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Will resistance to ketolides develop in Streptococcus pneumoniae?

R Leclercq1

  • 1CHU de Caen, Service de Microbiologie, France. leclercq-r@chu-caen.fr

The Journal of Infection
|August 2, 2002
PubMed

Insights

Rising antibacterial resistance necessitates new treatments. Ketolides, like telithromycin, offer a novel solution for respiratory tract infections, effectively combating resistant pathogens without promoting further resistance.

Area of Science:

  • Microbiology
  • Pharmacology
  • Infectious Diseases

Background:

  • Increasing resistance to macrolide, lincosamide, and streptogramin B (MLSB) antibacterials, particularly in Streptococcus pneumoniae, limits treatment options for respiratory tract infections (RTIs).
  • Development of novel antibacterial agents that do not select for resistance is crucial for preserving future antibacterial efficacy.

Purpose of the Study:

  • To introduce ketolides, a new class of antibacterials exemplified by telithromycin, as a potential solution for empirical treatment of RTIs.
  • To highlight the unique structural modifications of ketolides and their implications for overcoming MLSB resistance.

Main Methods:

  • Analysis of the chemical structure of ketolides, focusing on the keto function at position 3 and the C11,12-carbamate side chain.
  • Evaluation of ketolides' interaction with bacterial 23S rRNA and their binding affinity to ribosomes, including MLSB-resistant strains.
  • Assessment of ketolides' potential for resistance and cross-resistance selection in vitro and in vivo.

Main Results:

  • Ketolides possess a novel structure distinct from traditional macrolides, which prevents the induction of MLSB resistance in vitro.
  • The structural modifications enhance ketolides' binding to bacterial ribosomes, including those in MLSB-resistant strains.
  • Ketolides demonstrate intrinsic activity against respiratory pathogens, retain efficacy against resistant strains, and exhibit a low potential for selecting resistance.

Conclusions:

  • Ketolides represent a new class of antibacterials with a unique mechanism of action effective against respiratory pathogens.
  • Their ability to avoid inducing MLSB resistance and retain activity against resistant strains makes them valuable for empirical RTI treatment.
  • Ketolides offer a promising therapeutic option with a low risk of resistance development, safeguarding future antibacterial efficacy.

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