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抗菌化疗的当前趋势(作者译)

[Current trends in antibacterial chemotherapy (author's transl)].

作者信息

Bergogne-Berezin E

出版信息

Nouv Presse Med. 1980 Oct 25;9(39):2909-14.

PMID:7443422
Abstract

Antibiotics account for about 15% of world pharmaceutical consumption, but with the rapid development of antibacterial agents capable of reaching most bacterial cell target structures, many bacterial species have become resistant, including S. pneumoniae, H. influenzae and N. gonorrhoeae, which until recently had remained susceptible to penicillin. Moreover, intrinsically resistant species have been selected and are now responsible for nosocomial infections. These shortcomings of chemotherapy, as well as the toxicity and side-effects of a number of drugs, have prompted a search for antibiotics with wider spectrum, lesser sensitivity to bacterial enzymes, reduced toxicity and improved pharmacokinetic properties. During the last 20 years, attempts to extract new antibiotics from natural sources have met with little success, but considerable progress has been achieved in the hemisynthesis of known molecules, such as 6-aminopenicillanic acid or 7-aminocephalosporanic acid, and various changes in these molecules have yielded a variety of new beta-lactam compounds, some of which being still under study and other in clinical use. Changes in the original aminoglycoside molecules have also produced compounds that are less toxic and less susceptible to inactivating enzymes. Among macrolides and sulfonamides, recent developments, although limited, have led to new products or to synergistic combinations. Finally, the search for new compounds which would inhibit two successive steps in the bacterial metabolic pathways constitutes a modern, rational and promising approach to antibacterial chemotherapy.

摘要

抗生素约占全球药品消费量的15%,但随着能够作用于大多数细菌细胞靶结构的抗菌剂迅速发展,许多细菌种类已产生耐药性,包括肺炎链球菌、流感嗜血杆菌和淋病奈瑟菌,这些细菌直到最近对青霉素仍敏感。此外,固有耐药菌已被筛选出来,现在是医院感染的罪魁祸首。化疗的这些缺点以及许多药物的毒性和副作用,促使人们寻找具有更广泛抗菌谱、对细菌酶敏感性较低、毒性降低且药代动力学性质改善的抗生素。在过去20年中,从天然来源提取新抗生素的尝试收效甚微,但在已知分子如6-氨基青霉烷酸或7-氨基头孢烷酸的半合成方面取得了相当大的进展,这些分子的各种变化产生了多种新的β-内酰胺化合物,其中一些仍在研究中,另一些已在临床使用。原始氨基糖苷类分子的变化也产生了毒性较小且不易被灭活酶作用的化合物。在大环内酯类和磺胺类药物中,尽管进展有限,但最近的发展已产生了新产品或协同组合。最后,寻找能够抑制细菌代谢途径中两个连续步骤的新化合物,构成了一种现代、合理且有前景的抗菌化疗方法。

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