobacter pylori and prevent the development of antibiotic resistance. The gliadin nanoparticles (GNP) vis-à-vis lectin-conjugated gliadin nanoparticles (LGNP) of triple therapy were prepared by a desolvation method and evaluated for percent entrapment efficiency, percent yield, in vitro drug release study and mucoadhesion properties of formulations. The maximum percent entrapment efficiency of formulations was in the range of 65-85%. The percent yield of formulation was about 84 +/- 2.68%. The maximum percent cumulative release of all the three drugs from formulations was in the range of 22-76%. The specificity of lectin-conjugated particles was assessed by an in vitro agglutination assay method. The developed formulation was also assessed for in vitro antibacterial study, in vivo clearance efficacy and histopathological evaluation of formulations. In the in vitro antibacterial study, the LGNP with triple therapy showed a 94.83% eradication rate that is 7.4% more than that of GNP with triple therapy (88.28%) and about 16% more than that of the plain triple therapy (P < 0.001). The targeted lectin-conjugated formulations exhibited a superior in vivo clearance efficacy when compared to the non-conjugated formulations and plain drugs.

Aim: To compare the efficacy of a 7-d vs 10-d triple therapy regarding H pylori eradication, endoscopic findings and histological gastric inflammatory inactivation in the Ecuadorian population., Methods: 136 patients with dyspepsia and H pylori infection were randomized in 2 groups (68 per group): group 1, 7-d therapy; group 2, 10-d therapy. Both groups received the same medication and daily dosage: omeprazole 20 mg bid, clarithromycin 500 mg bid and amoxicillin 1 g bid. Endoscopy was performed for histological assessment and H pylori infection status before and 8 wk after treatment., Results: H pylori was eradicated in 68% of group 1 vs 83.8% of group 2 for the intention-to-treat analysis (ITT) (P = 0.03; OR = 2.48; 95% CI, 1.1-5.8), and 68% in group 1 vs 88% in group 2 for the per-protocol analysis (PP) (P = 0.008; OR = 3.66; 95% CI, 1.4-10). Endoscopic gastric mucosa normalization was observed in 56.9% in group 1 vs 61.2% in group 2 for ITT, with similar results for the PP, the difference being statistically not significant. The rate of inflammatory inactivation was 69% in group 1 vs 88.7% in group 2 for ITT (P = 0.007; OR = 3.00; 95% CI, 1.2-7.5), and 69% in group 1 vs 96% in group 2 for PP (P = 0.0002; OR = 7.25; 95% CI, 2-26)., Conclusion: In this Ecuadorian population, the 10-d therapy was more effective than the 7-d therapy for H pylori eradication as well as for gastric mucosa inflammatory inactivation.

Surveillance of Helicobacter pylori antimicrobial susceptibility reflecting the general population in Japan is limited. The antimicrobial susceptibilities of 3,707 H. pylori strains isolated from gastric mucosa samples of previously untreated patients diagnosed with gastroduodenal diseases at 36 medical facilities located throughout Japan between October 2002 and September 2005 were evaluated. Using an agar dilution method for antimicrobial susceptibility testing of H. pylori, the MIC distributions and trends during the study period for clarithromycin, amoxicillin, and metronidazole were studied. While the MIC(50) and MIC(90) for clarithromycin did not change during the 3-year period, the MIC(80) showed a 128-fold increase. Furthermore, the rate of resistance increased yearly from 18.9% (2002 to 2003) to 21.1% (2003 to 2004) and 27.7% (2004 to 2005). With a resistance rate of 19.2% among males compared to 27.0% among females, a significant gender difference was observed (P < 0.0001). Our study shows that in Japan, there is an evolving trend towards increased resistance to clarithromycin with geographical and gender differences as well as between clinical disease conditions. No significant changes in resistance were observed for amoxicillin and metronidazole during the period. While the benefit of H. pylori antimicrobial susceptibility testing has been debated in Japan, current empirical regimens are not based on susceptibility data representative of the general population. The development of an effective H. pylori eradication regimen in Japan will require continued resistance surveillance as well as a better understanding of the epidemiology of resistance.

