Solithromycin Can Specifically Induce Macrolide-Lincosamide-Streptogramin B Resistance

Area of Science:

• Microbiology
• Molecular Biology
• Pharmacology

Background:

• Solithromycin, a novel fluoroketolide antibiotic, is investigated for its potential to induce resistance mechanisms.
• Macrolide-lincosamide-streptogramin B (MLSB) resistance is often mediated by erm genes.
• The specific induction profile of solithromycin on erm gene expression is not fully characterized.

Purpose of the Study:

• To determine the exact activity of solithromycin in inducing erm gene expression.
• To compare solithromycin's induction potential with other ketolides and antibiotics.
• To assess the risk of solithromycin promoting MLSB resistance.

Main Methods:

• Utilized a lacZ reporter assay to quantify erm gene expression.
• Performed double-disk diffusion tests to evaluate antibiotic resistance patterns.
• Determined minimal inhibitory concentrations (MICs) after exposure to subinhibitory antibiotic concentrations.

Main Results:

• Solithromycin, telithromycin, and cethromycin did not induce erm(A) or erm(C) gene expression.
• Solithromycin significantly induced erm(B) gene expression.
• The induction of erm(B) by solithromycin was less potent than erythromycin, rokitamycin, and telithromycin, but greater than cethromycin and clindamycin.

Conclusions:

• Solithromycin does not induce erm(A) and erm(C) gene expression, suggesting a lower risk of cross-resistance for these specific resistance mechanisms.
• Solithromycin exhibits a weaker induction of erm(B) gene expression compared to certain macrolides.
• Further research is warranted to fully understand the clinical implications of solithromycin's erm(B) gene induction potential.