Primary and secondary clarithromycin resistance in Helicobacter pylori and mathematical modeling of the role of macrolides

Éva Kocsmár, György Miklós Buzás, Ildikó Szirtes, Ildikó Kocsmár, Zsófia Kramer, Attila Szijártó, Petra Fadgyas-Freyler, Kató Szénás, Massimo Rugge, Matteo Fassan, András Kiss, Zsuzsa Schaff, Gergely Röst and Gábor Lotz ()
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Éva Kocsmár: Semmelweis University
György Miklós Buzás: Ferencváros Health Center
Ildikó Szirtes: Semmelweis University
Ildikó Kocsmár: Semmelweis University
Zsófia Kramer: Semmelweis University
Attila Szijártó: Semmelweis University
Kató Szénás: Péterfy Hospital
Massimo Rugge: University of Padua
Matteo Fassan: University of Padua
András Kiss: Semmelweis University
Zsuzsa Schaff: Semmelweis University
Gergely Röst: University of Oxford
Gábor Lotz: Semmelweis University

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: Abstract Clarithromycin is a macrolide antibiotic widely used for eradication of Helicobacter pylori infection, and thus resistance to this antibiotic is a major cause of treatment failure. Here, we present the results of a retrospective observational study of clarithromycin resistance (Cla-res) in 4744 H. pylori-infected patients from Central Hungary. We use immunohistochemistry and fluorescence in situ hybridization on fixed gastric tissue samples to determine H. pylori infection and to infer Cla-res status, respectively. We correlate this information with macrolide dispensing data for the same patients (available through a prescription database) and develop a mathematical model of the population dynamics of Cla-res H. pylori infections. Cla-res is found in 5.5% of macrolide-naive patients (primary Cla-res), with no significant sex difference. The model predicts that this primary Cla-res originates from transmission of resistant bacteria in 98.7% of cases, and derives from spontaneous mutations in the other 1.3%. We find an age-dependent preponderance of female patients among secondary (macrolide-exposed) clarithromycin-resistant infections, predominantly associated with prior use of macrolides for non-eradication purposes. Our results shed light into the sources of primary resistant cases, and indicate that the growth rate of Cla-res prevalence would likely decrease if macrolides were no longer used for purposes other than H. pylori eradication.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22557-7

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DOI: 10.1038/s41467-021-22557-7

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