The yearly prevalence between 1994 and 2005 of primary resistance to amoxicillin, metronidazole, and clarithromycin of 377 Helicobacter pylori strains isolated from children was studied. All the H. pylori strains were susceptible to amoxicillin, 138/377 (36.7%) were resistant to metronidazole, 86/377 (22.8%) to clarithromycin, and 30/377 (7.9%) to both metronidazole and clarithromycin. Over the entire period, resistance to clarithromycin did not change, whereas metronidazole resistance decreased significantly from 43.3% (1994-1998) to 32% (1999-2005), P = 0.001.

Objective: to assess the efficacy of rabeprazole (RPZ), amoxicillin (Am), and clarithromycin (Cla) (7 vs. 14 days) in the eradication of H. pylori, and to determine the effect of strain-specific antibiotic resistance and host CYP2C19 status., Material and Methods: first, we determined the CYP2C19 status of 100 healthy subjects to establish a sample size for the clinical trial. Then, 59 H. pylori-infected patients were randomized to receive RPZ (20 mg daily) plus Cla (500 mg b.d.) and Am (1,000 mg b.d.) for 7 vs. 14 days. The MIC for Am and Cla were determined using the agar dilution method. The CYP2C19 genotype was determined by the PCR-RFLP method., Results: In the per-protocol analysis (PP) eradication rates were 89.7 and 72% for the 7- and 14-day groups (p = 0.159). In the intention to-treat analysis (ITT) eradication rates were 86.7 and 62.1% in the 7- and 14-day groups, respectively (p = 0.06). None of the strains was resistant to Am, and 4 strains were resistant to Cla: 3 (11.1%) in the 14-day group and 1 (4%) in the 7-day group. Neither strain-specific antibiotic resistance nor host CYP2C19 status influenced eradication rates., Conclusions: both 7- and 14-day therapies were effective for H. pylori eradication. Strain resistance and CYP2C19 status do not seem to influence eradication rates in the studied population.

Background: Previous studies in Alaska have demonstrated elevated proportions of antimicrobial resistance among Helicobacter pylori isolates., Materials and Methods: We analyzed H. pylori data from the Centers for Disease Control and Prevention (CDC)'s sentinel surveillance in Alaska from July 1999 to June 2003 to determine the proportion of culture-positive biopsies from Alaska Native persons undergoing routine upper-endoscopy, and the susceptibility of H. pylori isolates to metronidazole [minimum inhibitory concentration (MIC) of > 8 g metronidazole/mL), clarithromycin (MIC > or = 1), tetracycline (MIC > or = 2) and amoxicillin (MIC > or = 1)] using agar dilution., Results: Nine-hundred sixty-four biopsy specimens were obtained from 687 participants; 352 (51%) patients tested culture positive. Mean age of both culture-positive and culture-negative patients was 51 years. Metronidazole resistance was demonstrated in isolates from 155 (44%) persons, clarithromycin resistance from 108 (31%) persons, amoxicillin resistance from 8 (2%) persons, and 0 for tetracycline resistance. Metronidazole and clarithromycin resistance varied by geographic region. Female patients were more likely than male subjects to show metronidazole resistance (p < .01) and clarithromycin resistance (p = .05)., Conclusions: Resistance to metronidazole and clarithromycin is more common among H. pylori isolates from Alaska Native persons when compared with those from elsewhere in the USA.

The discovery of Helicobacter pylori (H. pylori) provided a possibility to cure effectively patients with peptic ulcers. Recent studies have shown varying susceptibility of H. pylori strains to antibiotics and increasing resistance to some of the recommended drugs. The purpose of the present study was to evaluate the efficacy of the currently recommended eradication schemes and to assess the increasing resistance of H. pylori strains to recommended antibiotics. Furthermore, the effect of probiotics (Lacidofil) on the efficacy of first-line treatment with amoxicillin and clarithromycin was analyzed. The study population consisted of 641 patients: 192 received amoxicillin with clarithromycin and proton pump inhibitor (PPI), 241 - tetracycline, tinidazole, bismuth and PPI, 53 - amoxicillin with clarithromycin and PPI supplemented with Lacidofil. The efficacy of eradication treatment was evaluated by the (13)C-urease breath test. The microbiological examination included 111 samples of H. pylori. The present study demonstrated low efficacy of the tetracycline, tinidazole, bismuth and PPI scheme i.e. 71.4%, moderate efficacy of the amoxicillin with clarithromycin and PPI scheme i.e. 85.9%, whereas the supplementation with Lacidofil significantly increased the efficacy of eradication to 94.3%. The microbiological examination revealed a relatively high level of primary resistance to clarithromycin (22.2%) and a high level to metronidazole (46.7%), with no resistance to amoxicillin. However, the most important finding is the high level of secondary resistance to clarithromycin and metronidazole (more than 66% in both cases). The present findings suggest the need for modification of the recommended eradication schemes.

