Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi · 2026
Synergistic activity of mitomycin C in combination with ciprofloxacin against severe Vibrio vulnificus infection.
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Yeh Cheng-Fa, Chen Chi-Chung, Lai Chih-Cheng, Hsu Ping-Yu, Liu Jin-Wei, Tang Hung-Jen, Su Wen-Pin
Аннотация
BACKGROUND: Vibrio vulnificus is a highly virulent pathogen associated with rapidly progressive sepsis and necrotising soft-tissue infection, particularly among patients with diabetes or chronic liver disease. Effective treatment options remain limited, especially in the setting of high bacterial burden or immunocompromis.
METHODS: We performed an integrated preclinical assessment of mitomycin C (MMC) alone and in combination with ciprofloxacin (CIP) using in vitro susceptibility testing and a neutropenic murine model challenged with increasing inocula of V. vulnificus. Myelotoxicity, organ-specific toxicity, and the development of resistance under subinhibitory MMC exposure were evaluated through haematological profiling and histopathology.
RESULTS: MMC demonstrated potent in vitro activity and conferred complete protection in mice challenged with low bacterial inocula (103-104 colony-forming units (CFU)/mL). Although efficacy declined with increasing bacterial burden, combination therapy with MMC and ciprofloxacin significantly improved survival across all inoculum levels, achieving complete protection at concentrations up to 1.4 ⨯ 107 CFU/mL and partial protection at 4.3 ⨯ 107 CFU/mL. The combination regimen was not associated with dose-dependent myelosuppression, and no hepatotoxicity or nephrotoxicity was observed. Exposure to subinhibitory concentrations of MMC did not result in increased minimum inhibitory concentrations over time.
CONCLUSIONS: MMC-CIP combination therapy demonstrated synergistic efficacy against severe V. vulnificus infection in a neutropenic mouse model and may represent a promising therapeutic option. Dose-limiting myelotoxicity and the potential for resistance necessitate cautious dosing and further clinical investigation. This study addresses a critical therapeutic gap in severe V. vulnificus infection by proposing a mechanistically rational, dose-optimized adjunctive strategy supported by robust preclinical evidence.
METHODS: We performed an integrated preclinical assessment of mitomycin C (MMC) alone and in combination with ciprofloxacin (CIP) using in vitro susceptibility testing and a neutropenic murine model challenged with increasing inocula of V. vulnificus. Myelotoxicity, organ-specific toxicity, and the development of resistance under subinhibitory MMC exposure were evaluated through haematological profiling and histopathology.
RESULTS: MMC demonstrated potent in vitro activity and conferred complete protection in mice challenged with low bacterial inocula (103-104 colony-forming units (CFU)/mL). Although efficacy declined with increasing bacterial burden, combination therapy with MMC and ciprofloxacin significantly improved survival across all inoculum levels, achieving complete protection at concentrations up to 1.4 ⨯ 107 CFU/mL and partial protection at 4.3 ⨯ 107 CFU/mL. The combination regimen was not associated with dose-dependent myelosuppression, and no hepatotoxicity or nephrotoxicity was observed. Exposure to subinhibitory concentrations of MMC did not result in increased minimum inhibitory concentrations over time.
CONCLUSIONS: MMC-CIP combination therapy demonstrated synergistic efficacy against severe V. vulnificus infection in a neutropenic mouse model and may represent a promising therapeutic option. Dose-limiting myelotoxicity and the potential for resistance necessitate cautious dosing and further clinical investigation. This study addresses a critical therapeutic gap in severe V. vulnificus infection by proposing a mechanistically rational, dose-optimized adjunctive strategy supported by robust preclinical evidence.