Alfa Institute of Biomedical Sciences (AIBS), 9 Neapoleos Street, 151 23 Marousi, Athens, Greece.
Expert Opin Pharmacother. 2013 Aug;14(12):1585-97. doi: 10.1517/14656566.2013.806486. Epub 2013 Jun 8.
Aminoglycosides are of the oldest antibiotics. Even though representatives of the class are used in various applications, the use that has established aminoglycosides in medicine is their antimicrobial activity.
Current knowledge on mechanism of action, adverse events, strategies to overcome toxicity and increase efficacy of aminoglycosides, as well as therapeutic uses and future perspectives of this class of antibiotics.
Aminoglycosides are still the treatment of choice for diseases such as brucellosis and plague. Toxicity, along with the discovery of equally potent and less toxic antibiotics, has shelved aminoglycosides the past 30 years. However, this has largely saved them from resistance development. Apart from retaining efficacy, strategies to overcome toxicity, especially once daily administration, has made aminoglycosides a safer choice. Further, plazomicin is a very promising synthetic aminoglycoside that escapes all clinically significant aminoglycoside-modifying enzymes and has completed a clinical Phase II trial. Despite being in clinical practice for > 60 years, issues such as the synergistic role of aminoglycosides in Gram-positive endocarditis remain controversial. Prospective randomized trials are needed to clarify the benefit of aminoglycosides in this setting. Nonetheless, in an era of emerging resistance, aminoglycosides are valuable weapons against multidrug-resistant pathogens.
氨基糖苷类抗生素是最古老的抗生素之一。尽管该类别的代表药物在各种应用中都有使用,但使氨基糖苷类抗生素在医学中确立地位的是其抗菌活性。
目前关于氨基糖苷类抗生素的作用机制、不良反应、克服毒性和提高疗效的策略,以及该类抗生素的治疗用途和未来前景的相关知识。
氨基糖苷类抗生素仍然是治疗布鲁氏菌病和鼠疫等疾病的首选药物。毒性以及同样有效但毒性较低的抗生素的发现,使得氨基糖苷类抗生素在过去 30 年中被搁置。然而,这在很大程度上使它们免受耐药性的发展。除了保持疗效外,克服毒性的策略,特别是每日一次的给药,使氨基糖苷类抗生素成为更安全的选择。此外,普拉佐米星是一种很有前途的合成氨基糖苷类抗生素,它能逃避所有临床上重要的氨基糖苷类修饰酶,并且已经完成了 II 期临床试验。尽管氨基糖苷类抗生素已经在临床实践中使用了超过 60 年,但氨基糖苷类抗生素在革兰氏阳性心内膜炎中的协同作用等问题仍然存在争议。需要前瞻性随机试验来阐明在这种情况下氨基糖苷类抗生素的益处。尽管如此,在出现新的耐药性的时代,氨基糖苷类抗生素仍是对抗多药耐药病原体的有效武器。