Helicobacter pylori possess various virulence factors, including cagA and vacA genes, that are associated with more aggressive symptoms such as bleed-ing ulcer and gastric cancer. Although there are different treatment regimens, there is still a failure rate of up to 20% due to antibiotic resistance, among other causes. In our country resistance to metronidazole and clarithromycin is increasing, especially in children, although they are still susceptible to amoxicillin and tetracycline. In order to determine the susceptibility pattern to these antibiotics 36 H. pylori clinical isolates were studied. MIC was determined by agar diffusion and agar dilution, and vacA and cagA genes were detected by conventional PCR. All isolates were susceptible to amoxicillin and tetracycline. Resistance to metronidazole by diffusion or dilution tests was 35.7% and 36.1%, respectively, and to clarithromycin, 21.4% and 22.3%, respectively. There was one strain that showed intermediate resistance to clarithromycin (MIC 0.38 mg/l), using agar diffusion, and that was included among the resistant strains. Three discrepancies were observed between the diffusion and dilution methods. The vacA s1 allele was detected in 17.2% of the strains, and vacA s2 in 82.8%; 51.7% of the total were cagA+. In conclusion, all strains tested in our study were susceptible to amoxicillin and tetracycline, allowing them to be considered as first-line antibiotics, while clarithromycin and metronidazole maintain a slight increase in their resistance level. The cagA+ strains were detected in expected quantities, while the s1 allele of the vacA gene was detected in lower quantities.

Objective: A combination of esomeprazole, amoxicillin and clarithromycin may be used for Helicobacter pylori eradication. We explored the potential for interactions between these drugs., Methods: In 2 randomized, 4-way crossover studies, healthy CYP2C19 extensive metabolizers (EMs) received esomeprazole 40 mg once daily (n = 20) or 20 mg twice daily (b.i.d.) (n = 20), clarithromycin 500 mg b.i.d., amoxicillin 1 g b.i.d. or the combination of the 3 drugs for 7 days. In a third randomized, 2-way, crossover study, 6 healthy CYP2C 19 poor metabolizers (PMs) received esomeprazole 40 mg once daily with and without clarithromycin 500 mg b.i.d. for 1 week., Results: Triple therapy with esomeprazole 40 mg increased the area under the plasma concentration-time curve during the dosing interval (AUCtau) from 13.31 micromol x h/l (11.12-15.93) for esomeprazole alone to 22.69 micromol x h/l (18.94-27.17) for triple treatment. Respective AUCtau values with esomeprazole 20 mg b.i.d. were 4.97 micromol.h/l (3.97-6.21) and 11.29 micromol x h/l (9.03-14.12). Clarithromycin and amoxicillin plasma levels were largely unchanged by combination therapy. In PMs, the esomeprazole AUC also approximately doubled when administered in combination with clarithromycin. All treatments were well tolerated., Conclusion: Clarithromycin decreases the metabolism rate of esomeprazole, leading to approximately doubled AUC values, both in EMs and PMs.

We evaluated pulsatile dosing of clarithromycin and amoxicillin alone or combined against Streptococcus pneumoniae with various susceptibilities. When combined, pulsatile amoxicillin with clarithromycin was superior to either 8- or 12-h dosing against the intermediate strain and was identical for the susceptible strain. Pulse dosing of antimicrobials warrants further investigation.

