A Victory for Natural Product Anti-infectivesPosted 7/21/11 by Neal Connors. Filed under News and Updates.
I read in Fierce Biotech’s April 6, 2011 e-newsletter that an FDA advisory committee has recommended approval of San Diego-based Optimer Pharmaceutical’s fidaxomicin, a narrow spectrum antibacterial for the treatment of Clostridium difficile infections. C. difficile is responsible for 20% of antibiotic-associated diarrhea cases in hospitals.
Full FDA approval of a drug usually follows a positive review from its advisory committees. Approval of any new antibiotic is welcome news given the increase in resistant pathogens. However as a natural product “geek”, I was thrilled to learn that fidaxomicin is a natural product produced by fermentation of Dactylosporangium aurantiacum subspecies hamdenesis.
If I have done my homework correctly, this class of RNA polymerase inhibitors was originally discovered by Abbot Laboratories in the late 1980s and referred to as the tiacumicins (J. Antibiot. 40:567-574 and J. Antibiot. 40:575-588). The tiacumicins have a core, unsaturated 18-membered macrolide ring and seven-carbon and 6-deoxy sugars. MICs vs C. difficile are in the sub-µg/ml range with a very low resistance frequency (Antimicrobial Agents and Chemotherapy 35:1108-1111).
At every SIM meeting, the praises of natural products are sung yet natural product discovery efforts at “big pharma” have all but disappeared and it seems that some decent natural product antibiotics became collateral damage to the dismantling of these research programs. I am not certain how prevalent C. difficile infections were in the late 1980s and early 1990s but presently it is a medical concern and it is nice to see a natural product rescued by Optimer and soon made available to patients. This news serves to remind us that useful natural product drugs are still out there to be found or, in the case of fidaxomicin, waiting to be re-born.
About Neal Connors
Dr. Neal Connors is currently the owner/president of Phoenix BioConsulting, LLC (www.phoenixbioconsulting.com); a company providing consulting services to the fermentation, industrial microbiology, biotechnology, and legal sectors.