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.