Synergistic and additive in vitro interactions of imipenem, trimethoprim-sulfamethoxazole, amikacin, and clofazimine against clinical isolates of Nocardia wallacei.

Nocardia wallacei presents a therapeutic challenge due to its frequent in vitro resistance to commonly used antimicrobials, including trimethoprim-sulfamethoxazole (TMP-SMX), imipenem, and amikacin. Current nocardiosis treatment guidelines provide general recommendations but lack species-specific guidance for N. wallacei. Given the limited therapeutic options for this species, evaluating combination therapies may support treatment optimization. We assessed the potential synergistic and additive effects between TMP-SMX, imipenem, amikacin, and clofazimine using the checkerboard titration method in 16 clinical isolates. Synergy, defined by a Fractional Inhibitory Concentration Index (FICI) of 0.25-0.5, was observed when TMP-SMX was combined with amikacin, clofazimine, or imipenem. Clofazimine demonstrated additive activity when combined with imipenem or amikacin (FICI = 0.53-0.625). The amikacin-imipenem combination also yielded additive effects (FICI = 0.75-1). These findings suggest that multiple dual-drug combinations may enhance in vitro efficacy against N. wallacei despite reduced monotherapy activity.