Synergistic effect of repurposed mitomycin C in combination with antibiotics against Aeromonas infection: in vitro and in vivo studies.

Abstract

Background Aeromonas infections pose a significant threat, presenting a potentially life-threatening condition associated with high mortality rates. This study investigates the potential of mitomycin C (MMC), an anticancer drug, as a novel antimicrobial agent against Aeromonas infections. Methods The minimum inhibitory concentrations (MICs) of MMC and antibiotics against clinical isolates of Aeromonas species were assessed, using broth microdilution. Synergistic effects of MMC with antibiotics were assessed through time-kill studies. Additionally, we analyzed MMC's intracellular killing effects using a representative Aeromonas isolate. Efficacy of combined therapies was evaluated in neutropenic mice model. Results We found that only three antibiotics-ciprofloxacin (CIP), levofloxacin (LVX), and tigecycline (TGC) maintained susceptibility rates exceeding 90% under high inoculum conditions. Significantly, in vitro investigations demonstrated a synergistic effect over a 24-hour period when combining the 1/8x MIC of MMC with the 1x or 1/2x MICs of LVX, in a time–kill study. Furthermore, in vivo in neutropenic mice, the combination of 2 mg/kg and 1 mg/kg MMC with LVX resulted in 100% and 80% survival, respectively, whereas treatment with either drug alone resulted in 0% survival rate. Conclusions These findings suggest that MMC can be repurposed as an antimicrobial agent, particularly with a minimized dose and in combination with antibiotics.