Combating Multidrug-Resistant Bacteria: Current Strategies for the Discovery of Novel Antibacterials

The introduction of effective antibacterial therapies for infectious diseases in the mid‐20th century completely revolutionized clinical practices and helped to facilitate the development of modern medicine. Many potentially life‐threatening conditions became easily curable, greatly reducing the incidence of death or disability resulting from bacterial infections. This overwhelming historical success makes it very difficult to imagine life without effective antibacterials; however, the inexorable rise of antibiotic resistance has made this a very real and disturbing possibility for some infections. The ruthless selection for resistant bacteria, coupled with insufficient investment in antibacterial research, has led to a steady decline in the efficacy of existing therapies and a paucity of novel structural classes with which to replace them, or complement their use. This situation has resulted in a very pressing need for the discovery of novel antibiotics and treatment strategies, the development of which is likely to be a key challenge to 21st century medicinal chemistry. Resistance is futile: With bacterial resistance on the rise, a number of approaches are currently being explored to ensure that new drugs are being brought to the clinic. It is necessary for the next generation of antibacterials to not only have an improved drug profile but also overcome the latest bacterial resistance mechanisms. Insight into the current strategies being developed is discussed, in particular recent research within the area of quinolone quorum sensing modulators.