Scienceblogs.com/Superbug

But: Imagine — as is generally accepted to be true — that it will take about 10 years, and about $1 billion dollars, to get that novel antibiotic through the development pipeline and into the marketplace. And then imagine that — as has been shown for a number of drugs, most recently the new antibiotic daptomycin — bacteria begin developing resistance to your drug within a year of its deployment in patients. And after that, imagine — as has been cited in a number of papers — that once local resistance to your antibiotic appears in approximately 20% of isolates, physicians will cease prescribing your antibiotic, for fear their patient will be one of that 20%.

So, to recap: 10 years, $1 billion; short course; short market life; rapid obsolescence.

Would you make that investment? Or would you, if you were a pharma company, opt instead to make insulin, which Type 1 diabetics will take every day for the rest of their lives? Or statins, which at this point we’re practically ready to put in the water supply? Or a cancer drug that costs $10,000 per dose? Or Viagra, or Cialis?

If you’re a company that is responsible to its shareholders, or listening to its analysts — or even capable of doing basic math — the answer’s obvious: Antibiotics lose. Which goes a long way to explaining why so many companies have backed off from making antibiotics, and why many of the few antibiotics in the pipeline are “me too” formulations, rather than new compounds with truly new mechanisms of action.

How to respond to this impasse has been an active debate for a while, largely focused on proposals to give market incentives, changes in tax credits, or patent extensions to pharma companies to persuade them to stay in or re-enter the marketplace. The Infectious Diseases Society of America, the specialty society for infectious-disease physicians (many of whom are also academic researchers), has been addressing this through its campaign “10x 20″, which has a goal of getting 10 new compounds into if not through the pipeline by the year 2020.

But, as a new article in the British Medical Journal points out, good incentivizing demands complexity — not just in developing both “push” and “pull” mechanisms (say, tax incentives to fund research v. prizes and wildcard patent extensions), but also in making sure that the incentives can be taken advantage of by companies of all sizes, not just the international mega-pharmas:

The characteristics of an ideal incentive mechanism and the desire for an equitable approach that engages developers of all sizes would suggest that neither push, pull, nor lego-regulatory mechanisms would be optimal to spur the desired investment in antibiotics …. Rather, elements of each should be combined. The exact shape of the ideal package is, however, as yet unclear. (Morel et al.)

 And an accompanying editorial emphasizes that new antibiotics are not the only things needed; new diagnostic tests, for instance, need funding as well:

Catchy as 10×20 sounds, the public sector strategy for funding such research and development must prioritise among different health technologies, such as diagnostics and vaccines, to combat antibiotic resistance. For example, three million children die each year from acute respiratory bacterial infections in developing countries, but penicillin sensitive pneumococcal strains have declined to a half, even a quarter, in some countries. A diagnostic test for bacterial pneumonia would save an estimated 405 000 lives a year, by targeting treatment and avoiding overprescription of antibiotics. New vaccines may also reduce reliance on drugs as the use of pneumococcal vaccine has suggested. (So et al.)

This is a hard discussion. I confess, as a longtime reporter, I flinch reflexively at the thought of handing more money to the pharmacos. At the same time, the state of the market demonstrates that the current model is not working. And though I would much prefer we focus on the ecological model of preserving antibiotics as a resource — dialing back on overuse and encouraging rigorous stewardship — it’s clear that we’ll always need new drugs for the most serious, most resistant infections.

So some sort of incentivizing seems necessary. And the multi-layered approach recommended in the BMJ, with appropriate attention paid to incentivizing the development of tests and vaccines as well, seems worth heeding.

The incidence of methicillin-resistant S aureus (MRSA) infections during this period increased 10-fold, from 2 to 21 cases per 1000 admissions, whereas the methicillin-susceptible S aureus infection rate remained stable. Among patients with S aureus infections, antibiotics that treat MRSA increased from 52% to 79% of cases, whereas those that treat only methicillin-susceptible S aureus declined from 66% to <30% of cases. Clindamycin showed the greatest increase, from 21% in 1999 to 63% in 2008. 

