National and Regional US Antibiotic Resistance to Helicobacter pylori: Lessons From a Clinical Trial.
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ABSTRACT:
SUBMITTER: Hulten KG
PROVIDER: S-EPMC8267964 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundResistance of Helicobacter pylori (H. pylori) to antibiotics is increasing worldwide. To determine the status of H. pylori resistance and its patterns in clinical patients, an investigation utilizing susceptibility testing for commonly used antibiotics was needed.MethodsTotal of 2283 H. pylori strains were collected from 2013 to 2016. The resistance and its patterns of these strains were tested by agar dilution method. The resistance rate and minimal inhibition concentration (MIC) in different gender groups were also analyzed.ResultsThe overall resistance rates were as following: amoxicillin (1.58%), clarithromycin (22.73%), levofloxacin (24.75%), furazolidone (1.49%), doxycycline (9.20%), cefetamet (97.20%), ceftriaxone (49.60%), cefuroxime (25.20%), gentamicin (3.73%), azithromycin (85.60%), rifampicin (2.80%), metronidazole (92.53%), ornidazole (94.27%), tinidazole (87.20%), ciprofloxacin (43.20%), and moxifloxacin (38.53%). There were only 64.08% strains pan-susceptible to amoxicillin, clarithromycin, levofloxacin, and furazolidone, followed by mono resistance (23.17%), double resistance (11.13%), triple resistance (1.36%), and quadruple resistance (0.26%). Significant differences in the resistance rate and MIC were also observed in different gender groups.ConclusionAntibiotic resistance trends of H. pylori is increasing in clinical patients. With the increasing resistance, it is imperative to individualized therapy based on the results of drug susceptibility testing.
| S-EPMC6817019 | biostudies-literature
Project description:Antibiotic resistance is the major reason for Helicobacter pylori treatment failure, and the increasing frequency of antibiotic resistance is a challenge for clinicians. Resistance to clarithromycin and metronidazole is a particular problem. The standard triple therapy (proton pump inhibitor, amoxicillin, and clarithromycin) is no longer appropriate as the first-line treatment in most areas. Recent guidelines for the treatment of H. pylori infection recommend a quadruple regimen (bismuth or non-bismuth) as the first-line therapy. This treatment strategy is effective for areas with high resistance to clarithromycin or metronidazole, but the resistance rate inevitably increases as a result of prolonged therapy with multiple antibiotics. Novel potassium-competitive acid blocker-based therapy may be effective, but the data are limited. Tailored therapy based on antimicrobial susceptibility test results is ideal. This review discussed the current important regimens for H. pylori treatment and the optimum H. pylori eradication strategy.
| S-EPMC7459868 | biostudies-literature
Project description:Helicobacter pylori is a major human pathogen. Diagnosis of H. pylori infection and determination of its antibiotic susceptibility still mainly rely on culture and phenotypic drug susceptibility testing (DST) that is time-consuming and laborious. Whole genome sequencing (WGS) has recently emerged in medical microbiology as a diagnostic tool for reliable drug resistance prediction in bacterial pathogens. The aim of this study was to compare phenotypic DST results with the predictions based on the presence of genetic determinants identified in the H. pylori genome using WGS. Phenotypic resistance to clarithromycin, metronidazole, tetracycline, levofloxacin, and rifampicin was determined in 140 clinical H. pylori isolates by E-Test®, and the occurrence of certain single nucleotide polymorphisms (SNPs) in target genes was determined by WGS. Overall, there was a high congruence of >99% between phenotypic DST results for clarithromycin, levofloxacin, and rifampicin and SNPs identified in the 23S rRNA, gyrA, and rpoB gene. However, it was not possible to infer a resistance phenotype for metronidazole based on the occurrence of distinct SNPs in frxA and rdxA. All 140 H. pylori isolates analysed in this study were susceptible to tetracycline, which was in accordance with the absence of double or triple nucleotide substitutions in the 16S rRNA gene.
| S-EPMC6351930 | biostudies-literature
Project description:Rapid diagnosis and treatment of Helicobacter pylori (H. pylori) presents a challenge. We aimed at investigating the presence of H. pylori, susceptibility profile, and associated mutations in an effort to validate the effectiveness of GenoType HelicoDR assay in H. pylori typing in our environment. Two hundred and fifty-four biopsy specimens were cultured and DNA extracted from seventy-eight positive cultures using the Qiagen DNA extraction kit. The GenoType Helico DR which employs reverse hybridisation was used to confirm the presence of H. pylori, determination of its susceptibility to antimicrobials, and detection of mutations conferring resistance to clarithromycin and fluoroquinolones. The organism was isolated from 168/254 (66.1 %) of the specimens by culture. Of the 78 strains used for further investigation, 12/78 (15.38%) were resistant to clarithromycin while 66/78 (84.61%) were susceptible. For fluoroquinolone, 70/78 (89.74%) strains were susceptible while 8 (10.26%) were resistant. Mutations were observed in 17 strains with A2147G being the most prevalent; A2146C and D91N were the least. The reverse hybridisation assay is an easy and fast technique in confirming the presence of H. pylori, its antimicrobial profile, and associated mutations. Analysis regarding the suitability of this assay for H. pylori typing is warranted in other regions.
