RM Alden Research Lab, Culver City, California, USA.
Antimicrob Agents Chemother. 2012 May;56(5):2493-503. doi: 10.1128/AAC.06305-11. Epub 2012 Jan 30.
The in vitro activities of LFF571, a novel analog of GE2270A that inhibits bacterial growth by binding with high affinity for protein synthesis elongation factor Tu, fidaxomicin, and 10 other antimicrobial agents were determined against 50 strains of Clostridium difficile and 630 other anaerobic and aerobic organisms of intestinal origin. LFF571 possesses potent activity against C. difficile and most other Gram-positive anaerobes (MIC(90), ≤ 0.25 μg/ml), with the exception of bifidobacteria and lactobacilli. The MIC(90)s for aerobes, including enterococci, Staphylococcus aureus (as well as methicillin-resistant S. aureus [MRSA] isolates), Streptococcus pyogenes, and other streptococci were 0.06, 0.125, 2, and 8 μg/ml, respectively. Comparatively, fidaxomicin showed variable activity against Gram-positive organisms: MIC(90)s against C. difficile, Clostridium perfringens, and Bifidobacterium spp. were 0.5, ≤ 0.015, and 0.125 μg/ml, respectively, but >32 μg/ml against Clostridium ramosum and Clostridium innocuum. MIC(90) for S. pyogenes and other streptococci was 16 and >32 μg/ml, respectively. LFF571 and fidaxomicin were generally less active against Gram-negative anaerobes.
LFF571 是一种新型的 GE2270A 类似物,通过与蛋白质合成延伸因子 Tu 高亲和力结合来抑制细菌生长,我们测定了其对 50 株艰难梭菌和 630 株其他肠道来源的厌氧和需氧菌的体外活性。LFF571 对艰难梭菌和大多数其他革兰氏阳性厌氧菌(MIC90,≤0.25μg/ml)具有强大的活性,但双歧杆菌和乳杆菌除外。需氧菌(包括肠球菌、金黄色葡萄球菌(包括耐甲氧西林金黄色葡萄球菌[MRSA]分离株)、化脓性链球菌和其他链球菌)的 MIC90 分别为 0.06、0.125、2 和 8μg/ml。相比之下,非达霉素对革兰氏阳性菌的活性存在差异:对艰难梭菌、梭状芽孢杆菌和双歧杆菌的 MIC90 分别为 0.5、≤0.015 和 0.125μg/ml,但对脆弱拟杆菌和无动力拟杆菌的 MIC90 >32μg/ml。对化脓性链球菌和其他链球菌的 MIC90 分别为 16 和>32μg/ml。LFF571 和非达霉素对革兰氏阴性厌氧菌的活性通常较低。