Friday, March 28, 2008

The unfolding superbug disaster in Britain

Superbugs kill at least 10,000 people in Britain each year - 20 times the number who die of Aids. Why is the British government funding AIDS research much more than superbug research? And why are known preventive measures not being taken?

Like many, Brian Clinch was under the impression that, despite the failures of the past, the British health service was tackling the frightening epidemic of antibiotic-resistant superbugs. That was before a visit to Norway made him realise that this record-breaking tide of resistant infections is far from under control and is also a problem of our own making. Clinch, a former RAF pilot from Dorset, has kidney failure and needs dialysis three times a week. It was only when he went for dialysis treatment in the Norwegian city of Stavanger three months ago that he discovered he was one of the tens of thousands of Britons unwittingly infected with the deadly superbug methicillin-resistant Staphylococcus aureus (MRSA).

The day after arriving in the oil-refining port on Norway's Atlantic coast, he went to the city's university hospital. Dialysis had been arranged on the understanding that he had been tested for MRSA in the UK. But a routine throat swab in Stavanger showed Clinch was carrying MRSA. "All hell broke loose," he says. "The results of the MRSA tests arrived after they'd given me one session of dialysis. They were angry and deeply unimpressed with the dialysis centre in England. "I felt like a complete pariah. I was taken into an isolation room and everyone put on gowns, masks and bootees before they came anywhere near me. It's obvious they are frightened to death of getting these infections in Norway, and are doing everything they can to keep them out."

He is right. Norway, with its population of 4.7m, had only 332 cases of MRSA in 2006, and has the lowest rate of antibiotic-resistant bacteria in Europe. About 1 in 200 of the infections found in patients' bloodstreams in Norway is caused by a treatment-resistant "superbug", while in Britain, getting on for half of all infected patients have been colonised by strains of bacteria that normal antibiotics cannot treat.

Norway, which, like Britain, runs a publicly funded health service free at the point of delivery, prides itself on its "search and destroy" policy for killer infections. But the contrast between its health services and our chaotic hospital system is a stark reflection of a difference in approach that has much more to do with attitude than money.

The public area of Stavanger's 950-bed hospital resembles nothing so much as an up-market hotel. Leather armchairs are arranged around a virtual log fire; seemingly relaxed visitors sip coffee and nibble pastries. The town is comparable to Ipswich in size and affluence, but first impressions of the hospital suggest it is wealthier. But beyond the reception, the 1970s-built wards tell a different story. Norway's cash-limited national health service is suffering exactly the same colossal pressure as our own NHS.

In the infectious-diseases unit there are 19 people on trolleys in the corridor. At least 11 more lie in the corridors of other departments. The wait may be long, and patients may end up temporarily in the wrong department as staff struggle to allocate beds. It is a sight familiar to anyone who has observed the treatment lottery of the British NHS, and the enormous battle between restricted supply and limitless demand for healthcare. But even under the pressure of winter infections, Stavanger's problems with capacity are not reflected in infection rates.

The atmosphere is busy but calm. The gleaming corridors are populated with cheery cleaners; there is a sense of belonging among the workforce that is often absent among the clock-watching agency workers who increasingly maintain large chunks of our own hospitals.

Stavanger has a policy of not moving infected patients around; if they have several conditions, doctors from different specialities come to them, not the other way round. And isolation rooms are available, complete with negative air pressure to prevent infections from being wafted outside. Barrier nursing methods involving gloves, aprons and scrupulous hand-washing are strictly applied with infectious patients.

Jon Sundal, the head of infectious diseases at Stavanger, complains of a relentless battle to keep his unit under control. "There is a shortage of nurses - the five new single rooms cannot be staffed," he says. Nevertheless, even with bed occupancy running at over 100%, conditions in his hospital offered a stark contrast to the grime of most of Britain's healthcare facilities. "We saw the writing on the wall early on with antibiotic resistance," says Olav Nataas, head of medical microbiology at Stavanger. "We had one serious outbreak in the 1980s, and since then we just haven't allowed it to happen, except when we sent some waiting-list patients to Britain for hip replacements and they came back infected. "I don't think hospital cleaning has much to do with it. What works is screening. You test everyone, and you isolate and treat everyone you find with it. In England you can't do that now because you have too many cases."

It is legitimate to ask if Britain's NHS has lurched into a ruinously expensive crisis that may yet see the entire service implode. It is also legitimate to ask how our microbial surveillance system, let alone our hospital cleaning services, has failed us so badly: why did scientists not warn us of this disaster in the making, and is it too late to do anything about it?

