The antibiotic pipeline: What can we expect?
Ursula Theuretzbacher · International Journal of Infectious Diseases · 2016
Abstract: Antibiotic resistance is widespread. Despite the recognized and growing need for new antibiotics, today most large pharmaceutical companies have dropped active antibacterial drug discovery programmes. While antibiotics are regarded as non-profitable compared to other fields, small companies—mostly backed by promising academic discoveries—are stepping in to drive research and early clinical development in the antibiotics field. In the 1980s and 90s the antibiotic pipelines were satisfying the need for improved antibiotics against the prevalent resistant strains at that time. Currently, extensively- or pan-resistant Gram-negative bacteria require novel antibiotics without co- and cross-resistance to known drug classes. A few research&development programs based on classical antibacterial compounds against Gram-negative bacteria that bind to new targets or have a new mode of action are in the early research phase and their potential is difficult to assess. Due to such thin discovery pipelines, attitudes have changed and antibacterial approaches outside the mainstream are increasingly pursued and publicly funded. These alternative methodologies range from peptides and peptidomimetics to antibodies, prophylactic and therapeutic vaccines, adjunctive therapies, bacteriophage cocktails. The value of such approaches as well as the regulatory pathways are not clear yet. Potentiating strategies have seen a resurgence in recent years and are focused on blocking specific resistance mechanisms such as beta-lactamases, resistance-regulating determinants, preventing transfer of resistance plasmids or on protecting the microbiome, disrupting biofilms, targeting dormant bacteria, blocking virulence factors, or supporting the immune system. In response to relaxed regulatory requirements and economic incentives, recent years have seen a trend towards reviving old drugs (e.g. fosfomycin, fusidic acid, minocycline, aztreonam), modifying old drugs (e.g. colistin) or potentiating old drugs (e.g. combination of approved drugs, ß-lactamase-inhibitor combinations). These approaches will not solve our major problems with resistant bacteria but may buy some time.