Thomson Jodi M, Bonomo Robert A
Department of Pharmacology, Case Western Reserve University School of Medicine Louis Stokes Cleveland Veterans Affairs Medical Center, 10701 East Boulevard, Cleveland, OH 44106, USA.
Curr Opin Microbiol. 2005 Oct;8(5):518-24. doi: 10.1016/j.mib.2005.08.014.
Beta-lactam antibiotics are the cornerstone of our antibiotic armamentarium. By inhibiting bacterial cell wall synthesis, they are highly effective against Gram-positive and Gram-negative bacteria. Unfortunately, bacteria have evolved sophisticated resistance mechanisms to combat the lethal effects of beta-lactam antibiotics. Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae are all able to evade killing by penicillins, cephalosporins and carbapenems. This multi-drug resistant phenotype that challenges health care workers worldwide is caused by an array of resistance determinants. These include altered expression of outer membrane proteins and efflux pumps, along with an increasing arsenal of beta-lactamases. Future strategies in beta-lactam design must take into account the complex nature of resistance in Gram-negative pathogens.
β-内酰胺类抗生素是我们抗生素库的基石。通过抑制细菌细胞壁合成，它们对革兰氏阳性菌和革兰氏阴性菌都非常有效。不幸的是，细菌已经进化出复杂的耐药机制来对抗β-内酰胺类抗生素的致死作用。铜绿假单胞菌、鲍曼不动杆菌和肺炎克雷伯菌都能够逃避青霉素、头孢菌素和碳青霉烯类药物的杀伤。这种挑战全球医护人员的多重耐药表型是由一系列耐药决定因素引起的。这些因素包括外膜蛋白和外排泵表达的改变，以及越来越多的β-内酰胺酶。未来β-内酰胺类药物设计策略必须考虑革兰氏阴性病原体耐药性的复杂性质。
