Drugs to Fight Deadly Superbugs in Short Supply

An antibiotic apocalypse looms, and only seven new drugs are in development to combat the most lethal superbugs, including carbapenem-resistant Enterobacteriaceae (CRE), the often incurable “nightmare bacteria” that the Centers for Disease Control and Prevention (CDC) warned about last month, citing a new report from the Infectious Disease Society of America (IDSA).

"We're on the precipice of returning to the dark days before antibiotics enabled safer surgery, chemotherapy and the care of premature infants," says Dr. Helen Boucher, an infectious diseases specialist at Tufts Medical Center in Boston and lead author of the IDSA report, published online in Clinical Infectious Diseases.

With the seven new drugs years away, if they win FDA approval at all, “we’re down to one last-resort antibiotic to fight an epidemic of highly resistant gram-negative bacterial infections,” reports Brian Currie, MD, vice president and medical director for research at Montefiore Medical Center in NYC.

This last-resort drug—polymyxin—can be potentially toxic to the brain and kidneys, adds Dr. Currie, “but in this era of desperation, it’s all we have left, and now, ominously, there are CRE isolates [the so-called “nightmare bacteria”] that don’t respond to it, which means we have nothing to fall back on.”

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“We’re All at Risk”

The drug pipeline for new weapons against deadly superbugs is “on life support, and novel solutions are required to resuscitate it—now,” IDSA president David Relman, MD said in a statement. 

“We’re all at risk,” adds Dr. Boucher.

Each year, nearly two million Americans develop healthcare-acquired infections—most of them triggered by antibiotic-resistant bacteria—and 100,000 of them die. The World Health Organization (WHO) and the CDC have called antibiotic resistance one of the single greatest health threats of our time, while the IDSA has warned of a looming “antibiotic apocalypse” since 2004.

In fact, just one superbug, MRSA, kills more Americans each year than HIV/AIDS, emphysema, Parkinson’s disease, and homicide combined. In March, the CDC warned of a four-fold rise in CRE that kills up to 50 percent of those infected. Cases of CRE, which occur in healthcare settings, were reported in nearly 200 U.S. hospitals in the first six months of 2012 alone.

Billions Spent to Develop “Lifestyle Drugs,” Not Antibiotics

Compare the seven drugs being developed for these resistant bacteria to the nearly 1,000 new cancer drugs that are currently in development. Furthermore, Dr. Currie notes that billions of dollars are being spent to come up with new "lifestyle drugs," such as the next blockbuster treatment for erectile dysfunction, while a potential epidemic of drug-resistant bacterial infections has already spread to at least 41 states and every continent of the world.

In fact, only two new antibiotics have been FDA-approved since 2009, the IDSA reports, along with hundreds of drugs for other conditions. The average cost of bringing a new drug to market is $1.3 billion, Forbes reports, and it can range up to $11 billion. “It costs the same amount of money to develop a new drug that patients will take for the rest of their lives as it does to develop an antibiotic that patients might take for several days,” says Dr. Currie, who is also assistant dean for clinical research at Albert Einstein College of Medicine and a fellow of IDSA.

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Gram-Negative Bacteria—the Most Dangerous Superbugs

Gram-negative bacteria (so named because they don’t turn purple during a lab test called the Gram stain test, while Gram-positive bacteria do) trigger a wide range of infections, including food poisoning, cholera, pneumonia, and STDs, according to the National Institutes of Health. Among the Gram-negative bacteria that have developed antibiotic resistance are:

  • E. Coli, the leading cause of urinary tract infections (UTIs). There are reports of E. Coli infections in 37 states that are resistant to more than 15 types of antibiotics, including carbapems, which the CDC calls the last line of defense when all other treatments fail. Up to 50 percent of these infections are fatal.
  • Klebsiella pneumonia, which causes many types of healthcare-associated infections, including pneumonia, UTIs, and bloodstream infections. The most deadly form is called CRKP (carbapenem-resistant Klebsiella pneumonia) and is resistant to almost all antibiotics. 
  • Neisseria gonorrhoeae, which causes the sexually transmitted disease gonorrhea, the second most commonly reported infectious disease in the US. Cases of difficult-to-treat “super gonorrhea” have been reported in the US and the CDC says it’s “only a matter of time” before there will be no treatment at all, meaning that the STD could actually be fatal, the Atlantic reports. 

Deaths from Untreatable Infections on the Rise

Lack of effective antibiotics killed Josh Nahum in 2006. Amazingly, the 27-year-old from Colorado survived a skydiving accident that caused several broken bones. While in the intensive care unit, he was successfully treated for one hospital-acquired bacterial infection (MRSA), only to be hit by an even more dangerous, gram-negative superbug called Enterobacter aerogenes.

After a grotesque battle with an untreatable infection that left him a ventilator-dependent quadriplegic, he died two weeks later. His family now works to raise awareness of gram-negative bacterial infections.

If we don’t act immediately to avoid overuse of existing treatments, and develop more new antibiotics, says IDSA, “we face a future that may resemble the days before these ‘miracle’ drugs were developed; where people die of common infections and many medical interventions we take for granted—including surgery, chemotherapy, organ transplantation and care for premature infants—become impossible.”

What You Can Do to Stay Safe

Gram-negative bacteria, while mainly a threat in healthcare settings, mutate more easily than other bacteria, Dr. Currie notes. “This tribe of bacteria has exhibited an ability to accept DNA with resistance genes that makes them immune to 18 different penicillin-like drugs, including the most powerful medications we have.”

What makes these bacteria particularly dangerous adds Dr. Currie, “is that even when they’re killed, their cell walls release endotoxin, which causes an inflammatory cascade in the patient that can lead to sepsis [an overwhelming infection]. Even with excellent care, the person may not survive.”

The best defense against healthcare-acquired infection is to insist the medical providers wash their hands and wear gloves before examining you. As I reported recently, you can also reduce risk for contagious diseases by up to 51 percent by washing your hand frequently. In fact, 40 million Americans a year fall ill due to germs spread by hands, which can harbor up to 500,000 bacteria per square centimeter.

Other ways to combat antibiotic resistance include:

  • Avoiding unnecessary use: Antibiotics don’t work on viral illnesses like colds and flu. New guidelines for kids’ ear infections from the American Academy of Pediatrics advise observation or “watchful waiting” instead of an immediate antibiotic prescription in many cases.
  • If your doctor prescribed antibiotics, always ask why and if there is any other treatment, including watchful waiting.
  • If antibiotics are legitimately prescribed, always make sure your child takes the full course of medication, even if the symptoms clear up. Incomplete treatment may lead to tomorrow’s superbugs.

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