The reason why this deadly E coli makes doctors shudder

It is past time for health authorities to curb the antibiotic misuse that created the resistance of this aberrant E Coli strain

The massive outbreak of E coli O104 in Europe has infected more than 1,800 people and left more than 500 with the potentially deadly complication known as haemolytic-uremic syndrome. It has leapfrogged borders to at least 13 countries and killed about 20 of its victims. As health authorities try to trace the outbreak to a food that can be removed from the market, it has focused international attention on the complex paths that agricultural produce follows in an era of global trade.

One aspect of the epidemic, though, has received little notice: this aberrant strain is resistant to multiple classes of antibiotics. Among all the urgent issues raised by this outbreak, that drug resistance should ring the loudest warning bells – and prompt serious consideration of curbing the vast overuse of antibiotics that has created it.

O104’s resistance profile has been briefly mentioned, but as a curiosity that distinguishes the strain rather than as a concern. That is largely because the safest way to treat infections caused by an E coli strain that also produces toxins, as this one does, is to refrain from using antibiotics – since when the drugs kill the bacteria, they cause the toxins to be released and bring on the illness’s worst symptoms.

So since antibiotics are not being used against this E coli, whether they would work if tried has become just a matter of academic interest – one finding among many being posted on the internet by volunteer researchers performing rapid analyses all over the world.

But even though it may be irrelevant for the current victims, the significant antibiotic resistance in this E coli strain is worth a second look. That is partly because Shiga-toxin-producing E coli strains such as O104:H4, and its much better-known close relative, O157:H7, are rarely resistant – so at the least this represents the acquisition of new defences by an already formidable foe.

But what is more important is that resistance factors forming O104’s new protections have been burgeoning in Europe for at least a decade. Their movement into this strain demonstrates how freely resistance factors can leapfrog among organisms once they emerge. And that should underline how important it is to slow down the evolution of antibiotic resistance, by cutting back inappropriate use of antibiotics in everyday medicine and on farms.

According to Germany’s Robert Koch Institute, O104 is resistant to more than a dozen antibiotics in eight classes: penicillins; streptomycin; tetracycline; the quinolone nalidixic acid; the sulfa drug combination trimethoprim-sulfamethoxazol; three generations of cephalosporins; and the combination drugs amoxicillin/clavulanic acid, piperacillin-sulbactam, and piperacillin-tazobactam. Indifference to so many drugs signals that O104 possesses what is called ESBL resistance – and in fact, according to the Koch analysis, the strain harbors two genes that confer that resistance, TEM-1 and CTX-M-15 – a property that has been making doctors shudder since the 1990s, when strains of ESBL-resistant Klebsiella, a bacterium that causes serious hospital-acquired infections, began pingponging through Europe.

Because they primarily affected patients in intensive care units, these strains caused little alarm in the outside world. But after about 2001 these resistance factors moved into everyday life and started causing havoc. In a kind of genetic hand-shaking manoeuvre that bacteria perform all the time, the resistance genes moved into some strains of E coli – not the food-borne, toxin-making form, but rather the common variety that causes urinary tract infections and other normally minor illnesses.

Suddenly hospitals in Birmingham and Shropshire began reporting significant outbreaks of ESBL E coli infections, and doctors who don’t practise in hospitals began talking to each other about young women experiencing recurrent bladder infections that few drugs could affect. This wasn’t only a phenomenon of the 2000s. In March 2010, the University Hospital of North Staffordshire experienced an outbreak of ESBL Klebsiella in which a patient died.

Where are these resistance factors coming from? The development of resistance is an inevitable biological process; it’s what bacteria do to protect themselves against deadly compounds, whether the compounds were made naturally by other bacteria or artificially in a drug-development lab. But excessive exposure to antibiotics hastens the process and makes its results unpredictable.

That excessive exposure happens any time anyone takes antibiotics for a health problem for which they are inappropriate, such as colds or ear infections. It happens even more when low-dose antibiotics are deployed by the tonne in large-scale agriculture, without any surveillance to report back what bugs are emerging. Researchers in Spain and the US say there are links between large-scale agriculture and the emergence of ESBL: they have found bacteria harbouring that resistance in the meat of supermarket chickens.

Even if investigators identify the vegetables from which this outbreak may have originated, they may never be able to say how the resistant bacteria found their way on to the produce. In 2006, the US experienced a nationwide outbreak of E coli O157 in fresh spinach, and though investigators suspected manure from either livestock or feral pigs near the farms, they were never able to prove contamination occurred.

But we already know where the antibiotic resistance in this outbreak has come from – and given bacteria’s promiscuous propensity to trade genetic material, we know that O104 is keeping that resistance going by harbouring it and handing it off to yet another species. It’s past time that governments and health authorities do what they can to slow down the evolution of drug resistance, by curbing the antibiotic misuse that brings it into the world.

http://www.guardian.co.uk/commentisfree/2011/jun/05/deadly-ecoli-resistance-antibiotic-misuse