DNA Sequence Analysis of rdxA andfrxA from 12 Pairs of Metronidazole-Sensitive and -Resistant Clinical Helicobacter pyloriIsolates

ABSTRACT We previously reported that inactivation of rdxAand/or frxA converted Helicobacter pylorifrom metronidazole sensitive to metronidazole resistant. To examine the individual roles of rdxA and frxA in the development of metronidazole resistance in H. pylori, we examined the status of rdxA and frxA from 12 pairs of metronidazole-sensitive and -resistant H. pylori isolates obtained following unsuccessful therapy containing metronidazole. Arbitrary primed fingerprinting analyses revealed that the genotypes of 11 sensitive and resistant pairs of strains were essentially identical. Amino acid sequence identities of RdxA and FrxA from the 14 metronidazole-sensitive isolates ranged from 92 to 98% and 95 to 98%, respectively, compared to that of H. pylori J99 (MIC, 1 μg/ml). All strains with high-level metronidazole resistance (MICs, 128 μg/ml) contained premature truncation of both RdxA and FrxA caused by nonsense and/or frameshift mutations. Strains with intermediate resistance to metronidazole (MICs, 32 to 64 μg/ml) contained a single premature truncation and/or altered RdxA and FrxA caused by nonsense, frameshift, and unique missense mutations. The low-level metronidazole-resistant strains (MICs, 8 μg/ml) contained unique missense mutations in FrxA but no specific changes in RdxA. The results demonstrate that alterations in both the rdxA and frxA genes are required for moderate and high-level metronidazole resistance and that metronidazole resistance that develops during anti-H. pylori therapy containing metronidazole is most likely to involve a single sensitive strain infection rather than a coinfection with a metronidazole-resistant strain.

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Conspicuous consumption of luxury experiences: an experimental investigation of status perceptions on social media

Journal of Product & Brand Management ◽

10.1108/jpbm-08-2020-3047 ◽

2021 ◽

Vol ahead-of-print (ahead-of-print) ◽

Author(s):

Carolin Siepmann ◽

Lisa Carola Holthoff ◽

Pascal Kowalczuk

Keyword(s):

Social Media ◽

Personal Characteristics ◽

Conspicuous Consumption ◽

Individual Characteristics ◽

Luxury Goods ◽

Content Type ◽

The Status ◽

Self Actualization ◽

The Individual ◽

High Level

Purpose As luxury goods are losing their importance for demonstrating status, wealth or power to others, individuals are searching for alternative status symbols. Recently, individuals have increasingly used conspicuous consumption and displays of experiences on social media to obtain affirmation. This study aims to analyze the effects of luxury and nonluxury experiences, as well as traditional luxury goods on status- and nonstatus-related dimensions. Design/methodology/approach After presenting the theoretical foundation, the authors conduct a study with 599 participants to compare status perceptions elicited by the conspicuous consumption of luxury goods, luxury experiences and nonluxury experiences. The authors investigate whether experiences that are visibly consumed on Instagram are replacing traditional luxury goods as the most important status symbols. Furthermore, the authors examine the effects of the content shown on nonstatus-related dimensions and analyze whether status perceptions differ between female and male social media communicators. Finally, the authors analyze how personal characteristics (self-esteem, self-actualization and materialism) influence the status perceptions of others on social media. Findings The results show that luxury goods are still the most important means of displaying status. However, especially for women, luxury experiences are also associated with a high level of social status. Thus, the results imply important gender differences in the perceptions of status- and nonstatus-related dimensions. Furthermore, the findings indicate that, in particular, the individual characteristics of self-actualization and materialism affect status perceptions depending on the posted content. Originality/value While the research has already considered some alternative forms of conspicuous consumption, little attention has been given to experiences as status symbols. However, with their growing importance as substitutes for luxury goods and the rise of social media, the desire to conspicuously consume experiences is increasing. The authors address this gap in the literature by focusing on the conspicuous display of luxury and nonluxury experiences on social media.

