Development of metals as antimicrobials: knowledge gaps and future directions

We now find ourselves in the antimicrobial resistance era, where antibiotic-resistant bacteria are of increasing concern, leading to a need for new and novel antimicrobial agents. Unfortunately, interest in developing new antibiotics in the pharmaceutical industry has dwindled over the decades. Regardless, academic researchers over the past decade have made strides in exploring alternative options, and out of this, we see the field revisiting historical infection control agents. From this, we now see a field of research exploring the efficacy of metal-based antimicrobials (MBAs) and metalloantibiotics. These antimicrobial agents are formulated as metal salts, alloys, metal complexes, organometallics, and nanomaterials. Many effective formulations have been developed for various applications in which metals are used as antimicrobials that are effective against antibiotic-resistant strains. This critical opinion focuses on the use of metal salts as antimicrobial and antibiofilm treatments. The review identifies potential misinterpretations of mechanisms, knowledge gaps, areas that have been overlooked, and potential ideas to move forward. The goal here is to understand the challenges of dissecting the primary and secondary modes of action of MBAs to formulate effective antimicrobials containing metal elements. Finally, parameters that metal formulations must meet to become successful treatments without falling to the same fate as antibiotics are suggested.