Evolution of Helicobacter pylori Resistance to Antibiotics: A Topic of Increasing Concern

Boyanova, Lyudmila; Hadzhiyski, Petyo; Gergova, Raina; Markovska, Rumyana

doi:10.3390/antibiotics12020332

Cited by 65 publications

(57 citation statements)

References 64 publications

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“…Antibiotics used in first-line PPI-TT are clarithromycin, amoxicillin and metronidazole or, more restrictive, levofloxacin and, in selected cases, furazolidone. Treatment failures with PPI-TT occur with increasing frequency and are primarily related to antibiotic resistance, insufficient acid suppression and inadequate adherence to medications 10,[251][252][253] . Acid suppression with PPI (omeprazole, esomeprazole, lansoprazole, pantoprazole or rabeprazole in double standard dose) is essential and aims to raise intragastric pH to 6 or higher, which optimizes the stability, bioavailability and efficacy of antibiotics 254,255 .…”

Section: Ppi Triple Therapymentioning

confidence: 99%

Helicobacter pylori infection

Malfertheiner

Camargo

El-Omar

et al. 2023

Nat Rev Dis Primers

317

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Helicobacter pylori infection causes chronic gastritis, which can progress to severe gastroduodenal pathologies, including peptic ulcer, gastric cancer and gastric mucosa-associated lymphoid tissue lymphoma. H. pylori is usually transmitted in childhood and persists for life if untreated. The infection affects around half of the population in the world but prevalence varies according to location and sanitation standards. H. pylori has unique properties to colonize gastric epithelium in an acidic environment. The pathophysiology of H. pylori infection is dependent on complex bacterial virulence mechanisms and their interaction with the host immune system and environmental factors, resulting in distinct gastritis phenotypes that determine possible progression to different gastroduodenal pathologies. The causative role of H. pylori infection in gastric cancer development presents the opportunity for preventive screen-and-treat strategies. Invasive, endoscopy-based and non-invasive methods, including breath, stool and serological tests, are used in the diagnosis of H. pylori infection. Their use depends on the specific individual patient history and local availability. H. pylori treatment consists of a strong acid suppressant in various combinations with antibiotics and/or bismuth. The dramatic increase in resistance to key antibiotics used in H. pylori eradication demands antibiotic susceptibility testing, surveillance of resistance and antibiotic stewardship.

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Section: Ppi Triple Therapymentioning

confidence: 99%

Helicobacter pylori infection

Malfertheiner

Camargo

El-Omar

et al. 2023

Nat Rev Dis Primers

317

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“…The latest systematic review and meta-analysis in 2018 reported that the primary amoxicillin resistance in H. pylori has a generally low prevalence (≤10 %) in all World Health Organisation regions, except in the Eastern Mediterranean region (14 %) [7]. However, according to the latest review by Boyanova et al [8], a trend of rising amoxicillin resistance was detected in various countries including China (from 4.3 % in 1998-1999 to 25.9 % in 2016-2017) [9], Iran (from 9.0 % in 1999-2000 to 36.0 % in 2017-2019) [10], Vietnam (from ≤1.1 % in 2013-2015 to 25.7 % in 2020) [11] and Bulgaria (from 4.2 % in 2007-2014 to 8.9 % in 2015-2021) [12]. In Malaysia, consistent reports published between 2011 to 2019 showed a 0 % rate for both primary and secondary amoxicillin resistance [13][14][15][16][17] until a recent study reported a 3.9 % (2/51) secondary resistance rate in 2022 [18].…”

Section: Introductionmentioning

confidence: 99%

Genetic variations of penicillin-binding protein 1A: insights into the current status of amoxicillin-based regimens for Helicobacter pylori eradication in Malaysia

