Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China; Key Laboratory of Clinical Pharmacology of Antibiotics, National Health and Family Planning Commission, Shanghai, China.
Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China; Key Laboratory of Clinical Pharmacology of Antibiotics, National Health and Family Planning Commission, Shanghai, China.
Int J Antimicrob Agents. 2014 Dec;44(6):514-9. doi: 10.1016/j.ijantimicag.2014.07.027. Epub 2014 Sep 24.
This study evaluated the in vitro anti-anaerobic activity and spectrum of levornidazole, its metabolites and comparators against 375 clinical isolates of anaerobic bacteria, including Gram-negative bacilli (181 strains), Gram-negative cocci (11 strains), Gram-positive bacilli (139 strains) and Gram-positive cocci (44 strains), covering 34 species. Minimum inhibitory concentrations (MICs) of levornidazole, its five metabolites and three comparators against these anaerobic isolates were determined by the agar dilution method. Minimum bactericidal concentrations (MBCs) of levornidazole and metronidazole were measured against 22 strains of Bacteroides fragilis. Levornidazole showed good activity against B. fragilis, other Bacteroides spp., Clostridium difficile, Clostridium perfringens and Peptostreptococcus magnus, evidenced by MIC90 values of 0.5, 1, 0.25, 2 and 1mg/L, respectively. The activity of levornidazole and the comparators was poor for Veillonella spp. Generally, levornidazole displayed activity similar to or slightly higher than that of metronidazole, ornidazole and dextrornidazole against anaerobic Gram-negative bacilli, Gram-positive bacilli and Gram-positive cocci, especially B. fragilis. Favourable anti-anaerobic activity was also seen with levornidazole metabolites M1 and M4 but not M2, M3 or M5. For the 22 clinical B. fragilis strains, MBC50 and MBC90 values of levornidazole were 2mg/L and 4mg/L, respectively. Both MBC50/MIC50 and MBC90/MIC90 ratios of levornidazole were 4, similar to those of metronidazole. Levornidazole is an important anti-anaerobic option in clinical settings in terms of its potent and broad-spectrum in vitro activity, bactericidal property, and the anti-anaerobic activity of its metabolites M1 and M4.
本研究评估了左旋甲硝唑及其代谢物和对照药物对 375 株临床厌氧分离株的体外抗厌氧活性和谱，包括革兰氏阴性杆菌（181 株）、革兰氏阴性球菌（11 株）、革兰氏阳性杆菌（139 株）和革兰氏阳性球菌（44 株），涵盖 34 个种。采用琼脂稀释法测定左旋甲硝唑、其五种代谢物和三种对照药物对这些厌氧分离株的最低抑菌浓度（MIC）。采用琼脂稀释法测定左旋甲硝唑和甲硝唑对 22 株脆弱拟杆菌的最低杀菌浓度（MBC）。左旋甲硝唑对脆弱拟杆菌、其他拟杆菌、艰难梭菌、产气荚膜梭菌和大消化链球菌具有良好的活性，MIC90 值分别为 0.5、1、0.25、2 和 1mg/L。左旋甲硝唑和对照药物对韦荣球菌的活性较差。一般来说，左旋甲硝唑对厌氧革兰氏阴性杆菌、革兰氏阳性杆菌和革兰氏阳性球菌的活性与甲硝唑、奥硝唑和右旋甲硝唑相似或略高，尤其是脆弱拟杆菌。左旋甲硝唑代谢物 M1 和 M4 也具有良好的抗厌氧活性，但 M2、M3 和 M5 则不然。对 22 株临床脆弱拟杆菌，左旋甲硝唑的 MBC50 和 MBC90 值分别为 2mg/L 和 4mg/L。左旋甲硝唑的 MBC50/MIC50 和 MBC90/MIC90 比值均为 4，与甲硝唑相似。从体外活性、杀菌特性和代谢物 M1 和 M4 的抗厌氧活性来看，左旋甲硝唑是临床治疗厌氧菌感染的一个重要选择。
