Emergence of resistance during therapy with the newer β-lactam antibiotics: role of inducible β-lactamases and implications for the future
Emergence of resistance during therapy with the newer β-lactam antibiotics: role of inducible β-lactamases and implications for the future
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使用新型 β-内酰胺抗生素治疗期间出现耐药性：诱导型 β-内酰胺酶的作用及其对未来的影响
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发表时间：
1983
期刊：
影响因子：
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通讯作者：
Sanders We
中科院分区：
文献类型：
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作者：
C. Sanders;Sanders We
许多β -内酰胺类抗生素已经被开发出来，它们对β -内酰胺酶的水解具有相对的抗性。这一特性扩大了药物的抗菌谱，超出了它们的前身。然而，它似乎也导致了新药物的几个问题，包括微生物对多种β -内酰胺类抗生素的交叉耐药，偶尔也对氨基糖苷类产生耐药性。最常涉及的菌株是肠杆菌、沙雷氏菌和假单胞菌属，它们具有特征性的诱导型内酰胺酶。这些酶的抑制是对多种β -内酰胺类抗生素产生耐药性的一种机制。由于在大多数情况下药物不容易被这些酶水解，抗性是由非水解屏障机制产生的；也就是说，β -内酰胺酶与药物结合，从而阻止它们接近目标蛋白质。渗透性和青霉素结合蛋白的改变是产生耐药性的其他可能机制；然而，这些还没有得到广泛的研究。除了出现耐药性的问题外，潜在的问题还包括多重-内酰胺耐药菌株作为医院病原体的影响以及联合使用-内酰胺类抗生素之间的拮抗作用。只有通过仔细评估这些新型β -内酰胺类抗生素的相对优缺点，才能确定它们在化疗和化疗预防中的适当地位。
A number of beta-lactam antibiotics that are relatively resistant to hydrolysis by beta-lactamases have been developed. This characteristic has expanded the antibacterial spectrum of the drugs beyond that of their progenitors. However, it also appears responsible for several problems that have been observed with the new drugs, including the development of microbial cross-resistance to multiple beta-lactam antibiotics and occasionally to the aminoglycosides. Strains most often involved are Enterobacter, Serratia, and Pseudomonas-genera that characteristically possess inducible beta-lactamases. Derepression of these enzymes is one mechanism shown to be responsible for the development of resistance to multiple beta-lactam antibiotics. Since in most instances the drugs are not susceptible to hydrolysis by these enzymes, resistance is produced by a nonhydrolytic barrier mechanism; i.e., the beta-lactamases bind the drugs, thus preventing their access to target proteins. Alterations in permeability and in penicillin-binding proteins are other possible mechanisms by which resistance may develop; however, these have not been investigated extensively. In addition to the problem of emergence of resistance, potential problems include the impact of multiply beta-lactam-resistant strains as nosocomial pathogens and antagonism between beta-lactam antibiotics used in combination. Only through a careful assessment of the relative advantages and disadvantages of these new beta-lactam antibiotics can their appropriate place in chemotherapy and chemoprophylaxis be identified.