| S-EPMC3655586 | biostudies-literature
Project description:BACKGROUND: Helicobacter pylori is the etiological agent for diseases ranging from chronic gastritis and peptic ulcer disease to gastric adenocarcinoma and primary gastric B-cell lymphoma. Emergence of resistance to antibiotics possesses a challenge to the effort to eradicate H. pylori using conventional antibiotic-based therapies. The molecular mechanisms that contribute to the resistance of these strains have yet to be identified and are important for understanding the evolutional pattern and selective pressure imposed by the environment. METHODS AND FINDINGS: H. pylori was isolated from 102 patients diagnosed with gastrointestinal diseases, who underwent endoscopy at University Malaya Medical Centre (UMMC). The isolates were tested for their susceptibility on eleven antibiotics using Etest. Based on susceptibility test, 32.3% of the isolates were found to have primary metronidazole resistance; followed by clarithromycin (6.8%) and fluoroquinolones (6.8%). To further investigate the resistant strains, mutational patterns of gene rdxA, frxA, gyrA, gyrB, and 23S rRNA were studied. Consistent with the previous reports, metronidazole resistance was prevalent in the local population. However, clarithromycin, fluoroquinolone and multi-drug resistance were shown to be emerging. Molecular patterns correlated well with phenotypic data. Interestingly, multi-drug resistant (MDR) strains were found to be associated with higher minimum inhibitory concentration (MIC) than their single-drug resistant (SDR) counterparts. Most importantly, clarithromycin-resistant strains were suggested to have a higher incidence for developing multi-drug resistance. CONCLUSION: Data from this study highlighted the urgency to monitor closely the prevalence of antibiotic resistance in the Malaysian population; especially that of clarithromycin and multi-drug resistance. Further study is needed to understand the molecular association between clarithromycin resistance and multi-drug resistance in H. pylori. The report serves a reminder that a strict antibiotic usage policy is needed in Malaysia and other developing countries (especially those where H. pylori prevalence remained high).
| S-EPMC4086822 | biostudies-literature
Project description:The gram-negative bacterium Helicobacter pylori (H. pylori) causes chronic gastritis, gastric and duodenal ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma. Treatment is recommended in all symptomatic patients. The current treatment options for H. pylori infection are outlined in this review in light of the recent challenges in eradication success, largely due to the rapid emergence of antibiotic resistant strains of H. pylori. Antibiotic resistance is a constantly evolving process and numerous studies have shown that the prevalence of H. pylori antibiotic resistance varies significantly from country to country, and even between regions within the same country. In addition, recent data has shown that previous antibiotic use is associated with harbouring antibiotic resistant H. pylori. Local surveillance of antibiotic resistance is warranted to guide clinicians in their choice of therapy. Antimicrobial resistance is assessed by H. pylori culture and antimicrobial susceptibility testing. Recently developed molecular tests offer an attractive alternative to culture and allow for the rapid molecular genetic identification of H. pylori and resistance-associated mutations directly from biopsy samples or bacterial culture material. Accumulating evidence indicates that surveillance of antimicrobial resistance by susceptibility testing is feasible and necessary to inform clinicians in their choice of therapy for management of H. pylori infection.
| S-EPMC4123372 | biostudies-literature
Project description:Helicobacter pylori is a Gram-negative bacterium that colonizes the gut of over 50% of the world's population. It is responsible for most peptic ulcers and is an important risk factor for gastric cancer. Antibiotic treatment for H. pylori infections is challenging as drug resistance has developed to antibiotics with traditional mechanisms of action. H. pylori uses an unusual pathway for menaquinone biosynthesis with 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN) catalyzing an essential step. We validated MTAN as a target with a transition-state analogue of the enzyme [Wang, S.; Haapalainen, A. M.; Yan, F.; et al. Biochemistry 2012, 51, 6892-6894]. MTAN inhibitors will only be useful drug candidates if they can both include tight binding to the MTAN target and have the ability to penetrate the complex cell membrane found in Gram-negative H. pylori. Here we explore structural scaffolds for MTAN inhibition and for growth inhibition of cultured H. pylori. Sixteen analogues reported here are transition-state analogues of H. pylori MTAN with dissociation constants of 50 pM or below. Ten of these prevent growth of the H. pylori with IC90 values below 0.01 ?g/mL. These remarkable compounds meet the criteria for potent inhibition and cell penetration. As a consequence, 10 new H. pylori antibiotic candidates are identified, all of which prevent H. pylori growth at concentrations 16-2000-fold lower than the five antibiotics, amoxicillin, metronidazole, levofloxacin, tetracyclin, and clarithromycin, commonly used to treat H. pylori infections. X-ray crystal structures of MTAN cocrystallized with several inhibitors show them to bind in the active site making interactions consistent with transition-state analogues.
