The Impact of Copper Ions on the Activity of Antibiotic Drugs

Abstract

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.

Metronidazole Interaction with Cu2+ and Zn2+: Speciation Study in Aqueous Solution and Biological Activity Evaluation

“… 20 Furthermore, it has recently been pointed out that Cu + and Cu 2+ have a significant impact on antibiotic activity. 23 There is growing interest in Cu 2+ complexes, as it has been shown that they can prevent or even reverse antimicrobial resistance to classical antibiotics. 23 − 26 To date, there appear to be few studies on in vitro to in vivo translation, which is attributed to the lack of knowledge of the molecular mechanisms underlying Cu 2+ –antibiotic interactions under physiological conditions.…”

“… 23 There is growing interest in Cu 2+ complexes, as it has been shown that they can prevent or even reverse antimicrobial resistance to classical antibiotics. 23 − 26 To date, there appear to be few studies on in vitro to in vivo translation, which is attributed to the lack of knowledge of the molecular mechanisms underlying Cu 2+ –antibiotic interactions under physiological conditions. 23 So far, the exact mechanism for bacterial damage caused by Cu 2+ has not been fully explained.…”

“… 23 − 26 To date, there appear to be few studies on in vitro to in vivo translation, which is attributed to the lack of knowledge of the molecular mechanisms underlying Cu 2+ –antibiotic interactions under physiological conditions. 23 So far, the exact mechanism for bacterial damage caused by Cu 2+ has not been fully explained. Therefore, the aim of this study is to verify the ability of MNZ (or L, which indicates “ligand”) to form complexes with Cu 2+ and Zn 2+ ions and to demonstrate that complexation allows for increased drug bioactivity.…”