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Sylvia Pagan Westphal

New antibiotics — stat

As resistance builds to today’s drugs, FDA must help usher in more

By Sylvia Pagan Westphal
December 23, 2010

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AMID ALL the drugs available to us, antibiotics are remarkable in that, when they work, they cure. Because of them, we have forgotten about the era when microbes won the battle most of the time and a fever could be a death sentence.

Yet not long from now, that scenario may recur on a worryingly frequent basis. Some serious infections involve bacteria that are resistant to most, if not all, antibiotics, so doctors are running out of options.

And while the obvious solution is to develop new antibiotics, mounting tension between drug makers and the US Food and Drug Administration is standing in the way.

The latest strain of bacteria to make headlines is NDM-1, which was first identified in India. That country is facing a serious crisis of antibiotic resistance due to its prolonged misuse and overuse of antibiotics. Yet reports of NDM-1 in hospital patients are also surfacing from the United States and several other developed countries.

There’s more bad news: NDM-1 belongs to a category known as “gram-negative” bacteria, which have thick outer shells that make them harder to kill with drugs.

Infectious-disease experts are worried about other bacteria in the same category; one is Acinetobacter baumannii, known as the “Iraqibacter” due to its presence in wounds from soldiers in Iraq and Afghanistan, which is becoming increasingly resistant to all antibiotics. The issue isn’t just the growing resistance; what’s worse is that the pipeline for future antibiotics against the gram-negatives is essentially empty. If we run out of options to treat these bugs today, there will be nothing new on the horizon for the next 10 to 15 years.

Doctors and patients have an important role to play in preserving the effectiveness of existing drugs. The more frequently we use antibiotics for conditions, like sinusitis, that would go away on their own, the more we’re likely to become living repositories of antibiotic resistant bacteria.

Yet the ultimate solution is to get more antibiotics into use. While this should be a high priority for the FDA, the agency must move faster to make it happen.

A big scandal in 2006, surrounding an antibiotic called Ketek, placed a spotlight on the inadequacy of some clinical trials to study antibiotics. Since then, the FDA has begun to reconsider the kinds of clinical studies it will accept to approve these drugs. The FDA’s tougher stance is well intentioned — the main goal, after all, is to protect the public — but it’s made companies more nervous about embarking on clinical trials until they know for sure what the agency wants in studies. Unfortunately, the FDA has been moving at glacial speed in providing industry with that clear set of rules — known in medical parlance as “guidance” — as to the proper design of clinical trials for testing antibiotics.

Here’s one example: After a January 2008 workshop on a condition known as community-acquired pneumonia, the FDA published a draft version in March 2009 of its intended guidance for testing antibiotics on this disease. There was a period of public comment, after which the agency convened an advisory committee meeting to discuss the matter in December of that year. Almost another year later, companies still don’t have a definite sense on how to design trials in this important therapeutic area.

It’s not that drugs can’t get approved in the absence of finalized guidance. But without clarity fewer companies are likely to invest the hundreds of millions needed to get more antibiotics on the market.

The situation is even worse with the highly resistant gram-negative bacteria. The traditional model to design clinical trials is useless: Normally, you test the experimental antibiotic against the best existing antibiotic. When there is no best existing antibiotic, what do you test against? How do you design these studies? Nobody in industry seems to have the right answers, and FDA has not given guidance on this crucial issue.

Recognizing the serious public health problem ahead of us, the Obama administration joined forces last year with the European Union to establish a transatlantic task force to tackle antibiotic resistance. The task force’s top priority should be to ensure that the ground rules are clear for those trying to develop new antibiotics. Every year without transparency is a year wasted in a battle that we’ve already begun to lose.

Sylvia Pagán Westphal is a regular contributor to the Globe’s opinion pages.