To translate, for those not used to reading scientific literature:

• a 10-fold increase in MRSA diagnoses over 10 years
• a 3-fold increase in what was not the most commonly prescribed drug, one useful for the different resistance profile of community infections 
• clindamycin (used in mild and also invasive infections) eclipsing vancomycin (last-resort drug for invasive cases) as the most-used drug — which could be a sign of changes in prescribing patterns, changes in seriousness of the cases seen, or a warning that with so much use, clindamycin resistance could emerge more quickly, as happened when vancomycin came off the shelf in the 1990s and began to be used more.

It will take me a while to download and read the paper (hard to do in the car), but that’s the topline news. Update to come.

But there’s important sad news today that I want you all to know about. Revere, the peerless author of the marvelous public health blog Effect Measure, is bowing out of the blogosphere. For more than 5 years now, Revere (a collective voice of an unknown number of public health experts —for simplicity, let’s say “he”) has been a reliable, thoughtful, expert, humorous and deeply knowledgeable guide to the intricacies of public health and public health politics. He has taken a particular interest in the possibility of pandemic flu and has been the unofficial leader of the loosely knit but fiercely loyal group of bloggers and crowdsourcers who call themselves Flublogia. And though few would admit it, Revere’s posts have been consistent agenda-setters in newsrooms all across the planet; insiders knew that, if Revere said something, it would start showing up in newspapers and on wires about 12 hours later.

If you are a Revere reader and missed this news, get over there and leave a note in the quickly lengthening comment string. If you never made the blog’s acquaintance, now would not be too soon.

As of last week, 8,173 hospitals had signed up (1899 in the United States, FYI).

If I sound skeptical, it’s because we all know that merely supporting hand-washing (or the gel equivalent) is an easy thing to do. If you asked any hospital in the US, you would hear 100% support for hand-washing — including in the hospitals where healthcare workers miss 50% of opportunities to wash their hands. It’s in the granular details of implementation — and the relentless laser-like focus on execution practiced, for instance, by Novant Health Care in North Carolina, whose story is told in SUPERBUG — that change really happens.

Whether this WHO campaign can bring that focus and create that change… we’ll just have to see.

The WHO campaign’s page includes videos, guidelines, and plans for a global survey to be executed on May 5.

It’s so exciting to see people completely get the book, and twice that when it is people you know.

Sample quote:

Superbug is not about an entomological caped crusader.

It’s more like a grown-up version of Scary Stories to Tell in the Dark.

The bug in question is MRSA, an antibiotic-resistant bacteria that kills more Americans every year than AIDS. Superbug is the story of how we created our own monster-under-the-bed, how it spreads through hospitals and communities, and why it’s damn near impossible to control. If you have a cut or a pimple while reading this book, you are pretty much guaranteed to freak yourself out. And I mean that in the best possible way.

Coincidentally, constant reader Pat Gardiner of the UK alerted me to a gathering being held on the same day in Ireland, by the quasi-government agency SafeFood—which reports to the North-South Ministerial Council of Ireland, which deals with whole-island issues under the Good Friday agreement, which is more about the Irish political structure than you probably ever wanted to know.

The conference was titled Antimicrobial resistance and food safety and featured government officials and academic researchers from across Ireland. Here’s the agenda, and here’s the press release with the names of key speakers. Even more important, here are links to a report on antibiotic resistance in food that Safefood released in advance of this conference: executive summary and whole thing.  I especially recommend from p.25 in the big report for an accessible discussion of the connections between ag antibiotic use and human health. Key quote among many:

The majority of the evidence acquired through outbreak and epidemiological investigations of sporadic infections, field studies, case reports, ecological and temporal associations and molecular sub-typing studies support the causal link between the use of antimicrobial agents in food animals and human illness. A few papers have questioned this but these have not survived detailed scrutiny.

It’s refreshing to see a government body engage seriously with this emerging issue, which we’ve been talking about for, well, years now, on this blog (sometime this month we passed our 3-year anniversary). I wish, wistfully, that the government doing the discussing was ours.

Melissa Graham of Chicago had a great corporate life — and then she re-evaluated, became a chef and caterer, and began organizing in Chicago for sustainable local food, farmers’ markets, and a family-friendly food system. She blogs at the food and food-policy blog The Local Beet. And she’s written a reaction to SUPERBUG that not only completely gets the book, but is emotional and thoughtful and moving besides.