Objective: To determine drug susceptibility pattern of Helicobacter pylori to metronidazole, clarithromycin, amoxicillin and tetracycline in patients presenting with dyspepsia at the Kenyatta National Hospital., Design: Cross-sectional descriptive study., Setting: Kenyatta National Hospital, Nairobi., Subjects: Two hundred and sixty-seven patients aged 15 to 85 years, presenting with dyspepsia and referred for upper gastro-intestinal endoscopy were recruited into the study., Results: Between October 2003 and April 2004, 138 male and 129 female patients aged 15-85 years, with a mean age of 45.4 years were studied. Gastritis was the most common endoscopic finding, occurring in 55%, followed by normal-looking mucosa in 27% and peptic ulcer disease in 16% of the patients. The rapid urease test was positive in 184 patients (69%). The culture yield was 62% of these CLO (Campylobacter like organisms) positive biopsies. The MIC90 (minimum inhibitory concentration) was 256 mg/l for metronidazole, 1.5 mg/l for clarithromycin, 1.5 mg/l for tetracycline and 0.75 mg/l for amoxicillin. The MIC values for amoxicillin were significantly higher in the female patients (p = 0.02) but showed no significant variation for age. The MIC values for metronidazole, tetracycline and clarithromycin showed no significant difference for age or gender. MIC values for tetracycline were significantly higher for patients with duodenitis and duodenal ulcer p = 0.009 and 0.02, respectively., Conclusion: All isolated H. pylori organisms were resistant to metronidazole. The susceptibility of the H. pylori isolates was 93.6% for clarithromycin, 95.4% for amoxicillin and 98.1% for tetracycline. The MIC90 for amoxicillin and clarithromycin were found to be close to the upper limit of the susceptibility range. There was a rising MIC90 for tetracycline and metronidazole compared to that found in a previous study in 1991.

Objectives: Amoxicillin and clarithromycin have been proven to be effective in the treatment of community-acquired pneumonia. This study investigated the in vivo bactericidal efficacy of a novel, pulsatile dosing strategy for amoxicillin and clarithromycin, when used as monotherapy and combination therapy., Methods: A neutropenic murine pneumonia model was used to assess the bactericidal activity of amoxicillin and clarithromycin, when the same total daily dose was administered as a traditional regimen (every 8 h and every 12 h, respectively) or as a pulsatile regimen (four doses of antibiotic given every 2 h over the first 6 h of the day) against three isolates of Streptococcus pneumoniae of varying resistance profiles. The three isolates consisted of SP21 (macrolide and penicillin susceptible), SP100 [mef(A) gene], and SP107 [mef(A) + erm(B) genes]., Results: Pulsatile dosing showed similar reductions in bacterial density for amoxicillin and clarithromycin when either drug was given alone compared with traditional dosing regimens against all three bacterial isolates. When amoxicillin and clarithromycin were combined, improved activity was found compared with monotherapy. Overall, when comparing the different combination regimens, the pulsatile regimens provided similar activity compared with the traditional regimens. For one isolate, SP107, pulsatile amoxicillin combination regimens were less effective compared with traditionally dosed amoxicillin combination regimens., Conclusions: Pulsatile dosing resulted in comparable bactericidal activity against the three isolates tested and may represent an alternative dosing strategy, which may help to alleviate problems with patient adherence to drug therapy.

The drug treatment, the combination of lansoprazole + amoxicillin + clarithromycin, for Helicobacter pylori infection with gastroduodenal ulcer was approved for the national heath insurance November 2000 in JAPAN, and has been widely applied. However, failures of eradication have been counted in 10-20% of the cases. The major reason of the failure has been reported as the drug resistance of the H. pylori. Here, we surveyed the antimicrobial resistance of 70 clinical isolates in a Showa University Hospital 2001, 1 to 2002, 1. As a result, the ratio of primary resistance to amoxicillin was about 1.4%, and clarithromycin was about 11.4%. Among 70 H. pylori positive cases, 14 cases were treated with eradication 3 drug combination therapy. In 5 cases, H. pylori were detected after eradication treatment and these five strains acquired the second resistance to neither amoxicillin nor clarithromycin. To distinguish the cause of H. pylori culture-positive after eradication treatment is whether the failure of eradication itself or re-infection, we attempted the analysis of the restriction pattern of H. pylori genome (genome type) using pulsed-field gel electrophoresis. In all 5 cases, genome types of before and after treatment were identical, suggesting the failure of eradication treatment. Three of 5 cases, isolates before and after treatment were susceptible to both of amoxicillin and clarithromycin. Thus, the reason of failure of eradication is considered to ingestion compliance, not antimicrobial agent resistance nor reinfection. The rest of 2 cases, the primary resistance to clarithromycin may result the failure of eradication. Test for drug susceptibility and genome type analysis of H. pylori are significant in certification of an authenticity of an eradication treatment.

