Monday, October 13, 2014

Mass Production of Antibiotics

Since the discovery of antibiotics, natural products have been used as killers of disease causing bacteria.  This has prevented untold pain, suffering, and created a revolution in healthcare, however, it is now outdated and these early antibiotics are now largely ineffective. As new pathogens emerge, scientists struggle to keep up with ways to kill them. The “new” pathogens in this scenario being pathogens that have evolved resistance genes from unfettered use of antibiotics.  Antibiotics are now manufactured in three ways[35]:
  • Collected from live microorganisms
  • Semi-synthetically produced from natural products
  • Chemically synthesized based on the structure of natural products




Pharmaceutical companies have largely abandoned the research and production of new antibiotics and rely now on the technology industry to supply the new drugs. Synthetic biology is now the preferred method of antibiotic production and newer, targeted antibiotics are developed at an amazing pace[36].
                                                http://www.ncbi.nlm.nih.gov/pubmed/21829093



Tuberculosis (TB) is a contagious disease caused by the Mycobacterium tuberculosis (Mtb) bacteria causing 1.3 million deaths per year.

Antibiotic drugs have been the first line of defense against TB for nearly four decades, but now 92 countries have reported strains of a super-TB called Multidrug-resistant (MDR) TB.  MDR TB requires harsh antibiotic treatment with severe side effects and can take two years to cure. Some strains have become resistant to all available drugs, and have been termed Extensively drug-resistant (XDR) TB.

Scientists have taken spectinomycin, a bacterially derived antibiotic used to treat gonorrheal infections, and made chemical modifications to create a new class of semi-synthetic  antibiotics called spectinamides.  This new antibiotics are effective against MDR and XDR TB, and scientists are elated as many lives will be saved.  Dr. Richard E. Lee of St. Jude Children’s Research Hospital, leader of the international effort to develop this new drug remarked:[37]

“This study demonstrates how classic antibiotic substances derived from natural products can be redesigned to create potent semi-synthetic compounds that overcome intrinsic drug resistance mechanisms,” Lee says. “I hope the result will be drugs that are more effective against tuberculosis and offer a faster route to a cure with fewer side effects.”

Any bets on how long this new semi-synthetic antibiotic will be an effective treatment?


Special thanks to Dr. Grace Liu, PHARMD, from Animal Pharm for contributions to this article.


[35] Demain, AL. "Antibiotics: natural products essential to human health." 2009. <http://www.ncbi.nlm.nih.gov/pubmed/19291695>
[36] Takano, E. "A turning point for natural product discovery--ESF-EMBO ..." 2012. <http://www.ncbi.nlm.nih.gov/pubmed/22296491>
[37] "Development of Antibiotics to Treat Tuberculosis - NIH ..." 2014. 3 May. 2014 <http://www.nih.gov/researchmatters/february2014/02102014tuberculosis.htm>

5 comments:

  1. Wow!

    "Fecal capsules resolve Clostridium difficile infection in 90% of patient"

    http://www.medicalnewstoday.com/articles/283766.php

    ReplyDelete
  2. Hmmm. This is interesting, and very new! Fecal pills seemed to fizzle out last year with less-than-stellar reviews. This new paper mentions 'frozen' fecal capsules.

    I wonder, do they mean 'freeze-dried' or actual 'frozen poop'? And, how do they encapsulate it to ensure it opens in the colon?

    I remember several papers that used RS for encapsulation since it isn't degraded until it hits the large intestine.

    Thanks, Gemma!

    ReplyDelete
  3. "Preparation of Frozen Inocula
    .
    Processing was carried out under aerobic conditions. A fecal suspension was generated in normal saline without preservatives using a commercial blender. Materials were sequentially sieved to remove particulate material. The final slurry was concentrated by centrifugation and resuspended in saline at one-tenth the volume of the initial sample with 10% glycerol added as a bacterial cryoprotectant. Fecal matter solution was pipetted into size 0 capsules (650 µL), which were closed and then secondarily sealed in size 00 capsules. Capsules were stored frozen at −80°C (−112°F). One to two hours prior to administration, they were transferred to −20°C, then transported to the clinic on dry ice. Commercially available acid-resistant hypromellose capsules (DRCaps, Capsugel) were used. Stability of capsules in an acid environment mimicking the stomach was tested internally by evaluating trypan blue–filled capsules. At 37°C (99°F) and a pH of 3 or less, the capsules were stable for 115 minutes before dye was released. These results are comparable with data published after we conducted our internal evaluation.20 Each inoculum was prepared from the feces of a single donor and a full treatment of 30 capsules contained sieved, concentrated material derived from a mean of 48 g of fecal matter (mean per capsule, 1.6 g; range, 1.0-2.05 g)."

    http://jama.jamanetwork.com/article.aspx?articleid=1916296
    Oral, Capsulized, Frozen Fecal Microbiota Transplantation for Relapsing Clostridium difficile Infection

    Love the blog (already a follower ;-) ) and just wanted to mention: you have the best blog list ever! Just one look and I know where to go to for new stuff. Thanks!

    Alexandra

    ReplyDelete
  4. And, Alexandra, I am a fan of yours already, too! A well-cited, easy-to-read excerpt is not easy to pull off in a Blogger comment.

    Perfect, thanks!

    This makes me wonder if it could change the nature of fecal transplants, especially the DIY types.

    There was much talk a while back about a paper from the 1940's that talked about WWII soldiers in Saharan Africa eating freshly deposited camel poop as a cure for dysentery, learned by watching the locals. It's been written about here:

    http://www.rense.com/general4/bac.htm



    ReplyDelete
  5. Interesting blog posted..............

    ReplyDelete