| Background and aims:Helicobacter pylori(Hp)is associated with a variety of gastrointestinal and extragastric diseases,and Hp eradication treatment can be effective in preventing and treating Hp-associated diseases.In recent years,the eradication rate of Hp has been decreasing over years,and antibiotic resistance and host factors are considered to be the main reasons for eradication failure,while the role of iatrogenic factors is often overlooked.The failure of eradication due to irrational and irregular medication by physicians could be avoided but is objectively real.Failure to eradicate Hp not only affects the efficacy and increases the burden on patients,but also induces secondary antibiotic resistance,which further increases antibiotic resistance and increases the rate of drug resistance,making remedial treatment more difficult.Therefore,this study aims to investigate the role of medical factors in Hp eradication failure in order to reduce unnecessary treatment failure and assess the impact of eradication failure on antibiotic resistance,including changes in resistance rate,resistance pattern,and MIC(minimal inhibitory concentration)distribution.Also,we intended to explore the risk factors for antibiotic resistance to provide theoretical support for clinicians’ decisions on drug use.Methods:1.The study of iatrogenic factors of Hp eradication failurePatients who had failed to eradicate Hp and had a clear detailed regimen from December 2019 to December 2022 at the Hp-specific outpatient clinic of the Department of Gastroenterology,The First Affiliated Hospital of Nanchang University,were included.The clinical information of the patients was obtained through questionnaires,which mainly included baseline information such as gender,age,contact information,history of penicillin allergy,family history of gastric cancer or peptic ulcer,history of previous Hp eradication(the number of Hp eradication,detailed medication regimens,treatment intervals,etc.),gastroscopic diagnosis within six months,method of confirming the diagnosis of Hp eradication failure,and histopathological diagnosis by gastroscopy.Definition of unreasonable iatrogenic factors: According to the Maastricht V/VI consensus and the fifth and sixth consensus on the management of H.pylori infection in China,factors that are contrary to the consensus are defined as unreasonable iatrogenic factors.2.The study of the impact of Hp eradication failure on antibiotic resistancePatients who underwent Hp antimicrobial sensitivity testing for Hp eradication failure at our Institute of Gastroenterology from November 2018 to December 2022 and who also had previous eradication regimens,as well as patients who underwent antimicrobial sensitivity testing before initial Hp eradication treatment from2018-2022,were included.Hp strains were isolated and cultured from patients’ gastric mucosa,and the E-test method was used to test the susceptibility of Hp to amoxicillin,clarithromycin,metronidazole,levofloxacin,tetracycline and rifampicin.Kirby-Bauer was used to test the susceptibility of Hp to furazolidone resistance.Statistical analysis was performed to calculate the effect of primary resistance rate,secondary resistance rate and eradication failure on resistance,including changes in resistance rate,resistance pattern and MIC distribution.Binary logistic regression was used for the multifactorial analysis of risk factors for Hp resistance,and the difference was considered statistically significant at P﹤0.05.Results:1.The study of iatrogenic factors of Hp eradication failure:(1)Patients and regimens enrolled: 628 patients meeting the criteria were included,28 were penicillin allergic,and a total of 300 patients experienced failure of rescue therapy.A total of 1039 regimens were included in the analysis,of which there were 573 first-line regimens and a total of 466 remedial regimens.(2)Unreasonable iatrogenic factors in first-line treatment failure: a total of 573 regimens were specified,of which:(i)94/573(16.4%)were non-penicillin allergic patients and 7/573(1.2%)were allergic patients who used triple regimens containing at least one antibiotic with high resistance rate;(ii)68/573(11.9%)were non-penicillin allergic patients who used quadruple regimens containing two antibiotics with high resistance rate antibiotic regimens;(iii)37/573(6.5%)regimens were non-high dose dual therapy;(iv)111/573(19.4%)regimens had an inadequate treatment duration;(v)55/573(9.6%)regimens were used quinolones in first-line treatment;(vi)46/573(8.0%)regimens were used insufficient doses of antibiotics;(vii)20/573(3.5%)regimen with insufficient dose of acid inhibiting agents;(viii)3/573(0.5%)regimens with insufficient dose of bismuth.(3)Iatrogenic factors in remedial treatment failure: there were 466 regimens,of which:(i)75/466(16.1%)triple regimens and 15/466(3.2%)regimens of non-high dose dual therapy were used as remedial treatment;(ii)101/466(21.7%)regimens were repeatedly used the original treatment regimen;(iii)198/466(42.5%)regimens repeatedly used the highly resistant antibiotics;(iv)111/466(23.8%)regimens with a duration less than 14 days in rescue treatment;and(v)205/333(61.6%)regimens with a time interval less than 6 months between adjacent regimens.2.The study of the impact of Hp eradication failure on antibiotic resistance:(1)Enrolled patients: 860 and 247 patients were included in primary and secondary resistance isolates,respectively.(2)Primary and secondary resistance rates of Hp: the primary resistance rates of amoxicillin,metronidazole,clarithromycin,levofloxacin,furazolidone,tetracycline,rifampicin were 5.93%,83.84%,28.84%,26.28%,0%,0.35%,1.16%;while the secondary resistance rates were 25.10%,92.31%,79.76%,63.16%,0%,1.06%,1.06%,respectively.(3)Influence of the number of treatments / the courses of medications on the resistance rates of Hp:(1)The resistance rate of amoxicillin,metronidazole,clarithromycin and levofloxacin increased significantly with the increase of eradication number(P﹤0.05~0.001),and showed a linear trend;(2)The resistance rate of amoxicillin,clarithromycin and levofloxacin increased significantly with the increase of dose number(P﹤0.001),and the MIC value increased significantly with the increase of the number of doses(P﹤0.001).(4)Resistance patterns of Hp:(i)The most predominant pattern of primary resistance was metronidazole mono-resistance(41.16%),and the most predominant pattern of secondary resistance was multidrug resistance where metronidazole,clarithromycin and levofloxacin were all resistant(36.44%).(ii)The all-sensitive strains of Hp isolated from the stomach of patients before initial treatment and patients who failed eradication therapy were 10.81% and 4.85%,respectively,and the multi-drug resistant strains were 43.95% and 84.62%,respectively.(5)Risk factors for Hp resistance:(i)the number of eradication courses was a risk factor for amoxicillin,metronidazole,clarithromycin and levofloxacin resistance;(ii)age was a risk factor for levofloxacin resistance;(iii)peptic ulcer was negatively correlated with clarithromycin and levofloxacin resistance.Conclusion:1.There are many iatrogenic factors that contribute to the failure of Hp eradication in clinical practice,including the combination and repeated use of the antibiotics with high resistance rates,repeated use of the same regimen,insufficient doses of drugs,and insufficient medication period.2.Antibiotics with high resistance rate such as metronidazole,clarithromycin and levofloxacin should be selected with caution for first-line treatment and should be avoided for remedial treatment unless supported by antimicrobial sensitivity test results.3.The primary and secondary resistance rates of metronidazole,clarithromycin and levofloxacin are very high,far exceeding the alert line of 15%.The resistance rates of furazolidone,tetracycline and rifampicin are low and stable,while the secondary resistance rate of amoxicillin is high and warrants vigilance.4.The number of eradication treatments was the most important risk factor for antimicrobial resistance of Hp.In conclusion,the success of initial Hp eradication is crucial. |
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