Ng,

Chua,

Kee

et al. 2024

Journal of Medical Microbiology

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Introduction. Resistance towards amoxicillin in Helicobacter pylori causes significant therapeutic impasse in healthcare settings worldwide. In Malaysia, the standard H. pylori treatment regimen includes a 14-day course of high-dose proton-pump inhibitor (rabeprazole, 20 mg) with amoxicillin (1000 mg) dual therapy. Hypothesis/Gap Statement. The high eradication rate with amoxicillin-based treatment could be attributed to the primary resistance rates of amoxicillin being relatively low at 0%, however, a low rate of secondary resistance has been documented in Malaysia recently. Aim. This study aims to investigate the amino acid mutations and related genetic variants in PBP1A of H. pylori, correlating with amoxicillin resistance in the Malaysian population. Methodology. The full-length pbp1A gene was amplified via PCR from 50 genomic DNA extracted from gastric biopsy samples of H. pylori-positive treatment-naïve Malaysian patients. The sequences were then compared with reference H. pylori strain ATCC 26695 for mutation and variant detection. A phylogenetic analysis of 50 sequences along with 43 additional sequences from the NCBI database was performed. These additional sequences included both amoxicillin-resistant strains (n=20) and amoxicillin-sensitive strains (n=23). Results. There was a total of 21 variants of amino acids, with three of them located in or near the PBP-motif (SKN402-404). The percentages of these three variants are as follows: K403X, 2%; S405I, 2% and E406K, 16%. Based on the genetic markers identified, the resistance rate for amoxicillin in our sample remained at 0%. The phylogenetic examination suggested that H. pylori might exhibit unique conserved pbp1A sequences within the Malaysian context. Conclusions. Overall, the molecular analysis of PBP1A supported the therapeutic superiority of amoxicillin-based regimens. Therefore, it is crucial to continue monitoring the amoxicillin resistance background of H. pylori with a larger sample size to ensure the sustained effectiveness of amoxicillin-based treatments in Malaysia.

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“…Although the resistance is still rather low, 13 a significant increase in overall amoxicillin resistance was detected in patients form Bulgaria, China, Vietnam, and Iran. 14 Therefore, using amoxicillin in combination is highly recommended to enhance its eradication efficacy against H. pylori than in single agent use. 15 Therefore, we manage to modify the parent amoxicillin drug to a new compound conjugates.…”

Section: Introductionmentioning

confidence: 99%

“…H. pylori is associated with mucosa‐associated lymphoid tissue (MALT) lymphoma as well. Although the resistance is still rather low, 13 a significant increase in overall amoxicillin resistance was detected in patients form Bulgaria, China, Vietnam, and Iran 14 . Therefore, using amoxicillin in combination is highly recommended to enhance its eradication efficacy against H. pylori than in single agent use 15 .…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial screening involving Helicobacter pylori of nano‐therapeutic compounds based on the amoxicillin antibiotic drug

Hassan,

Nader,

Nagy

et al. 2023

Helicobacter

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Nano‐structure Cu(II) complex [Cu(AMAB)2]Cl2 with Schiff base (AMAB) derived from the condensation between 4‐(dimethylamino)benzaldehyde and amoxicillin trihydrate was prepared. (AMAB) Schiff base and its Cu(II) complex were identified and confirmed by different physicochemical techniques. The Schiff base (AMAB) was coordinated to copper ion through carbonyl oxygen and imine nitrogen donor sites. X‐ray powder diffraction shows a cubic crystal system of the Cu(II) complex. The density functional theory was used to optimize the structure geometries of the investigated compounds. The molecular docking of the active amino acids of the investigated proteins' interactions with the tested compounds was evaluated. The bactericidal or bacteriostatic effect of the compounds was screened against some bacterial strains. The activity of Cu‐chelate against Gram‐negative bacteria was mainly more effective than its (AMAB) ligand and vice versa in the case of Gram‐positive bacteria. The biological activity of the prepared compounds with biomolecules calf thymus DNA (CT‐DNA) was determined by electronic absorption spectra and DNA gel electrophoresis technique. All studies revealed that the Cu‐chelate derivative exhibited better binding affinity to both CT‐DNA than the AMAB and amoxicillin itself. The anti‐inflammatory effect of the designed compounds was determined by testing their protein denaturation inhibitory activity spectrophotometrically. All obtained data supported that the designed nano‐Cu(II) complex with Schiff base (AMAB) is a potent bactericide against H. pylori, and exhibits anti‐inflammatory activity. The dual inhibition effects of the designed compound represent a modern therapeutic approach with extended spectrum of action. Therefore, it can act as good drug target in antimicrobial and anti‐inflammtory therapies. Finally, H. pylori resistance to amoxicillin is absent or rare in many countries, thus amoxicillin nanoparticles may be beneficial for countries where amoxicillin resistance is reported.

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Evolution of Helicobacter pylori Resistance to Antibiotics: A Topic of Increasing Concern

Cited by 65 publications

References 64 publications

Helicobacter pylori infection

Helicobacter pylori infection

Genetic variations of penicillin-binding protein 1A: insights into the current status of amoxicillin-based regimens for Helicobacter pylori eradication in Malaysia

Antimicrobial screening involving Helicobacter pylori of nano‐therapeutic compounds based on the amoxicillin antibiotic drug

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