She says, in part:

Before reading Superbug, the question of confinement raised animals was an ethical one for me – whether the misery inflicted upon animals and, for that matter, the humans working in those facilities by the putrid conditions outweighed the need to eat cheap meat. Even the environmental degradation resulting from the inevitable careless management of CAFOs seemed a distant and intangible casualty. For me, Superbug has changed the argument from one of ethics to a moral imperative. In every hamburger of unknown origin, I see Tony Love’s face or even worse that of Carlos Don IV.

Carlos was another healthy kid who left on a school trip to the mountain and returned with a 104°F fever. The first doctor diagnosed Carlos with walking pneumonia so his mother kept him home bundled and hydrated until she realized that he was beginning to hallucinate. She rushed Carlos to the hospital and the doctor’s ultimately diagnosed his condition as MRSA. A long slow death march ensued during which Carlos’s lungs dissolved and clotting choked off the blood to his lower intestines, legs and arms. In two weeks, he was dead.

After reading Carlos’s story late in the evening, I woke a bewildered little locavore from a dead sleep to scrub his hands clean. I hugged him as tightly as I could.

…[recently] I had the pleasure to hear Ruth Reichl speak and she implored the audience to stop eating confinement raised animals. As she put it, if everyone stopped buying them and eating them, the practice would be history. Knowing what I now know, I think it’s our moral duty.

To give the post the traffic it deserves, please go here.

But a piece over the weekend was especially meaningful to me and I wanted to call it out: Flu blogger and DailyKos diarist DemfromCT featured the book on his DailyKos page. (And, behold the power of networks: 178 comments this morning. Wow.)

Liz Borkowski at The Pump Handle kindly reproduced Dem’s post.

This builds, of course, on early, consistent and indefatigable support from flu blogger Mike Coston of Avian Flu Diary.

As the book’s acknowledgments say (p. 218!), I am so grateful for our blog community’s support. Sincere thanks to all.

“Cows on Drugs” — a superb history of the 30-year-old fight to get unnecessary antibiotics out of food animals. Note, written by a former commissioner of the Food and Drug Administration, not exactly a wild-eyed radical:

More than 30 years ago, when I was commissioner of the United States Food and Drug Administration, we proposed eliminating the use of penicillin and two other antibiotics to promote growth in animals raised for food. When agribusiness interests persuaded Congress not to approve that regulation, we saw firsthand how strong politics can trump wise policy and good science.Even back then, this nontherapeutic use of antibiotics was being linked to the evolution of antibiotic resistance in bacteria that infect humans. To the leading microbiologists on the F.D.A.’s advisory committee, it was clearly a very bad idea to fatten animals with the same antibiotics used to treat people. But the American Meat Institute and its lobbyists in Washington blocked the F.D.A. proposal.

Antibiotic resistance in your kitchen, playroom, car... — After years of begging from health advocates, the FDA and EPA are taking a second look at the chemical compound triclosan, an antibacterial that is put into, well, almost anything you can name: soaps, hand sanitizers, cutting boards, toys. Triclosan is suspected of interfering with hormone regulation in the body, and also increases resistance in organisms in our environment. (When I ask you to use hand sanitizers that contain only alcohol or salts, not antibacterials, triclosan is one of the things I’m thinking of.) The FDA will report its findings in a year. I’d rather see it happen sooner, but it’s a great move.

No progress on hospital-acquired infections — The Agency for Healthcare Research and Quality, part of the Department of Health and Human Services, has published its 2009 National Healthcare Quality Report. The news is not good. To quote the agency’s own language: “Very little progress has been made on eliminating health care-associated infections.” This is all hospital-acquired infections, not just MRSA, but MRSA is a leading organism. The ugly details:

• Post-operative bloodstream infections up 8%
• Post-operative catheter-associated urinary-tract infections up 3.6%
• “Selected infections due to medical care” up by 1.6%
• Bloodstream infections as a result of central lines unchanged.

(NB, three professional organizations — the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, and the Association for Professionals in Infection Control — put out a statement in response to this report saying it “presents an outdated and incomplete picture on healthcare-associated infections (HAIs) in our healthcare system.” The gist of the statement seems to be that they’ve got better numbers coming… soon. When there’s actual data, I’ll let you know.)