The aim of this study was to determine the susceptibilities to clarithromycin, amoxycillin and metronidazole of Helicobacter pylori isolates from the antrum and corpus of Japanese patients examined during the period 1995-2001. There was an increase, from 6.2% in 1995 to 22.1% in 2000-2001, in the proportion of patients infected with clarithromycin-resistant H. pylori. Of patients infected with clarithromycin-resistant H. pylori, 39.1% were infected with both clarithromycin-susceptible and -resistant H. pylori. Furthermore, the MIC90 of clarithromycin for H. pylori rose from < 1 mg/L in 1995-1998 to 8 mg/L in 1999. In contrast, the MIC90s of amoxycillin and metronidazole were < or = 0.125 and 4 mg/L, respectively, throughout the study period. The results showed that, while most H. pylori isolates were susceptible to amoxycillin and metronidazole, resistance to clarithromycin among H. pylori isolates increased markedly in Japan during 1995-2001. The results also indicated a need to test the susceptibility of H. pylori isolates from more than two samples obtained from two different sites in the stomach of a single patient in order to diagnose the presence of clarithromycin-resistant H. pylori correctly.

Aim: To investigate the effectiveness of 4 d' anti-Helicobacter pylori therapy on the H pylori-infected Mongolian gerbils based on physiological and pathological changes., Methods: We used 6-wk-old male gerbils orally inoculated with H pylori (ATCC43504, 2X10(8) CFU/mL). Seven weeks after H pylori inoculation, the animals of study group received 4 d' anti-H pylori triple therapy (H pylori-eradicated group). Seven days later, all animals of the H pylori-eradicated and control groups (H pylori-infected and H pylori-uninfected groups) were sacrificed. We examined gastric mucosal lesions macroscopically, studied gastritis microscopically and determined the stomach weight ratio, myeloperoxidase (MPO) activity and prostaglandin (PG) E(2) level., Results: The results showed that both macroscopic and histological gastric damages were significantly less in H pylori-eradicated group than H pylori-infected group. Stomach weight ratio, MPO activity and PGE(2) levels were significantly higher in H pylori-infected group than those in the other two groups., Conclusion: Four days' anti-H pylori therapy was effective in the improvement of H pylori-induced gastric lesions in Mongolian gerbils.

Background: The effects of bacterial eradication therapy cannot be fully explained simply by elimination of the target bacteria, if one considers the effects of eradication therapy in H. pylori-negative cases of low-grade malignancy MALTomas of the rectum. The present study was undertaken to examine the possibility and mechanism of direct induction of apoptosis of the tumor cells by the antibiotics used for bacterial eradication therapy., Materials and Methods: A B cell lymphoma cell line (300-19) derived from BALB/c mice was co-cultured with amoxicillin or clarithromycin, and amoxicillin and clarithromycin at concentrations equal to or 1/10 x MIC of either drug. Cells co-cultured with 1/100 x MIC of the standard anti-tumor agents, adriamycin, vincristine and cyclophosphamide, served as positive controls. Cells cultured without any antibiotic or anti-tumor agent served as controls. In each group, the following analyses were performed: (i) the time-course of changes in the cellular morphology, (ii) the time-course of occurrence of DNA fragmentation, (iii) the appearance of apoptotic changes as evaluated by trypan blue staining, (iv) Bcl-2 expression as examined by immunoblotting; and (v) the expression of TNFR1, Fas, FasL and caspase-3, -8 and -9, as evaluated by immunoblotting., Results: Cells treated with amoxicillin and clarithromycin showed the formation of apoptotic bodies, and degeneration and detachment of the cells in a dose-dependent manner. DNA fragmentation was induced in these cells to a degree similar to that seen in cells treated with the anti-tumor agents. Trypan blue staining also demonstrated apoptosis of the cells and loss of cell viability. Bcl-2 expression was seen only in the control group and FasL was never seen, while the expression of TNFR1, Fas and caspase-3, -8 and -9 was seen in the amoxicillin-treated group, clarithromycin-treated group, amoxicillin and clarithromycin-treated group and the positive control group., Conclusion: Antibiotics used for the eradication of H. pylori can also directly induce apoptosis in mouse B cell lymphoma cells, an action which involves the TNF system.

