9.5E: Finding New Antimicrobial Drugs
Antimicrobial resistance has created a public health crisis in the treatment of infectious diseases and necessitates the discovery of new drugs.
Learning Objectives
- Explain the reasons for low production of new antibiotics and discuss the proposed mechanisms to evade antimicrobial resistance
Key Points
- Finding new antimicrobial drugs requires researchers, pharmaceutical, and biotech companies to invest in new technology and discover new sources for antibiotic development.
- Proposed mechanisms to circumvent antimicrobial resistance range from exploring the list of resistance genes to antibody-based therapy and vaccines.
- Finding new candidates to target is essential but it needs to be accompanied by awareness on antibiotic misuse with the prospect to eliminate the root of the problem.
Key Terms
- mimetic : A substance with similar pharmacological effects to another substance.
Antimicrobial resistance: the problem
Antibiotics, more than any other medicines, have improved the life expectancy of mankind, however, multi-drug resistance has become common in pathogenic bacteria and multiple drugs are losing efficacy. Recent reports on the occurrence of panresistant gram-negative strains, i.e. strains resistant to every registered antibacterial drug, indicate that we are on the verge to lose the battle, taking us back to the pre-antibiotic era. There is world-wide consensus that the medical need for novel antiinfective drugs is enormous and that we are running out of time. Many achievements of modern medicine, not only treatment of infectious diseases, depend on the availability of efficacious antibiotics, still, the antibacterial development pipeline is slow and the number of new drugs reaching the market is alarmingly low. There are many reasons for this at all levels of the discovery and development process. Investments into antibiotic research and technologies is minimal; socioeconomic considerations together with regulatory hurdles have prompted pharmaceutical companies to exit the field and innovative biotech companies were confronted with problems beyond their control. Answers are needed as to where and how we can find new lead compounds with unprecedented activities?
Finding new antimicrobial drugs: the solution
Research on new antimicrobial compounds is geared towards innovative targets to circumvent resistance. Some of the proposed areas to investigate include: collecting and examining the list of antimicrobial resistance genes (e.g. exploring the resistome), targeting teichoic acid biosynthesis as a new method to compromise the bacterial wall integrity, producing ribosomal inhibitors to target protein synthesis, targeting outer-membrane transporters with protein epitope mimetics (e.g. mimetics of the cationic antimicrobial peptides that form part of the immune response to microbes), and developing antibody-based strategies and vaccines. Using bacteriophages for treatment of bacterial infection has also seen renewed interest and promise in recent years. In some cases, alternative treatments such as re-establishing normal flora can be extremely effective. For instance, fecal transplants have become a standard treatment for Clostridium difficile infections over the past decade or so.
The initiative to develop new antimicrobial agents is urgently needed but is a long process from invention, to development, to actual clinical application. It is also necessary to initiate a worldwide awareness on antibiotic misuse and overuse as a mean to address the root of the problem for antimicrobial resistance.