Things that make you go "hmmm"...

I’ve been in an undisclosed location for the past week or so. Hint—if I were to hop on the above watercraft and drive directly across the above body of water, I’d be in the city that in the Potawatomi language translates (roughly) as “fine land”.

In among my beach reading I ran across this article, about a recent biowarfare exercise:

“AVI BioPharma, Inc., and the Naval Research Center recently announced the successful completion of a rapid-response exercise conducted by the Joint Project Manager Transformational Medical Technologies…..In a total of 18 days, AVI conceived, designed and manufactured two novel RNA-based drug candidates, one against a Gram negative bacterial target and one against a viral target.”

Eighteen days to conceive, design and manufacture a drug active against a Gram negative pathogen! Meanwhile, the only option for treatment of many multiple-drug resistant Gram negative infections is a drug that’s over 50 years old.

NDM-1 containing Enterobacteriaceae

With yesterday's report suggesting a decline in MRSA, it is now time to switch gears and panic about other organisms. As Dan said so well yesterday, "MRSA isn't the only bug out there, it's just the most famous." Today's report is from Lancet ID by researchers in UK, Pakistan and India on a novel resistance mechanism in Gram-negative bacteria called the NDM-1. NDM-1 stands for New Dehli metallo-B-lactamase 1. I guess when you name it "1" you are expecting a "2" and maybe a "3". Even the Great War wasn't called WWI until World War II started or at least ended.

The report is very nice and includes background information discussing the rise of various resistance mechanisms in GNR including ESBLs (CTX-M-15) and KPCs. The group initially discovered the NDM-1 containing resistance gene in a patient in Sweden after the patient returned from a hospital admission in New Dehli. This new report includes descriptions of isolates collected in Chennai (south India), Haryana (north India), UK and other areas in India, Bangladesh and Pakistan. Little information is given as to how the samples were obtained. After initial screening, all isolates were tested for presence of the bla(ndm-1) by PCR.

As an example of the results, from Chennai there were 3521 isolates of Enterobacteriaceae screened with 141 (4%) resistant to carbapenems. 44 of the 141 were NDM-1 positive, which is about 1% of all of the isolates. Most were E coli (19), K pneumoniae (14) and E cloacae (7). By 2009, NDM-1 strains were the dominant carbapenemase-producers in the UK. In most isolates NDM-1 was carried on plasmids although 3 UK isolates carries the NDM-1 on their chromosome.

All of this is quite concerning. It is not this specific gene/mechanism that's troubling, it's the constant introduction and spread of many different types of resistant GNRs in our inter-connected world. Look at the figure. The chickenpox spread of NDM-1 that now covers India and the UK will soon spread to Germany, the US and beyond. While we have new classes of antibiotics recently introduced that are active against MDR-Gram positive bacteria, we have very few new classes in the pipeline that are active against GNR. When the US Surgeon General, Dr. William H Stewart said in the 1960's that it was "time to close the book on infectious disease" and/or "the war against infectious diseases has been won", he probably wasn't thinking about Gram negative bacteria.

Lancet ID article

link to newer NDM-1 post

Move over, MRSA!

This morning's New York Times has a piece by Andrew Pollack on healthcare associated infections. That in itself is not a surprise anymore since the general public is quite interested in the topic. What is surprising is that the article isn't about MRSA--it's about Acinetobacter and the lack of effective drugs to treat multidrug resistant gram-negative organisms. Could this be a harbinger that the fixation on MRSA is starting to wane? Pollack remains, to my knowledge, the only journalist that has linked the frenzy to culture inpatients for MRSA with big profits by the companies who manufacture the MRSA testing kits.