The war against bacteria, from the past to present and beyond

Introduction: : The human defense against microorganisms dates back to the ancient civilizations, with attempts to use substances from vegetal, animal or inorganic origin to fight infections. Today, the emerging threat of multidrug-resistant bacteria highlights the consequences of antibiotics inappropriate use, and the urgent need of novel effective molecules. Methods and materials: We extensively researched on more recent data within the databases PubMed, Medline, Web of Science, Elsevier's EMBASE, Cochrane Review for the modern pharmacology in a period ranging from 1987 until 2021. Furthermore, the historical evolution was defined through a detailed analysis of past studies on the significance of medical applications in the ancient therapeutic field. Areas covered: To examine history of antibiotics development and discovery, the most relevant biochemical aspects of their mode of action, and the biomolecular mechanisms conferring bacterial resistance to antibiotics. Expert opinion: : The list of pathogens showing low sensitivity or full resistance to most currently available antibiotics is growing worldwide. Long after the "golden age" of antibiotic discovery, the most novel molecules should be carefully reserved to treat serious bacterial infections of susceptible bacteria. A correct diagnostic and therapeutic procedure can slow down the spreading of nosocomial and community infections sustained by multidrug-resistant bacterial strains.