IDSA Releases Hit List of Dangerous Bugs

WASHINGTON, DC, MARCH 1, 2006--The Infectious Diseases Society of America (IDSA) today renewed its call for federal legislation to galvanize the pharmaceutical and biotechnology industries into fighting the growing epidemic of antimicrobial resistance, releasing a “Hit List” of the six top-priority dangerous, drug-resistant microbes. These six “superbugs” are especially dangerous because few or no new drugs are being developed to treat them.

The Hit List was drawn from an article in the March 1 issue of Clinical Infectious Diseases.

“These are life-threatening drug-resistant infections, and we’re seeing them every day,” says IDSA President Martin J. Blaser, MD. “What is worse is that our ammunition is running out and there are no reinforcements in sight.”

Congress has not passed the comprehensive legislation needed to stimulate antimicrobial research and development that IDSA called for in its July 2004 report, Bad Bugs, No Drugs: As Antibiotic Discovery Stagnates…A Public Health Crisis Brews.

The new article and Hit List, written by the authors of the Bad Bugs report, re-focus attention on the issue by identifying what experts in the field believe are “the microbes where the gap between public health threat and drug development are the greatest,” says John G. Bartlett, MD, chair of IDSA’s Antimicrobial Availability Task Force and one of authors of the article. “These are the germs we see in hospitals every day that we don’t have good treatments for.”

“These organisms are a serious threat to public health, but it’s much more profitable for a pharmaceutical company to make a cholesterol drug that you take for a lifetime than an antibiotic you take for a week,” says George H. Talbot, MD, lead author of the article. “IDSA is concerned that market forces are not going to solve this problem,” he adds.

IDSA’s Bad Bugs, No Drugs report showed a steady 20-year decline in the number of new FDA-approved antimicrobials and total withdrawal from the field by many major pharmaceutical companies.

The authors of the report revisited the issue and found a few more drugs in the pipeline. “But the germs that are the biggest problems are not the ones getting the most attention from the major pharmaceutical companies,” Dr. Talbot says. “Action is needed — and soon,” he adds, “because it takes years for a new drug to go from the lab to the medicine cabinet.”

IDSA is urging Congress to pass comprehensive legislation to encourage the pharmaceutical industry to re-enter this essential field. Congress should establish a commission to set antimicrobial discovery priorities. Companies that develop novel antimicrobials should be rewarded with market exclusivity rights. And research, development, and manufacturing should be encouraged through tax credits.
“Investments in stimulating antimicrobials research and development will also pay dividends in other areas of infectious diseases preparedness, including biodefense,” Dr. Bartlett notes. “It’s urgent that Congress make this investment now.”

THE HIT LIST:
Methicillin-resistant Staphylococcus aureus (MRSA): MRSA infections constitute the majority of health care-associated infections, increasing lengths of hospital stay, severity of illness, deaths, and costs. While these infections used to be limited primarily to hospitals, they are becoming increasingly common in communities nationwide, especially where groups of people are in close quarters, including military facilities, sports teams, and prisons. The number of infected children jumped 28 percent between 2001 and 2004. Several treatment options are available for MRSA, but many have harsh side effects, and resistance is growing to each of them. Most of the drugs in development must be given by injection—a painful, inconvenient, and expensive route. Drugs that can be taken by mouth are desperately needed.

Escherichia coli and Klebsiella species: These bacteria are major causes of urinary tract, gastrointestinal tract, and wound infections. They are becoming resistant to a growing number of antibiotic classes at the same time as the frequency of outbreaks is increasing. Failure to treat with the appropriate antibiotics during a recently documented K. pneumoniae outbreak increased the mortality rate from 14 percent to 64 percent. Both microbes tend to rapidly evolve resistance to new drugs, but few are available or under development. New therapies are badly needed.

Acinetobacter baumannii: A. baumannii "is a prime example of a mismatch between unmet medical need and the current antimicrobial research and development pipeline," according to the Clinical Infectious Diseases article. The bacterium is a growing cause of hospital-acquired pneumonia. Mortality rates range from 20 to 50 percent. The number and hardiness of drug-resistant strains are growing. Soldiers are also returning from Iraq and Afghanistan with cases of highly resistant Acinetobacter wound infections. Doctors have been forced to resort to an old drug, colistin, which had previously been abandoned as too toxic. But only one new drug is on the horizon to treat Acinetobacter infections, and it is considered to be too toxic for children.

Aspergillus: This fungal infection is a growing problem among immunocompromised patients such as cancer patients, organ transplant recipients, and people with HIV, and the number of infections is expected to keep increasing as the number of immunocompromised patients increases. Existing drugs are toxic or interact with other drugs. Resistance to them is growing. Even with the best, newly approved antifungals, death rates from Aspergillus infection are 50-60 percent. Few new antifungal drugs are in the pipeline, and their ability to combat Aspergillus infections is uncertain because drug companies are choosing to conduct clinical trials on other, easier-to-study fungal infections.

Vancomycin-resistant Enterococcus faecium (VRE): VRE is a major cause of bloodstream infections, infections of the heart, meningitis, and intra-abdominal infections. A recent survey of 494 U.S. hospitals found a VRE rate of 10 percent of across all patient groups. Rates are as high as 70 percent among high-risk groups. While drugs are available to treat VRE, they have serious shortcomings. Current drugs do not rapidly kill VRE, and only one is available in an oral formulation.

Pseudomonas aeruginosa: This germ causes severe infection that can be life-threatening, particularly in immunocompromised patients. Rates of P. aeruginosa hospital-acquired pneumonia have nearly doubled, from 9.6 percent in 1975 to 18.1 percent in 2003. Infections following surgery and urinary tract infections from P. aeruginosa have doubled. The germ poses a particular threat to children with cystic fibrosis (CF). Antibiotics can keep CF patients alive for decades, but eventually highly resistant germs take over. With almost no alternatives left, these patients die unless they receive lung transplants. No novel drug candidates have entered human trials. New ideas, research, and products are desperately needed.