And thus spoke Dr. Rosen, as he read from the Book of Doom:
“The Archangel FDA shall fix upon the antibiotic pipeline a seal. And the seal shall be unbroken by any, be they monolithic pharmaceutical company or earnest researcher. And the pipeline shall narrow ever more, until I say unto you, it shall be easier for a camel to pass through the eye of a needle than for a new antibiotic to pass through the sealed pipeline.”
Normally a jovial and witty speaker, Dr. Theodore Rosen assumed a peculiar air during a talk at the summer meeting of the American Academy of Dermatology —a nearly indefinable mixture of gravitas and utter befuddlement. He agrees wholeheartedly with the new prudence of the Food and Drug Administration with regard to approving the vast majority of medications. Most of the time. But desperate times call for desperate measures.
“We are being bombarded every year by increasingly resistant bacteria,” Dr. Rosen told me. “Some of these are relatively trivial, some are really bad—like MRSA—and some are wreaking havoc.”
So what’s the FDA doing about it? Not a whole lot, Dr. Rosen contends.
The agency’s exacting standards hamper research, he says. Noninferiority trials are standard for proving antibiotic efficacy, but there doesn’t seem to be any standard about just how noninferior the new drug has to be against its gold standard comparator. Is it 12%? 10%? Is it a moving target? Does it depend on the pair of drugs being compared?
There seem to be more questions than answers. But the result is that FDA has only approved one new antibiotic – televancin—since 2007. And there’s just no assurance that this will be sufficient. A quick Google search of resistant bacteria reads like a marquee of summer horror flicks (if you’re geeky enough).
Top billing has to go to NDM-1, New Delhi metallo-β-lactamase 1, which has conferred multidrug-resistance to Escherichia coli and Klebsiella pneumoniae in India, Pakistan, and the U.K. The bugs were highly resistant to all antibiotics except tigecycline and colistin.
Plagued by the Middle Ages? Yes, the disease that killed more than 200 million folks way back when is still alive and kicking – stronger than ever. Far from geezing, Yersina pestis has acquired a bagful of new tricks, including resistance to at least eight antimicrobials, among them streptomycin, tetracycline, and chloramphenicol. “Do we really want to let this genie out of the bag?” Dr. Rosen asked.
According to the World Health Organization, 2008 saw 9.5 million new tuberculosis cases and nearly 2 million deaths. About 150,000 deaths were due to multi-drug resistant strains; the bugs have been spotted in 58 countries.
In just one New York City hospital, 432 ceftazidime-resistant Klebsiella pneumoniae cases were found during a 19-month study period—17% of all the Klebsiella infections. The spike occurred in tandem with a ceftazidime war against multidrug resistant Acinetobater infections in the same institution.
Another jolly article confirms one of Dr. Rosen’s scariest points – not only are the stronger Klebsiellae adapting to our stronger antibiotics, they’re sharing that knowledge with their lowly E. coli cousins.
Slow as it may be to respond, this crisis is not solely of FDA’s making. Farmers, patients, and physicians each play key roles. Food animals are pumped full of antibiotics from conception until slaughter, providing a fast track for bacterial evolution. The fittest bugs survive and spread to farm workers, and even to the groundwater that sustains us all.
Patients remain notoriously unreliable when it comes to antibiotics, from nervous mamas demanding amoxicillin for baby’s every cough, to grownups who, feeling better after half a scrip, hoard the rest against a future bout of illness.
Docs are culpable as well, especially dermatologists Dr. Rosen said. “We treat acne and rosacea with antibiotics forever, instead of moving on as quickly as possible to topical therapies.”
FDA needs to quickly come to grips with the global rise of drug-resistant microbes, Dr. Rosen said. An overhaul of profit-driven animal husbandry is way overdue. On a more human scale, physicians need to keep pounding away at their patients to use antibiotics wisely and only as prescribed.
“And we need to listen to our own preaching, too,” he said. “It’s time to get real.”