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E-Test or Agar Dilution for Metronidazole Susceptibility Testing of Helicobacter Pylori: Importance of the Prevalence of Metronidazole Resistance

10.21203/rs.3.rs-677597/v1 ◽

2021 ◽

Author(s):

Jinnan Chen ◽

Yu Huang ◽

Zhaohui Ding ◽

Xiao Liang ◽

Hong Lu

Keyword(s):

Helicobacter Pylori ◽

Susceptibility Testing ◽

Resistance Rate ◽

Test Method ◽

Major Error ◽

Metronidazole Resistance ◽

Agar Dilution ◽

H Pylori ◽

High Level ◽

Level Resistance

Abstract Background: A number of studies have shown that E-test overestimated the presence of Helicobacter pylori (H. pylori) resistance compared to agar dilution.Objective: The purpose of this study was to explore whether E-test could be an alternative for agar dilution to detect the metronidazole susceptibility of H. pylori.Method: E-test and agar dilution were used to assess susceptibility of H. pylori to metronidazole, clarithromycin and levofloxacin in 281 clinical isolates obtained from China where resistance was high. Cohen kappa analysis, McNemar test, essential and categorical agreement analysis were performed for these two methods. Results: Overall, the result of E-test showed similar prevalence of resistance rate to all antibiotics compared with agar dilution. The essential agreement (EA) of E-test method and agar dilution in the evaluation susceptibility of H. pylori to clarithromycin and levofloxacin were moderate, with 89.0% and 79.7% respectively, but only 45.9% for metronidazole. Results showed categorical agreement (CA) between E-test and agar dilution were 100% for both clarithromycin and levofloxacin. As for metronidazole, the CA was 98.7%, no major error was identified, and rate of very major error was 1.8%.Conclusion: E-test can be an alternative method to detect the metronidazole susceptibility of H. pylori in regions where high-level resistance is common.

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Dynamic Capabilities and Where to Find Them

Journal of Management Inquiry ◽

10.1177/1056492617730126 ◽

2017 ◽

Vol 29 (1) ◽

pp. 3-16 ◽

Cited By ~ 2

Author(s):

Seidali Kurtmollaiev

Keyword(s):

Dynamic Capabilities ◽

Sufficient Conditions ◽

Resource Base ◽

Firm Level ◽

Individual Level ◽

The Status ◽

The Individual ◽

High Level ◽

Necessary And Sufficient ◽

Intention To Change

Despite its immense popularity, the dynamic capabilities framework faces fierce criticism because of the ambiguous and contradictory interpretations of dynamic capabilities. Especially challenging are the aspects related to the nature of dynamic capabilities and the issue of agency. In an attempt to avoid circular and overlapping definitions, I explicate dynamic capabilities as the regular actions of creating, extending, and modifying an organizational resource base. This implies that the individual’s intention to change the status quo in the organization and the individual’s high level of influence in the organization are necessary and sufficient conditions for dynamic capabilities. This approach overcomes challenges associated with current interpretations of dynamic capabilities, necessarily focusing on the actions and interactions of individuals in organizations. Following the micro-foundations movement, I present a multilevel approach for studying the individual-level causes and the firm-level effects of dynamic capabilities.

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Analysis of rdxA and Involvement of Additional Genes Encoding NAD(P)H Flavin Oxidoreductase (FrxA) and Ferredoxin-Like Protein (FdxB) in Metronidazole Resistance of Helicobacter pylori

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.44.8.2133-2142.2000 ◽

2000 ◽

Vol 44 (8) ◽

pp. 2133-2142 ◽

Cited By ~ 78

Author(s):

Dong-Hyeon Kwon ◽

Fouad A. K. El-Zaatari ◽

Mototsugu Kato ◽

Michael S. Osato ◽

Rita Reddy ◽

...

Keyword(s):

Helicobacter Pylori ◽

Resistant Strain ◽

Resistance Mechanisms ◽

Sensitive Strain ◽

Metronidazole Resistance ◽

Genes Encoding ◽

Resistant Strains ◽

Flavin Oxidoreductase ◽

H Pylori

ABSTRACT Metronidazole (Mtz) is a critical ingredient of modern multidrug therapies for Helicobacter pylori infection. Mtz resistance reduces the effectiveness of these combinations. Although null mutations in a rdxA gene that encodes oxygen-insensitive NAD(P)H nitroreductase was reported in Mtz-resistant H. pylori, an intact rdxA gene has also been reported in Mtz-resistant H. pylori, suggesting that additional Mtz resistance mechanisms exist in H. pylori. We explored the nature of Mtz resistance among 544 clinical H. pyloriisolates to clarify the role of rdxA inactivation in Mtz resistance and to identify another gene(s) responsible for Mtz resistance in H. pylori. Mtz resistance was present in 33% (181 of 544) of the clinical isolates. There was marked heterogeneity of resistance, with Mtz MICs ranging from 8 to ≥256 μg/ml.rdxA inactivation resulted in Mtz MICs of up to 32 μg/ml for 6 Mtz-sensitive H. pylori strains and 128 μg/ml for one Mtz-sensitive strain. Single or dual (with rdxA) inactivation of genes that encode ferredoxin-like protein (designatedfdxB) and NAD(P)H flavin oxidoreductase (frxA) also increased the MICs of Mtz for sensitive and resistant strains with low to moderate levels of Mtz resistance. fdxB inactivation resulted in a lower level of resistance than that from rdxAinactivation, whereas frxA inactivation resulted in MICs similar to those seen with rdxA inactivation. Further evidence for involvement of the frxA gene in Mtz resistance included the finding of a naturally inactivated frxA but an intact rdxA in an Mtz-resistant strain, complementation of Mtz sensitivity from an Mtz-sensitive strain to an Mtz-resistant strain or vice versa by use of naturally inactivated or functionalfrxA genes, respectively, and transformation of an Mtz-resistant Escherichia coli strain to an Mtz sensitive strain by a naturally functional frxA gene but not an inactivated frxA gene. These results are consistent with the hypothesis that null mutations in fdxB,frxA, or rdxA may be involved in Mtz resistance.

