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

Lefamulin combined with rifampin shows strong in vitro synergy against macrolide- and rifampin-susceptible Rhodococcus equi isolates.

This in vitro study evaluated lefamulin, a pleuromutilin antibiotic with favorable intrapulmonary disposition, as a potential therapeutic option against Rhodococcus equi, the primary causative agent of pneumonia in foals. Researchers tested minimum inhibitory concentrations (MICs) for lefamulin alone and in combination with rifampin against both macrolide- and rifampin-susceptible (MRS, n=43) and macrolide- and rifampin-resistant (MRR, n=61) R. equi isolates using gradient diffusion and broth microdilution methods. MIC values were consistently higher via broth microdilution (median 32 µg/mL) than gradient diffusion (median 12 µg/mL) across both isolate groups. Synergistic activity was assessed via checkerboard assay and fractional inhibitory concentration index (FICI). Synergy was demonstrated in 80% of MRS isolates (16/20) compared to only 30% of MRR isolates (6/20), with FICI values significantly lower for MRS isolates. Notably, MIC values for lefamulin alone exceeded concentrations considered therapeutically relevant in humans, suggesting monotherapy would be inadequate. However, the pronounced synergistic effect observed when lefamulin was combined with rifampin in MRS isolates provides a compelling rationale for further investigation. The authors conclude that pharmacokinetic studies evaluating lefamulin's pulmonary disposition in foals, particularly in combination with rifampin, are warranted as the field seeks alternatives to combat emerging antimicrobial resistance in rhodococcal pneumonia.

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