Elizabethkingia anophelis has emerged as a critical human pathogen, and a number of
isolated reports have described the successful treatment of Elizabethkingia infections with vancomycin,
a drug that is typically used to target Gram-positive bacteria. This study employed in vitro broth
microdilution checkerboard and time-kill assays, as well as in vivo zebrafish animal models to
evaluate the individual and combination antimicrobial effects of vancomycin and rifampin against
E. anophelis. The minimum inhibitory concentration ranges of vancomycin and rifampin against
167 isolates of E. anophelis were 16–256 mg/L and 0.06–128 mg/L, respectively. The checkerboard
assay results revealed a synergistic effect between vancomycin and rifampin in 16.8% (28/167) of
the isolates. Time-kill assays were implemented for 66 isolates, and the two-drug combination had a
synergistic interaction in 57 (86.4%) isolates. In vivo zebrafish studies revealed that treatment with
vancomycin monotherapy, rifampin monotherapy, or vancomycin–rifampin combination therapy
yielded a higher survival rate than the control group treatment with 0.9% saline. The results of this
study support the use of vancomycin to treat E. anophelis infections.