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Antimicrobial Resistance in Respiratory Tract Streptococcus pneumoniae Isolates: Results of the Canadian Respiratory Organism Susceptibility Study, 1997 to 2002

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.47.6.1867-1874.2003 ◽

2003 ◽

Vol 47 (6) ◽

pp. 1867-1874 ◽

Cited By ~ 122

Author(s):

George G. Zhanel ◽

Lorraine Palatnick ◽

Kimberly A. Nichol ◽

Tracy Bellyou ◽

Don E. Low ◽

...

Keyword(s):

Streptococcus Pneumoniae ◽

Antimicrobial Resistance ◽

Antibiotic Consumption ◽

Multidrug Resistant ◽

Medical Centers ◽

Intermediate Resistance ◽

Susceptibility Study ◽

Resistant Strains ◽

Canadian Provinces ◽

High Level

ABSTRACT A total of 6,991 unique patient isolates of Streptococcus pneumoniae were collected from October 1997 to June 2002 from 25 medical centers in 9 of the 10 Canadian provinces. Among these isolates, 20.2% were penicillin nonsusceptible, with 14.6% being penicillin intermediate (MIC, 0.12 to 1 μg/ml) and 5.6% being penicillin resistant (MIC, ≥2 μg/ml). The proportion of high-level penicillin-resistant S. pneumoniae isolates increased from 2.4 to 13.8% over the last 3 years of the study, and the proportion of multidrug-resistant S. pneumoniae isolates increased from 2.7 to 8.8% over the 5-year period. Resistant rates (intermediate and resistant) among non-β-lactam agents were as follows: macrolides, 9.6 to 9.9%; clindamycin, 3.8%; doxycycline, 5.5%; chloramphenicol, 3.9%; and trimethoprim-sulfamethoxazole, 19.0%. Rates of resistance to non-β-lactam agents were higher among penicillin-resistant strains than among penicillin-susceptible strains. No resistance to vancomycin or linezolid was observed; however, 0.1% intermediate resistance to quinupristin-dalfopristin was observed. The rate of macrolide resistance (intermediate and resistant) increased from 7.9 to 11.1% over the 5 years. For the fluoroquinolones, the order of activity based on the MICs at which 50% of isolates are inhibited (MIC50s) and the MIC90s was gemifloxacin > clinafloxacin > trovafloxacin > moxifloxacin > grepafloxacin > gatifloxacin > levofloxacin > ciprofloxacin. The investigational compounds ABT-773 (MIC90, 0.008 μg/ml), ABT-492 (MIC90, 0.015 μg/ml), GAR-936 (tigecycline; MIC90, 0.06 μg/ml), and BMS284756 (garenoxacin; MIC90, 0.06 μg/ml) displayed excellent activities. Despite decreases in the rates of antibiotic consumption in Canada over the 5-year period, the rates of both high-level penicillin-resistant and multidrug-resistant S. pneumoniae isolates are increasing in Canada.

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High Primary Antibiotic Resistance of Helicobacter pylori Strains Isolated from Pediatric and Adult Patients in Poland during 2016–2018

Antibiotics ◽

10.3390/antibiotics9050228 ◽

2020 ◽

Vol 9 (5) ◽

pp. 228

Author(s):

Paweł Krzyżek ◽

Dorota Pawełka ◽

Barbara Iwańczak ◽

Radosław Kempiński ◽

Konrad Leśniakowski ◽

...

