The United States government proposed several important steps last week that, if accomplished, will significantly change how this country attempts to counter the advance of antibiotic resistance, bringing us within reach of the more complete programs which exist in Europe. But as significant as it is, the new program has some perplexing gaps that left experts attending to the issue disappointed.
This all happened on Thursday, several things at the same time:
- The White House published a National Strategy for Combating Antibiotic-Resistant Bacteria.
- Simultaneously, President Obama signed an Executive Order directing the enactment of the strategy.
- And the President’s Council of Advisors on Science and Technology (PCAST) released its long-awaited report on antibiotic resistance (which I’ve previously written about here and here).
Taking the White House steps first, the Executive Order creates a within-government Task Force for combating resistance — jointly chaired by the secretaries of Health and Human Services, Agriculture and Defense — and a Presidential Advisory Council of non-government experts to guide and comment on the Task Force actions, which would be implementing the strategy.
The strategy calls for:
- Slowing down the overuse and misuse of antibiotics, which drive the emergence of resistant organisms (a task usually called “antibiotic stewardship”);
- Improving the amount and quality of data about the appearance of antibiotic resistance that is reported to state and federal surveillance programs;
- Creating new, quick diagnostic tests that can identify resistance within bacteria at the bedside or in a medical office (which would cut down the amount of antibiotics that are misprescribed);
- Accelerating research into new antibiotics, getting pharma back into the business of making the drugs, and looking for drug alternatives such as vaccines and non-antibiotic treatments;
- Forging international collaborations, with the World Health Organization and governments: sharing data on resistance, strategizing on stewardship, and (this is important) working out mechanisms to declare international crisis points when highly resistant strains emerge.
There is a lot to like in the strategy, which sets specific measurable objectives for each of those goals above. The goals are for the year 2020, six years from now, and they include (this is just a sample):
- Have 95 percent of hospitals report data on their antibiotic use to a surveillance project run by the Centers for Disease Control called the National Healthcare Safety Network, and use that data to check that by 2020, inappropriate use for patients in hospitals drops by one-fifth from this year, 2014, and inappropriate use for patients being seen in medical offices goes down by half from 2010.
- Create a regional laboratory network for testing resistant bacteria and make the data publicly available electronically.
- Create reimbursement incentives (such a via Medicaid) that force the use of new point-of-care diagnostics.
- Get two new antibiotic into Phase III trials by 2016 and two more to the point of New Drug Application by 2018.
- Stand up one national reference lab in each of 30 countries to analyze and share resistance data across borders.
Many of these benchmarks are contained in the third big action taken Wednesday, the issuing of the PCAST report, which is twice as long as the Strategy. Unlike the Strategy, the report not only sets objectives, but assigns spending recommendations to them. Overall, it calls for a doubling of the current federal funding for antibiotic resistance, from $450 million to $900 million (per year), and it also sets out specific funding levels. Again, a sampling:
- Creating that public database of resistance factors in the US: $5 million
- Creating a granular national surveillance and detection program: $50 million
- Funding basic (pre-clinical, proof of concept) research at the National Institutes of Health: $150 million
- Creating incentives to get pharma firms back into antibiotics manufacturing (not included in the $900 million): up to $1 billion payments to manufacturers to “buy” the drug from them, that is, guaranteeing them an up-front payment when a drug is licensed, rather than asking them to rely on revenues from sales, which can be undercut by the development of resistance. (This is technically called “delinkage.”)
So if all these look good, and they do, what’s the problem? Longtime readers will see what has not yet been mentioned: exerting control over the misuse of antibiotics in animal production. This is significant, because agriculture uses more than three times as many antibiotics in the United States every year as people do — and the more antibiotics go out into the ecosystem, the more pressure is exerted on bacteria to mutate away from being susceptible to the drugs.
Yet the PCAST report has little to say about this issue. While it has a chapter that addresses animal agriculture, it is short and, in tone, oddly different from the rest of the report. Where the previous chapters recommend tough and specific action — establishing new surveillance networks, embarking on new research, requiring reporting from hospitals, recommending the spending of enormous amounts of money — the animal-ag chapter recommends only sticking with the Food and Drug Administration’s current voluntary plan, creating a “national education” program, and “monitoring” meat production’s use of drugs to see if the numbers change. Strangely, the chapter examines some pieces of research into the link between agricultural antibiotic use and human illness, only to critique each one as insufficient — without, for instance, recommending support for new research. In fact, that chapter may be the only one in the report that does not contain any dollar-specific objectives or benchmarks; it fundamentally takes a wait-and-see approach.
The underlying feeling is that the authors of the report are not interested in investigating any connection between on-farm antibiotic use and off-farm antibiotic resistance — which is especially disappointing when you consider thst there are hundreds of research articles exploring that connection published since the 1970s. One partial explanation may be that, within the Antibiotic Resistance Working Group responsible for the report — two co-chairs and 14 members — there are only two people who could address the issue from their professional expertise: Dr. Lonnie King, Dean of Ohio State’s College of Veterinary Medicine (formerly with the CDC); and Dennis Treacy, executive vice president of meat-production giant Smithfield Foods.
If you compare the PCAST report and the National Strategy that it is supposedly informing, an intriguing tension emerges, because the Strategy actually specifies more direct action on animal-antibiotic use than the report does. (For any of the other issues, it is the reverse: more detail within the report.) For one, the Strategy, but not the report, lists as a goal “Strengthen national One-Health surveillance efforts,” referencing the concept that human and animal health are intimately connected. Beyond that, the Strategy calls for:
- collecting additional data regarding farm antibiotic use;
- supporting new research on antibiotic alternatives for animal production;
- wrapping state veterinary and food-safety laboratories into the new national reference-laboratory structure, and include resistant organisms they find in the new data bank;
- collecting antibiotic-resistance data from live animals on farms (which is not now allowed);
- increasing the amount of data that veterinary antibiotic manufacturers must tender to the federal government;
- setting up an analytical framework supported by multiple agencies for mathematically modeling the relationship between on-farm antibiotic use and resistance in livestock;
- fully sequencing the gut microbiota of at least one food-animal species to interrogate the action of growth promoters and identify alternatives.
When I read those prescriptions (which are scattered through multiple pages of the Strategy), I get the feeling that someone who was involved with its drafting takes the impact of antibiotic use in food animals more seriously than the PCAST authors do. In my read, the two documents represent two different views of the importance of this issue to the ever-increasing problem of resistance. I wonder which view will win out.
A quick sample of opinions on the initiatives, not comprehensive:
- Congresswoman Louise Slaughter, author of the Preservation of Antibiotics for Medical Treatment Act, who has long wanted to see more done to curb agricultural antibiotic use:
- economist Kevin Outterson, evaluating the proposed spending, including the incentives for antibiotics and diagnostics;
- the Trust for America’s Health (“We are concerned that the PCAST report does not make powerful enough recommendations around the routine agricultural use of medically-important antibiotics in food animal production”);
- the Infectious Diseases Society of America;
- the Natural Resources Defense Council;
- the Animal Health Institute.