Heteroresistance to clarithromycin and metronidazole in patients with a Helicobacter pylori infection: a systematic review and meta-analysis

Kouhsari, Ebrahim; Sadeghifard, Nourkhoda; Khadiv, Arezoo; Sayadi, Hojjat; Amiriani, Taghi; Ghafourian, Sobhan; Valadbeigi, Hassan; Krutova, Marcela

doi:10.1186/s12941-022-00509-3

Cited by 19 publications

(25 citation statements)

References 35 publications

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“…26 Heteroresistance for H. pylori was first described in different studies in the 90s when a Belgian microbiologist decided to seed the biopsy samples obtained from the antrum and from the corpus on separate plates. 27,28 This discovery could help to understand better the failure to eradicate H. pylori. However, the emergence of heteroresistance in H. pylori strains has never been discussed in published guidelines, 9 and most laboratories still seed the biopsies on the same plate to lower the cost (in the last pediatric guideline, it is even recommended to place different samples into the same transport jar).…”

Section: Discussionmentioning

confidence: 99%

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Antibiotic resistance, heteroresistance, and eradication success ofHelicobacter pyloriinfection in children

et al. 2023

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BackgroundAntibiotic resistance is a well‐known factor of Helicobacter pylori eradication failure. Heteroresistance indicates the coexistence of resistant and susceptible strains and might lead to underestimating antimicrobial resistance. This study aims to evaluate the susceptibility profile, the frequency of heteroresistance of H. pylori strains, and their effect on eradication success in a pediatric population.Materials and MethodsChildren aged 2–17 years who underwent an upper gastrointestinal endoscopy from 2011 to 2019 with positive H. pylori status were included. Susceptibility was measured by disk diffusion and E‐test. The difference in susceptibility profiles between isolates from the antrum and the corpus was used to detect heteroresistance. For those who received eradication treatment, we evaluated eradication rate and factors affecting treatment success.ResultsInclusion criteria were met by 565 children. Strains susceptible to all antibiotics were detected in 64.2%. Primary resistance rates for clarithromycin (CLA), metronidazole (MET), levofloxacin (LEV), tetracyclin (TET), and amoxicillin (AMO) were 11%, 22.9%, 6.9%, 0.4%, and 0% and secondary resistance rates were 20.4%, 29.4%, 9.3%, 0%, and 0%. Heteroresistance was present in untreated children in 2%, 7.1%, 0.7%, 0.7%, and 0% for CLA, MET, LEV, TET, and AMO. First‐line eradication rates were 78.5% in intention‐to‐treat (ITT), 88.3% in full‐analysis‐set (FAS), and 94.1% in per‐protocol (PP). Factors affecting eradication success were the duration of treatment when the triple‐tailored treatment was used, the number of daily doses of amoxicillin administered, and the patient's adherence to treatment.ConclusionsThis study shows the presence of relatively low primary resistance rates for H. pylori isolates but demonstrates the presence of heteroresistance in our population. Routine biopsies from the antrum and corpus must be considered for susceptibility testing to allow tailored treatments and increase eradication rates. Treatment success is affected by treatment choice, correct dosing of medications, and adherence. All these factors should be considered when evaluating the efficacy of an eradication regimen.

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Section: Discussionmentioning

confidence: 99%

“…Heteroresistance for H. pylori was first described in different studies in the 90s when a Belgian microbiologist decided to seed the biopsy samples obtained from the antrum and from the corpus on separate plates 27,28 . This discovery could help to understand better the failure to eradicate H. pylori .…”

Section: Discussionmentioning

confidence: 99%

Antibiotic resistance, heteroresistance, and eradication success ofHelicobacter pyloriinfection in children

et al. 2023

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“…A further issue concerning rising resistance rates is the presence of heteroresistance of H. pylori , where a heterogeneous population of H. pylori may exist within an individual, with one or several subpopulations exhibiting increased levels of antibiotic resistance compared with the main population 23 . Recent reviews have demonstrated the presence of heteroresistance to clarithromycin and/or metronidazole in approximately 7% and 14% of H. pylori –positive isolates 24 . In our study, 81 isolates were from patients who underwent repeated successful culture.…”

Section: Discussionmentioning

confidence: 99%

“…23 Recent reviews have demonstrated the presence of heteroresistance to clarithromycin and/or metronidazole in approximately 7% and 14% of H. pylori-positive isolates. 24 In our study, 81 isolates were from patients who underwent repeated successful culture. In these cases, prior culture-directed therapy was not successful at eradicating H. pylori, and the presence of heteroresistance is likely to be the cause.…”

Section: Discussionmentioning

confidence: 99%

Refractory Helicobacter pylori infection in Australia: updated multicentre antimicrobial resistance