The global use of antibiotics since the 1940s has achieved a simple Darwinian consequence: the fittest bacteria survive. Antibiotics work by disrupting the production of components needed to create new bacterial cells. Penicillin, for example, selectively interferes with the construction of bacterial cell walls, which have a different structure to the cell tissue of humans and other mammals. By the end of the 1940s, about half of the Staphylococcus aureus strains tested in hospitals had adapted to produce an anti-penicillin toxin called penicillinase. Within months of the launch of the antibiotic methicillin in 1960, the first resistant strains of Staphylococcus aureus were emerging. Shortly after that, bacteriologists began finding strains impervious to up to four common antibiotics.

Warnings about the dangers of antibiotic overuse started to emerge from laboratories, but because relatively few patients were affected and nobody knew what to do about it, the situation was ignored. Antibiotics continued to be consumed in ever-growing quantities by sick humans and farm animals alike.

The problem took off in 1991, when Britain contributed its own supercharged strain to the world lexicon of multi-drug-resistant superbugs. MRSA-16 first appeared in Northamptonshire, rapidly infecting 400 patients and 27 staff in three hospitals. Within 18 months it had been reported in 135 more hospitals. Nobody knows how it spread. Along with another British strain, MRSA-15, it went on to infect patients around the world, a pattern that continues. A meticulous Health Protection Agency study, mapping how the new strains popped up unexpectedly in new hospitals, was published in the Journal of Clinical Microbiology in 2004. But it was too long after the event to shed any light on how the infection had carried. Now research funding is focused on firefighting - casting around for ways to damp down the effects of the pathogens.

It is not just MRSA that is sweeping across Britain like a plague. Streptococcus, enterococcus and Escherichia coli (E coli) are among a host of bugs emerging in resistant forms and causing everything from pneumonia to tuberculosis, bone destruction and lethal damage to the heart. In addition, we are facing "hyper-virulent" new strains of the bacteria Clostridium difficile (C diff), which have colonised the sites left free by the effect of antibiotics, which kill off many harmless bacterial colonies in their path. Although C diff is not resistant to treatment, its spores linger indefinitely and, until recently, NHS staff were largely unaware of how to kill them. Consequently, it is the biggest killer of the current superbugs.

In 2006 it was mentioned on the death certificates of 6,480 people, against 1,652 deaths officially attributed to MRSA. However, these figures are recognised to be underestimates, as many superbug deaths are never identified. Mandatory surveillance of MRSA bloodstream infections is a recent innovation, the number of people carrying it with no symptoms is not recorded, and the formal collection of figures for death and disease associated with C diff (which causes unstoppable diarrhoea or gut perforation) only began in April 2007. The government estimates the annual cost of treatment for such cases to be over œ1 billion.

Officially, the total number of MRSA infections is 7,000-8,000 a year, while C diff is running at an annual 55,600 cases. Many experts believe the real total for all superbug infections is nearer 300,000 - how many are fatal is believed to be vastly higher than the official figures suggest. There is no way of knowing the true figure, as relatively few people are tested.

Meanwhile, a variety of new resistant pathogens are waiting in the wings. In September 2006, a variation of Staphylococcus aureus that produces a toxin called Panton-Valentine leukocidin (PVL) claimed its first British victims. Since then, anxiety over this threat has escalated. The pathogen selectively attacks the young rather than the old; it gets into bones and joints, causing crippling damage.

A multi-drug-resistant version of a common food-poisoning bug, ESBL (extended-spectrum beta-lactamase) E coli, is also causing anxiety. First identified in the 1980s, it has spread steadily to cause an average of 30,000 cases of blood poisoning and urinary-tract infections a year. Although it has officially been blamed for 57 deaths so far, the true total is believed to be many thousands. Government scientists think the source is meat and milk, colonised by superbugs as a result of overuse of agricultural antibiotics.

Jodi Lindsay, a senior expert at St George's hospital, London, and a world authority on superbugs, says: "It is inevitable things will get much worse. We don't know enough about how these bacteria behave, because not enough research is being done. We have increasing numbers of surgical operations, elderly people with long-term serious disease, and diabetics. All these patients have compromised immune systems and are at risk. Not only that, there is potential for new, really virulent strains of bacteria, capable of attacking healthy people."

Mark Enright, professor of molecular epidemiology at Imperial College London, says the real number of deaths in the UK from MRSA and C diff is "easily more than 10,000". He shares the concern that reservoirs of superbug infection in hospitals will increasingly spill out to attack otherwise healthy people: "You could be carrying a resistant form of MRSA and it could then get in through a superficial injury."

