Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
Life Sciences Department, Institute for Multidisciplinary Research, University of Belgrade, Kneza Višeslava 1, 11000 Belgrade, Serbia.
Molecules. 2023 Jun 30;28(13):5133. doi: 10.3390/molecules28135133.
Copper (Cu) is an essential trace metal and its concentration in body plasma is tightly regulated. An increase in Cu concentration in body fluids is observed in numerous pathological conditions, including infections caused by microorganisms. Evidence shows that Cu ions can impact the activity of antibiotics by increasing efficiency or diminishing/neutralizing antibiotic activity, forming complexes which may lead to antibiotic structure degradation. Herein, we represent the evidence available on Cu-antibiotic interactions and their possible impact on antimicrobial therapy efficiency. So far, in vitro studies described interactions between Cu ions and the majority of antibiotics in clinical use: penicillins, cephalosporins, carbapenems, macrolides, aminoglycosides, tetracyclines, fluoroquinolones, isoniazid, metronidazole. In vitro-described degradation or lower antimicrobial activity of amoxicillin, ampicillin, cefaclor, ceftriaxone, and meropenem in the presence of Cu ions suggest caution when using prescribed antibiotics in patients with altered Cu levels. On the other hand, several Cu-dependent compounds with antibacterial activity including the drug-resistant bacteria were discovered, such as thiosemicarbazones, disulfiram, dithiocarbamates, 8-hydroxiquinoline, phenanthrolines, pyrithione. Having in mind that the development of new antibiotics is already marked as inadequate and does not meet global needs, the potential of Cu-antibiotic interactions to change the efficiency of antimicrobial therapy requires further investigation.
铜(Cu)是一种必需的微量元素,其在血浆中的浓度受到严格调节。在许多病理情况下,包括由微生物引起的感染,都会观察到体液中铜浓度的增加。有证据表明,Cu 离子可以通过提高效率或削弱/中和抗生素活性,形成可能导致抗生素结构降解的复合物,从而影响抗生素的活性。本文介绍了 Cu-抗生素相互作用的证据及其对抗菌治疗效率的可能影响。到目前为止,体外研究描述了 Cu 离子与大多数临床使用的抗生素之间的相互作用:青霉素类、头孢菌素类、碳青霉烯类、大环内酯类、氨基糖苷类、四环素类、氟喹诺酮类、异烟肼、甲硝唑。体外描述的阿莫西林、氨苄西林、头孢克洛、头孢曲松和美罗培南在 Cu 离子存在下的降解或抗菌活性降低表明,在 Cu 水平改变的患者中使用规定的抗生素时应谨慎。另一方面,发现了一些具有抗菌活性的 Cu 依赖性化合物,包括耐药菌,如噻唑烷酮、双硫仑、二硫代氨基甲酸盐、8-羟基喹啉、菲咯啉、吡啶硫酮。考虑到新抗生素的开发已经明显不足,无法满足全球需求,Cu-抗生素相互作用改变抗菌治疗效率的潜力需要进一步研究。