Keyword(s):

Helicobacter Pylori ◽

Antibiotic Resistance ◽

Antimicrobial Resistance ◽

Effective Treatment ◽

Adult Patients ◽

Minimum Inhibitory Concentrations ◽

Treatment Naïve ◽

Resistant Strains ◽

H Pylori ◽

High Level

Monitoring the antibiotic resistance of H. pylori is an important step in the effective treatment of this bacterium, thus the aim of the present study was to assess the prevalence of antimicrobial resistance of H. pylori strains isolated from pediatric and adult patients with primary infections in 2016–2018. Antral biopsies from 334 treatment-naïve patients (126 children and 208 adults) were obtained. A total of 71 clinical H. pylori strains (22 from children and 49 from adults) were isolated and examined for amoxicillin (AMX), clarithromycin (CLR), metronidazole (MTZ), tetracycline (TET), and levofloxacin (LEV) susceptibility. The activity of the antibiotics was measured by E-tests. Strains were considered as resistant to antibiotics with minimum inhibitory concentrations (MICs) equal to ≥0.125 μg/mL (AMX), ≥0.5 μg/mL (CLR), ≥8 μg/mL (MTZ), and ≥1 μg/mL (TET and LEV). The highest prevalence of antibiotic resistance in H. pylori strains was observed for CLR and MTZ, at frequencies of 54.5% and 31.8% vs. 30.6% and 46.9% for children and adults, respectively. A much lower frequency of isolation of resistant strains was demonstrated for LEV and TET, this being 9.1% and 4.5% vs. 18.4% and 4.1% for pediatric and adult patients, respectively. The presence of AMX-resistant strains was not observed. The H. pylori strains isolated from Polish patients with primary infections showed a high level of antibiotic resistance to CLR and MTZ (>30%).

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Canadian national survey of prevalence of antimicrobial resistance among clinical isolates of Streptococcus pneumoniae. Canadian Bacterial Surveillance Network.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.40.9.2190 ◽

1996 ◽

Vol 40 (9) ◽

pp. 2190-2193 ◽

Cited By ~ 49

Author(s):

A E Simor ◽

M Louie ◽

D E Low

Keyword(s):

Streptococcus Pneumoniae ◽

Antimicrobial Agents ◽

Clinical Isolates ◽

Beta Lactam ◽

Surveillance Network ◽

Antibiotic Resistant ◽

Intermediate Resistance ◽

Resistant Strains ◽

High Level ◽

Level Resistance

The antimicrobial susceptibilities of 1,089 clinical isolates of Streptococcus pneumoniae obtained from 39 laboratories across Canada between October 1994 and August 1995 were determined. A total of 91 isolates (8.4%) demonstrated intermediate resistance (MIC, 0.1 to 1.0 microgram/ml) and 36 (3.3%) had high-level resistance (MIC, > or = 2.0 micrograms/ml) to penicillin. Penicillin-resistant strains were more likely to have been recovered from normally sterile sites (P = 0.005) and to be cross-resistant to several beta-lactam and non-beta-lactam antimicrobial agents (P < 0.05). These results indicate that there has been a recent significant increase in the prevalence of antibiotic-resistant S. pneumoniae in Canada.

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Genetics of Chromosomally Mediated Intermediate Resistance to Ceftriaxone and Cefixime in Neisseria gonorrhoeae

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00304-09 ◽

2009 ◽

Vol 53 (9) ◽

pp. 3744-3751 ◽

Cited By ~ 91

Author(s):

Shuqing Zhao ◽

Margaret Duncan ◽

Joshua Tomberg ◽

Christopher Davies ◽

Magnus Unemo ◽

...

Keyword(s):

Neisseria Gonorrhoeae ◽

Penicillin Resistance ◽

Penicillin G ◽

Small Contribution ◽

Resistance Determinants ◽

Individual Contributions ◽

Unknown Gene ◽

Resistant Strains ◽

The Individual ◽

High Level

ABSTRACT All strains of Neisseria gonorrhoeae with reduced susceptibility to ceftriaxone and cefixime (cephalosporin-intermediate-resistant [Cephi] strains) contain a mosaic penA allele encoding penicillin-binding protein 2 (PBP 2) with nearly 60 amino acid differences compared to the sequence of wild-type PBP 2, together with a set of resistance determinants (i.e., mtrR, penB, and/or ponA1) that are required for high-level penicillin resistance. To define the individual contributions of these determinants to reduced susceptibility to ceftriaxone and cefixime, we created isogenic strains containing the mosaic penA allele from the Cephi strain 35/02 (penA35) together with one or more of the other resistance determinants and determined the MICs of penicillin G, ceftriaxone, and cefixime. The majority of cefixime resistance is conferred by the penA35 allele, with only a small contribution coming from mtrR and penB, whereas ceftriaxone resistance is nearly equally dependent upon mtrR and penB. Unlike high-level penicillin resistance, the ponA1 allele does not appear to be important for Cephi. A strain containing all four determinants has increased resistance to ceftriaxone and cefixime but not to the levels that the donor Cephi strain does, suggesting that Cephi strains, similar to high-level-penicillin-resistant strains, contain an additional unknown determinant that is required to reach donor levels of resistance. Our data also suggest that the original Cephi strains arose from the transformation of penA genes from commensal Neisseria species into a penicillin-resistant strain already harboring mtrR, penB, ponA1, and the unknown gene(s) involved in high-level penicillin resistance.

