Synthetic lincosamides iboxamycin and cresomycin are active against ocular multidrug-resistant methicillin-resistant Staphylococcus aureus carrying erm genes

Abstract

Objective

Antimicrobial resistance is a global pandemic that poses a major threat to vision health as ocular bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA), are becoming increasingly resistant to first-line therapies. Here we evaluated the antimicrobial activity of new synthetic lincosamides in comparison to currently used antibiotics against clinical ocular MRSA isolates.

Methods

Antimicrobial susceptibility testing was performed by broth microdilution for two novel synthetic lincosamides (iboxamycin and cresomycin) and eight comparator antibiotics against a collection of 50 genomically characterised ocular MRSA isolates, including isolates harbouring erm genes (n = 25).

Results

Both drugs were active against widespread MRSA clonal complexes CC8 and CC5. The MIC₅₀ and MIC₉₀ of iboxamycin were 0.06 and 2 mg/L, respectively. Cresomycin (MIC₅₀ = 0.06 mg/L) also displayed good activity with an in vitro potency four-fold higher (MIC₉₀ = 0.5 mg/L) than iboxamycin. In isolates harbouring erm genes, MIC₉₀ were >16, 2, and 0.5 mg/L for clindamycin, iboxamycin, and cresomycin, respectively. The in vitro potencies of iboxamycin and cresomycin were similar or higher than that of comparator agents and were not impacted by multidrug-resistance phenotypes or by the presence of erm genes when compared with clindamycin.

Conclusions

Our results demonstrate that iboxamycin and cresomycin display potent in vitro activity against ocular MRSA isolates, including multidrug-resistant isolates harbouring erm genes.