由水生病原菌所引起之皮膚和軟組織感染，尤其是創傷弧菌（Vibrio vulnificus）與氣單胞菌屬（Aeromonas spp.）感染，病程進展迅速且死亡率高，於高菌量感染條件下尤易發生治療失敗。本研究旨在評估再定位抗腫瘤藥物絲裂黴素 C（mitomycin C, MMC）合併氟喹諾酮類抗生素，應用於水生病原相關感染之抗菌效力、作用機轉及系統性安全性。研究方法包括最低抑菌濃度測定、time-kill assay、細胞內殺菌試驗、細菌形態學觀察、RT-qPCR 基因表現分析，以及中性球低下小鼠感染模式之體內療效與毒性評估。結果顯示，MMC 對多種臨床相關水生病原菌具有廣泛抗菌活性，並可於體外高菌量條件下增強 ciprofloxacin（CIP）與 levofloxacin（LVX）之抗菌效果。在小鼠感染模式中，MMC 與氟喹諾酮類藥物合併治療，相較於單一藥物治療，可提升治療成效並增加宿主存活率，尤其在嚴重 V. vulnificus 感染中效果更為顯著。MMC 可誘導細菌延長與絲狀化，並上調 recA、lexA、uvrA、umuD 與 umuC 等 SOS 反應相關基因表現，顯示 MMC 所造成之 DNA 損傷與複製壓力可能進一步提升細菌對氟喹諾酮類藥物之敏感性。然而，MMC 或 CIP 暴露後之 MIC 上升現象，亦提示可能存在適應性藥物敏感性變化，仍待進一步釐清。在安全性方面，低劑量 MMC 於體內整體耐受性良好；MMC 2 mg/kg 可造成輕度血液學抑制，但未見明顯合併毒性，而 MMC 1 mg/kg 則於保留抗菌協同效應之同時僅產生極輕微毒性，且組織病理學檢查未見明顯肝腎損傷。綜合而言，本研究提供前臨床證據，支持再定位 MMC 可作為氟喹諾酮類抗生素之輔助增效藥物，應用於 Aeromonas spp. 與 V. vulnificus 所致之嚴重感染，尤其在高菌量條件下更具治療潛力。

Skin and soft tissue infections caused by aquatic pathogens, particularly Vibrio vulnificus and Aeromonas spp., are rapidly progressive and associated with high mortality, especially under high‑inoculum conditions. This study evaluated the antimicrobial activity, features of action, and systemic safety of repurposed mitomycin C (MMC) combined with fluoroquinolones against aquatic pathogen–associated infections. MMC exhibited broad antibacterial activity and enhanced the effects of ciprofloxacin (CIP) and levofloxacin (LVX) under high‑inoculum conditions in vitro. In murine infection models, MMC–fluoroquinolone combination therapy improved therapeutic efficacy and increased survival compared with monotherapy, particularly in severe V. vulnificus infection. MMC induced bacterial elongation and filamentation and upregulated SOS response–associated genes, including recA, lexA, uvrA, umuD, and umuC, suggesting that MMC‑mediated DNA damage and replication stress enhance fluoroquinolone susceptibility. However, post‑exposure MIC elevation following MMC or CIP treatment indicates that adaptive changes in susceptibility warrant further investigation. Low‑dose MMC regimens were generally well tolerated in vivo: MMC at 2 mg/kg caused mild hematologic suppression without obvious additional toxicity during combination therapy, whereas 1 mg/kg MMC produced minimal toxicity while preserving antimicrobial synergy, and no overt hepatic or renal injury was identified histologically. Overall, these findings provide preclinical evidence that repurposed MMC can enhance fluoroquinolone efficacy against Aeromonas spp. and V. vulnificus, particularly under high‑inoculum conditions, and support MMC‑based combination therapy as a potential adjunctive strategy for severe aquatic pathogen–associated skin and soft tissue infections.

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