- The Washington Times - Tuesday, March 19, 2013

Health officials are warning of the rise of the “superbugs” — bacteria and other pathogens that cannot be killed by modern medicine.

But many pharmaceutical companies are resisting the call to develop effective antibiotics and instead are shifting their resources to other products.

Exhibit A is AstraZeneca, one of the major companies still working on developing antibiotics.

Its new chief executive, Pascal Soriot, said Monday the drug giant was restructuring its workforce and will focus on three therapy areas: cancer, cardiovascular and metabolism disorders, and respiratory and inflammatory diseases. This means “reduced spending on anti-infectives,” according to Reuters.

Pfizer, Roche, Bristol-Myers Squibb and Eli Lilly have all reduced or eliminated their antibiotic research efforts, while Merck & Co. and GlaxoSmithKline are still actively pursuing such medicines, Reuters added.

The reason businesses resist making new antibiotics is rational: The drugs are expensive to develop but are used briefly by most patients and are aimed at pathogens that eventually learn how to build up a resistance to them.

As a result, there have always been relatively few antibiotic products in development, and now — gauging by what is in the pipeline — “none of them really is going to be active against these bacteria in the near term,” said Dr. Gary A. Roselle, national director of the Infectious Diseases Service for the Department of Veterans Affairs health care system.

“Incentivization” for drug development that may not have major monetary success is a big topic of discussion, added Dr. Roselle, who works at the Veterans Affairs Medical Center in Cincinnati. But in the meantime, “The current goal has to be prevention, wherever possible,” he said.

Public warnings have been issued about multidrug-resistant tuberculosis and gonorrhea, and a hospital-associated infection known as methicillin-resistant Staphylococcus aureus.

A new bug, described as a “nightmare bacteria,” was highlighted in early March by Dr. Thomas Frieden, director of the Centers for Disease Control and Prevention.

Carbapenem-resistant Enterobacteriaceae (CRE) refers to a family of mostly harmless bacteria that live in the gut, and includes E. coli, shigella, salmonella and klebsiella. These bacteria can cause illnesses, including pneumonia, diarrhea and urinary tract infections, if they are swallowed or enter the bloodstream through an open wound.

Carbapenem-resistant refers to some bacteria that become immune to even the “last-resort” class of drugs.

CRE “pose a triple threat” because few, if any, antibiotics can kill them; they are associated with a high mortality rate; and “they can spread their resistance to other bacteria,” Dr. Frieden said.

That last point is of great concern, Dr. Frieden said, because if CRE pathogens transfer their drug-resistance genes to another bacteria such as E. coli, it could make a common illness, such as a urinary tract infection, extremely difficult to treat.

Reports of the rise of the rare but potentially deadly CRE superbugs caught the attention of lawmakers on Capitol Hill.

Congressional hearings “should be held as quickly as possible to examine the appropriate federal response to this serious threat,” Democratic Reps. Henry A. Waxman of California, Frank Pallone Jr. of New Jersey and Diana DeGette of Colorado wrote recently to the Republican leaders of the House Committee on Energy and Commerce.

The committee worked on this issue in 2012, and President Obama signed a law that contained an incentive for antibiotic development: Generating Antibiotic Incentives Now would add five years of patent-exclusivity to qualified products used to fight infectious diseases such as CRE and tuberculosis. Such qualifying drugs would also get “priority review” by federal agencies.

The law is “a good first step, but much more is needed,” Robert Guidos, vice president for public policy and government relations at the Infectious Diseases Society of America, said Tuesday.

Another hearing on the drug-resistant pathogens would be good, he said, because there are many more ways to encourage drug-makers to keep fighting to find new antibiotics. Mr. Guidos cited research and development tax credits and reimbursement models as potential solutions.

Britain’s top medical officer said late last week she was exploring ways to offer the pharmaceutical industry greater financial incentives to target the new class of antibiotic-resistant germs, including public-private partnerships and government purchase guarantees for companies that develop useful but financially unrewarding drugs.

“We need to look at basic science, intellectual property and how to invest so we can develop products and get them into practice quickly to save lives,” Chief Medical Officer Sally Davies told the Financial Times.

Dr. Frieden called for stepped-up sanitation efforts in health care facilities, more diligent hand washing by all health care workers, and more discriminating use of antibiotics and invasive medical devices such as catheters.

“We need to continue to invest in research and test to prevent CRE infections in the first place” — and develop new antibiotics, Dr. Frieden added.

Providers of nursing home and other long-term health care say they are already “on top” of the multidrug-resistant bugs.

“We are very concerned about any kind of superbug that’s out there,” said Sandra Fitzler, senior director of clinical services at the American Health Care Association, the nation’s largest trade group for health care facilities that care for about 1 million elderly and disabled people a day.

“We’re very careful about those resistant organisms,” she said, noting that the CDC warnings prompted new reminders to facilities about hygiene, cleanliness, and overuse of antibiotics and catheters.

Fortunately, studies have shown that if CRE patients are quickly identified, and they and their medical equipment are isolated from others, current hospital sanitary protocols can greatly improve the odds that the infections will not spread. An Israeli study cited by the CDC, for instance, found that concerted efforts led that nation to slash its CRE incidence from 55.5 cases per 100,000 patient days to 11.7 cases per 100,000 patient days.

“We know it’s a serious problem, but we also know it’s a problem we can stop,” Dr. Frieden said.

He also recently tweeted: “Healthcare providers: Wash your hands before touching a patient every time! Prevent CRE.”

CRE death rates ranged from 38 percent to 44 percent in two studies; the CDC reported three deaths out of 72 CRE cases in three states from August to December 2011.

Mortality is typically related to specific situations, such as when the pathogen enters the bloodstream of a patient whose health is already compromised. Use of invasive medical devices is a risk factor; thus, patients in long-term acute-care hospitals, nursing homes, rehabilitation centers and military hospitals are at elevated risk, CDC data showed.

The CDC issued its warning about CRE in a March 5 Vital Signs report, and elaborated on the pathogen in its Morbidity and Mortality Weekly Report on March 8.

CRE, first seen in the United States in 1996, is still “relatively uncommon,” the CDC said, but it decided to raise concerns about it because it found at least one case of CRE in a recent survey of 42 states. “We only have a limited window of opportunity to stop this infection from spreading to the community and spreading to more organisms,” Dr. Frieden said.