Pretreatment Antibiotic Resistance in<i>Helicobacter pylori</i>Infection: Results of Three Randomized Controlled Studies

Realdi, Giuseppe; Dore, Maria Pina; Piana, Andrea; Atzei, Antonella; Carta, Maurizio; Cugia, Luigi; Manca, Alessandra; Are, Bianca Maria; Massarelli, Giovannino; Mura, I; Maida, A.; Graham, David Y.

doi:10.1046/j.1523-5378.1999.99002.x

Cited by 94 publications

(91 citation statements)

References 20 publications

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“…This variation may be caused by the wide use of metronidazole in developing countries for other infectious diseases, such as protozoal diseases (17). The resistance rate to metronidazole (63.8%) in our research is comparable with the earlier studies (20-23), but was higher than what was reported by others (17,(24)(25)(26). Our results suggest that metronidazole combined with other antimicrobial agents can be still used for H. pylori treatment, because there is moderately low resistance when it was experienced in combination with other antimicrobial agents.…”

Section: Discussionsupporting

confidence: 87%

Antibiotic Susceptibility of Helicobacter pylori Clinical Isolates in Hamadan, West of Iran

Majlesi¹,

Khorasani²,

Khalilian³

et al. 2013

Int J Enteric Pathog

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A B S T R A C TBackground: Surveillance data on Helicobacter pylori antibiotic susceptibilities are limited in Hamadan, Iran. Since antibiotic resistance is one of the reasons in therapies failure. Objectives: Thus the resistance patterns of H. pylori strains to the antibiotics metronidazole, clarithromycin, amoxicillin and tetracycline were evaluated. Patients and Methods: Gastric biopsy specimens of 153 patients with nonulcer dyspepsia, peptic ulcer dyspepsia, and peptic cancer collected during May 2010 to February of 2011, and were cultured on Brucella agar (Merck, Germany) under microaerophilic conditions. H. pylori isolates were identified using standard biochemical test. Eighty three (54.2 %) specimens had positive results by culture. Antimicrobial susceptibility testing was performed by disc diffusion method. Results: Totally in vitro resistance rates were 63.8% for metronidazole, 26.5% for clarithromycin, and 7.2% for amoxicillin. Although, 25.3% of strains showed resistance to two antibiotics, and 3.6% to three antibiotics. Tetracycline resistance was identified in only two isolates. Fifty nine percent of the clarithromycin resistant strains also showed resistance to metronidazole. No gender and age associations with resistance were detected. Conclusion: Our results showed a high incidence of metronidazole resistance (often combined with clarithromycin-resistance) in the isolates. Continuous surveillance is recommended to examine the treatment strategies for H. pylori eradication.

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Section: Discussionsupporting

confidence: 87%

Antibiotic Susceptibility of Helicobacter pylori Clinical Isolates in Hamadan, West of Iran

Majlesi¹,

Khorasani²,

Khalilian³

et al. 2013

Int J Enteric Pathog

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“…The clearly demonstrated correlation between antibiotic resistance and treatment failure makes it necessary for decisions about H. pylori therapy to be based on susceptibility test results (2,11,19,22,35,37,42,44). The aim of the proficiency phase FIG.…”

Section: Discussionmentioning

confidence: 99%

“…The primary and secondary resistance rates reported worldwide vary from 1 to 58% for clarithromycin and from 5 to 76% for metronidazole (1,5,15,17,26,28,32,43). Resistance to one or both of these antibiotics significantly reduces treatment success (2,11,19,22,35,37,42,44). The clinical importance of resistance makes it necessary for antibiotic treatment decisions to be based on valid and reproducible in vitro susceptibility testing results.…”

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confidence: 99%

Multilaboratory Comparison of Proficiencies in Susceptibility Testing of Helicobacter pylori and Correlation between Agar Dilution and E Test Methods

Best

Haldane

Keelan

et al. 2003

Antimicrob Agents Chemother

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Susceptibility testing was performed at seven Canadian microbiology laboratories and the Helicobacter Reference Laboratory, Halifax, Nova Scotia, Canada, to assess susceptibility testing proficiency and the reproducibility of the results for clarithromycin and metronidazole and to compare the Epsilometer test (E test) method to the agar dilution reference method. Control strain Helicobacter pylori ATCC 43504 (American Type Culture Collection) and 13 clinical isolates (plus duplicates of four of these strains including ATCC 43504) were tested blindly. The National Committee for Clinical Laboratory Standards (NCCLS) guidelines for agar dilution testing were followed, and the same suspension of organisms was used for agar dilution and E test. Antimicrobials and E test strips were provided to the investigators. Methods were provided on a website (www.Helicobactercanada.org). Each center reported MICs within the stated range for strain ATCC 43504. Compared to the average MICs, interlaboratory agreements within 2 log 2 dilutions were 90% (range, 69 to 100%) for clarithromycin by agar dilution, with seven very major errors [VMEs], and 85% (range, 65 to 100%) by E test, with three VMEs. Interlaboratory agreements within 2 log 2 dilutions were 83% (range, 50 to 100%) for metronidazole by agar dilution, with six VMEs and eight major errors (MEs), and 75% (range, 50 to 94%) by E test, with four VMEs and four MEs. At lower and higher concentrations of antibiotic, E test MICs were slightly different from agar dilution MICs, but these differences did not result in errors. When a standardized protocol based on NCCLS guidelines was used, most participants in this study correctly identified clarithromycin-and metronidazole-susceptible and -resistant strains of H. pylori 93% of the time by either the agar dilution or E test method, and the numbers of errors were relatively equivalent by both methods.

