Macrolide resistance in Helicobacter pylori has become a major cause of triple-therapy failure in India. The primary molecular mechanism is:
- A A23S point mutation in 23S rRNA preventing clarithromycin binding to domain V of the large ribosomal subunit ✓
- B Upregulation of CmeABC efflux pump that actively exports clarithromycin from H. pylori
- C Acquisition of mef(A) gene encoding a proton-motive-force-dependent efflux pump
- D Production of an esterase that hydrolyzes the macrolide lactone ring extracellularly
Explanation
The predominant mechanism of macrolide resistance in H. pylori globally and in India is point mutations A2143G and A2142G in the 23S rRNA gene domain V. Clarithromycin's bacteriostatic action requires binding to domain V of the 23S rRNA (50S subunit), blocking translocation; these mutations alter the binding site, preventing drug-ribosome interaction. Testing for these mutations (PCR or sequencing-based susceptibility) is recommended before prescribing clarithromycin-based eradication regimens when resistance prevalence exceeds 15%. CmeABC efflux is an H. pylori resistance mechanism for other antibiotics. mef(A) is a macrolide efflux mechanism in streptococci.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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Written and medically reviewed by the StethoPrep medical team.