Chpt 46中 synthesized antibiotics.pptVIP

Ⅰ. HISTORY Ⅰ. Quinolones A. Chemistry B. Antimicrobial activity The first-generation and oldest quinolones exhibit limited gram-negative activity. Nalidixic acid 萘啶酸 does not achieve systemic antibacterial levels and are thus restricted to therapy of bladder infections caused by urinary pathogens, such as E. coli and Klebsiella and Proteus spp. Although they are bactericidal agents, their use is restricted by resistance. The second-generation drugs such as pipemidic acid 吡哌酸, demonstrate their most reliable activity against gram-negative organisms, including Enterobacteriaceae. Haemophilus spp. and STD agents, such as Neisseria gonorrhoeae, Chlamydia trachomatis, Ureaplasma urealyticum溶脲脲原体, and Moraxella catarrhalis卡他莫拉菌are also susceptible. Significantly greater activity against gram-positive organisms, such as S. pneumoniae, is demonstrated by the third (Norfloxacin 诺氟沙星, 氟哌酸) and fourth(Lomefloxacin 洛美沙星) generations. Methicillin-resistant Staphylococcus aureus and Enterococcus faecium are resistant. Norfloxacin 诺氟沙星, 氟哌酸, the common used drug, is the least active of the fluoroquinolones against both G+ and G-. Ciprofloxacin环丙沙星, 环丙氟哌酸, is the most active agent of this group against gram-negatives, P aeruginosa in particular. Levofloxacin左氟沙星 has superior activity against G+ organisms, including S pneumoniae. Lomefloxacin 洛美沙星 is the most likely drug of this group in inducing photosensitive dermatitis. C. Mechanism of Action The quinolone antibiotics target bacterial DNA gyrase and topoisomerase IV. For many gram-positive bacteria, topoisomerase IV is the primary activity inhibited by the quinolones. In contrast, for many gram-negative bacteria DNA gyrase is the primary quinolone target. Inhibition of DNA gyrase prevents DNA from rewind (formation of negative supercoils) after being copied, stopping DNA and protein synthesis. I