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Deep blue: macrolide-naive resistant, green: clarithromycin-containing eradication-naive but other macrolide treatment exposed resistant, light blue: resistant with a history of Helicobacter pylori eradication with a clarithromycin-containing treatment regimen.

Cla: clarithromycin.

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Full size image Primary and secondary resistance defined by prior Cla eradication According to the common definition of primary Cla-res in gastroenterology, the proportion of resistant patients with no prior history of clarithromycin-containing eradication treatment was Resistance mutations were found in Table 2 Clarithromycin resistance rates of H.

Full size table Primary and secondary resistance defined by any prior macrolide use Compared to the above approach, a anti aging anon of primary Cla-res that excluded any prior macrolide consumption found a significantly reduced percentage, as only 5. However, Analysis of primary and secondary resistance rates A significant sex difference was found in eradication-naive resistant cases: In contrast, no significant difference was found between macrolide-naive females and males when primary Cla-res rates were assessed by considering all prior macrolide consumption Table 2.

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However, in the macrolide-exposed group, women showed a significantly higher prevalence of Cla-res than men Table 2with higher average numbers of macrolide-dispensing occasions and boxes dispensed per person 3.

A significant difference was observed between rates of eradication-induced and other macrolide-treatment-related secondary resistance Table 2. Regarding the latter, clarithromycin therapy for purposes other than H.

The difference between secondary resistance rates observed after eradication and non-eradication use of clarithromycin was statistically significant Mathematical modeling of the transmission dynamics of H. Assuming that a heteroresistant infected individual exposes the infectee to both resistant and susceptible H.

By applying the results of the model to the 5.

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Table 3 Parameters and results outputs of the mathematical model. Full size table Fig. The results of the retrospective cohort analysis are framed in light blue.

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The conclusions of the constructed epidemiological model are framed in light red. The sources of primary resistance cases were inferred from the epidemiological model. Colors of the pie charts: Cla-resistant — light red, Cla-susceptible — light blue, No previous eradication therapy — dark cyan, Previous Cla eradication therapy — light brown, Macrolide-naive primary resistant — lavender, Non-eradication-purpose macrolide-exposed - dark blue, Spontaneous mutation — green, Transmission of resistant bacteria — light red.

Colors of the pie chart: Cla-susceptible bacteria — light blue, Cla-resistant bacteria — light red.

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Colors of the pie charts: Previous Cla eradication anti aging anon — light brown, Infection with resistant type — light red, Spontaneous mutation — green, Other macrolide use — dark blue. Full size image We have also modeled the effect of discontinuing macrolide use for indications other than H. With the current rate of macrolide consumption, we predict an increase of approximately 0.

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The model shows a noticeably slower long-term growth rate of Cla-res prevalence among infected individuals with the discontinuation of non-eradication-purpose macrolide use green line than with the current situation with a constant level of macrolide consumptionin which the model predicts a more rapidly increasing rate of Cla-res infections red line. Full size image Discussion We conducted one of the largest studies on Cla-res H.

We established a mathematical model to characterize the transmission dynamics of Cla-res H. Primary Cla-res of H. However, this approach has several limitations.

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Clarithromycin is used to treat various other bacterial infective diseases, which may lead to Cla-res of H. This bystander selection unintended selection of resistant H. Nevertheless, anti aging anon of the previously published studies on the epidemiology of Cla-res have used this definition of primary resistance because the prior antibiotic consumption of the patients for non-eradication purposes is frequently unknown.

Some authors have assessed macrolide consumption at the population level by using antibiotic sales data 1619which is not appropriate for revealing acquired Cla-res in individual cases. Others asked patients to list prior antibiotic treatments or reviewed their medical records armoiries de famille suisse anti aging available from treating hospitals, outpatient clinics, and family doctors 1625 However, human memory is prone to substantial gaps and errors Anti aging anon, antibiotic treatment data from individual treatment sites do not necessarily cover all possible sources of antibiotics; therefore, these inaccurate approaches commonly ignore the use of macrolides for non-eradication purposes.

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We found an overall H. Based on the common definition no prior eradication attempt with a clarithromycin-containing regimenthe primary Cla-res rate reached