This should be the golden era of antimicrobial medicine. Molecular biology has over the last two decades created new diagnostic tools like real-time PCR which can isolate and amplify minute quantities of bacterial DNA to identify individual species. Today’s researchers can design antimicrobial drugs that specifically target proteins, RNA, and DNA of individual pathogens.
Existing antibiotics obtained from fungi and plants often interfere with human biology, creating side effects that limit doses. Tomorrow’s antibiotics should defeat pathogens with minimal side effects, by acting only against molecules specific to bacteria, fungi, viruses, and protozoa.
This blog believes that nearly all diseases have an infectious origin. Infections outrun the immune system due to dietary and nutritional inadequacies. Diet, nutrition, and new antimicrobials should enable nearly all diseases to be defeated.
We are on the cusp of enabling nearly everyone to live to age 100 in good health. All we need is a renewed focus on antimicrobial research, and better diets.
Yet nothing is happening.
Via frequent commenter erp comes an excellent story that explains why (Trine Tsouderos, “Arsenal of antibiotics not being restocked: Dispute over rules for approving new drugs stalls production even as concern rises over deadly resistant bacteria,” Chicago Tribune, August 6, 2010):
Drug companies are abandoning the antibacterial business, citing high development costs, low return on investment and, increasingly, a nearly decade-long stalemate with the Food and Drug Administration over how to bring new antibiotics to market.
Soon, doctors fear, we could be defenseless against bacteria that can resist all existing antibiotics, which would mean more victims like Simon, dead from a staph infection that drugs used to conquer easily.
Dr. Brad Spellberg, an expert on antibiotic resistance, called the situation “catastrophic.”
At the core of the problem is a regulatory impasse over whether drug companies seeking FDA approval for antibiotics should be required to run much more stringent clinical trials.
The FDA says yes, citing advances in the science of clinical trial design and a series of humiliations involving trials for drugs the agency had approved, including the antibiotic Ketek….
But the pharmaceutical industry and some infectious-disease doctors say the proposed rules will make it so difficult and expensive to gain approval for new antibiotics that the few remaining companies will abandon the field altogether….
At times the debate has been so heated that the acting chairman of an FDA committee opened a 2009 meeting by warning that he didn’t want to read the next day about police “having to arrest scientists for breaking shop windows and turning over cars.”…
For years, new antibiotics often were approved based on clinical trials that didn’t have to show the new drug was better than an old one. Instead it had to fall within an acceptable margin of efficacy, which meant it could test somewhat worse and still be considered a success.
Just how much worse is OK with the FDA lies at the heart of the debate. The FDA wants the margins for these “non-inferiority trials” to be scientifically justified, and that may result in margins much tighter than before.
Whatever legal considerations may lie behind the FDA’s position, from a medical point of view its planned rules are ridiculous. To be clinically valuable, new antibiotics don’t need to be better than existing ones, just different. Against most diseases, combinations of antibiotics are the best therapy. Striking at a bacterium by several independent mechanisms is highly effective at impairing its activity and helping the immune system defeat it.
The fact that bacteria evolve resistance makes the need for a steady stream of new antibiotics even more critical.
Adding to the problem is that it is not feasible to organize clinical trials large enough to evaluate efficacy:
But showing one antibiotic is superior to another is hard because many antibiotics work so well, Spellberg said….
Placebo trials, in which the drug is tested against a look-alike but useless pill or injection, are also unrealistic, according to some experts. It’s nearly impossible to persuade patients with a painful sinus infection to enroll in a study with a 50 percent chance of getting a sugar pill and not a drug, they said….
Some are suggesting that for community-acquired pneumonia, antibiotics trials might require as many as 10,000 patients at a cost of about $50,000 a patient, or $500 million.
The solution is simple. Antimicrobials should be evaluated for safety only. Doctors can work out efficacy quickly through clinical experience.
Dr. David Shlaes, who worked in pharmaceutical antibiotic development for decades and is now a consultant to the industry, said it is absurd to be, in effect, questioning if antibiotics work.
“This is like asking how do I know parachutes work?… Those of us in infectious disease, we are all scratching our heads wondering: What the hell they are talking about?” said Shlaes, whose book, “Antibiotics: The Perfect Storm,” will be published this fall. “It is like proving gravity all over again.”
Soon after reading this story I learned that our next door neighbor, a 62-year-old man in seemingly fine health, died over the weekend from an MRSA infection he contracted while in the hospital for a surgical procedure. The antibiotics that might have saved him were never developed, due to clinical trial requirements that are about to become even more onerous.
“Nobody can run those trials,” said Shlaes. “[FDA administrators] live in a different world. Their world is numbers and logic. It is not patients and life.”
Dr. Shlaes is exactly right. The bureaucrats are not concerned about patients and life. They are concerned about drugs embarrassing them, as Vioxx did.
Without effective antibiotics, the whole medical system falls apart, experts say.
Yes. But when it does, how many will realize that the FDA, and the politicians who wrote their governing legislation, are to blame?