PMC

(A) Sub-inhibitory concentrations of cephradine (0.5xMIC, 4 μg/mL) enhanced the antibacterial and sterilizing activities of rifampicin and ethambutol (no growth observed after 60 days; upper right panel). (B) Dose dependent sterilizing activity of cephradine. Increased concentrations of cephradine (4xMIC, 32 μg/mL) enhanced the sterilizing activity of rifampicin (no growth observed after 60 days; bottom middle panel). (C) The stabilities of rifampicin and cephradine alone and in combination in 7H9 media were analysed by UPLC-MS/MS. MIC values of the individual drugs are used to express drug concentrations (i.e., 1, 4, 10-fold their MIC concentrations). RIF, rifampicin; CPD, cephradine; EMB, ethambutol. MIC_RIF = 0.03 μg/mL; MIC_CPD = 8 μg/mL; MIC_EMB = 2 μg/mL.

Fractional inhibitory concentrations of every drug within every pairwise combination were calculated and plotted as isobolograms to allow visual inspection of the drug interactions. A straight line indicates a non-interaction profile while curves closer to the axis origins and falling within the box indicate a synergistic profile. Isobologram curves are colour coded according to their synergistic profile. Red, synergistic interaction; Green, additive; and blue, no interaction. Cephradine, solid lines; faropenem, broken lines.