Digging in the Dirt - For Antibiotics

Not a week goes by without some claim of a new miracle antibiotic. Usually, when I read the press releases I yawn and go back to washing my hands. It's not like any of these magical compounds will ever make it to human studies. However, today's article in the NY Times describing a "powerful new antibiotic" piqued my interest. Dr. Kim Lewis from Northeastern University in Boston and her team just reported (Nature 7 January 2015) the discovery of a novel cell wall inhibitor called teixobactin. What was unique about their discovery was that they identified the compound by screening soil from a "grassy field in Maine." This is a big deal since 99% of environmental bacteria can't be cultured under typical laboratory conditions, so their method of "tricking the bacteria" into thinking they are back in their native 'dirt' is important.

Once the authors identified the compound teixobactin from the uncultured bacteria, they showed that it had excellent in-vitro activity against Gram-positive bacteria including enterococci, C. difficile, B. anthracis, and S. aureus (including VISA strains). (Table 1, below) They also tested the in-vivo efficacy against MRSA and S. pneumoniae in a mouse model and reported excellent results. Intriguingly, the authors said that "resistance has not developed...suggesting that the target is not a protein" and since there exists a similar lack of resistance development to vancomycin through mutations, they postulated "that teixobactin could be acting against the same (lipid II) target."

I agree with Dr. William Schaffner's comments in the NY Times as he called the study/method “ingenious” yet also cautioned that "it’s at the test-tube and the mouse level, and mice are not men or women, and so moving beyond that is a large step, and many compounds have failed.” I would add one additional caveat  - teixobactin had little activity against most Gram-negative bacteria including E coli, Klebsiella and Pseudomonas. (Table 1, above) Since the real resistance crisis is in multi drug-resistant Gram-negatives (think CRE, NDM-1), we better get back to digging in the dirt.

Did Google Flu Trends Miss the Mark This Year?

There is a nice review of how various influenza-like illness surveillance systems performed during the 2012-2013 influenza season by Declan Butler at Nature.com. There is some good news and some bad news. The good news is that the timing of the start and peak of the epidemic appear pretty well-aligned between the three methods. However, it appears that the "Google Flu Trends" peak was much higher than the CDC and "Flu Near You" peaks. Reasons for the possible divergence include timing of non-influenza ILIs in the community, a bad norovirus season and excess media coverage including CDC's alert of a bad/early season in early December 2012.

I think these reasons and others given in the article have a lot of face validity and certainly follow what many were feeling as the epidemic progressed. One thing I haven't seen in the coverage is whether the "peak" count of ILI is all that important. I'm more interested in the timing of the epidemic's beginning and the peak and not so interested in an absolute count. I suspect that the absolute number of infections helps in future years, but the timing is more important in the current year. I hope someone will comment or covertly tell me why the peak amount matters so much. It's not like ILI is the greatest definition anyway.

Another assumption I haven't seen discussed is whether Google Flu Trends actually got it wrong or was it the other methods which missed the mark. When you have an imperfect definition, it's hard to call any of these three methods a gold standard. Any attempt to pick a winner seems a bit arbitrary. If the intent is to match the CDC so rates can be compared from year-to-year, that's one thing. But what if we are burdening ourselves with a suboptimal gold standard. A lot of sunk costs go into any legacy system, but it's at least worth wondering occasionally if the legacy is worth continuing.

Image source: http://www.nature.com/news/when-google-got-flu-wrong-1.12413

MRSA vs Man vs MRSA: CA-MRSA and Vaccines

Maryn McKenna has a new Nature Feature on Robert Daum's early CA-MRSA report and his vaccine development efforts.  The article spans the period 1995 to present and discusses old and new vaccines, including Daum's  T_H17-targeted approach.  A nugget I didn't know is that Daum had an 18-month struggle with JAMA editors prior to publication of his early description of CA-MRSA cases in pediatric patients.  The article is now considered to be an early warning of the epidemic.  Probably shouldn't rely on publications in academic journals for early warning signals.  What are you waiting for?  Head on over there for the full read.

Source: Maryn McKenna: Vaccine Development: Man vs MRSA, Nature 01 Feb 2012

Gut check

A European research consortium just reported their analysis of gut microbiome diversity in 39 individuals from Europe, Japan and the United States. The figure below summarizes their findings: that the “metagenomes” of fecal communities cluster into three recognizable “enterotypes”, each dominated by a different genus (Bacteroides, Prevotella, and Ruminococcus).

This must be important, because it was published in Nature and extensively covered in the media, right? Probably, but the meaning and importance of these findings await much more work to correlate health and disease states with the composition and function of different microbial communities. To my simple mind, these findings suggest that perturbing the gut flora with antimicrobial therapy likely has a wide variety of adverse consequences, most of which we don’t yet understand.

Until we learn more, we’ll have to be satisfied with some of the straightforward correlations that these investigators uncovered. For example, in the words of one of the authors:

"If I have a stool sample I can tell how old you are," says Bork. "That seems useless because you already know how old you are…”