Select Committee on Science and Technology Seventh Report


CHAPTER 11 CONCLUSIONS AND RECOMMENDATIONS

  11.1     This enquiry 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. Antimicrobial resistance is a fact of life, and the recommendations which follow will not solve the problem; but they should put the United Kingdom in a better position to face it and live with it.

Can resistance be controlled?

  11.2     The evidence set out above in paragraphs 1.31-41 leads us to conclude that any antimicrobial agent must be expected to encounter resistance sooner or later. The emergence of resistance may be slow; but sometimes it is rapid, and either way it is inexorable. Resistance will take longer to emerge and spread if antimicrobial use is controlled and prudent from the start. Improving control of the use of antimicrobials can be expected to slow down the spread of resistance; and in some situations the frequency of resistance may even decline. But this must not be expected to happen in every case; and, if control is once again relaxed, reversion to high rates of resistance may be swift.

Prudent use in human medicine

  11.3     The present use of antimicrobials in medicine in the United Kingdom is controlled and conservative by international standards, but on the evidence we have received (paragraphs 2.3-9) there is still plenty of room for improvement. In general practice, where most antimicrobials in human medicine are prescribed, there are wide variations in practice; many such prescriptions (witnesses offered figures ranging from 5 to 50 per cent in different settings) are unjustified on strictly clinical grounds, and where a prescription is justified the drug used is often inappropriate (and more expensive than necessary). In hospital the volume of drugs is less, and control is tighter; but even in hospital many prescriptions are made by junior doctors without proper review, and there are doubts about some aspects of present practice in relation to both treatment and prophylaxis, in particular the duration of courses.

  11.4     We acknowledge the dilemma facing doctors and patients alike (paragraph 2.9), that what is prudent from the point of view of public health may be highly imprudent from the point of view of the individual patient, and vice versa. To use the stark example offered by the Minister for Public Health, if a child shows possible signs of meningitis, antibiotics are needed fast, and nothing must be said or done to deter the parent from seeking help or the doctor from giving it. This dilemma cannot be wished away; but we have learned that much can be done to reduce the area of uncertainty.

  11.5     We commend the current trend towards local antibiotic formularies and evidence-based clinical guidelines (paragraphs 2.10-14), giving professionals agreed definitions of prudent practice in particular situations. But the issuing of documents is not enough to turn policy into practice; it must be followed through in professional education, and continuing professional development.

  11.6     We recommend that the Education Committee of the General Medical Council and the medical Royal Colleges should review the evidence presented to us (paragraph 2.31) that undergraduate curricula give insufficient emphasis to infectious diseases and antimicrobial therapy. Given the consequences of poor practice for the development of resistance and therefore for public health, the Royal Colleges should increase the attention paid to antimicrobial therapy in their programmes of postgraduate education and vocational training.

  11.7     We commend those health authorities which are devoting resources to continuing professional development of doctors in the area of prescribing. On the evidence presented to us, this is best achieved by prescribing audit and feedback (paragraph 2.34), and by educational outreach (paragraph 2.35); we recommend that health authorities should step up their efforts in these areas, since they are not only effective but cost-effective.

  11.8     We do not recommend that GPs should be required to establish antimicrobial susceptibility before prescribing (paragraph 2.22). This, we believe, would at present be impracticable, and would overload diagnostic services which are already stretched. But improved access to microbiological testing clearly reduces uncertainty in prescribing. We recommend that industry and the grant-giving bodies should give priority to work on rapid affordable systems for diagnosis and susceptibility testing (paragraphs 2.16-18); where promising developments emerge, they should be quick to move them towards the market.

  11.9     It has been put to us (paragraph 2.23) that the systems for licensing new anti-infectives could be recruited to the fight against resistance. We recommend that the Medicines Control Agency should consider whether the drug licensing system could be used more effectively to encourage prudent use in the interest of public health. Any change might of course involve amendment of the Medicines Act 1968.

  11.10     We do not recommend further controls on the promotional activities of the pharmaceutical industry in the United Kingdom; we accept the evidence (paragraphs 2.24-25) that a system of self-regulation is in place through the ABPI. There is clear evidence that some doctors are induced to prescribe new drugs where older drugs would do; but this is a matter for the continuing professional development referred to above. We commend the work of the WHO, through its Division of Emerging and other Communicable Diseases Surveillance and Control, to equip professionals and regulators in the developing world to respond appropriately to pharmaceutical promotions (paragraph 9.3).

