Deus ex machina (Part 4): Flavonoid-like Molecules

Flavo-Noid?

When I started the Deus ex machina "meme" three weeks ago, I had no idea that so many potential novel antimicrobials would just suddenly appear.  First we had tiny magnets, then we had DNA or RNA gold nanoparticles and now word comes that there is a newly synthesized family of flavonoid-like molecules with antibacterial and antifungal activity.

Fowler et al. in PLoS ONE examined flavonoids, which are abundant plant metabolites with anti-infective activity. They used a natural flavonoid scaffold to create novel flavanones and tested their efficacy versus E coli, B subtilis, Cryptococcus neoformans and Aspergillus fumigatus. They screened eight molecules and found that 4-chloro-flavanone was the most potent antimicrobial compound.  What did Ralph Waldo Emerson say? I think it's that "We judge of man's wisdom by his hope."  Keep hope alive.

Source: Fowler et al. PLoS ONE 2011

Via:  Hampton T, JAMA 2011

Deus ex machina (Part 3): DNA Gold Nanoparticles

Dr. Chad Mirkin

Yesterday, NPR's Science Friday had a discussion of a novel antimicrobial based a platform of spherical nucleic acids that have been developed at Northwestern. Dr. Chad Mirkin, director of the International Institute for Nanotechnology at Northwestern University, discussed the possibility that DNA or RNA gold nanoparticles could be designed to invade bacterial cells and "either turn off resistance so that a conventional antibiotic will work or, better yet, stop replication and ultimately cause bacterial cell death." Sounds pretty exciting and human trials are expected soon.

The most important thing mentioned was that DARPA, the research arm of the Defense Department, has called for development of new, next-generation antibiotics.  You can see by the host Ira Flatow's comments (quotes below) that he is perplexed as to why the Defense Department is leading the charge.

FLATOW: "And why is it that DARPA has to jump in here? What's wrong with our own medical system?"

FLATOW: "So what you're saying is that the people are willing to spend money on the military to do this where they might not in the civilian case."

Transcript: Hitting The 'Off' Switch On Antibiotic Resistance

Listen to the program (NPR 12/2/2011)

Deus ex machina: duabus partibus (Part Two) - Tiny Magnets

With infectious diseases, there is always another miracle around the corner.  The problem is that the miracle typically stays around the corner. Come on down...The next contestants in the search for a miracle cure are..."tiny magnets."

Researchers in Switzerland are developing nanomagnets that could remove harmful compounds (e.g. bacteria) from the blood. The technology involves magnetized nanoparticles coated with carbon and pathogen-directed antibodies. The plan is that the antibodies attach to the pathogens and then the whole compound is removed from the blood with hemodialysis. Sounds pretty exciting. Probably exciting enough to hold off on further investments in infection prevention research, not!

Source: Technology Review (MIT): 11/28/2011

Deus ex machina and antibiotic resistance

Last night, I watched a movie with my young kids. The "plot" involved friends traveling with one of their moms to Japan and then getting lost.  It was a bit scary for my kids. I was even a bit worried, since I had no idea how they would ever be found, but this was a Disney movie, so I knew it had to have a happy ending. Just when it all looked lost, the mom realized she had placed a tracking device under her son's skin when he was a baby and she also happened to have the required GPS tracking device in her purse.  Boom! Kids found, all was well. Ridiculous. Sure, my kids were happy, but where is the lesson there?

Flashback to a conversation I had three weeks ago with a visiting professor in general internal medicine.  She is a very well-known clinical researcher in oncology, an area that is well-funded unlike antibacterial resistance, and I wondered what she thought of the lack of new antibiotics in the pipeline, the rise of novel resistance mechanisms in Gram-negatives like NDM-1 and how she thought this would impact oncology.  Her response? Her jaw dropped.  She thought that there was always another antibiotic in the pipeline or in the ID physicians back pocket to pull out and save her patients. It had actually never occurred to her that we have had close to zero new classes of antibiotic in decades.  It was like life was a Disney movie and we could just pull a new antibiotic out of the air to save the day. Ridiculous.

But, whose fault is that?  I don't think it is the oncologist's fault. Is it the ID physician's fault who always sounds so smart and attempts to prove her usefulness by pretending that a polymixin is a useful new antibiotic! Is it the funding agencies that have ignored bacterial infections since the 1960's and certainly since the 1980's?  Is it the pharmaceutical companies that closed most antibacterial drug discovery units or governmental rules (patents) that bias against antibacterial investments?  Of course, the answer is all of the above and more.  All I can offer is that we have to stop pretending that some magical antibiotic will be discovered. There will be no 10x20 to rescue our patients.  I would settle for 2x20 or how about "1 good one by 20".

As ID physicians, I think we need to stop pretending that we have effective antibiotics. We need to be more honest about the hopelessness of the situation. If a well-trained practicing oncologist isn't aware of the problem, we aren't doing our job. When we face facts, we will have a better chance of convincing the public and government to actually invest in infection prevention and antibacterial drug discovery. This isn't some Disney movie.