That doctors have resorted to such an old, dangerous drug — colistin causes kidney damage — highlights the lack of new antibiotics coming out of the pharmaceutical pipeline even in the face of a global epidemic of hospital-acquired bugs that quickly grow resistant to the toughest drugs.
It’s a case of evolution outrunning capitalism.
Between 1945 and 1968, drug companies invented 13 new categories of antibiotics, said Allan Coukell, director of medical programs at the Pew Health Group.
Between 1968 and today, just two new categories of antibiotics have arrived.
In 2011, the Food and Drug Administration approved one new antibiotic, which fights one of the many bacteria, Clostridium difficile, causing deadly hospital-borne infections.
“What kept us out of trouble for the last 60 years is that every time drug resistance caught up to us, the pharmaceutical companies would go back to the drawing board and develop the next generation of drugs to keep us ahead of the game,” said Brad Spellberg, an infectious diseases physician in Los Angeles who heads a microbial resistance task force for the Infectious Diseases Society of America. “That’s the part of the equation that’s changed. Drug companies are no longer trying to get one step ahead.”
Experts point to three reasons pharmaceutical companies have pulled back from antibiotics despite two decades of screaming alarms from the public health community: There is not much money in it; inventing new antibiotics is technically challenging; and, in light of drug safety concerns, the FDA has made it difficult for companies to get new antibiotics approved.
As a result, only four of the world’s 12 largest pharmaceutical companies are researching new antibiotics, said David Shlaes, a drug development veteran and consultant.
Last year, Pfizer, the world’s biggest drug company, closed its Connecticut antibiotics research center, laying off 1,200 workers. The company said it was moving the operation to Shanghai. But Shlaes said Pfizer is struggling to open the Chinese facility and has largely abandoned antibiotics.
While a new antibiotic may bring in a billion dollars over its lifetime, Shlaes said, a drug for heart disease may net $10 billion. Depression and erectile dysfunction drugs — typically taken daily for years, unlike antibiotics, which are used short-term — are also more profitable than antibiotics.
Congress recognized the problem earlier this year, inserting a provision in an FDA authorization bill to grant an additional five years of market exclusivity — meaning no competition from generics — for companies inventing new antibiotics.
“It’s a great first step,” said Spellberg, but he added that the provision “is not strong enough to turn things around.”
Shlaes said that concerns about antibiotic safety — driven by deaths linked to the drug Ketek that came to light in 2006 — have made the FDA reluctant to approve new antibiotics. “They’ve basically made it impossible for companies to develop and market antibiotics in the U.S.,” he said.
Ed Cox, head of the FDA’s office of microbial products, said the agency is “looking at new approaches” for speeding up the approval of new antibiotics, such as requiring smaller clinical studies and allowing research with patients such as those who have multiple infections. “We’re trying hard to address the challenges” faced by the drug industry in developing antibiotics, Cox said.
Such changes are “in the discussion and planning stage,” Cox added. “But this is a critical step so that folks in industry wanting to develop [antibiotics] can do so.”
Shlaes characterized the moves at FDA as “trying to paint themselves out of a corner.”
It’s an especially tight corner that hospital physicians find themselves in. Ten years ago, the Centers for Disease Control and Prevention reported that 1.7 million annual hospital-borne infections in the United States caused 99,000 deaths. The CDC is now updating those figures.
In a recent survey of infectious disease specialists, Spellberg said, 60 percent reported encountering infections resistant to every antibiotic.
“That’s the real crisis,” said Henry Masur, chief of NIH’s Critical Care Medicine Department, who last year watched six patients die from the bacterium Klebsiella pneumoniae when even colistin, that old warhorse, stopped working. “The problem here is that we’re not developing antibiotics fast enough to keep up with this.”