There is evidence that such a problem is already occurring in other parts of the world. A new form of MRSA, USA300, has emerged not in hospitals but in the wider community in America. It is killing 18,000 a year - considerably more than the number killed by HIV/Aids, and, most worryingly, the victims include a number of otherwise healthy children. The latest flurry of anxiety was in Brooklyn, New York, in October, when Omar Rivera, a previously fit 12-year-old, suffered the telltale crop of pus-filled spots associated with USA300. Within days he was dead. In other parts of America, three other children, aged 4, 11 and 17, died the same month.

A team at the University of California in San Francisco has been tracking the infection. Last month they published a study showing that a variant of USA300 was spreading in gay communities on the East and West Coasts. And a new "community" strain of C diff in the US has targeted children, pregnant women and new mothers, with fatal results. There has been at least one similar death in the UK, but testing was not available to confirm if it was the same pathogen.

Europe also has a "community" MRSA: ST80. Officially it is considered less of a threat because, it is argued, levels of poverty in western Europe are not as severe as in the US. Without the immune-system damage caused by malnutrition, the infection is less likely to cause an epidemic.

All that is known about USA300, and other virulent community-acquired strains of staphylococcus, is that they generally include Panton-Valentine leukocidin, and that this lethal toxin can jump between different types of bacteria. If a PVL-carrying bacterium infects someone already carrying a cold virus, it can spur the onset of a deadly form of necrotising or tissue-killing pneumonia, which kills 60% of those who develop it. Although guidelines for GPs to alert them to this new threat to public health are being issued later this spring, Lindsay and other scientists complain that Britain persists in spending too little on basic research to tell us more about the nature of these brand-new infectious agents.

Many scientists have also attacked our slow and patchy response to the problem of antibiotic resistance. "In the early 1990s, microbiologists were divided," says Hugh Pennington, emeritus professor of bacteriology at Aberdeen University. "For everyone who argued the case for containment, there'd be many more who maintained that Staph aureus had been with us for ever, and it did not make much difference if strains were methicillin-resistant or not."

As a result, investigating how microbes developed their resistance, how infections spread, why particular resistant strains appeared in some areas but not in others, did not seem that important to healthcare planners. Microbiology began to feature less and less in medical training. According to the Royal College of Pathologists, there are now only 645 fully qualified hospital microbiologists in Britain, of whom only 387 are working in the NHS in England. Up to 10% of hospital microbiology posts are unfilled because of a shortage of qualified applicants.

At the same time that the superbugs were taking hold, those with the expertise to tackle them were keen to work instead in Aids research, with its support from glamorous figures such as Princess Diana and Elizabeth Taylor. The pattern inexplicably continues. According to the Department of Health, 3.8m pounds has been spent by the government since 2002 under the umbrella of "clinical microbial research", while 14m a year is spent on Aids, which kills fewer than 500 here annually. And it has become clear that a recently allocated 16.5m that microbiologists believed was for research into antibiotic resistance will be shared with research projects on sexually transmitted diseases and hepatitis. "Asking why we put so much money into Aids research is a very good question," said Brian Duerden, government inspector of microbiology and infection control. "Medical research is highly political and highly fashion-driven."

Dr Peter Dukes, programme manager of the Infections and Immunity Research Board at the Medical Research Council (MRC), blamed the paucity of research proposals and the shortage of researchers in the field of antibiotic resistance: "When the MRC offered to fund a research project six years ago, 20 proposals were received and only one was good enough to sponsor." Given America's sinister new USA300 infection, our persistent preoccupation with Aids may soon look very misguided indeed.

Microbiologists who have remained in the NHS are dismayed that their warnings of disaster from antibiotic resistance have been ignored by hospital managers focused on performance indicators and productivity targets, which concentrated on waiting times. "We needed to do more screening, but there were never the resources. Even now they are cutting back," said a consultant intensive-care specialist at a large provincial hospital. "There used to be two consultant microbiologists here, but one left and was not replaced. So we had no expert on intensive-care ward rounds to advise on appropriate antibiotics and infection control."

New government directives require hospitals to carry out MRSA screening on patients being admitted - though not those having outpatient or day-surgery procedures. The consultant said the extra testing burden, without any extra staff to do it, had meant that vital surveillance for other new infections was not happening.

In addition, as pressure has been ratcheted up to channel funds into meeting a range of "patient episode" productivity targets, basic hospital cleaning has been scaled back and contracted out. Those working in healthcare seem increasingly ignorant of the basics of hygiene. Healthcare workers increasingly fail to wash their hands as they race between beds, which are meant to be kept 100% occupied. Increasing numbers of patients are unnecessarily admitted to wards from accident-and-emergency departments, simply to avoid breaking the maximum four-hour permitted A&E wait. In December it was reported that the hotel costs of caring for extra patients who were not actually sick enough to need treatment had wasted 2 billion over the past five years.

