Trends in resistance to clarithromycin: from phenotypic to genomic approaches.

Microb Genom

Host-Pathogen Interactions Unit, Research Institute for Medicines (iMed-ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisboa, Portugal.

Published: March 2020

AI Article Synopsis

  • Clarithromycin, a common macrolide antibiotic, is facing increasing resistance worldwide, leading to treatment failures in infections.
  • The resistance mechanisms primarily involve specific point mutations in the 23S rRNA gene, especially A2142C and A2143G, found in certain resistant strains.
  • High-throughput next-generation sequencing methods are effective in detecting these resistance mutations, revealing that low-frequency variants can emerge due to exposure to clarithromycin, contributing to a rise in resistance rates.

Article Abstract

For a long time infections have been treated using the macrolide antibiotic, clarithromycin. Clarithromycin resistance is increasing worldwide and is the most common cause of treatment failure. Here we review the mechanisms of antibiotic resistance to clarithromycin, detailing the individual and combinations of point mutations found in the 23S rRNA gene associated with resistance. Additionally, we consider the methods used to detect clarithromycin resistance, emphasizing the use of high-throughput next-generation sequencing methods, which were applied to 17 newly sequenced pairs of strains isolated from the antrum and corpus of a recent colonized paediatric population. This set of isolates was composed of six pairs of resistant strains whose phenotype was associated with two point mutations found in the 23S rRNA gene: A2142C and A2143G. Other point mutations were found simultaneously in the same gene, but, according to our results, it is unlikely that they contribute to resistance. Further, among susceptible isolates, genomic variations compatible with mutations previously associated with clarithromycin resistance were detected. Exposure to clarithromycin may select low-frequency variants, resulting in a progressive increase in the resistance rate due to selection pressure.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7200067PMC
http://dx.doi.org/10.1099/mgen.0.000344DOI Listing

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