In 2013, the Centers for Disease Control and Prevention (CDC) published a report on the burden and threats of antibiotic-resistant germs (CDC, 2013a). Bacteria resistant to different classes of antibiotics rapidly emerge worldwide and endanger the efficacy of antimicrobial. This resistance crisis can mostly be attributed to the overuse and misuse of antibiotics, but also to the lack of innovation and new drug development. Antibiotic research is not any longer attractive to the pharmaceutical industry, higher profits are made with new anti-cancer therapies and with other chronic conditions such as diabetes. “If we’re not careful, we will soon be in a post antibiotic era” (CDC, 2013b). What are the reasons for the decline in this field of research and are there any advancements in antibiotic drug research and development?
The era of antibiotics started in 1928 with the discovery of penicillin by Sir Alexander Fleming (Fleming, 1929). They should revolutionize modern medicine and increase general life expectancy. However, shortly after the introduction of penicillin, penicillin resistance in bacteria emerged and should become a substantial clinical problem. Discovery of new beta-lactam antibiotics such as methicillin in the 1960s only temporarily restored confidence, as antibiotic related resistance developed shortly after; the first case of methicillin-resistant Staphylococcus aureus (MRSA) in 1962 in the UK. This mêlée of antibiotic introduction and antibiotic resistance should go on for decades to come and still is happening at present day.
Causes of antibiotic resistance are diverse. Mostly, they are a result of overuse and misuse. Often, wrong antibiotics are prescribed and duration of antibiotic therapy is faulty. Overuse of antibiotics in agriculture to promote growth of farm animals and to prevent infectious diseases additionally contributes to increased resistance. Unfortunately, we are standing against this resistance with only few new antibiotics. The development of new antibiotics by pharmaceutical companies and academia slowed over the past decade due to funding cuts and due to being considered unprofitable. While 19 new antibiotics were approved in between 1980 and 1984, only 6 were approved by the Food and Drug Administration (FDA) since 2010. Many big pharma companies pulled out of research and the companies left didn’t do much progress. Thus, a combination of poor prospect and profit, as well as difficulties in getting regulatory approval slowed down the field.
Nevertheless, there has been a recent revive in antibiotic R&D and several antibiotics are in the pipeline for clinical trials. These include a variety of classes of antibiotics such as aminoglycosides, tetracyclines and beta-lactamase inhibitors. But also new approaches are being investigated (e.g. inhibiting endotoxin production by germs), as well as new sources of natural antibiotics. Teixobactin for instance was isolated from Eleftheria terrae and represents a new class of antibiotic that inhibits cell wall synthesis (Ling et al., 2015).
References, recommended articles in bold
Blog written by Lucas Kraft
CDC. (2013a). Antibiotic Resistance Threats in the United States, 2013. Retrieved from https://www.cdc.gov/drugresistance/threat-report-2013/index.html
CDC. (2013b). CDC Telebriefing on today’s drug-resistant health threats (press briefing transcript). Retrieved from https://www.cdc.gov/media/releases/2013/t0916_health-threats.html
Fleming, A. (1929). On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of B. influenzae. 1929. British Journal of Experimental Pathology, 10(3), 226–236. http://doi.org/10.1038/146837a0
Ling, L. L., Schneider, T., Peoples, A. J., Spoering, A. L., Engels, I., Conlon, B. P., … Lewis, K. (2015). A new antibiotic kills pathogens without detectable resistance. Nature, 517(7535), 455–459. http://doi.org/10.1038/nature14098
Ventola, C. L. (2015a). The antibiotic resistance crisis: part 1: causes and threats. P & T : A Peer-Reviewed Journal for Formulary Management, 40(4), 277–83. http://doi.org/Article
Ventola, C. L. (2015b). The antibiotic resistance crisis: part 2: management strategies and new agents. P & T : A Peer-Reviewed Journal for Formulary Management, 40(5), 344–52. Retrieved from http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4422635&tool=pmcentrez&rendertype=abstract