Many microbiologists point to the decline of attention to hygiene as a basic function of healthcare as nurse training has become increasingly academic and classroom-based. "The only infection-control procedure proven to work is scrupulous hand-washing, a basic approach explained by Florence Nightingale during the Crimean war and seemingly lost in the intervening 150 years," said Richard Wise, former chairman of the government's specialist advisory committee on antimicrobial resistance, and adviser to the Health Protection Agency Board. "Not washing the hands between patients should be made a disciplinary offence."

Most hospitals have bottles of alcohol-based hand disinfectant by their doors, but Duerden says that until recently their inefficacy against C diff spores was "not common knowledge" outside microbiology circles - an unacceptable level of ignorance, insists Wise, who said it had been known about "for donkey's years".

Olav Nataas, however, insists the search-and-destroy process is key: "We know hand-washing is never 100%," he says. "This preoccupation with cleaning is not the main issue. It is identifying the infection as rapidly as possible and treating it in a way that does not risk others."

It is this uncertainty among Britain's scientists, healthcare administrators and politicians that has led to the latest disagreement about hospital cleaning. This month, every hospital in Britain is meant to have completed a special "deep clean", for which an extra 57m has been allocated. How exactly a deep clean is performed is less clear. There are no prescriptions for cleaning materials, training for cleaners, or methods of checking whether things are actually clean.....

Many patients have paid a high price for our confused health policies. In Britain's worst outbreak of superbug infection, there were 90 deaths and 1,170 C diff infections across three hospital sites in Maidstone, Kent, between April 2004 and September 2006. A report on the disaster by the Healthcare Commission in October described patients being left to lie in their own infection-laden excrement, a shortage of nurses and an ignorance of the risks of moving infected patients between wards. There were a further 33 avoidable deaths from C diff between 2003 and 2005 at Stoke Mandeville hospital in Buckinghamshire. An inquiry found that managers ignored advice to isolate those infected and instead concentrated on shutting down more beds to cut costs.

The cost of compensating superbug victims is also soaring. The NHS Litigation Authority has paid out 12.5m for 287 cases, plus a record-breaking 5m in January to the actress Leslie Ash, 49, whose career has been ruined. An anticipated 1m will go to Shaun Franks, 39, who underwent surgery for a broken ankle. His leg was taken over by an immovable colony of MRSA, which could only be eradicated from his body by amputation of the leg. During his treatment, staff at Northampton general hospital unwittingly used an antibiotic that accelerated the growth of the MRSA. "It has been a nightmare," said Franks. "I lost my job, my relationship - everything. Every time I thought I was getting better, it would come back again."

There is no question that ignorance of good practice has played a significant part in the spread of superbugs in Britain. A study in the late 1990s by Otto Cars, an expert in infectious diseases at Uppsala University, Sweden, compared antibiotic use across Europe. British doctors were administering over 18 daily doses per 1,000 people, compared with 13 in Germany and Sweden and 11 in Denmark. Most of the prescriptions were for coughs and colds - 90% of which are caused by viruses, not bacteria.

Duerden admits that the first comprehensive campaign to educate GPs and the public about the overuse of antibiotics only got off the ground eight years ago with the launch of a cartoon character, Andybiotic. But a survey of almost 11,000 adults published in the British Medical Journal last year indicated that most people still did not understand the risks.

Hajo Grundmann, now a senior infection-control adviser to the Dutch government, worked for seven years in Britain's NHS before returning home in 2001. He runs the Eurosurveillance database, monitoring levels of antibiotic-resistant infections in 31 countries. Britain has the highest rate in western Europe. "It is connected with the high workload," he says. "I worked in Nottingham. We were able to isolate MRSA cases at first, but when the waiting-list initiative came in, there was huge pressure on beds. As soon as the pressure goes up, hand-washing goes down. But the British problem is also due to people's attitudes. It just has not been taken seriously enough." ....

There are, however, measures being launched by the government: to increase the number of hospital matrons to 5,000 to oversee hygiene by May, and make available 270m a year for hygiene campaigns, extra infection-control nurses and pharmacists to tackle over-reliance on antibiotics.

But that does not explain why we continue to invest in areas such as Aids research, or the hypothetical risk of pandemic flu, yet hope that drugs developed in the middle of the last century will protect us against new infections that are killing thousands each year.

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