抗生素概论(英文教学)Review of Antibiotics教程文件.pptVIP

* Slide 2. The tetracyclines are a well-established class of antibiotics that have had a role in treating microbial infections since the 1940s.1 Widespread emergence of bacterial resistance to tetracyclines, which is associated with efflux pump and ribosomal protection mechanisms, has severely limited their effectiveness. A new class of antibiotics, the glycylcyclines, has been developed to overcome bacterial resistance to tetracyclines. Tigecycline, brand name TYGACIL?, is the first agent in this new class of antimicrobial agents to undergo testing in randomized, large-scale, double-blind, active-comparator–controlled clinical trials. Tigecycline is a semisynthetic derivative of minocycline. It was discovered after other attempts to add substituents to the C-9 position of minocycline led to compounds with poor antibacterial activity.2 Tigecycline is formed by addition of a tert-butyl-glycylamido group to the C-9 position of minocycline.3 This glycylcycline, the first commercially available in its class, possesses the broad spectrum of activity that was typical of tetracyclines, and expands the spectrum by adding activity against tetracycline-resistant bacteria.3,4 The addition of activity against tetracycline-resistant bacteria is a result of tigecycline’s insensitivity to bacteria that express tet gene products, which are responsible for antibiotic resistance due to efflux pumps and ribosomal protection mechanisms.5 Glycylcyclines, which include tigecycline, have 5 times higher affinity for the 30S ribosome than tetracycline.6 Tigecycline binds to additional sites on the 30S ribosome.7 References Chopra I. New developments in tetracycline antibiotics: glycylcyclines and tetracycline efflux pump inhibitors. Drug Resist Updates. 2002;5:119-125. Chopra I, Roberts M. Tetracycline antibiotics: mode of action, applications, molecular biology, and epidemiology of bacterial resistance. Microbiol Mol Biol Rev. 2001;65:232-260. Tygacil? (tigecycline) Pres