Combining lefamulin with rifampin provides in vitro synergistic antimicrobial effects against Rhodococcus equi isolates susceptible to macrolides and rifampin.

OBJECTIVE

Because of lefamulin's antimicrobial spectrum and intrapulmonary disposition, the objective of this study was to estimate MICs for macrolide- and rifampin-susceptible (MRS) and macrolide- and rifampin-resistant (MRR) isolates of Rhodococcus equi to lefamulin either alone or in combination with rifampin.

METHODS

Gradient diffusion and broth microdilution were performed to determine MICs for lefamulin alone using MRS (n = 43) and MRR isolates (61) of R equi. Twenty MRR and 20 MRS isolates were tested for synergistic effects using a checkerboard assay and the fractional inhibitory concentration index as an outcome measure.

RESULTS

For both MRR and MRS isolates, MIC values were significantly higher using broth microdilution (median MIC, 32 µg/mL; range, 8 to 64 µg/mL) than gradient diffusion (median MIC, 12 µg/mL; range, 5 to 28 µg/mL) testing. The fractional inhibitory concentration values of MRR isolates (median, 0.562; range, 0.250 to 1.000) were significantly higher than those of MRS isolates (median, 0.280; range, 0.039 to 1.038). In addition, the proportion of isolates exhibiting synergistic interaction was significantly greater among MRS isolates (16 of 20 [80%]) than among MRR isolates (6 of 20 [30%]).

CONCLUSIONS

Overall, the MIC values for lefamulin against R equi were high relative to concentrations considered therapeutic in humans. When combined with rifampin, lefamulin exhibited synergistic effects for MRS but not MRR isolates.

CLINICAL RELEVANCE: Need exists for alternative antimicrobials to treat rhodococcal foal pneumonia. Results indicate that studies in foals of the pharmacokinetics and pulmonary disposition of lefamulin in combination with rifampin are warranted.