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14 November 2008

Restoring the Magic of a Miracle Drug

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“We need our own kind of Kyoto treaty for antibiotics: the point is, we should treat antibiotics as a non-renewable source”

“We need our own kind of Kyoto treaty for antibiotics: the point is, we should treat antibiotics as a non-renewable source”, says professor Antonio Cassone, research director of the Italian Istituto Superiore di Sanità. “On top of antibiotic resistance, the major problem we face is that pharmaceutical companies produce very few new antibiotics. Compared to the 80s, when we did have new antibiotics every year, to which bacteria were still susceptible, today we have next to none. So, in order to hold on to them and preserve their effectiveness, we need to use antibiotics more correctly”.

Given the current antibiotic consumption figures, widespread development of resistance had always been a matter of “when”, rather than “if”. Pathogens can become superbugs, often aided by extra chromosomal elements such as plasmids and transposons that can transfer antibiotic resistance genes even across bacteria cells belonging to different species. There is an argument that points to the extensive livestock use of antibiotics in some countries as a potential source of drug resistance. But the main focus of European Antibiotic Awareness Day is that antibiotics consumption in human medicine has become undisputably excessive. France, Greece, Cyprus and Italy lead this trend in Europe. However, as the latest EARSS (European Antimicrobial Resistance Surveillance System) figures show, this has now turned into a serious public health threat across the board.

Time is of the essence here. While trying to preserve antibiotics’ undermined effectiveness, science is already looking for viable alternatives: “First, we must find new vaccines against bacteria which are responsible for the majority of antibiotic-resistant hospital infections, like MRSA, fluoroquinolone-resistant E.Coli or Pseudomonas”, Professor Cassone suggests. “But we need to fight infectious diseases also by producing new antibodies against virulence agents. Indeed, nowadays we are working hard on immunotherapy and vaccination therapy. These weapons might become available within the next decade”.

When it comes to accounting for the wide difference in antibiotics use across Europe, cultural factors seem to be at play. “Our latest survey of 2,200 Italian patients shows that people may get antibiotics more easily from relatives and friends and up to 30% buy them from their trusted pharmacist without a prescription”, Professor Cassone adds. “More people in Southern Europe also seem to think mistakenly that flu, coughs and colds can be treated with antibiotics, and our survey has established that around a third of antibiotics prescriptions in Italy are made for these conditions. The thing is, a lot of people in Italy demand antibiotics from their doctor. Patients’ pressure is very strong and quite often doctors cannot resist it, although their diagnosis is mostly correct in the first place. Also, more than 50% of the people we interviewed have admitted they did not finish the course and kept the leftovers for future use”.

Yet, even within Italy, this trend seems to mirror the wider European kind outlined by the EARSS monitoring network, which was set up by the European Commission in 1998: less common in the North, more so in the South. The UK seems to be a notable Northern exception, given the rate of superbug outbreaks in hospitals, which might depend both on overcrowded wards and failing hygiene standards.

A recent report by the UK Healthcare Commission showed that 60% of hospitals in England are still failing to deal with superbug infections effectively. The worst case was Maidstone and Tunbridge Wells NHS Trust, where 90 patients died definitely or probably from contracting Clostridium difficile between 2004 and 2006. Some British campaigners point out that while a number of hospital trusts have met government targets and successfully reduced superbug rates, 20% of other hospital trusts actually had a higher incidence of Clostridium difficile infection rates between April and June 2008. MRSA Action UK reports a lingering disparity in reducing superbug rates depending on where patients live, branding it a dangerous “postcode lottery”.

Clinical antibiotic resistance had first been noticed back at the end of the 40s. Alexander Fleming himself had previously warned of the dangers of resistance to penicillin in the laboratory by exposing the microbes “to non-lethal quantities of the drug”. Even if today’s human medicine consumption alone cannot seemingly account for all high resistance rates, scientists agree a more judicious use of antibiotics is now imperative.

Reducing the difference in antibiotic consumption between Northern and Southern Europe is one of the aims of European Antibiotic Awareness Day, says leading Belgian microbiologist Herman Goossens, GRACE’S project leader. It was him who conducted the first placebo-controlled, double-blind study at University Hospital in Antwerp, which was published by The Lancet in 2007, to show directly that antibiotic use leads to resistance. “It is worthwhile to organize national media campaigns like the ones in Belgium, France, Spain and Greece, but we also need other interventions towards more appropriate antibiotic prescribing, like providing support to the physicians through guidelines and recommendations”, professor Goossens says. “You shouldn’t go the other way either, of course. If the doctor says you need antibiotics, you should take them. Antibiotics should be used for the right indications”.

In the community, professor Goossens adds, “the most important bacteria which are more likely to develop resistance are Streptococcus Pneumoniae and E. Coli. In hospitals, MRSA is still the most important, although in eight countries in Europe MRSA infections are declining. Sometimes the other dangerous ones are Pseudomonas and Acinetobacter. It might also well be that animal meat in the food chain plays a role in the emergence of ESBL producing organisms (drug-resistant pathogens like E.coli and Klebsiella, whose enzymes destroy antibiotics and which are associated with increased mortality, Ed.) in the community and also in hospitals. We see people entering hospital with these previously acquired infections”.

Professor Goossens, who was chair of the WHO Conference on the Use of Quinolones in Food Animals and Potential Impact on Human Health in 1998 and is also directly involved in EARSS, makes clear that “certain types of bacteria” could well come from the intensive use of antibiotics in livestock. He adds: “I don’t think we should wait for new antibiotics over the next 5 to 10 years, although I do hope the industry will continue investing in developing new antimicrobial drugs. For the moment, we have to concentrate on promoting judicious antibiotic use and hospital hygiene”.
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