Emerging Helicobacter pylori levofloxacin resistance and novel genetic mutation in Nepal

Miftahussurur, Muhammad; Shrestha, Pradeep Krishna; Subsomwong, Phawinee; Sharma, Rabi Prakash; Yamaoka, Yoshio

doi:10.1186/s12866-016-0873-6

Cited by 48 publications

(60 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…40 Miftahussurur et al reported that mutations at Asn-87 and/or Asp-91 were predominantly in levofloxacinresistant strains, and the gyrB mutation had a steady relationship with gyrA 87-91 mutations. 41 None of the substitutions found in gyrB proved conferring resistance in this study. These findings revealed that the mutations of genes related to H. pylori resistance are diversified, especially in children.…”

Section: Discussionmentioning

confidence: 58%

Mutations in the Antibiotic Target Genes Related to Clarithromycin, Metronidazole and Levofloxacin Resistance in Helicobacter pylori Strains from Children in China

Zhang

Wen

Xiao

et al. 2020

IDR

View full text Add to dashboard Cite

Purpose: This study aimed to characterize common mutations of antibiotic-resistant gene of clarithromycin, metronidazole and levofloxacin in Helicobacter pylori (H. pylori) and determine their association with antibiotic resistance of H. pylori for providing a strategy for eradication therapy of H. pylori infection in children. Patients and Methods: The antibiotic resistance to clarithromycin, metronidazole and levofloxacin for H. pylori strains isolated from children was determined by E-test. The mutation of domain V of 23S rRNA, rdxA and frxA genes, gyrA and gyrB genes was performed by PCR-based sequencing of DNA fragments. Results: Out of the 79 H. pylori strains examined, 66 (83.5%) were resistant to at least one of the tested antibiotics and 13 (16.5%) were fully sensitive. A total of 29 (36.7%) strains were resistant to clarithromycin. Analysis of the 23S rRNA gene showed that most mutations occurred at the A2143G and T2182C sites, showing a frequency of 82.8% (24/29) and 89.7% (26/29) respectively. In the 11 sensitive strains to clarithromycin, the frequency of A2143G mutation was only 45.5%, which was significantly lower than that in resistant strains (P<0.05). There were 54 strains (68.4%) resistant to metronidazole, with most mutations occurring at G47A and T184G in the rdxA gene. T184G mutation was recognized in metronidazole-sensitive strains, but no G47A mutation was identified. Twelve strains (15.2%) were resistant to levofloxacin. Position 91 mutation of the gyrA gene occurred only in resistant strains, whereas position 87 mutations were detected in both sensitive and resistant strains to levofloxacin. Conclusion: In H. pylori resistant strains isolated from children in China, most mutations occurred at A2143G of the 23S rRNA gene for clarithromycin; G47A mutation of rdxA gene for metronidazole; and at 91 mutation of gyrA gene for levofloxacin. It is suggested that susceptibility testing together with screening the mutation of antimicrobial-resistant gene prior to treatment is important for the eradication of H. pylori in children.

show abstract

Section: Discussionmentioning

confidence: 58%

Mutations in the Antibiotic Target Genes Related to Clarithromycin, Metronidazole and Levofloxacin Resistance in Helicobacter pylori Strains from Children in China

Zhang

Wen

Xiao

et al. 2020

IDR

View full text Add to dashboard Cite

show abstract

“…Another observation was the detection of a D99N substitution (gyrA) in an isolate phenotypically levofloxacin resistant (MHP11). A previous study from Nepal found that a mutation at this position confers resistance, but a D99V substitution was noted (40). WGS revealed clinically significant mutations in isolates testing phenotypically sensitive, which highlights an advantage of WGS over phenotypic testing.…”

Section: Discussionmentioning

confidence: 76%

“…We examined our isolates for point mutations that may be associated with metronidazole resistance and found a mutation at position R16 that was associated with six of the eight phenotypically resistant isolates that lacked a truncation in rdxA ( Table 2; Table S2). This mutation has previously been associated with metronidazole phenotypic resistance (37,39,40). The detection of either a truncated rdxA gene or a mutation at position R16 correlated (kappa coefficient, 0.76) with 88% of phenotypic testing results (Table 2).…”

Section: Resultsmentioning

confidence: 85%

Helicobacter pylori Infections in the Bronx, New York: Surveying Antibiotic Susceptibility and Strain Lineage by Whole-Genome Sequencing

