Effect of metronidazole resistance on Helicobacter pylori eradication regimens

Abstract

Objectives Guidelines suggest bismuth‐containing quadruple therapy (BQT) or concomitant therapy (CT) as first‐line therapy in our geographic area. Both schedules contain metronidazole. We aimed to evaluate the effect of metronidazole resistance to Helicobacter pylori (H. pylori) eradication therapy. Methods We recruited treatment‐naïve subjects with H. pylori infection who received either CT or BQT during January 2020 and December 2021. Before therapy, a fecal sample was collected using the THD fecal test device from each patient. H. pylori DNA was extracted and mutations of rdxA and frxA genes and A2143G for metronidazole and clarithromycin resistance were investigated using real‐time polymerase chain reaction with a high‐resolution melting curve. Results Ninety‐six patients were enrolled, including 29 received BQT and 67 received CT. The overall eradication rate was 94.8% (100% for BQT and 92.5% for CT). Metronidazole resistance was found in 18 (18.8%) subjects, while clarithromycin resistance was found in 19 (19.8%). All 18 patients with metronidazole resistance achieved successful eradication (five treated with BQT and 13 with CT). The eradication rate in metronidazole‐sensitive strains was 93.6%. Of these, 24 received BQT with 100% success, and 54 had CT with five failures (successful eradication in 90.7%). Two patients with treatment failure were resistant to clarithromycin, and the remaining three were susceptible to both clarithromycin and metronidazole. No statistical significance was observed in the eradication rate between metronidazole‐resistant and ‐sensitive strains (100% vs 93.6%, P = 0.58). Conclusion Metronidazole resistance does not influence the eradication rate of BQT and CT regimens in our geographical area, even if such results need to confirmed in a larger sample.

Helicobacter pylori Secondary Antibiotic Resistance after One or More Eradication Failure: A Genotypic Stool Analysis Study

“…The treated solution was finally taken from the reservoir and processed for DNA extraction using a QIAamp DNA Stool Minikit (Qiagen, Hilden, Germany). After this last phase, real-time PCR was performed to assess point mutations linked to H. pylori resistance to clarithromycin amoxicillin, metronidazole, levofloxacin, and tetracycline as previously described [16,50,51]. In particular, the following genes implied in antimicrobial resistance were amplified: pbp1 for amoxicillin, rdxA/frxA for metronidazole, 23S rRNA for clarithromycin, gyrA for levofloxacin, and 16S rRNA for tetracycline [52].…”

Antibiotic resistance in Helicobacter pylori: From potential biomolecular mechanisms to clinical practice

“…Compared with the current standard of culture, the gastric juice PCR contains the strengths of performing the antibiotics susceptibility and overcomes the shortcomings of low accuracy 138 . Similarly, PCR‐based sequencing to detect resistance‐associated mutations using fecal samples is also useful for finding antibiotic‐resistant H. pylori strains 137,139 . Although the specificity of the detection from fecal samples compared with traditional antimicrobial susceptibility testing was lower than that from isolates, this fecal detection method is suitable especially for asymptomatic subjects including children 137 .…”

“… 138 Similarly, PCR‐based sequencing to detect resistance‐associated mutations using fecal samples is also useful for finding antibiotic‐resistant H. pylori strains. 137 , 139 Although the specificity of the detection from fecal samples compared with traditional antimicrobial susceptibility testing was lower than that from isolates, this fecal detection method is suitable especially for asymptomatic subjects including children. 137 Moreover, it is convenient and low cost with minor sample requirements, good resolution, and rapid automatic detection.…”

“…In this situation, the culture method for drug susceptibility will have higher accuracy than the gene detection technology. In addition, it is worth noting that MTZ resistance does not influence the eradication rate of bismuth‐containing quadruple therapy and concomitant therapy regimens, 139 which further limits the application of molecular detection in MTZ. Fourth, in terms of what can be detected, the molecular detection method only detects common resistance mutations.…”

Antibiotic resistance, susceptibility testing and stewardship in Helicobacter pylori infection

“…Increasing the metronidazole dose and duration may overcome antibiotic resistance [24]. While sequential regimen is discouraged [25], the marginal effect of metronidazole resistance in affecting therapeutic outcome allows quadruple therapy to remain as an effective eradication regimen [26].…”