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“…In contrast, single-and double-base-pair mutations mediated only low-level tetracycline resistance and decreased growth rates in the presence of tetracycline, explaining the preference for the TTC mutation in tetracycline-resistant H. pylori isolates.Tetracycline is a cheap and effective antibiotic for the treatment of Helicobacter pylori infections (7,8), but in the past few years the incidence of tetracycline resistance has significantly increased (1,5,6,9,13). The only known mechanism mediating tetracycline resistance in H. pylori involves mutations at positions 926 to 928 in both the 16S rRNA genes (2,4,12).…”

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confidence: 99%

Effects of 16S rRNA Gene Mutations on Tetracycline Resistance in Helicobacter pylori

Gerrits

Berning

Vliet

et al. 2003

Antimicrob Agents Chemother

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The triple-base-pair 16S rDNA mutation AGA 926-928 3TTC mediates high-level tetracycline resistance in Helicobacter pylori. In contrast, single-and double-base-pair mutations mediated only low-level tetracycline resistance and decreased growth rates in the presence of tetracycline, explaining the preference for the TTC mutation in tetracycline-resistant H. pylori isolates.Tetracycline is a cheap and effective antibiotic for the treatment of Helicobacter pylori infections (7,8), but in the past few years the incidence of tetracycline resistance has significantly increased (1,5,6,9,13). The only known mechanism mediating tetracycline resistance in H. pylori involves mutations at positions 926 to 928 in both the 16S rRNA genes (2,4,12). H. pylori strains with high-level tetracycline resistance (Tet r ) carried the triple-base-pair mutation AGA 926-928 3TTC in both copies of the 16S rRNA genes (4, 12), whereas strains with low-level Tet r contained only single-and double-base-pair mutations in the exact same region (2). As the different mutations were present in unrelated strains, it is still unclear whether high-level tetracycline resistance requires the AGA 926-928 3 TTC mutation or whether single-or double-base-pair mutations at these positions may suffice for high-level tetracycline resistance. Therefore, we have created all possible combinations of single, double, and triple mutations at the 16S rRNA gene positions 926 to 928 in H. pylori strain 26695 and have determined the effects of the mutations on levels of tetracycline resistance, stability, and growth rate.Site-directed mutagenesis at positions 926 to 928 was carried out by using a three-step PCR approach (3, 10) with primers listed in Table 1, followed by natural transformation to H. pylori reference strain 26695 (4). Tet r H. pylori colonies were selected on plates containing tetracycline (1 g/ml). For each possible base pair mutation or combination thereof, eight Tet r transformants from at least two independent transformation experiments were selected. Both alleles of the 16S rRNA genes were amplified by PCR (4) to confirm the presence of the desired base pair mutations. With the exception of the AGC mutants, all mutants contained the desired mutations in both alleles of the 16S rRNA genes. All AGC mutants were heterozygous and contained the AGC mutation in the rrnA gene and a TTC mutation in the rrnB gene.The effects of the 16S rRNA mutations on both the stability and the level of tetracycline resistance were determined by subculturing two mutants of each type for 20 passages on Columbia agar plates supplemented with 7% lysed horse blood (BioTrading, Mijdrecht, The Netherlands) in either the presence or absence of tetracycline (1 g/ml). After each five rounds of subculturing, the MIC of tetracycline was determined by using E-test (AB Biodisk, Solna, Sweden) (4). In addition, for all mutants at time point zero (t 0 ) and after passage 20 (t 20 ), the 16S rRNA genes were sequenced. The stability of the various types of mutations and their effects on t...

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Pretreatment Antibiotic Resistance inHelicobacter pyloriInfection: Results of Three Randomized Controlled Studies

Abstract: Pretreatment antibiotic-resistant H. pylori can, in part, explain the low cure rate of the infection and the variability in outcome in reported trials.

Cited by 94 publications

References 20 publications

Antibiotic Susceptibility of Helicobacter pylori Clinical Isolates in Hamadan, West of Iran

Antibiotic Susceptibility of Helicobacter pylori Clinical Isolates in Hamadan, West of Iran

Multilaboratory Comparison of Proficiencies in Susceptibility Testing of Helicobacter pylori and Correlation between Agar Dilution and E Test Methods

Effects of 16S rRNA Gene Mutations on Tetracycline Resistance in Helicobacter pylori

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