Lin Rong-Dih, Chin Yi-Ping, Lee Mei-Hsien
Department of Internal Medicine, Ho-Ping Branch, Taipei City Hospital, Taipei 100, Taiwan.
Phytother Res. 2005 Jul;19(7):612-7. doi: 10.1002/ptr.1695.
Extended-spectrum beta-lactamases (ESBLs) are plasmid-mediated class A enzymes commonly found in the family Enterobacteriaceae, mainly in Klebsiella pneumoniae. Flavonoids have also been reported to possess antimicrobial activity. In this study, the in vitro activities of 18 antibiotics and 12 flavonoids against 20 ESBL-producing K. pneumoniae isolates were evaluated. All of these isolates were susceptible to imipenem and cefmetazole, but were resistant to ampicillin, ampicillin/sulbactam, aztreonam, cefazolin, cefoperazone, cefotaxime, ceftazidime, ceftriaxone, cefuroxime, piperacillin and ticarcillin. Susceptibilities to amikacin, amoxicillin/clavulanate, cefoxitin, ciprofloxacin and gentamicin were variable. Myricetin, a flavonol, inhibited ESBL-producing K. pneumoniae isolates at a high minimum inhibitory concentration (MIC) (MIC(90) value 256 mg/mL), but exhibited significant synergic activity against ESBL-producing K. pneumoniae in separate combination with amoxicillin/clavulanate, ampicillin/sulbactam and cefoxitin. Because of the low-toxic nature of flavonoids, the combination of antibiotics and flavonoids is a potential new strategy for developing therapies for infections caused by ESBL-producing bacteria in the future.
超广谱β-内酰胺酶（ESBLs）是由质粒介导的A类酶，常见于肠杆菌科细菌中，主要是肺炎克雷伯菌。据报道，黄酮类化合物也具有抗菌活性。在本研究中，评估了18种抗生素和12种黄酮类化合物对20株产ESBLs肺炎克雷伯菌分离株的体外活性。所有这些分离株对亚胺培南和头孢美唑敏感，但对氨苄西林、氨苄西林/舒巴坦、氨曲南、头孢唑林、头孢哌酮、头孢噻肟、头孢他啶、头孢曲松、头孢呋辛、哌拉西林和替卡西林耐药。对阿米卡星、阿莫西林/克拉维酸、头孢西丁、环丙沙星和庆大霉素的敏感性各不相同。杨梅素，一种黄酮醇，在高最低抑菌浓度（MIC）（MIC90值为256mg/mL）时抑制产ESBLs肺炎克雷伯菌分离株，但与阿莫西林/克拉维酸、氨苄西林/舒巴坦和头孢西丁单独联合使用时，对产ESBLs肺炎克雷伯菌表现出显著的协同活性。由于黄酮类化合物的低毒性，抗生素与黄酮类化合物联合使用是未来开发产ESBLs细菌感染治疗方法的一种潜在新策略。
