MECHANISM OF CLARITHROMYCIN RESISTANCE IN CLINICAL ISOLATES OF HELICOBACTER-PYLORI

Seventy-three Helicobacter pylori-positive patients were treated with a combination of clarithromycin and ranitidine in order to eradicate t he bacterium. Eradication was successful in 79.5%. In 15 patients erad ication failed, and in 11 cases this was due to clarithromycin resista nce. In one patient the infecting strain was resistant at the onset of treatment, while in the remaining 10 patients resistance developed du ring therapy. These isolates had also become resistant to various othe r antibiotics. Random amplified polymorphic DNA and restriction fragme nt end-labeling analysis of the isolates showed close genetic relatedn ess between pre- and post-treatment isolates, indicating that resistan ce was the result of selection of variants of the infecting strain rat her then infection with an exogenous resistant strain. Nucleotide sequ ence comparisons revealed that all resistant isolates had a single bas e pair mutation in the 23S rRNA. Since this single point mutation resu lts in co-resistance to various antibiotics at high frequencies, cauti on should be taken when using clarithromycin as a single antibiotic.