Resistance to Clarithromycin and Fluoroquinolones in Helicobacter pylori Isolates: A Prospective Molecular Analysis in Western Romania

<b>Background and Objectives:</b><i>Helicobacter pylori</i> (<i>H. pylori</i>) infection remains one of the most common chronic bacterial infections worldwide and is associated with a wide range of gastrointestinal disorders, including gastritis, peptic ulcer disease, and gastric cancer. Increasing rates of antibiotic resistance, particularly to clarithromycin and fluoroquinolones, represent a major therapeutic challenge. The objective of this study was to determine the prevalence of resistance-associated mutations in <i>H. pylori</i>-positive gastric biopsy samples from western Romania. <b>Materials and Methods:</b> We conducted a prospective study from January to December 2024, enrolling 138 patients undergoing gastroscopy. Biopsies were collected from the gastric antrum, and <i>H. pylori</i> infection was confirmed using the rapid urease test (RUT). Positive samples were further analyzed with the GenoType HelicoDR assay to detect mutations in the <i>23S rRNA</i> gene (clarithromycin resistance) and <i>gyrA</i> gene (fluoroquinolone resistance). Clinical, demographic, and endoscopic data were also collected. <b>Results:</b><i>H. pylori</i> infection was confirmed in 41.3% of the patients (57), of whom 63.2% (36) were treatment-naïve and 36.8% (21) had prior eradication therapy. Among treatment-naïve patients, clarithromycin resistance was identified in 19.4%, whereas previously treated patients showed a markedly higher resistance rate of 47.6% (<i>p</i> = 0.018). All clarithromycin-resistant cases carried the A2147G (<i>23S</i> MUT3) mutation. Fluoroquinolone resistance was present in 13.9% of naïve patients and increased to 23.8% in those with prior eradication therapy, with resistance linked to <i>gyrA</i> mutations at codons 87 (N87K) and 91 (D91 variants). Combined resistance to both antibiotics was observed only in a subset of previously treated patients. <b>Conclusions:</b> Primary resistance to clarithromycin in western Romania exceeds the 15% threshold defined by international guidelines, making clarithromycin-based triple therapy unsuitable as an empirical first-line option. The findings support the use of bismuth quadruple therapy as the preferred empirical regimen in this region. Also, molecular testing proved effective for rapid identification of resistance-associated mutations.