1. Introduction
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The discovery of antibiotics was one of the greatest achievements in medicine of the twentieth century. Their introduction into clinical use reduced morbidity and mortality driven by bacterial infections. From the 1930s to the 1960s, the number of newly identified antibiotics reached its peak; therefore, this period is regarded as the “Golden Age of Antibiotics”. At the same time, strains of antibiotic-resistant bacteria were observed [1]. In the following decades, the overuse and/or misuse of different antimicrobial agents—which has been accelerated by overprescribing antibiotics by clinicians as well as by their widespread use in industry, including animal husbandry and agriculture branches—led to the uncontrolled spread of antibiotic resistance throughout the microbe populations. The most virulent, nosocomial, multidrug-resistant pathogens of clinical importance form a group, which has been referred to as “ESKAPE”. This group includes species such as Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp., with “ESKAPE” acting as an acronym [2]. Current reports have indicated that a growing number of antibiotic-resistant microorganisms are negatively correlated with the number of effective antibiotics; no new antimicrobial agents have been introduced recently. In light of such data, it is not surprising that the World Health Organization (WHO) has recognized a constantly increasing level of antibiotic resistance, accompanied by a growing number of multidrug-resistant microbes, as a major public health threat of global concern, with the prospect of a return to the “pre-antibiotic era” [3,4]. According to the Centers for Disease Control (CDC) report, antibiotic-resistant microorganisms solely are responsible for two million illnesses in the United States per year; amongst which 23.000 are fatal [5]. Furthermore, it is estimated that ten million people could die from infections caused by antibiotic-resistant bacteria by 2050 [6].
New strategies are being implemented to overcome antimicrobial resistance, some of which focus on the research and development of antibiotics. As a result, since 2017, several new antibiotics have been developed and approved by the U.S. Food and Drug Administration (FDA) and/or the European Medical Agency (EMA) [7,8,9], including cefiderocol, ceftobiprole, rifamycin, eravacycline, sarecycline, omadacycline, plazomicin, contezolid, lefamulin, pretomanid, as well as a combination of imipenem, cilastatin, and relebactam [9]. In addition, dozens of other antimicrobial drugs that act against pathogens on the WHO priority pathogens list are currently under development [7,8,9]. Among the targets of the newly approved antibiotics are mostly the carbapenem-resistant Enterobacteriaceae (CRE), oxacillinase-48-producing Enterobacteriaceae (OXA-48), and β-lactamase-producing Enterobacteriaceae (ESBL) [7,8,9]. This review provides a brief overview of the mechanisms of action of the clinically important antibiotic groups, as well as the mechanisms underlying microbial resistance to particular antimicrobial agents. It is believed that knowledge of these mechanisms should lead to the development of new drugs or their new combinations. This, in turn, may improve the effectiveness of infection therapy caused by bacterial strains resistant to currently available antibiotics. We also briefly present promising nanomedicine-based approaches that aim to improve the efficacy of the old antibiotics, as well as current strategies that focus on searching for new ones.
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