et al. 2020

View full text Add to dashboard Cite

The emergence of drug resistance in Helicobacter pylori has resulted in a greater need for susceptibility-guided treatment. While the alleles associated with resistance to clarithromycin and levofloxacin have been defined, there are limited data regarding the molecular mechanisms underlying resistance to other antimicrobials. Using H. pylori isolates from 42 clinical specimens, we compared phenotypic and whole-genome sequencing (WGS)-based detection of resistance. Phenotypic resistance correlated with the presence of alleles of 23S rRNA (A2142G/A2143G) for clarithromycin (kappa coefficient, 0.84; 95% confidence interval [CI], 0.67 to 1.0) and gyrA (N87I/N87K/D91Y/D91N/D91G/D99N) for levofloxacin (kappa coefficient, 0.90; 95% CI, 0.77 to 1.0). Phenotypic resistance to amoxicillin in three isolates correlated with mutations in pbp1, pbp2, and/or pbp3 within coding regions near known amoxicillin binding motifs. All isolates were phenotypically susceptible to tetracycline, although four bore a mutation in 16S rRNA (A926G). For metronidazole, nonsense mutations and R16H substitutions in rdxA correlated with phenotypic resistance (kappa coefficient, 0.76; 95% CI, 0.56 to 0.96). Previously identified mutations in the rpoB rifampin resistance-determining region (RRDR) were not present, but 14 novel mutations outside the RRDR were found in rifampin-resistant isolates. WGS also allowed for strain lineage determination, which may be important for future studies in associating precise MICs with specific resistance alleles. In summary, WGS allows for broad analyses of H. pylori isolates, and our findings support the use of WGS for the detection of clarithromycin and levofloxacin resistance. Additional studies are warranted to better define mutations conferring resistance to amoxicillin, tetracycline, and rifampin, but combinatorial analyses for rdxA gene truncations and R16H mutations have utility for determining metronidazole resistance.

show abstract

“…A significant and welcome increase was noted over the last year in the number of studies addressing the important topic of antimicrobial resistance in H. pylori infection. These are summarized in Table . A key message emerging is the relentless rise in antibiotic resistance, especially to clarithromycin and levofloxacin.…”

Section: Antimicrobial Resistancementioning

confidence: 99%

Treatment of Helicobacter pylori infection 2017

et al. 2017

View full text Add to dashboard Cite

Over the last decade, it has been widely reported that the success of Helicobacter pylori eradication treatment is falling. A steady decline was observed in the number of patients achieving eradication with standard first-line triple therapy of two antibiotics and a proton pump inhibitor [1][2][3]. It now appears that the first-line eradication therapies most commonly used in everyday clinical practice fall considerably short of the 80% intention-to-treat (ITT) eradication rates that are considered the minimal acceptable levels as recommended in the Maastricht guidelines [4]. Interestingly, two studies emerged from Asian centers in the last 12 months, which show that, in this part of the world at least, eradication levels using standard therapies remain close to 80%. A Malaysian study showed a standard 1-week pantoprazole, amoxycillin, and clarithromycin regimen to be well tolerated and highly efficacious with a per-protocol eradication rate of 84% [5]. A Japanese study showed remarkably consistent per-protocol eradication rates from 2001 to 2009 fluctuating between 75 and 78% for standard 7-day triple-therapy regimens [6]. A limit of many studies especially those including clarithromycin or levofloxacin is that H. pylori susceptibility to the drugs, which is the main prediction of failure, was not tested. LevofloxacinThe use of levofloxacin as a first-line therapy has been examined in great depth in the last year. Levofloxacin may be used as a substitute for clarithromycin in either a standard triple or sequential regimen. A large study comparing the antibiotics in either regimen shows a clear advantage to levofloxacin in both combinations. Per-protocol cure rates for triple therapy were 66% for omeprazole-clarithromycin-amoxycillin compared with 83% for omeprazole-levofloxacin-amoxycillin and 81% for omeprazole-amoxycillin-clarithromycin-metronidazole vs 85% for omeprazole-amoxycillin-levofloxacinmetronidazole, with no difference in compliance rates or adverse events [7]. It has been proposed that sequential levofloxacin-based regimens are of most benefit in areas where clarithromycin resistance is in excess of 15%, and another study in such an area showed eradication rates of 81% with clarithromycin sequential therapy compared with 96% with levofloxacin sequential therapy. A third arm in this study looked at the dose of levofloxacin required and illustrated no benefit in increasing the dose from 250 to 500 mg [8]. Indeed, another study went so far as to suggest that once-daily dosing of a levofloxacin-based triple regimen may be as efficacious as twice daily [9]. The literature from Asia also seems to support levofloxacin as a good alternative first-line therapy. A study on a triple regimen showed per-protocol eradication rates of 78% for standard clarithromycin-containing therapies compared with 83% for a levofloxacin-based regimen [10]. Another study from the Middle East looked at whether combining clarithromycin and levofloxacin in the same regimen could be Keywords Peptic ulcer disease, resistance, compli...

show abstract

Emerging Helicobacter pylori levofloxacin resistance and novel genetic mutation in Nepal

Cited by 48 publications

References 48 publications

<p>Mutations in the Antibiotic Target Genes Related to Clarithromycin, Metronidazole and Levofloxacin Resistance in <em>Helicobacter pylori</em> Strains from Children in China</p>

<p>Mutations in the Antibiotic Target Genes Related to Clarithromycin, Metronidazole and Levofloxacin Resistance in <em>Helicobacter pylori</em> Strains from Children in China</p>

Helicobacter pylori Infections in the Bronx, New York: Surveying Antibiotic Susceptibility and Strain Lineage by Whole-Genome Sequencing

Treatment of Helicobacter pylori infection 2017

Contact Info

Product

Resources

About