Helicobacter pylori Resistance: Morphomolecular Analysis of Formalin-Fixed Paraffin-Embedded (FFPE) Biopsy Specimens From 374 Patients

Background: Antibiotic resistance is the leading cause of Helicobacter pylori eradication failure worldwide. Molecular testing of formalin-fixed paraffin-embedded (FFPE) gastric biopsy specimens enables simultaneous histopathological evaluation and detection of resistance-associated mutations. Objective: This study aimed to investigate associations between histopathological findings and molecularly detected antibiotic resistance in H. pylori-positive FFPE gastric biopsies. Methods: We analyzed FFPE biopsy specimens of 374 patients with H. pylori gastritis (mean age, 53.4 years; 40.1% male (n = 150); 59.9% female (n = 224)) using a strip assay-based molecular test to detect H. pylori and mutations conferring resistance to clarithromycin (R-CLA), fluoroquinolones (R-FLU), and dual resistance (R-CLA×FLU). Histological parameters, according to the updated Sydney system, included gastritis, chronic inflammation (mild, moderate, and severe), neutrophilic activity (absent, mild, moderate, and severe), H. pylori density (mild, moderate, and severe), atrophy, and intestinal metaplasia. Associations with these parameters were assessed by binary logistic regression. Results: We found 67.1% resistance-associated mutations, most of them with R-CLA (n = 163; 64.9%), followed by R-CLA×FLU (n = 52; 20.7%) and R-FLU (n = 36; 14.3%). Overall, gastritis activity was mild in 213 patients (57%), moderate in 118 (31.6%), and severe in 20 (5.3%); chronic gastritis was absent in 23 patients (6.1%), mild in 87 (23.3%), moderate in 224 (59.9%), and severe in 63 (16.8%). H. pylori density was mild in 168 patients (44.9%), moderate in 149 (39.8%), and severe in 57 (15.2%). Severe H. pylori density was significantly associated with antibiotic resistance overall (odds ratio, 2.26; 95% confidence interval, 1.02-5.01; p = 0.045). Increasing age was significantly associated with resistant infections (p = 0.009). Gastric atrophy showed a nonsignificant trend toward association with clarithromycin and fluoroquinolone resistance (p = 0.06 for R-FLU and p = 0.07 for R-CLA, respectively). Conclusions: Morphomolecular analysis of FFPE gastric biopsies represents a practical approach for routine H. pylori resistance testing. High H. pylori density may indicate an increased likelihood of antibiotic resistance. Given increasing resistance rates worldwide, molecular resistance testing is suggested to support individualized eradication therapy and improved antimicrobial stewardship.