Objectives

AUTHOR=André Camille , Schrank Cassandra L. , Cheng Jaramillo Ana Victoria , Mylonakis Eleftherios , Wuest William M. , Gilmore Michael S. , Kim Wooseong , Bispo Paulo J. M. TITLE=Antimicrobial activity of a new class of synthetic retinoid antibiotics and comparator agents against ocular staphylococci JOURNAL=Frontiers in Antibiotics VOLUME=2 YEAR=2023 URL=https://www.frontiersin.org/journals/antibiotics/articles/10.3389/frabi.2023.1101450 DOI=10.3389/frabi.2023.1101450 ISSN=2813-2467 ABSTRACT=Objectives

Antimicrobial resistance is global pandemic that poses a major threat to vision health as ocular pathogens, especially staphylococcal species, are becoming increasingly resistant to first-line therapies. Here we evaluated the antimicrobial activity of a new class of synthetic retinoids in comparison to currently used antibiotics against clinically relevant ocular staphylococcal isolates.

Methods

Antimicrobial susceptibility testing was performed by broth microdilution for 3 novel synthetic retinoids (CD1530, CD437, and a CD437 analogue) and 7 comparator antibiotics, against a collection of 216 clinical isolates.

Results

CD437 MIC₅₀ and MIC₉₀ were 2 µg/mL for Staphylococcus aureus, and 1 µg/mL and 2 µg/mL respectively, for coagulase-negative staphylococci (CoNS). CD1530 (MIC₅₀ = 2 µg/mL for all species) also displayed good activity with an in vitro potency slightly lower (2-fold) for S. aureus (MIC₉₀ = 4 µg/mL) when compared to CD437. A CD437 analogue also demonstrated good in vitro activity (MIC₅₀ = 2 µg/mL for all species) and potency (MIC₉₀ = 2 µg/mL for MRSA and 4 µg/mL for MSSA and CoNS). In vitro potencies were similar or higher than that of comparator agents, and were not impacted by multidrug resistance phenotypes.

Conclusion

Our results demonstrate that synthetic retinoids display potent in vitro activity against ocular staphylococcal species, including multidrug-resistant isolates.