WHO: Antimicrobial Resistance

Last week the WHO released a report covering global surveillance for antimicrobial resistant bacterial pathogens. The report starts off by highlighting the major gaps in knowledge about the magnitude of the MDR-bacterial problem and suggests that the post-antibiotic era is a very real threat. While the levels of resistance in the report are very alarming, the authors also note that worldwide surveillance lacks coordination, so it's likely we're only seeing the very tip of the iceberg.  One interesting aspect of Dr. Fukuda's introduction was his acknowledgment that TB, malaria and HIV have much better surveillance systems and should serve as models for MDR-bacterial surveillance.

The report focuses on "nine" bacteria-drug combinations: E coli vs 3rd gen. cephalosporins and fluoroquinolones,  K. pneumoniae vs 3rd gen. cephalosporins and carbapenems, MRSA, S. pneumoniae vs. penicillin, nontyphoidal Salmonella and Shigella vs. fluoroquinolones and N. gonorrhoea vs. 3rd gen. cephalosporins.

I think the take home point is summed up in the reports Figure 1, which I've pasted below.  No new antibiotic classes since 1987. We can safely say that the bacteria didn't take a 30-year break while we rested on the laurels of the prior generation(s).

The report is 232 pages long, so you have two options if you want to learn more: (1) Head over to the WHO website and read the whole thing or (2) Listen to my 15-minute interview on Iowa Public Radio from last week. Just click on the audio player below or head over to IPR's page and listen there.



For additional reading on the US burden of antimicrobial resistant bacteria:

1) Sievert DM et al. ICHE January 2013 (2009-2010 NHSN Summary)

2) CDC 2013 Antibiotic Resistance Threats Report

1955 - Dawn of the Antibiotic Era and Lessons for the Future

It's easy to fall into despair when pondering the decades long rise of antibiotic-resistant bacterial pathogens and the simultaneous decline in funding for antibacterial discovery, surveillance systems and infection prevention. But this wasn't always the case.  Back before 1969 when it may or may not have been said that "It is time to close the book on infectious diseases, and declare the war against pestilence won," clinicians appreciated antibiotics and even understood the idea of antimicrobial stewardship.

A case in point is this 1955 article in JAMA by GE Burch titled "Cardiology for General Practitioners." After pointing out that the first therapy mentioned by Dr. Burch was antibiotics, I would like to call your attention to a few of his thoughts:

"The most important single therapeutic development in the field of cardiology has been the advent of antibiotics. These drugs have not only made it possible to convert almost all fatal diseases, such as bacterial endocarditis and endarteritis, to almost nonfatal ones but have played an important role in control of infections in all cardiovascular disease states. Until the introduction of these drugs, the physician was often able to manage satisfactorily the cardiac disturbances, such as congestive failure, only to have the patient die of bronchopneumonia or urinary tract infection. The fear of secondary infection as a threat to life was constantly present, and the more chronic or prolonged the illness and the older or more debilitated the patient, the greater was the chance for infection. Once it developed, the physician was virtually helpless, despite the many therapeutic rituals used. Most physicians well remember the preantibiotic era."

and the homage to stewardship:
"It is not necessary, or even advisable, however, to administer those of the so-called broad spectrum type to all patients with cardiovascular disease, without regard for the specific problem."

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After reading Dr. Burch's review I'm convinced that our current situation has several potentially modifiable causes: (1) a lack of understanding of how critical effective antimicrobials are to the practice of modern medicine, (2) a failure to include clinical judgment when selecting antimicrobials and finally (3) a pre-antibiotic era that has been completely lost to history. Addressing all of these will be required if we are to avert a post-antibiotic future.

We're in the post-antibiotic age

We're so very lucky to have lived in the "age of antibiotics."  However, most of us were neither alive nor cognizant prior to 1943, so we don't have a concept of the morbidity and mortality prevented by antibiotics. In some regards, this pre-1943 period is the future we're facing.  Author and science journalist Maryn McKenna has a wonderful article up on medium.com where she discusses this post-antibiotic past and future using a touching story of her great uncle along with facts such as "one out of every six recipients of new hip joints would die" without antibiotics. She also discussed this article on yesterday's CBC "Sunday Edition" radio broadcast (audio available here).

As if we need other things to add to our phobia lists, there's a new case-report published in JAC last Friday of an elderly Spanish woman with chronic renal disease and recurrent UTIs. She initially presented with pyelonephritis caused by a susceptible E coli. However, after 1 week of therapy she developed sepsis and renal failure that was unresponsive to meropenem and died. MDR E Coli was isolated, which was resistant to all tested antibiotics except fosfomycin, tigecycline and tetracycline. Further analysis identified numerous resistance and virulence genes (see figure above). Importantly, the authors state that this is "the first report of the co-production of KPC-3, VIM-1, SHV-12, OXA-9 and CMY-2 in a unique clinical multiresistant E. coli isolate."

With air pollution, it's risky to breathe and with water pollution it's risky to drink. I guess now it's risky to pee.

h/t Christina Vandenbroucke-Grauls

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”.