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Antibiotic Susceptibilities ofHelicobacter pyloriStrains Isolated in the Province of Alberta

Canadian Journal of Gastroenterology ◽

10.1155/1998/672746 ◽

1998 ◽

Vol 12 (4) ◽

pp. 295-298 ◽

Cited By ~ 12

Author(s):

Diane E Taylor ◽

Qin Jiang ◽

Richard N Fedorak

Keyword(s):

Helicobacter Pylori ◽

Antibiotic Resistance ◽

Gastric Biopsy ◽

Minimal Inhibitory Concentrations ◽

Antibiotic Susceptibilities ◽

Biopsy Specimens ◽

Metronidazole Resistance ◽

Agar Dilution ◽

Resistant Strains ◽

H Pylori

The incidence of antibiotic resistance to amoxicillin, clarithromycin, erythromycin, metronidazole and tetracycline inHelicobacter pyloristrains isolated from gastric biopsy specimens obtained in Alberta was investigated. Results for all antibiotics were obtained using agar dilution, and in addition to metronidazole, the E test was used. Resistance to amoxicillin and tetracycline was not detected. Metronidazole resistance determined using agar dilution was approximately 12% (95% CI 4% to 26%) when minimal inhibitory concentrations (MICs) were at least 8 µg/mL, but fell to 2% (95% CI 0.1% to 13%) when MICs were set at 32 µg/mL or greater. The E test for metronidazole resistance (MIC 8 µg/mL or greater) yielded a slightly higher percentage of resistant strains compared with agar dilution tests (14%, 95% CI 5% to 29%). One of the 31 strains was resistant to clarithromycin (MIC 8 µg/mL) and erythromycin (MIC 16 µg/mL). Thus, the incidence of resistance to clarithromycin, part of the currently used triple therapy for eradication ofH pylori, was 3% (95% CI 0.1% to 17%).

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Resistotype of Helicobacter pylori isolates: the impact on eradication outcome

Journal of Medical Microbiology ◽

10.1099/jmm.0.069781-0 ◽

2014 ◽

Vol 63 (5) ◽

pp. 703-709 ◽

Cited By ~ 16

Author(s):

Hanafiah Alfizah ◽

Ahmad Norazah ◽

Razlan Hamizah ◽

Mohamed Ramelah

Keyword(s):

Helicobacter Pylori ◽

Antibiotic Resistance ◽

Eradication Therapy ◽

Fluoroquinolone Resistance ◽

23S Rrna ◽

Nonsense Mutations ◽

Metronidazole Resistance ◽

Resistant Strains ◽

H Pylori ◽

The Impact

Antibiotic resistance is increasing worldwide, and it has been regarded as the main factor reducing the efficacy of Helicobacter pylori therapy. The aim of this study was to determine the phenotype and genotype of antibiotic-resistant strains of H. pylori in the Malaysian population and to evaluate the impact of antibiotic resistance to eradication outcome. One hundred and sixty-one H. pylori isolates were analysed in this study. Metronidazole, clarithromycin, fluoroquinolone, amoxicillin and tetracycline susceptibilities were determined by Etest. PCR followed by DNA sequencing was carried out to determine mutations. The medical records of the patients infected with resistant strains were reviewed to determine the eradication outcome. Metronidazole resistance was encountered in 36.6 % of H. pylori isolates, whereas clarithromycin and fluoroquinolone resistance was observed in 1.2 and 1.9 % of isolates, respectively. All strains tested were susceptible to amoxicillin and tetracycline. Frameshift and nonsense mutations in rdxA and frxA genes resulting in stop codons contributed to metronidazole resistance, which leads to reduced eradication efficacy. A2142G and A2143G mutations of 23S rRNA were identified as causing failure of the eradication therapy. Mutation at either codon 87 or 91 of the gyrA gene was identified in fluoroquinolone-resistant strains. However, the effect of resistance could not be assessed. This study showed that frameshift and nonsense mutations in rdxA or frxA genes and point mutations in the 23S rRNA affected the efficacy of H. pylori eradication therapy.

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