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[摘要]：Solithromycin (CEM-101, OP-1068) is the first fluoroketolide in clinical development and belongs to the macrolide antibiotic class. It has broad-spectrum activity against macrolide- and ketolide-resistant bacteria. In addition, it has activity against community-acquired inducibly methicillin-resistant Staphylococcus aureus, enterococci, including vancomycin -resistant enterococci, gonococci, atypical bacteria such as Legionella spp., Myco plasma spp., Urea plasma spp. and Chlamydia spp., Mycobacterium avium-intracellulare (MAC) complex, including extensively drug-resistant strains, Plasmodium vivax and Plasmodium falciparum, including azithromycin-resistant strains, and it was curative against Plasmodium berghei in a murine model. Unlike telithromycin, solithromycin does not significantly inhibit nicotinic acetylcholine receptors. Solithromycin has also been shown to be a potent inhibitor of cytokine (TNF-alpha and IL-8) release and matrix metalloproteinase (MMP) expression, which has been correlated with the antiinflammatory effects of older macrolides. Solithromycin has been well tolerated in phase I studies, with high plasma, tissue and intracellular concentrations. The compound does not have the significant gastrointestinal motility or bitter taste concerns associated with other macrolides. Oral capsule formulations are being tested in phase II clinical trials for community-acquired bacterial pneumonia and an intravenous formulation, which appears to be well tolerated to date, is currently in phase I studies. |
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