臨床產氣單胞桿菌抗藥性分析與白藜蘆醇作為抗菌輔助劑之潛力評估

Analysis of Antimicrobial Resistance in Clinical Aeromonas Isolates and the Potential of Resveratrol as an Antimicrobial Adjuvant

產氣單胞桿菌（Aeromonas spp.）為廣泛存在於水域環境中的伺機性病原菌，常引發腸胃炎、傷口感染及敗血症等臨床疾病，其抗藥性問題日益受到重視。本研究旨在針對臨床分離之產氣單胞桿菌進行抗生素敏感性與抗藥基因分布分析，並進一步探討天然多酚白藜蘆醇（Resveratrol）作為潛在抗菌輔助劑的可行性。本研究共收集100株產氣單胞桿菌，經MALDI-TOF質譜鑑定，因為資料庫限制，部分菌種無法細鑑定，僅能鑑定至數的層級Aeromonas spp.，其餘主要A. caviae與A. hydrophila。抗生素敏感性結果顯示，菌株對第三代頭孢菌素（Cefotaxime、Ceftazidime）維持高度敏感性（90-100%），但A. hydrophila對Imipenem敏感率僅29%，與CphA金屬β-內醯胺酶基因呈高度相關。Cefoxitin敏感性亦下降至65-85%，顯示AmpC酶基因MOX、AQU-1可能為主因。進一步測試白藜蘆醇之最小抑菌濃度（MIC）介於16–256μg/mL，A. enteropelogenes與A. media對其最為敏感。斑馬魚胚胎毒性試驗結果指出，白藜蘆醇於250μg/mL以下未見明顯毒性，但超過500μg/mL胚胎死亡率與畸形率明顯上升。綜合結果，白藜蘆醇具備良好抑菌能力及生物相容性，具潛力作為臨床抗菌輔助劑，惟應控制使用濃度以確保安全。

Aeromonas spp. are opportunistic pathogens widely distributed in aquatic environments and are commonly associated with diseases such as gastroenteritis, wound infections, and septicemia. The growing concern over their antimicrobial resistance has prompted further investigation. This study aimed to analyze the antibiotic susceptibility and resistance gene profiles of clinical Aeromonas isolates, and to evaluate the potential of the natural polyphenol resveratrol as an antimicrobial adjuvant. A total of 100 Aeromonas isolates were collected and identified using MALDI-TOF mass spectrometry. Due to limitations of the database, some isolates could only be identified to the genus level (Aeromonas spp.), while the others were mainly A. caviae, with A. hydrophila being the predominant species. Antibiotic susceptibility results showed that the isolates maintained high sensitivity (90–100%) to third-generation cephalosporins (Cefotaxime and Ceftazidime). However, A. hydrophila exhibited a low sensitivity rate of only 29% to Imipenem, which was strongly associated with the presence of the cphA metallo-β-lactamase gene. Cefoxitin susceptibility also declined to 65–85%, suggesting that the MOX and AQU-1 AmpCβ-lactamase genes may be responsible. Further testing showed that the minimum inhibitory concentration (MIC) of resveratrol ranged from 16–256μg/mL, with A. enteropelogenes and A. media being the most sensitive species. Zebrafish embryo toxicity tests indicated that resveratrol exhibited no significant toxicity at concentrations below 250μg/mL, whereas embryo mortality and malformation rates significantly increased above 500μg/mL. Overall, resveratrol demonstrated promising antibacterial activity and biocompatibility, highlighting its potential as a clinical antimicrobial adjuvant, although its concentration must be carefully controlled to ensure safety.