Objective: To investigate the prevalence of Helicobacter pylori (Hp) resistant to clarithromycin, amoxicillin and metronidazole in children., Methods: A total of 44 Hp clinical isolates were cultured from children patients with Hp gastritis and peptic ulcer who underwent gastroscopy during the period from October 2002 to November 2003 in Children's Hospital affiliated to Medical College of Zhejiang University. Nineteen of the patients were girls and 25 boys. The mean age was 8.66 +/- 2.66 years (3 approximately 14 years). The susceptibilities of the 44 Hp strains to clarithromycin, amoxicillin and metronidazole were tested by agar dilution test to determine minimum inhibitory concentration (MIC)(50), MIC(90) and resistance rates were also calculated., Results: Among the 44 Hp strains isolated from children, 8, 4, and 14 strains were resistant to clarithromycin, amoxicillin and metronidazole and the resistant rate was 18.2% (8/44), 9.1% (4/44) and 31.8% (14/44), with MICs for all strains ranging from < 0.125 microg/ml to 64 microg/ml, < 0.125 microg/ml to 64 microg/ml and < 0.125 microg/ml to 128 microg/ml, respectively. MIC(50) and MIC(90) of clarithromycin, amoxicillin and metronidazole were < 0.125 microg/ml, 8 microg/ml; < 0.125 microg/ml, 0.5 microg/ml; 0.5 microg/ml, 128 microg/ml, respectively. The prevalence of Hp resistant to clarithromycin was higher in children than that in adults, while to metronidazole was lower than that in adults with high MICs (32 - 128 microg/ml) and MIC(90) (128 microg/ml) of metronidazole for resistant isolates. Three multidrug resistant strains (6.8%) were simultaneously resistant to these three antibiotics., Conclusions: The prevalence of Helicobacter pylori resistant to metronidazole was high in children, and the rate of resistance to clarithromycin was higher than that isolated from adults. Amoxicillin-resistant strains were now found, and multidrug resistant strains which resistant to the three antibiotics also emerged.

MICs of clarithromycin and amoxycillin for 253 isolates of Helicobacter pylori were measured by an air-dried microplate method and compared with the results obtained by the agar plate dilution method. The air-dried microplate method is performed by coating each well of a 96-well microplate with the test antibiotic and air-drying it. There were no marked differences between the air-dried microplate method and agar plate dilution methods in the MIC(50) and MIC(90) values or MIC ranges of clarithromycin obtained for the 253 isolates of H. pylori. More specifically, the MICs of clarithromycin for 114 (45.1 %) of the 253 isolates were the same by the air-dried microplate method as the agar plate dilution method, and the differences in the MICs of clarithromycin for a further 114 isolates (45.1 %) varied within one twofold dilution. The MICs of amoxycillin by the former method were in close agreement with the MICs obtained by the latter method: MICs of amoxycillin for 199 (78.7 %) of the 253 isolates were the same by both methods, and the differences in the MICs of amoxycillin for 42 isolates (16.6 %) varied within one twofold dilution. These results indicate that the air-dried microplate method is a useful method for determination of MICs, because the results obtained were in close agreement with those obtained by the standard agar plate dilution method. The air-dried microplate method is, therefore, a convenient and reliable method for determining the MICs of clarithromycin and amoxycillin for H. pylori isolates.

Inflammation is crucial for the pathogenesis of both infectious and chronic obstructive pulmonary diseases. It is therefore important to modulate pulmonary inflammation in patients with these lung disorders. Macrolide antibiotics modulate inflammation in vitro and in in vivo by inhibiting the production of proinflammatory cytokines and prostaglandin E2, neutrophil chemotactic activity and elastase activity. This study evaluates the effect of clarithromycin (500 mg b.i.d. x 7 days) in comparison to amoxicillin (1 g t.i.d. x 7 days) in patients with community acquired pneumonia by testing plasma levels of IL-6, IFNgamma and IL-10 before starting therapy and at the 3rd and 7th days of therapy. Clarithromycin significantly decreased plasma levels of IL-6 and significantly increased those of IFNgamma and IL-10 at the 3rd and 7th day in comparison to basal levels. In patients treated with amoxicillin a significant decrease in IL-6 plasma levels was observed at the 7th day of therapy, probably in relation to the resolution of inflammatory symptoms. In the same patients IFNgamma plasma levels decreased during treatment while IL-10 plasma levels were unaffected.

