Pathophysiology of antibiotic resistance: Clarithromycin

Resistance of Helicobacter pylori to antibiotics ranges from 3 % to 10% and may exceed these levels in some countries. The pathophysiology of clarithr omycin resistance is reviewed, including the mode of action by which the an tibiotic inhibits protein synthesis and the mechanism of resistance, which involves a mutation at position 2142 or 2143 in the V loop domain of the 23 S rRNA genes. Mutations of A2142G confer a higher minimum inhibitory concen tration than mutations of A2143G. The former demonstrate cross-resistance t o macrolide, lincosamide and streptogramin antibiotics, whereas the latter are susceptible to streptogramin B. In vitro mutagenesis combined with natu ral transformation were used to create several types of clarithromycin-resi stant mutants. H pylori strains with A2142G and A2143G mutations had a high er growth rate than those with A2142C, A2143 or A2142T mutations. Data from this study indicate why clarithromycin-resistant clinical isolates of H py lori are more likely to have A2142G or A2143G mutations and only occasional ly A2142C mutations.