WHO's 'priority pathogens' list highlights urgent need for new drugs

The World Health Organization has released its first list of the world's most dangerous superbugs 12 families of bacterial supervillains consideredthe most serious threats to human health.

The WHO calls it a list of "priority pathogens" because the bacteria have developed resistance to key antibiotic drugs. And that is making health care more complicated, as doctors are forced to try one drug after another to treat hospital-acquired infections.

A study in The Lancet warnssuperbugs are already causing many post surgical infections which is making routine surgery more dangerous.

There are predictions that without effective antibiotics, much of modern health care would be in jeopardy, including cancer chemotherapy, births by cesarean section, and organ transplantation.

With this list, the WHO is again raising the alarm over the growing health threat created by the rise of bacteria resistant to multiple drugs. The list is intended to help guide research and development by identifying themost serious threats, the ones that most urgently need new drugs.

At the top of the list, in a black box labeled "critical," are three of the most fearsome resistant bacteria in the world(Acinetobacter baumannii, Pseudomonasaeruginosa,and Enterobacteriaceae).

This trio of bugs thrives in hospitals and residential care facilities, infecting patients already weak and dependent on ventilators and catheters.They can cause potentially deadly blood and respiratory infections and are resistant to even the most powerful antibiotics.

Ingenious bacteria

They are part of group known as Gram negative bacteria, which have developed an ingenious system to protect themselves against any molecule that might kill them. They have two cellular walls, making it harder for drugs to penetrate the double exterior membranes. They're also equipped with pumps and other tools to reject drug molecules.

"So if you can't get the molecule in, it can't act and kill the bacteria," saidCarolyn Shore, head of the antibiotic innovations group at Pew Charitable Trusts. The U.S.-based non-profit is working with scientists and industry to develop new antibiotics.

No truly novel antibiotics have made it to the market since the mid-1980s, and it took almost two decades for those drugs to be approved for human use.

"Antibiotic resistance is growing, and we are fast running out of treatment options. If we leave it to market forces alone, the new antibiotics we most urgently need are not going to be developed in time," Dr. Marie-Paule Kieny, WHO's assistant director-general for health systems and innovation, said in a press release.

The second and third categories on the priority list include increasinglydrug-resistant bacteria that cause more common diseases such as as sexually transmittedgonorrhoea and foodborne illness caused by salmonella.

Only 1 in 5 drugs is approved

There are about 40 new antibiotics in clinical development, but only about onein fivenew drugs are successfully approved for human use. Of the drugs the pipeline now, only a fraction would be effective against Gram negative bugs. "The pipeline remains thin,' Shore said.

And most of the largest pharmaceutical companies abandoned antibiotic development years agobecause it wasn't profitable.

"Because there wasn'ta huge return on investmentand the high cost of [research and development]outweighs the revenue of any potential new product, a lot of the big companies got out of the space," said Shore.

Themoreyou use an antibiotic the less effective it becomes over time. Carolyn Shoreof Pew Charitable Trusts

The reality of the antibiotic market works against the traditional pharmaceutical marketing strategy.Ratherthan being used as widely as possible, the drugs have to be reserved and used only when needed.

"Themoreyou use an antibiotic the less effective it becomes over time," said Shore. "So it's really important to limit the use of newproducts except when necessary to ensure they have longevity."

At McMaster University in Hamilton, Gerry Wrightdiscovered a compound that can disarm Gram negative bacteria and restore their vulnerability to existing drugs. Hisdiscovery made the cover of Naturethree years ago.

"Getting it into development has been an exercise in frustration and disappointment," he said.

The Canadian Institutes of Health Research rejected his application for funding. Finally the U.S. National Institutes of Health supported some early pre-clinical studies and now the technology has been transferred to the private sector for further development.

For Dr. MichaelGardam, an infectious disease specialist at UHN hospitalsin Toronto,the scariest bug on the list is in the red zone, at Number5, vancomycin-resistantStaphylococcus aureus,

"That's theone we've worried about foryears," he said. "I've never seen it because it's still a very rare phenomenon. If that weresomethingthat were to get going it would be very frightening."

That's because the garden variety Staphylococcus aureusbacteria is one of the most common human pathogens, causing a range of infections from skin boils and bone abscesses to meningitis and respiratory infections.

The WHO experts decided which bacteria to put on the priority pathogen list based on the severity of the infection they cause, how common they are in community settings outside of hospitals, and how easily they spread from animals to people, and from person to person. The WHO also considered how many drugs remain effective against the listed bacteria.

The full WHO list:

Priority 1: Critical

• Acinetobacter baumannii, carbapenem-resistant.
• Pseudomonas aeruginosa, carbapenem-resistant.
• Enterobacteriaceae, carbapenem-resistant, ESBL-producing.

Priority 2: High

• Enterococcus faecium, vancomycin-resistant.
• Staphylococcus aureus, methicillin-resistant, vancomycin-intermediate and resistant.
• Helicobacter pylori, clarithromycin-resistant.
• Campylobacter spp., fluoroquinolone-resistant.
• Salmonellae, fluoroquinolone-resistant.
• Neisseria gonorrhoeae, cephalosporin-resistant, fluoroquinolone-resistant.

Priority 3: Medium

• Streptococcus pneumoniae, penicillin-non-susceptible.
• Haemophilus influenzae, ampicillin-resistant.
• Shigella spp., fluoroquinolone-resistant.

McMaster'sWright says even though not all of the bugs on the WHO's priority pathogen list are immediate threats in Canada, the listis an accurate reflection of the international challenges in antibiotic resistance.

We're only a plane ride away from all of these things. Gerry Wright, McMaster University

"Because we're only a plane ride away from all of these things, although Number 1 and Number 2 on the list are not a huge problem in Canada right now, they could be tomorrow. So we need to take all this very seriously."

Researchers in Canada are working on new approaches to antibiotic therapy, including searching for novel methods to attack bacteria, and ways to shut off acquired resistance genes so that old drugs are once again effective.

The WHO also warns that new drugs by themselves won't solve the antibiotic resistance problem. It's also calling on health officials to develop ways to reduce the risk of infections, and encourage the responsible use of existing drugs in both humans and animals.

• Old drugs could become our new antibiotics