Mechanisms of resistance to telithromycin in Streptococcus pneumoniae

Tamiko Hisanaga1, Daryl J Hoban, George G Zhanel

  • 1Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada. thisanga@shaw.ca

Insights

Ketolide resistance in Streptococcus pneumoniae is rare but documented. Mutations in ribosomal binding sites and resistance genes like erm(B) can cause resistance, potentially increasing with telithromycin use.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Antimicrobial Resistance

Background:

  • Ketolides are an important class of antibiotics.
  • Reports of ketolide resistance in Streptococcus pneumoniae are scarce.
  • Understanding resistance mechanisms is crucial for effective treatment.

Purpose of the Study:

  • To investigate the mechanisms of ketolide resistance in Streptococcus pneumoniae.
  • To identify genetic mutations associated with elevated telithromycin minimum inhibitory concentrations (MICs).
  • To assess the potential for increased ketolide resistance with rising antibiotic usage.

Main Methods:

  • Analysis of laboratory-derived and clinical isolates of resistant Streptococcus pneumoniae.
  • Identification of mutations in 23S rRNA (domains II and V) and ribosomal proteins (L4 and L22).
  • Investigation of the role of the erm(B) resistance determinant and ribosomal methylation.

Main Results:

  • Specific mutations in telithromycin-binding sites (23S rRNA domains II and V, ribosomal proteins L4 and L22) are linked to resistance.
  • Mutations in the erm(B) gene are also associated with elevated telithromycin MICs.
  • Combined mutations and ribosomal methylation may lead to significant resistance, even against efflux-positive strains.

Conclusions:

  • Ketolide resistance in Streptococcus pneumoniae, while infrequent, is mediated by specific genetic mutations.
  • The emergence of resistance is a concern, particularly with increased use of antibiotics like telithromycin.
  • Further monitoring of ketolide resistance is warranted.

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