Last night, the Journal of the American Medical Association posted ahead of print an editorial by Dr. James Hughes, former director of the National Center for Infectious Diseases at the CDC and now a professor of medicine and global health at Emory University. It’s a blunt and eloquent plea for attention to a problem that many people haven’t yet faced up to: We’re running out of antibiotics.
Antimicrobial agents have saved millions of lives and improved the outcomes for countless patients since these drugs were introduced in the early 1930s. However, the effectiveness of these lifesaving resources is at risk. Many medical advances that physicians and patients take for granted—including cancer treatment, surgery, transplantation, and neonatal care—are endangered by increasing antibiotic resistance and a distressing decline in the antibiotic research and development pipeline. (JAMA Hughes)
Drug resistance is a biologic inevitability — but in the 83-year history of the antibiotic miracle, starting from Fleming’s first recognition of natural penicillin, whenever resistance made one drug useless, another drug came along to save us. Those days are over.
Think for a moment like a pharma company. It’s generally accepted that it takes 10 years and about $1 billion to get a new drug from concept to marketplace. At the end of that investment of time and money, you’re left with a drug that is only taken for weeks at a time, that bacteria will develop some resistance to within a year, that doctors will cease to prescribe once approximately 20 percent of infections demonstrate resistance — and which, if it’s a very, very promising drug, doctors may not prescribe at all, because they want to preserve it for the most dire cases.
if you were a shareholder in that hypothetical company, wouldn’t you want them to make Viagra instead? Or insulin, which people take every day for the rest of their lives? Or any other drug for chronic lifestyle diseases, which manage those conditions but do not cure them, and therefore don’t undermine their own market?
Viewed through the lens of market forces, the surprise isn’t that so few companies are still making antibiotics — the surprise is that any company is.
From 1983 to 1987, 16 new antibiotics were approved by the US Food and Drug Administration (FDA); from 2003 to 2007, just 5 were approved. Since 2008, only 2 have been. (Hughes)
The especially bad news is this: It isn’t only antibiotics we are running out of. I have a story in the February Annals of Emergency Medicine that outlines such how many drugs have run short or been unavailable in the past year: more than 140, according to the American Society of Health System Pharmacists, including crucial antibiotics (clindamycin), diuretics (Lasix), pain medications (morphine), stimulants (epinephrine), anesthetics (propofol) and key drugs for emergency intubation (succinylcholine).
The nonprofit Institute for Safe Medication Practices surveyed 1,800 clinicians and health-system pharmacists last fall about the shortage, and here’s what they heard:
- 80% said they faced difficulty obtaining comparable drugs;
- 78% said there were significant costs to obtaining comparable drugs;
- 70% said they had been unable to find comparable alternatives;
- 64% believed the shortages posed a risk of adverse patient outcomes
- and more than 1,000 of them reported significant adverse events because of the shortages: overdoses, under-doses, and life-threatening mix-ups.
As with antibiotics, these shortages are occurring because there are so few manufacturers making these drugs. Some critically necessary compounds are made by only a single manufacturer. If that manufacturer suffers a production breakdown — or decides to stop making the drug — it’s just gone. The FDA has no power to keep manufacturers in the market if they want to get out.
What the government might have the power to do is to improve market conditions so that manufacturers want to stay in it, or come back into it if they have already left. How best to do that is the subject of ferocious argument (see this post and this one for some of the discussion) and the objective of a piece of legislation, the STAAR Act, that is backed by a number of medical societies. (I don’t know if it has been reintroduced yet in this Congress, but will check.)
It’s clear though that something has to be done. Hughes, again:
The stakes could not be higher. Without action, deaths and morbidity from antimicrobial resistance will continue to increase and the drug development pipeline will run dry. There is a moral obligation to patients and to the nation to prevent the unthinkable outcome of a return to the pre-antibiotic era and to ensure that these precious resources are available for future generations.
Cite: Hughes JM. Preserving the Lifesaving Power of Antimicrobial Agents. JAMA. Published online February 22, 2011. doi: 10.1001/jama.2011.279.