Alván G, Nord C E
Department of Clinical Pharmacology, Huddinge University Hospital, Karolinska Institute, Stockholm, Sweden.
Drug Saf. 1995 May;12(5):305-13. doi: 10.2165/00002018-199512050-00003.
Monobactams and carbapenems are 2 classes of beta-lactam antibiotics that were introduced in the 1980s. This review considers the monobactam aztreonam and the carbapenems imipenem and meropenem. Imipenem is administered together with cilastatin, which inhibits the enzymatic breakdown of imipenem in the kidney. The antibacterial activities of these drugs are quite different from older beta-lactams. Aztreonam is directed towards aerobic Gram-negative bacteria, especially Pseudomonas aeruginosa, while imipenem and meropenem are active against both aerobic and anaerobic Gram-positive and Gram-negative bacteria. Thus, these drugs should be reserved for patients who have a special need for them. They are also structurally different from older beta-lactams and possess different adverse drug reaction profiles. It was initially suggested that aztreonam would be less immunogenic than previous beta-lactams because reactive breakdown products acting as haptens are less likely to be formed. Clinical reports now support this assumption, and, in particular, cross hypersensitivity between aztreonam and other beta-lactams seems to be rare which makes the drug a useful therapeutic alternative. However, hypersensitivity to aztreonam does occur. The predominant concern in terms of adverse reactions to imipenem/cilastatin is the increased tendency to cause seizures compared with other beta-lactams. The risk of producing a seizure is highly associated with inadequate dose adjustment in relation to kidney function. If appropriate care is taken, seizures occur in less than 1% of patients treated. However, it is possible that concomitant administration of other drugs with neurotoxic profiles (e.g. theophylline and cyclosporin) given in overdose, may increase the risk of seizures.(ABSTRACT TRUNCATED AT 250 WORDS)
单环β-内酰胺类抗生素和碳青霉烯类抗生素是20世纪80年代引入的两类β-内酰胺抗生素。本综述探讨了单环β-内酰胺类抗生素氨曲南以及碳青霉烯类抗生素亚胺培南和美罗培南。亚胺培南与西司他丁联合使用,西司他丁可抑制亚胺培南在肾脏中的酶解。这些药物的抗菌活性与较老的β-内酰胺类抗生素有很大不同。氨曲南主要针对需氧革兰氏阴性菌,尤其是铜绿假单胞菌,而亚胺培南和美罗培南对需氧和厌氧革兰氏阳性菌及革兰氏阴性菌均有活性。因此,这些药物应保留给有特殊需求的患者。它们在结构上也与较老的β-内酰胺类抗生素不同,且具有不同的药物不良反应谱。最初有人认为氨曲南的免疫原性低于先前的β-内酰胺类抗生素,因为作为半抗原的反应性分解产物形成的可能性较小。现在的临床报告支持这一假设,特别是氨曲南与其他β-内酰胺类抗生素之间的交叉过敏似乎很少见,这使得该药成为一种有用的治疗选择。然而,对氨曲南的过敏反应确实会发生。与其他β-内酰胺类抗生素相比,亚胺培南/西司他丁不良反应方面的主要问题是引起癫痫发作的倾向增加。癫痫发作的风险与肾功能剂量调整不当高度相关。如果采取适当的护理措施,接受治疗的患者中癫痫发作的发生率不到1%。然而,过量使用其他具有神经毒性的药物(如茶碱和环孢素)可能会增加癫痫发作的风险。(摘要截取自250字)