Fingolimod potentiates minocycline against multidrug-resistant Elizabethkingia.

OBJECTIVES

Elizabethkingia spp. are intrinsically resistant to multiple antimicrobial classes and are emerging nosocomial pathogens. This study evaluated the antibacterial activity of fingolimod against Elizabethkingia and its interaction with minocycline.

METHODS

Sixteen residual clinical isolates were examined. Baseline single-agent susceptibility was assessed by a single disk-diffusion determination and by VITEK 2. Fingolimod MIC and MBC values were measured by broth microdilution. Biofilm formation was quantified by crystal violet staining. Fingolimod-minocycline interactions were evaluated by checkerboard and time-kill assays. Preliminary protective activity was examined in a Galleria mellonella model infected with EA12.

RESULTS

Disk diffusion and VITEK 2 showed method-dependent discordance for piperacillin-tazobactam. Fifteen of 16 isolates formed biofilm; 13 of these 15 were weak and two were moderate producers. Fingolimod MICs ranged from 6.25 to 25 μg/mL. Fingolimod reduced the minocycline MIC by 4-8-fold in six synergistic isolates. The combination produced preliminary, isolate-specific protection in Galleria mellonella infected with EA12.

CONCLUSION

Fingolimod exhibits antibacterial activity against Elizabethkingia spp. and potentiates minocycline in a subset of isolates. These findings support further development of fingolimod-based combination strategies and optimization of the fingolimod scaffold.