Emergence of resistance during therapy with the newer beta-lactam antibiotics: role of inducible beta-lactamases and implications for the future.
Emergence of resistance during therapy with the newer beta-lactam antibiotics: role of inducible beta-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。
DOI：
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发表时间：
1983
期刊：
影响因子：
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通讯作者：
W. Sanders
中科院分区：
文献类型：
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作者：
C. Sanders;W. Sanders
一些对β-内酰胺酶具有相对耐受性的β-内酰胺类抗生素已经开发出来。这一特性使药物的抗菌谱超出了其前体药物的抗菌谱。然而，它似乎也是新药观察到的几个问题的原因，包括微生物对多种β-内酰胺类抗生素的交叉耐药性的发展，偶尔对氨基糖苷类抗生素的交叉耐药性。最常见的菌株是肠杆菌、沙雷氏菌和假单胞菌--具有诱导β-内酰胺酶特征的属。这些酶的解阻抗是导致对多种β-内酰胺类抗生素产生耐药性的机制之一。由于在大多数情况下，药物不容易被这些酶水解，因此耐药性是由非水解性屏障机制产生的；即，β-内酰胺酶结合药物，从而阻止它们接触目标蛋白。通透性和青霉素结合蛋白的改变是其他可能的耐药机制；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，潜在的问题还包括作为医院病原体的多重β-内酰胺耐药菌株的影响，以及联合使用β-内酰胺类抗生素之间的拮抗。只有通过仔细评估这些新的β-内酰胺类抗生素的相对优势和劣势，才能确定它们在化疗和化学预防中的适当位置。
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.