Impact of Previous Exposure to Macrolide Antibiotics on Helicobacter pylori Infection Treatment Outcomes

Helicobacter pylori (H. pylori) guidelines, including the recent ACG clinical guideline, recommend avoiding clarithromycin-based triple therapy (TT-C) among patients with past macrolide exposure. Data to support this recommendation are scarce, and the impact of macrolide exposure on quadruple therapies is unclear. We aimed to determine the impact of macrolide exposure on the efficacy of H. pylori treatment in our region.Methods:We searched the Clalit Health Services database to identify subjects aged 25-60 years who underwent the first-ever ¹³C-urea breath test between 2010 and 2015. Patients who underwent a previous H. pylori stool antigen test or gastroscopy were excluded. Pharmacy dispensation data were retrieved.Results:We identified 7,842 subjects (36.1% male individuals, age: 40.3 ± 10.5 years), including 3,062 (39.0%) with previous macrolide exposure. The efficacy of TT-C was 74.3% and 82.4% among subjects with and without macrolide exposure, respectively (odds ratio (OR), 0.62; 95% confidence interval (CI), 0.55-0.70; P < 0.0001). TT success was adversely affected by exposure to clarithromycin (55.5%; OR, 0.31; 95% CI, 0.24-0.39; P < 0.0001), roxythromycin (74.4%; OR, 0.65; 95% CI, 0.58-0.74; P < 0.0001), and erythromycin (73.9%; OR, 0.72; 95% CI, 0.57-0.89; P < 0.01) but not by exposure to azithromycin. A greater time elapsed because exposure to clarithromycin and roxythromycin was associated with higher eradication (OR, 1.007; 95% CI, 1.002-1.012; P < 0.01 and OR, 1.004; 95% CI, 1.002-1.006; P < 0.0001). A higher dose of clarithromycin and roxythromycin was associated with a lower likelihood of successful eradication (OR, 0.99988; 95% CI, 0.99982-0.99996; P < 0.01 and OR, 0.99981; 95% CI, 0.99971-0.99992; P < 0.001). The efficacies of sequential and concomitant therapies were 82.7% and 81.3%, respectively, and were not significantly affected by macrolide exposure.Conclusions:TT-C is adversely affected by previous exposure to macrolide antibiotics. Sequential, concomitant, and bismuth-based treatment may be preferred in this setting.