Funding for antibacterial resistance research. Not so much.

At least no funding for ESCKAPE pathogen research

I just got back from attending the World HAI Forum in Annecy and the 1st ICPIC meeting in Geneva.  Both great meetings.  I will share my thoughts on the implications of ICPIC in a later post.

Last year at IDSA, Roy (Trip) Gulick stated that there are now 10,000 possible ART combinations for HIV treatment.  When he said that, I instantly got a sinking feeling in my gut.  Right now, there are many people colonized and infected with resistant bacteria for which we have NO EFFECTIVE THERAPY.  Sorry for shouting.  Think about the MDR-Acinetobacter or NDM-1 strains that are circulating.  Pretty soon we won't even have effective therapy for community UTIs.  

As I thought about why this might be, I looked for the federal funding picture for antibacterial resistance research, but there were no published data.  So, we found the numbers ourselves.  I presented the data last week and Marin McKenna kindly described our findings at the World HAI Forum on her Wired Superbug blog.  She did a much better job describing our research findings than I could have.  If you're interested in reading about how much NIH/NIAID spends on antibacterial resistance research, head on over to her blog...

NDM-1 in a US Military Hospital



source: wikipedia

Maryn McKenna has an interesting take on the MMWR report of NDM-1 in a US military hospital in Afghanistan. The patient had NDM-1 containing Providencia stuartii in a blood isolate collected early in 2011. This is the first case of NDM-1 in P. stuartii and in a US military hospital.  The parallels she draws to previous Acinetobacter infections in military hospitals are interesting. However, I'm not sure you can compare a specific species (Acinetobacter) to a plasmid-borne metallo-ß-lactamase (NDM-1), which can hop from species to species.

Either way, we will eventually need to beef up surveillance, infection prevention research and antibacterial drug discovery.  GNRs are not going away. I suspect the worldwide response to the many MDR-bacterial threats is going to require a significant reorganization and renewed focus (e.g. 1940s and 1950s) on how we fund these efforts. The days of nickel and diming these efforts, are coming to a close...

Staring into the abyss: MDR-GNR edition

We’ve been following the emergence and global spread of the New Dehli metallo-beta-lactamase (NDM-1). The latest chapter of that story came out today in Lancet Infectious Diseases, in a fine example of the newly named field of pharmacoecomicrobiology (say that three times fast!). Tim Walsh and colleagues sampled tap water and wastewater from the epicenter (New Dehli) and from Cardiff, UK. They found NDM-1 positive bacteria in 4% of drinking water samples and 30% of wastewater samples in New Delhi, but none in Cardiff. More alarmingly, they found this highly mobile resistance gene in a wide array of pathogenic bacteria. In addition to the Enterobacteriaceae (in which it has already been described), they found stable carriage of NDM-1 encoding plasmids in Aeromonas, Shigella and Vibrio cholera. Susceptibility testing confirmed phenotypic expression, revealing resistance to broad spectrum cephalosporins and carbapenems. On one hand, this is quite predictable (and furthermore, we know that even short-term visitors to an area of endemic resistance for gut bacteria will carry that resistant flora back home). On the other hand, it speaks to the inevitability of our new post-antibiotic era. This era has already begun, and will proceed incrementally as we see the steady loss of antibiotic classes we once referred to as “last-resort”.

David Livermore fights NDM-1, the 'super' superbug

David Livermore and NDM-1

There is a new story at MSNBC.com highlighting David Livermore, NDM-1, and the myriad of reasons for the expansion of MDR-bacteria and hospital infections: little investment in antibiotic discovery and infection prevention.  I like this quote from the article in regards to infection prevention: "If it is done properly, it can ease the demand for drugs in the first place."  Dr. Livermore is the Director of the Antibiotic Resistance Monitoring & Reference Laboratory (ARMRL) at the HPA Centre for Infections in London. The story is surprisingly well-written, includes the usual human-interest angle and quite long but worth a read.

h/t Mark Vander Weg

Weekend Links or WeekeLinks?

Jackie Robinson Rotunda - Citi Field

Pretty busy around here.  I just gave a talk on seasonal variation in hospital pathogens at the ID research conference this morning.  I saw Dan there.  He is alive, but on service. I think he had 12 consults one afternoon.

We're moving to a new research building next week here at the Iowa City VA, so I'm busy packing up the stuff that I unpacked only 5 months ago when I arrived.  The building is called "Building 42."   42 is Jackie Robinson's uniform number.  Those of you that have seen my old office will remember the Jackie Robinson poster that I had hanging next to the Jim Henson-Kermit poster.  I think I will call the building the 'Robinson Building' or maybe just 'Jackie'.

Here are some interesting posts for your weekend reading pleasure:

1) Pig-Borne ST-398 S. aureus infection (France) - Clin Infect Dis

2) FDA and the 29-million pounds of livestock antibiotics - Maryn McKenna Superbug blog

3) First 2 cases of NDM-1 in S. Korea

4) Clinical outcomes in HAIs and antibiotic resistance in European ICUs (Lancet ID)

NDM-1 in the US (Boston, California and Illinois)

MGH - where one NDM-1 patient was treated

Out of ICAAC there is a report of three carbapenem-resistant (NDM-1) cases in the US, all of whom had medical care in India prior to travelling to the US. Per a Tribune article, "the three U.S. cases involved three different bacteria that remain susceptible to at least one of three antibiotics: colistin, polymixin and tigecycline, said Karen Bush, an Indiana University professor..."  If you'll notice, the reports all call NDM-1 a 'superbug.'  I find this funny since NDM-1 isn't even a bacteria but a gene that can be found in several pathogens, as described in this ICAAC report.  Anyway, gotta feel bad for MRSA.  Just when it let its guard down, this new guy just takes over.  Kinda like what Nadal has done to Federer.

Boston Globe Article
Chicago Tribune Article

Update:
NDM-1 MMWR report from June 25 (thanks to Maryn McKenna for the tip)

More on NDM-1s

A few weeks ago, Eli blogged on the emergence of NDM-1 producing Enterobacteriaceae in Asia. Now, 3 patients with the organisms have been detected in Canada. You can read about it here.

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