Antibiotics in failing health

By Karen Augé
Denver Post Staff Writer
The Denver Post

The last time a new tuberculosis drug was developed, Richard Nixon was in the White House and Dr. Michael Iseman was a young resident in a New York City hospital.

That drug, Rifampin, "was the biggest thing to hit TB in 30 years," said Iseman, now a doctor at National Jewish Medical and Research Center in Denver.

Since then, Iseman has become a recognized authority on TB and Rifampin has remained the centerpiece of TB treatment.

Now, however, a growing number of tuberculosis strains are not fazed by the drug - as in the highly publicized case of Andrew Speaker, who is being treated at National Jewish.

Tuberculosis isn't the only infection increasingly impervious to the antibiotics in medicine's arsenal.

In the past decade, federal agencies - such as the Centers for Disease Control and Prevention, the National Institutes of Health, and the Food and Drug Administration - have warned that antibiotic overuse has led to evolving drug-resistant bacteria.

At the same time, the agencies say, there is a dearth of research dollars for new antibiotics - creating a looming medical crisis.

"Infections that were once easily curable with antibiotics are becoming difficult, even impossible, to treat," the Infectious Disease Society of America warned in its report "Bad Bugs, No Drugs."

"The problem is dollars, not chemistry," said Christopher Spivey, a spokesman for the Boston-based Alliance for the Prudent Use of Antibiotics.

Antibiotics not as profitable

Antibiotic development requires huge investments of money, $400 million to $800 million, according to a study in the journal Clinical Infectious Diseases.

To provide as much income as drug companies get from the sale of one drug to a person who, for example, takes a weight-loss pill daily, a company would have to sell antibiotics to 200 to 500 people with an illness like pneumonia, Spivey said.

There are currently under development 50 drugs each for obesity, pain and Type II diabetes, according to PhRMA, a group representing the nation's leading drugmakers.

There are just nine new drugs in the works for tuberculosis and eight for malaria.

For staph infections and drug- resistant staph infections, PhRMA lists 23 drugs under development.

This isn't a new trend. FDA approval of new anti-bacterial drugs has dropped 56 percent in 20 years, according to a 2004 study by Brad Spellberg, a professor of medicine at the University of California, Los Angeles.

Work on new TB drugs has languished in part because of the widespread, mistaken belief that the disease was no longer a problem in this country, said Mel Spigelman, director of research and development for the Global Alliance for TB Drug Development.

Iseman said that on the world market drugmakers are discouraged from developing antibiotics.

"There is a tendency - in global use - for knock-offs," Iseman said. "Companies simply choose not to honor patent protections and it's done under the seemingly noble rubric of, 'we have patients dying of - whatever disease - in our country and we can't afford your drug, so we're going to make our own.' "

In its report, the infectious-disease society recommended incentives, such as tax breaks, for antibiotic research and development.

Difficult to draw attention

Still, drug companies don't get much public sympathy these days, which could make it politically tough for members of Congress to grant those tax breaks, Iseman said.

Antibiotic development "won't get on the radar until there is a really good killing plague," Spivey said.

In that respect, Speaker may have unintentionally done a favor for TB drug research by drawing attention to the disease, Spivey said.

Since 2000, interest in TB has picked up, said the TB Alliance's Spigelman.

While only a handful of new TB drugs are in the pipeline, even that is progress, Spigelman said.

"In 2000, we had zero," he said.

This year, the National Institutes of Health will spend $158 million on TB- drug research. The Bill and Melinda Gates Foundation has pledged $900 million over the next decade.

Four drug companies - Bayer, Novartis, AstraZeneca International and GlaxoSmithKline - now have units working on infectious diseases, including TB.

Bacteria, however, reproduce every 10 minutes or so, while it takes humans about 20 years to develop means to battle new strains, Iseman said.

"They have the ability to adapt to our drugs," he said. "So if you're in Vegas, you bet on the bugs."

Staff writer Karen Augé can be reached at 303-954-1733 or kauge@denverpost.com.



--------------------------------------------------------------------------------


A history of antibiotics and drug resistance
1920s-'50s: Scientists harness the power of living organisms to fight bacteria, ushering in the era of antibiotics.

1928: Scottish bacteriologist Alexander Fleming, above, accidentally discovers that a mold juice he names penicillin can kill staphylococcus bacteria.

1940: Oxford University pathologist Howard Florey isolates pure penicillin and demonstrates how it can cure a wide range of pathogens, including strep infections, gonorrhea and syphilis.

1943: Penicillin becomes the first antibiotic to be put in widespread use.

1944: Russian-born microbiologist Selman Waksman, working in the United States with soil microbiologist Albert Schatz, discovers streptomycin, a powerful antibiotic that proves effective against tuberculosis.

1958: American molecular geneticist Joshua Lederberg wins the Nobel Prize in medicine for demonstrating the way bacteria interact and exchange genetic material - a key concept behind drug resistance.

1967: The first penicillin-resistant pneumonococcal bacteria are reported in Papua New Guinea.

1968: Drug-resistant Shigella diarrhea kills 12,500 people in Guatemala.

1970-72: Penicillin-resistant gonorrhea spreads around the world, transmitted in part by U.S. servicemen, who contract the disease from prostitutes in Southeast Asia.

1976: Several weeks after attending an American Legion convention in Philadelphia, 34 people die from a mysterious form of pneumonia that thwarts available treatments and comes to be known as Legionnaires' disease.

1980s-'90s: The public-health effects of drug-resistant bacteria become clear, prompting new concerns about infectious diseases.

1986: The U.S. Food and Drug Administration, the Centers for Disease Control and Prevention, and the Department of Agriculture establish a national anti-

microbial-resistance monitoring system to track food-borne microbes.

1988-95: Studies in Finland, the Netherlands and other European countries find increased drug resistance in farm animals. Many of the livestock are fed antibiotics as growth-promoters.

1990: Puppeteer Jim Henson, creator of the Muppets, dies of toxic-shock syndrome induced by an aggressive strain of streptococcus that acts too quickly for antibiotics to work.

1992: An influx of immigrants sparks a tuberculosis epidemic in New York and other cities, forcing local officials to remobilize dormant TB prevention efforts. The federal government is spending just $55,000 a year monitoring drug resistance.

1995: A form of staph infection that is resistant to methicillin results in almost a half-billion dollars in direct medical costs and claims 1,409 lives in New York City hospitals.

1996: Japanese bacterial geneticists detect the world's first staph infection capable of resisting the powerful antibiotic vancomycin.

1997: Health officials report the percentage of antibiotic-resistant cases has surged from 2 percent in 1991 to 43 percent in 1997.

1998: The Institute of Medicine contends that overuse of antibiotics has brought about widespread drug resistance, estimating that as many as half of the prescriptions for the drugs given each year to outpatients are unnecessary. The U.S. Centers for Disease Control and Prevention spends more than $11 million a year monitoring drug resistance.

2000: The Food and Drug Administration approves one of the newest major new antibiotics, Bayer's ciprofloxacin hydrochloride, known as Cipro. Cipro makes news the following year as a treatment for a spate of unsolved anthrax poisonings.