| S-EPMC6709534 | biostudies-literature
Project description:BackgroundThe prevalence of Helicobacter pylori infection was never assessed in Armenia, nor was the prevalence of H. pylori resistance against the main antibiotics concerned, despite the fact that these data are fundamental to establish evidence-based recommendations for management of this infection. We aimed to fill this gap by assessing prevalence of H. pylori among adult population in Armenia and resistance of H. pylori strains to clarithromycin and levofloxacin.MethodsHelicobacter pylori seroprevalence was determined in 217 asymptomatic adult subjects submitted to a health checkup using an ELISA. Molecular methods were used to detect H. pylori in gastric biopsies from 91 adult dyspeptic patients [55 (60.4%) were positive] as well as the mutations associated with clarithromycin resistance by real-time PCR and with levofloxacin by sequencing the gyrA QRDR.ResultsHelicobacter pylori seropositivity was found to be 41.5% globally and increased with age from 13.6% (age 18-25 years) to 83.3% (age > 65 years). Only two cases were found with a A2142/43G mutation causing clarithromycin resistance, and 6 cases showed mutations associated with levofloxacin resistance.ConclusionsHelicobacter pylori infection is estimated to be about 42% among adults in Armenia and the low clarithromycin resistance allows the use of the standard triple therapy as a first line therapy.
| S-EPMC6555938 | biostudies-literature
Project description:ObjectiveThis study aimed to evaluate the resistance of Helicobacter pylori (H. pylori) to common antibiotics in Shanghai.MethodsA total of 1171 eligible subjects participated in the study. Antibiotic susceptibility to six common antibiotics was examined with the disk diffusion method. Mutations in resistant-related genes were identified via Sanger sequencing analysis.ResultsOverall, the resistance rates of strains to amoxicillin, clarithromycin, levofloxacin, metronidazole, tetracycline, and furazolidone were 0.1%, 27.8%, 31.1%, 79.9%, 0.1%, and 0.5%, respectively. Compared with untreated patients, resistance rates of clarithromycin (P < 0.01), levofloxacin (P < 0.01), and metronidazole were significantly higher in re-treated patients (P < 0.05). The total multiple resistance rate was 40.5%. Age (levofloxacin), gender (clarithromycin, levofloxacin, and metronidazole) and endoscopic findings (clarithromycin and levofloxacin) were independent factors influencing antibiotic resistance. High correlation was observed between the drug susceptibility test and molecular test for the resistance to clarithromycin and levofloxacin.ConclusionsThe resistance rates of H. pylori to amoxicillin, tetracycline, and furazolidone were low, whereas the resistance rates of H. pylori to clarithromycin, levofloxacin, and metronidazole were high, especially in re-treated patients. Our results indicate that the clinical resistance patterns of clarithromycin and levofloxacin could be guided by relevant gene mutations.
| S-EPMC9730088 | biostudies-literature
Project description:We evaluated the primary resistance of Helicobacter pylori (H. pylori) to routinely used antibiotics in Cambodia, an unexplored topic in the country, and assessed next-generation sequencing's (NGS) potential to discover genetic resistance determinants. Fifty-five H. pylori strains were successfully cultured and screened for antibiotic susceptibility using agar dilution. Genotypic analysis was performed using NGS data with a CLC genomic workbench. PlasmidSeeker was used to detect plasmids. The correlation between resistant genotypes and phenotypes was evaluated statistically. Resistances to metronidazole (MTZ), levofloxacin (LVX), clarithromycin (CLR), and amoxicillin (AMX) were 96.4%, 67.3%, 25.5%, and 9.1%, respectively. No resistance to tetracycline (TET) was observed. Multi-drug resistance affected 76.4% of strains. No plasmids were found, but genetic determinants of resistance to CLR, LVX, and AMX were 23S rRNA (A2146G and A2147G), GyrA (N87K and D91Y/N/G), and pbp1 (P473L), respectively. No determinants were genetically linked to MTZ or TET resistance. There was high concordance between resistant genotypes and phenotypes for AMX, LVX, and CLR. We observed high antibiotic resistance rates of CLR, MTZ, and LVX, emphasizing the need for periodic evaluation and alternative therapies in Cambodia. NGS showed high capability for detecting genetic resistance determinants and potential for implementation in local treatment policies.
| S-EPMC6617194 | biostudies-literature