This study aimed to determine the mutations associated with clarithromycin resistance in Helicobacter pylori isolates, and also to investigate its correlation with virulence factors iceA1, iceA2, vacA, cagA, babA2, and oipA and the type of disease and pathological findings.
In this study, it was found that, clarithromicin resistancewas significantly correlated with some virulence factors, type of disease, and degree of inflammatory. In the present study, the rate of clarithromycin resistance was 57.2% and the A2142G mutation was recognized as the most common mutation. According to the patients, they have not yet received antibiotic treatment for their infection, therefore should probably be considered as the actual primary resistance.
This resistance rate is higher than in southern European countries like Spain, (32.01 %), and Portugal (42.35%), that they have the highest resistance to clarithromycin among European countries[25, 26]. Level with some Asian countries such as Korea (60%), China (52%), India (58.8%) and some Northern European countries like Ireland (60.6%) and parts of the United States like Texas (50%) [11, 27–29]. Also, according to a 2012 report by Kargar et al, Which reported 35.98% of clarithromycin resistance in Chaharmahal and Bakhtiari Province , it has been shown that the resistance to clarithromycin has increased 1.5-fold over the past nine years. clarithromycin resistance is due to the increased macrolide intake not only in Helicobacter pylori treatment, but also due to increasing in the treatment of respiratory tract infections. Also for this reason, rapid and accurate screening of clarithromycin-resistant isolates is clinically important. The failure of first-line treatment due to resistance to this drug has not only chronicled the disease and the increased its other side effects, but has also led to the increased financial burden worldwide and to the limited use of antibiotics in treatment [19, 31]. In this study, it was found that, there is a significant correlation among virulence factor oipA gene, vacAm1m2 ,vacATotal, vacAs1s2, and iceA1 gene with antibiotic mutation in relation to clarithromycin (P = 0.033), (P = 0.001), (P = 0.010), and (P = 0.018). The majority of vacA oipA, and iceA1 positive isolates have mutation and resistance to clarithromycin. In fact, this result confirms the correlation between resistance and the presence of virulence factor iceA1, oipA, and vacA, but no significant correlation was found between clarithromycin resistance and virulence factors cagA and babA2. Studies on the association between virulence factors and antibiotic resistance are very conflicting, So far, no studies have been conducted in Iran on the correlation between the presence of virulence factor oipA, vacA, babA2, and iceA, and antibiotic resistance. The association of these factors with antibiotic resistance was reported for the first time in this study. The current study data on the association of virulence genes oipA, iceA, and vacA with clarithromycin antibiotic resistance are primarily consistent with data from Treiber , Karabiber , and Boyanova , and subsequently, the correlation between the presence of virulence factor and antibiotic resistance regardless of the type of factor the studies support and endorse Khan , Brennan , and wang . To justify this, it can be said that, isolates with virulence factors, especially oipA, produce inflammatory cytokines like IL-8 and cause aggressive disease like gastrointestinal ulcer. As a result, the patient has painful and uncomfortable symptoms, so starts taking antibiotic drugs that results in a failure in completing the course of treatment, and inadequate use and various other factors make the involved isolate resistant to antibiotics. The results of this study on virulence factors babA2 and cagA showed no significant correlation between the presence of these factors and clarithromycin resistance. This is consistent with the results of studies by Wang , Godoy , Baglan , Broutet , and Lõivukene . In this study, there was no significant correlation between age and sex of the patients with clarithromycin resistance. This is in line with the results of Korona  and Elviss  and contrasts with the results of Wang , Chang , and Treiber . In this study, a significant relationship was observed between the degree of chronic inflammation and Glandular Atrophy with antibiotic resistance. Frequency of clarithromycin resistance in the patients with moderate to severe chronic inflammation and mild to moderate Glandular Atrophy were different compared with the patients with mild chronic inflammation and those without Glandular Atrophy, based on our knowledge, we are reporting this for the first time.
In this study, there was a significant correlation between antibiotic resistance to clarithromycin and type of disease in the patients infected by Helicobacter pylori (P = 0.032). The frequency of clarithromycin resistance was significantly higher in the patients with gastrointestinal ulcer compared to the patients with gastritis. This study is in line with the study of Treiber  and contrary to the results of Wang , which can be interpreted as isolates that cause an aggressive state of the disease like peptic ulcer. Because of painful and irreversible symptoms, the patient received bacterial and infection treatment. The patient has begun taking antibiotics, and failure to complete the course of treatment, inadequate use, and various other factors have made the isolates involved, resistant to antibiotics. This study was performed the first time in Iran investigating the correlation among clarithromycin antibiotic resistance and disease type and pathologic findings in Helicobacter pylori, and reported a significant correlation between these variables.