Current combination therapies cure Helicobacter pylori infection in 75 to 85% of cases. However, many treatment failures are not explained by antibiotic resistance. Our goal was to explore treatment failures under in vivo conditions by using the H. pylori Sydney strain (SS1) mouse model. Mice infected with H. pylori (SS1) were treated with monotherapies or combination therapies used in human trials. Bacterial levels and distribution of organisms within the stomach were assessed 24 h after treatment to determine clearance and location of treatment failures and 29 days after treatment to determine cure rates. Except for treatment with metronidazole, mono- and dual therapies did not cure infection but resulted in decreases in bacterial levels and differences in distribution within the stomach. In cases of treatment failure when clarithromycin was used, omeprazole and dual therapy with omeprazole and amoxicillin resulted in organisms being cleared from the antrum, but organisms remained in the antrum-body transitional zone. The triple therapies of OMC and bismuth subcitrate, metronidazole, and tetracycline were successful in eradicating infection. Except for metronidazole monotherapy and triple therapy with OAC, there was good correlation between the Sydney strain mouse model and humans with respect to the success of antimicrobial therapy. The antrum-body transitional zone was identified as a sanctuary site in treatment failure. This could result from antimicrobial agents not functioning effectively at this site or bacteria in this location expressing products that protect them against antimicrobial agents. This is the first demonstration of a possible sanctuary site as a reason for failure of therapy.

Helicobacter pylori eradication failure generally concerns between 10 and 30% of the patients. When eradication failure occurs, it is necessary a) to try to identify the potential causes, b) to confirm the indication of eradicating H. pylori, and c) to choose a second line therapeutic strategy. Among the factors most frequently associated with failed eradication, are poor compliance, younger age, smoking, and weak gastric inflammatory activity. The major factor of resistance is related to the sensitivity of the bacterial strain to antibiotics used. In France, resistance to clarithromycin is around 10-15% and resistance to metronidazole around 30%. In order to limit development of resistance, it seems preferable to avoid associating clarithromycin and metronidazole in the first line treatment. At best, the first line treatment must follow the official recommendations (PPI-amoxicillin and clarithromycin). In the event of eradication failure, second line treatment calls upon tritherapy which, due to the low rate of resistance to amoxicillin, associates double-dose PPI, amoxicillin and the antibiotic not used during the first line treatment (metronidazole if clarithromycin was initially used and conversely). This approach allows to eradicate between 50 and 80% of the first-line failure patients. In case of further failure a culture with measurement of the strain sensitivity is required. Subsequent treatment associates PPI with the antibiotics to which the strain is sensitive for a longer duration. In some cases, other effective antibiotics, such as rifabutin, might be used in these circumstances.

The available results of triple therapy for the eradication of Helicobacter pylori (H. pylori), as recommended in European countries--i.e. combination of proton pump inhibitor (PPI) and two antibiotics among amoxicillin, clarithromycin, metronidazole for 7 days--lead to rates of failure of about 30%. Several clinical studies have been recently conducted to distinguish factors influencing effectiveness of therapy and to evaluate results of new regimens. Comparative trials have demonstrated the equivalence of omeprazole 20 mg, lansoprazole 30 mg, pantoprazole 40 mg, rabeprazole 20 mg and esomeprazole 20 mg, twice daily in these 7-days triple therapies. Efficacy of treatment is not affected by metronidazole resistance (44% in France) when amoxicillin-clarithromycin-based triple therapy is prescribed. The impact of clarithromycin resistance (14%) is much more important with failure of eradication in all cases treated by clarithromycin-based triple therapy. The eradication rate could be slightly improved by increasing the dose of clarithromycin but with more frequent side effects. To prolong the duration treatment improve also slightly the cure rate with a gain of less than 10%, but with an increasing rate of side effects. To date, the PPI-based triple therapies, as recommended in France, have not to be modified. The treatment of H. pylori infection has to be globally considered, with a first-line treatment leading to eradication in 70% of patients and a second-line treatment needed for the resting 30% of patients.