Since antibiotics became widely available in the 1940s they have completely transformed the medical community's approach to infectious diseases. Their use, combined with sanitation, nutrition and the advent of mass vaccination programmes, has led to a dramatic drop in once common infectious diseases.
But these miracle drugs, famously described by German microbiologist Paul Ehrlich as magic bullets that could eliminate bacteria without doing much harm to the cells of treated individuals, are now at the centre of an international public health problem.
Growing antimicrobial resistance to antibiotics is now so serious that unless the crisis is adequately contained, according to the World Health Organisation, it threatens to bring the world back to a preantibiotic age.
1Indeed, at the Global Resistance Day meeting in Toronto in September, Dr Rosamund Williams from WHO's anti-infective drug resistance surveillance and containment unit, said that the era of antibiotic treatment was over for some patients.
Several factors have led to this worrying situation. They include inappropriate prescribing (for viral infections over which antibiotics have no power) and overuse of antibiotics in humans, and the widespread use of antibiotics in animal husbandry and agriculture.
No one is more vulnerable to multi-drug resistance than those admitted to hospitals. Antibiotic resistance in hospitals makes infections harder to treat, increases the length and severity of illness and length of stay.
Dr David Livermore, head of the public health laboratory service antibiotic reference unit, says: 'We are seeing a gradual erosion of susceptibility to many antibiotics across the broad swathe of micro-organisms that cause ill-health in humans. The bacteria Salmonella, pseudomonas and klebsiella, which cause serious infection particularly in hospitalised patients, are among the bacteria manifesting high levels of resistance.'
Then there is the problem of hospital-acquired 'superbugs', methicillin-resistant staphylococcus aureus (MRSA) and vancomycin-resistant enterococcus (VRE), which are wreaking havoc on hospital wards around the world.
Furthermore, hospital-acquired infections rarely stay put, but spread into the community.
So what is being done to tackle antimicrobial resistance and are these measures adequate? Two years ago, a House of Lords select committee report warned: 'This inquiry has been an alarming experience which leaves us convinced that resistance to antibiotics and other anti-infective agents constitutes a major threat to public health and ought to be recognised as such more widely than it is at present.'
1 One of the report's main recommendations was that 'purchasers and commissioning agencies should put infection control and basic hygiene where they belong, at the heart of good hospital management and practice and should redirect resources accordingly'.
Yet earlier this year, a National Audit Office investigation said that while good practice existed in many hospitals, infection-control teams were under-resourced and generally lacked any direct involvement from chief executives.
2 There are over 100,000 hospital (otherwise known as nosocomial) infections a year in the NHS, of which infection control teams believed 15 per cent were preventable, says the NAO report. In June, health minister John Denham acknowledged unacceptable variations in the level of infection between hospitals. He announced that the new Commission for Health Improvement and the Audit Commission were to inspect hospitals' record in nosocomial infections and that a controls assurance unit would be set up to support trusts implementing controls assurance policies.
Honorary secretary of the Association of Medical Microbiologists Dr Judith Richards, who is also consultant medical microbiologist at Norwich public health laboratory service, said that it is too early to tell if such measures are likely to improve infection control. 'As with most announcements, the devil is in the detail and we haven't seen any detail yet, ' she added.
The House of Lords report acknowledged that surveillance - the collection of microbiological data for comparison, analysis and feedback - was key to the fight against resistance. Through tracking resistance, such programmes facilitate prudent prescribing and infection control.
WHO recommends that surveillance data be analysed and distributed to healthcare workers to assist them in prescribing drugs appropriately. Expert commentators expressed astonishment during the House of Lords inquiry that the UK lacked a standardised national data collection system, criticising the current system as selective and haphazard.
Professor Roger Finch, consultant microbiologist at Nottingham's City Hospital, said: 'At present, there is no national systematic monitoring arrangement prospectively studying trends in resistance that might provide robust data on which to make firm judgements.
Current data is selective in terms of sampling.'
Data on antibiotic resistance is reported voluntarily to the laboratory service from a selective number of laboratories, around 50, spread across the country.
Richard Wise, professor of clinical microbiology at City Hospital trust, Birmingham, and scientific adviser to the House of Lords report, said: 'The surveillance system we have in the UK is no worse than national surveillance systems in other countries. However, the problem with these systems is that they do not tell us anything about the pattern of antibiotic resistance in different populations and it is this quality of data that we need in order to make decisions about prescribing patterns for particular types of infection in particular populations such as urinary tract infections in women or respiratory tract infections in children.'
The Department of Health published its antimicrobial resistance strategy and action plan in June, citing three key areas of action to fight antibiotic resistance: surveillance, infection control and prudent prescribing.
However, despite the shortcomings of the UK's surveillance system outlined in the House of Lords report two years ago, there are no plans to change the way the UK currently collects antibiotic resistance data.
Dr Robert Masterton, consultant microbiologist at Edinburgh's Western General Hospital, agrees there are limitations to the UK's national surveillance system.
But he thinks that no single country or group alone can adequately address the emergence and expansion of antimicrobial resistance and that global surveillance programmes based on multidisciplinary cooperation are essential. 'Until recently, global efforts at surveillance have been largely unco-ordinated and random. But this scene is rapidly changing with WHO, among others, leading multidisciplinary initiatives, ' he says.
Dr Masterton adds there are also a number of international surveillance programmes, sponsored by the pharmaceutical industry, that are yielding valuable information for national governments about resistance patterns in particular groups.
He is the lead investigator for the Meropenem yearly susceptibility test information collection (MYSTIC) study, which collects data on antibiotic resistance in hospitals around the world (see box below). There are seven UK centres, including the Western General Hospital.
'MYSTIC is a unique surveillance programme because it is the only one that incorporates resistance mechanism assessments into the core programme and is the only project to link surveillance of resistant bacteria to active antibiotic usage, giving us data on which agents are most likely to be effective against multi-resistant bacterial strains, ' explains Dr Masterton.
Data from the programme shows antimicrobial resistance to certain carbapenem-class antibiotics does not increase with usage as it does for many other classes of antibiotics, suggesting a rethink of hospitals' strategy for the use of such agents.
Potent antibiotics, such as the carbapenems, are often held in reserve by hospitals to limit the development of resistance. But Dr Masterton suggests such thinking is misguided: 'It is often thought that the strong antibiotics need to be protected, that is, used as little as possible, to preserve them as a weapon against serious infection. The data so far does not support such an argument as MYSTIC has demonstrated that usage has not affected resistance.'
However, he argues that resistance to the carbapenems may develop over a longer period and the cost of these antibiotics compared to others remains a rational factor in prescribing.
Professor Wise concludes that more research is needed to link prescribing rates to resistance patterns. 'What we know about the link between prescribing and antibiotic resistance is fairly crude. The finer points are lost, but this information is necessary to deal more effectively with the problem of antimicrobial resistance.'
1 House of Lords select committee on science and technology. Resistance to Antibiotics and Other Microbial Agents. The Stationery Office, 1998.
2 National Audit Office. The Management and Control of Hospital-Acquired Infection in Acute NHS Trusts in England. The Stationery Office, 2000.