Beating back the superbugs

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Beating back the superbugs

Rationing antibiotics is a dead end in the battle on bacteria, but there are

other tactics

Palmer, Slate Published: Wednesday, December 09, 2009

Ever felt personally responsible for drug-resistant diseases? It's no wonder.

Virtually everyone -- permissive doctors, nagging patients, hospital

administrators, government bureaucrats and snotty kids -- has been blamed for

the problem. It's true: Bacteria are conquering our antibiotics much faster than

we're developing them. It's scary, too. When a passenger carrying an extremely

drug-resistant strain of tuberculosis boarded two flights in May 2007, hysteria

ensued. Panicked schools across the United States have closed their doors and

undergone thorough scrubbings after detecting MRSA.

It's more than a little embarrassing to be decisively losing a battle of wits to

unicellular organisms. At least the bacteria are smart enough to develop new

strategies every now and then. We plodding humans have been fighting antibiotic

resistance the same way for decades: by restricting access to antibiotics and

developing new drugs to kill off problem bugs. It hasn't worked, and it's never

going to. Until we make a tactical shift, resistance is going to become more

common and more dangerous. But these seemingly indomitable microbes have a soft

underbelly. To recognize it, you have to understand how bugs develop drug

resistance in the first place.

Antibiotic resistance is often described as a simple evolutionary response to

environmental pressures -- when a bacterial colony is exposed to drugs, the

cells that develop defences will survive and multiply. If it were this simple,

bacteria would rarely survive an antibiotic attack. The few cells that mutated

to defeat the drug would be killed off by your immune system before they could

flourish. But bacteria can transfer genes to one another. When one cell " solves "

a drug, it can package up the genetic recipe and transfer it to other bacteria.

An entire colony of bacteria can develop antibiotic resistance with a single

lucky mutation. And your body, which graciously hosts about two quadrillion

bacterial cells -- 20 times your total number of human cells -- is one enormous

genetic swap meet. Most of your resident bacteria are either helpful or

harmless. But some of them have been in our guts long enough to have seen our

full menu of antibiotics. So even the so-called " normal flora " can archive

antibiotic resistance and either go rogue themselves or spread it to more

virulent invaders.

Klebsiella pneumoniae is one such bacterium. It has resided in the human

gastrointestinal tract for as long as we have been able to identify microbes.

Each time someone is treated for strep throat, syphilis, Lyme disease, or any

other bacterial illness, it learns a little more about our medical arsenal. In

1996, doctors identified a strain of Klebsiella that produced an enzyme called

KPC, which has the ability to destroy virtually all modern antibiotics.

The mutant Klebsiella is harmless in the gastrointestinal tract, but if it

escapes to another part of the body -- because of poor hygiene or any number of

other minor slip-ups --it can turn a routine urinary-tract infection into a

life-and-death struggle. To make matters worse, Klebsiella has transferred the

genetic recipe for KPC to other -- sometimes more dangerous -- pathogens.

Doctors are now seeing strains of E. coli and Pseudomonas that can produce KPC.

To combat the bugs, doctors can either throw a cocktail of antibiotics at the

infection or dig up classes of antibiotics that were abandoned decades ago

because of their intolerable toxicity.

Mutant Klebsiella is now spreading around the world, jumping from person to

person. It is a particular problem in New York City, where hospital studies have

shown that as many as 60% of Klebsiella cells can produce KPC. When these

bacteria cause an infection, more than one-third of the victims die.

So far, researchers have responded to this outbreak using the traditional

strategies of blame and drug development. The former is useless: Tightening

antibiotic controls might help prevent the next emergency, but relying on it to

solve the problems we've already created is a bit like slamming shut the city

gates after the plague has entered. The latter is shortsighted: Drug development

has slowed to a near standstill --down by about 75% since the 1980s.

A little creativity might end this game of microbial Whac-A-Mole. Some

underfunded, underappreciated researchers have dreamed up truly innovative

strategies for stopping genetic transfer -- even turning the phenomenon against

our enemies. In vitro studies have shown that chemicals like ascorbic acid shut

down the movement of antibiotic resistance between cells. (Right now it's

effective only at concentrations that a person couldn't tolerate, but it's a

start.) Because almost all antibiotic resistance relies on genetic transfer,

this technique might be the solution we've been seeking since the very first

colony of bacteria solved penicillin in 1944. In the best-case scenario,

coupling antibiotics with anti-genetic transfer agents could eliminate the need

to ration antibiotics.

Other studies have suggested that we can " infect " bacteria with genetic

instructions that cause them to waste their resources copying useless genes,

leaving them no time to eat and reproduce. Another possibility is to train

bacteria genetically to coexist with us peacefully. For example, some bacteria

survive by releasing a toxin that helps them consume our intestinal material,

causing disease. If we can develop a gene that enables these strains to eat our

food instead of our flesh, they'll have been effectively disarmed. Antibiotic

resistance wouldn't even be a concern.

The objection to these strategies isn't scientific; it's financial. Developing a

new drug costs between US$800-million and US$1.7-billion, depending on whether

you include the cost of failures, so drug makers believe only blockbusters can

be profitable. Initial research suggests that the smarter, genetically based

strategies -- much like flu vaccines -- will have to be narrowly targeted at

specific outbreaks, because the genetic recipe that works on one strain of

bacteria may not work on even closely related pathogens. The chemicals that

inhibit the transfer of antibiotic resistance might not be patentable.

Nevertheless, unlike conventionaldrugdevelopment, this research has the

potential to open new avenues for treatment. It's a completely new way of

thinking about fighting disease. And the cost of antibiotic resistance is

difficult to ignore. Treating a patient who has garden-variety TB costs

US$12,000; treating one with a drug-resistant strain costs US$180,000. The

annual cost of antibiotic resistance may be as high as US$30-billion annually.

It's time to learn something from the bacteria: Adapt to survive.

http://www.nationalpost.com/arts/story.html?id=2320102