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Steven J. Projan

from: Antibiotics: Current Innovations and Future Trends (Edited by: Sergio Sánchez and Arnold L. Demain). Caister Academic Press, U.K. (2015) Pages: 109-112.

Therapeutic antibacterial drugs are considered among the safest of pharmaceuticals but this was not always the case. Indeed prior to the discovery of penicillin and, subsequently, other antibiotics, the safety profile of antibacterial drugs more closely resembled that of today's cytotoxic, chemotherapeutic agents used in oncology with narrow therapeutic windows and considerable side effects. Today's antibiotics are, in fact, safe by design. Where agents have defined toxicities (e.g. photosensitivity induced by fluoroquinolones) they are usually class effects and, rather than "idiosyncratic" are more frequently predictable based on pharmacokinetics and tissue distribution. As newer antibacterial drugs are being designed to be more "pathogen specific" the expectation is that these future drugs will have even better safety profiles than today's therapeutics.

The common perception of antibacterial drugs is that they are very safe, very useful and very important therapeutic agents, indeed the safety and tolerability of antibacterials are, in general are among the best of all prescribed drugs. This is not a matter of chance and it was not always the case. In 1908 Paul Ehrlich shared the Novel Prize for Medicine or Physiology (with Ilya Metchnikoff) for his work on immunotherapeutics (indeed the first Nobel Prize in that category went to Emil von Behring, also for immunotherapy) but Ehrlich was unhappy both with the efficacy of immunotherapeutics as well as their safety (e.g. "serum sickness"). He embarked on a bona fide medicinal chemistry/drug discovery campaign to find novel organic molecules based on arsenical compounds that were active versus trypanosomes and spirochetes. It should be noted that at the turn of the twentieth century mercury was still being used as treatment for syphilis, a bacterial infection caused by Treponema pallidum. Even today, mercury toxicity remains an important issue. The compound that Ehrlich's group eventually discovered, arsphenamine ("606") became known as Salvarsan and was both more effective and far safer than mercury treatment (not to mention less expensive) but was not without its own safety and tolerability issues (which are a subject of controversy even today) (Baumler,1984). Eventually arsphenamine was supplanted by penicillin, where even a single, intramuscular dose was found to be effective in the early stages of the disease with a significantly better safety profile. It should be realized that today's antibacterial drugs are safe not as a matter of chance but by design; the result of decades of microbial research, the development of in vitro and animal models of infection, brute force science and inventive medicinal chemistry, and careful (as well as some careless) clinical research resulting in the successful treatment of hundreds of millions (if not billions) of people read more ...

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