Schubert,

Ingram,

Warner

et al. 2023

Internal Medicine Journal

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Background and AimHelicobacter pylori infection is responsible for considerable morbidity and mortality worldwide and eradication rates are falling globally because of increasing antimicrobial resistance. However, there is a paucity of local data to guide the choice of eradication therapy in Australia. This study aimed to evaluate current Australian rates of H. pylori antibiotic resistance in patients who had failed prior eradication therapy.MethodsA retrospective analysis of routine culture and antibiotic susceptibility data from two pathology laboratories servicing multiple tertiary referral hospitals in Western Australia (WA) and South Australia (SA), between 2018 and 2022, was performed. Rates of antimicrobial resistance and prevalence of multiresistant isolates in both SA and WA were calculated and comparison of temporal trends and differences between the two states was conducted.ResultsA total of 796 H. pylori isolates revealed a clarithromycin resistance rate of 82%, metronidazole 68%, amoxicillin 4.4% and tetracycline 0.5%. Resistance to levofloxacin was observed in 22% and rifampicin 14%. Rates of resistance to clarithromycin were lower in SA compared with WA (incidence rate ratio [IRR]: 0.69, P = 0.0001). Multiresistant isolates were discovered in 63% of patients, with lower rates in SA compared with WA (IRR: 0.74, P = 0.002).ConclusionThis first multicentre, multistate study of H. pylori resistance in Australian patients exposed to prior therapy demonstrated high rates of antimicrobial resistance, including levofloxacin (>20%). This raises concern about recommending levofloxacin in empirical second‐line therapies. Increased monitoring and awareness of current H. pylori resistance rates in Australia are needed to guide local eradication practices.

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“…On the other hand, heteroresistance of H. pylori may also affect the efficacy of TT for the reason that both susceptible and resistant strains can be simultaneously present in different sites of a single stomach and that antibiotic susceptibility may change during treatment 59,60 . It was reported that heteroresistance to clarithromycin, levofloxacin, and metronidazole is not rare in H. pylori 61,62 …”

Section: Discussionmentioning

confidence: 99%

Efficacy of genotypic susceptibility‐guided tailored therapy for Helicobacter pylori infection: A systematic review and single arm meta‐analysis

Lin,

Huang,

Wang

et al. 2023

Helicobacter

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Background and AimThe prevalence of antibiotic resistance for Helicobacter pylori (H. pylori) has been increasing over the year, making it more difficult for traditional empirical therapy to successfully eradicate H. pylori. Thus, tailored therapy (TT) guided by molecular‐based antibiotic susceptibility testing (AST) has been frequently recommended. We conducted a single‐arm meta‐analysis to determine the efficacy of tailored therapy guided by molecular‐based AST.MethodsA systematic literature review was performed on multiple databases, and studies on molecular‐based TT were included. The eradication rates of TT by intention‐to‐treat (ITT) and per‐protocol (PP) analyses were pooled respectively.ResultsA total of 35 studies from 31 literature (4626 patients) were included in the single‐arm meta‐analysis. Overall, the pooled eradication rate of TT was 86.9% (95% CI:84.7%–89.1%) by the ITT analysis, and 91.5% (95% CI:89.8%–93.2%) by PP analysis. The pooled eradication rates of first‐line TT and rescue TT were 86.6% and 85.1% by ITT analysis and 92.0% and 87.9% by PP analysis, respectively. When tailored rescue therapy was based on the genotypic resistance to at least four antibiotics, the pooled eradication rates reached 89.4% by ITT analysis and 92.1% by PP analysis. For genotype‐susceptive strains, the pooled eradication rate of TT with targeted antibiotics was 93.1% (95% CI:91.3%–94.9%), among which the pooled eradication rate of tailored bismuth quadruple therapy was the highest (94.3%). Besides, the eradication rate of 7‐day TT or tailored triple therapy without bismuth for genotype‐susceptive strains could both reach more than 93.0%.ConclusionTailored therapy guided by molecular‐based AST can achieve somewhat ideal therapeutic outcomes. TT with a 7‐day duration or without bismuth for genotype‐susceptible strains can achieve good eradication efficacy. The effectiveness of TT can be improved to some extent by expanding the coverage of AST or by adding bismuth.

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Heteroresistance to clarithromycin and metronidazole in patients with a Helicobacter pylori infection: a systematic review and meta-analysis

Cited by 19 publications

References 35 publications

Antibiotic resistance, heteroresistance, and eradication success ofHelicobacter pyloriinfection in children

Antibiotic resistance, heteroresistance, and eradication success ofHelicobacter pyloriinfection in children

Refractory Helicobacter pylori infection in Australia: updated multicentre antimicrobial resistance

Efficacy of genotypic susceptibility‐guided tailored therapy for Helicobacter pylori infection: A systematic review and single arm meta‐analysis

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