RM Alden Research Laboratory, Culver City, CA, USA.
Clin Infect Dis. 2012 Aug;55 Suppl 2(Suppl 2):S143-8. doi: 10.1093/cid/cis339.
Fidaxomicin is bactericidal against Clostridium difficile. The combined results of 8 in vitro studies of 1323 C. difficile isolates showed the minimum inhibitory concentration (MIC) range of fidaxomicin to be ≤ 0.001-1 μg/mL, with a maximum MIC for inhibition of 90% of organisms (MIC(90)) of 0.5 μg/mL. Isolates from 2 phase III clinical trials demonstrated that fidaxomicin MICs of baseline isolates did not predict clinical cure, failure, or recurrence of C. difficile infections. No resistance to fidaxomicin developed during treatment in either study, although a single strain recovered from a cured patient had an elevated MIC of 16 µg/mL at the time of recurrence. For 135 strains, OP-1118, a major metabolite, had an MIC for inhibition of 50% of organisms of 4 μg/mL and an MIC(90) of 8 μg/mL. Changes in inoculum size (10(2)-10(5) colony-forming units/spot) or cation concentrations of calcium or magnesium appeared to have no effect on fidaxomicin MICs. Fidaxomicin has little or no activity against gram-negative aerobes and anaerobes or yeast.
非达霉素对艰难梭菌具有杀菌作用。8 项针对 1323 株艰难梭菌的体外研究的综合结果表明，非达霉素的最低抑菌浓度（MIC）范围为≤0.001-1μg/mL，最大 MIC（MIC90）为抑制 90%的细菌为 0.5μg/mL。来自 2 项 III 期临床试验的分离株表明，基线分离株的非达霉素 MIC 不能预测艰难梭菌感染的临床治愈、失败或复发。在这两项研究中，治疗期间均未出现对非达霉素的耐药性，尽管在复发时从治愈患者中分离出的一株具有 16μg/mL 的升高 MIC。对于 135 株 OP-1118，一种主要代谢物，其 MIC50 抑制半数细菌的浓度为 4μg/mL，MIC90 为 8μg/mL。接种物大小（102-105 个菌落形成单位/点）或钙或镁阳离子浓度的变化似乎对非达霉素 MIC 没有影响。非达霉素对革兰氏阴性需氧菌和厌氧菌或酵母几乎没有活性或没有活性。