  11.11     The evidence is clear (paragraphs 2.26-30) that prudent use is much harder to achieve if antimicrobials for internal use are available over the counter. We commend the Government and the ABPI for their firm stand against over-the-counter antibiotics, and urge them not to give way. Since this is an area of EU responsibility, and the position in several other Member States appears to be different, we recommend that the Government should engage in active diplomacy to ensure that, should the issue be raised in the Council of Ministers, their position is understood and their allies are in place; and, in the long term, to induce those Member States which are currently more relaxed about over-the-counter antibiotics to introduce more controls.

  11.12     On the evidence presented to us (paragraphs 2.3-7), it appears that the greatest bulk of imprudent use of antimicrobials in human medicine in the United Kingdom is the prescription of antibacterials by GPs for self-limiting or viral infections and in other inappropriate situations. This encourages resistance, for example, in the pneumococcus, and might give rise to resistance in the meningococcus, which would be a disaster for public health. The increased education for doctors which we recommend above should include education in communication skills (i.e. how to explain the reasons for refusing a prescription) and other ways to avoid prescribing on demand (e.g. delayed-action prescriptions) (see above, paragraph 2.37).

  11.13     We are disturbed by the evidence (paragraphs 2.36-39) that in many cases doctors prescribe unnecessarily under pressure from their patients, and under pressure of time. There is an urgent need for public health education in this area. We commend what is already being done; but we urge the Government and health authorities to do more. In particular, we recommend a campaign targeted at mothers of young children. One appropriate vehicle for such a campaign would be the popular women's magazines, with their enthusiasm for articles on health and parenting.

  11.14     The message for any such campaign requires careful consideration. It would be overstating the case dangerously to say that antibiotics are bad for you; nothing must be done to deter people from visiting their GP promptly, or from taking their medicine when necessary. But there is evidence (paragraphs 2.40-45) that unnecessary antibiotics not only have public health consequences, but also increase the risk to the individual patient that any subsequent infection will involve a more resistant strain (to say nothing of the possibility of an adverse reaction to the drug itself). The Government and the health authorities should present this evidence to the public.

  11.15     The problems of inappropriate prescribing are compounded by the failure of many patients to comply with therapy by taking their medicines as instructed (paragraphs 2.46-47); but "complete the course" is good advice only if the antibiotic is appropriate in the first place, and if the course is properly defined. The NHS should work with the relevant professional bodies to see that courses of antibiotics are defined according to the best available current information; wide variations in practice among different countries, as in the case of otitis media, suggest strongly that something may be wrong.

  11.16     Compliance is particularly important, and particularly difficult to achieve, in cases of tuberculosis. TB services in the United Kingdom are something of which the Health Services can feel justly proud; but the recent outbreaks of MDR-TB among AIDS patients in London hospitals, and the serious problems in the USA (which cost the City of New York, for example, $175m over four years), must serve as warnings. TB services involve measures to ensure compliance[77], along with port health controls (DH p 371), surveillance and facilities for isolation; cuts in these services to save pennies today would cost this country millions of pounds tomorrow, to say nothing of the cost in human suffering. We welcome the news that new TB guidelines from the Department of Health are to recommend more rapid diagnostic tests, and more stringent infection control, in cases of suspected MDR-TB; the Department must find the necessary resources.

  11.17     It is notoriously difficult to manage what cannot be measured; and we have heard much about the contrast between the excellent data on GP prescribing, captured by both the Prescription Pricing Authorities and GPs themselves, and the lack of data on antimicrobial use in hospitals (paragraphs 10.4-7). We draw this to the attention of those responsible for the NHS Information Technology Strategy. Information from the pharmacy stock-control system is not enough for these purposes; all hospitals should install computer systems for patient-specific prescribing information at ward level.

Prudent use in animals

  11.18     Even though we made it clear from the start that use of antibiotics in animals, fish and plants was not the primary focus of this enquiry, since the Working Group of the Advisory Committee on the Microbiological Safety of Food is looking at the issue in depth, few of our medical witnesses have forborne to express concern in this area. Concern focuses on the role of the growth promoter avoparcin (which the EU has recently prohibited) in inducing resistance to vancomycin and other glycopeptides; the role of fluoroquinolones used in veterinary medicine and prophylaxis in inducing resistance to this important class of drugs in Salmonella, Campylobacter and E. coli; and the possibility that the growth promoter virginiamycin has already induced resistance to the new streptogramin Synercid. The evidence that we have heard (paragraphs 3.7-13) strongly suggests that there is a continuing threat to human health from imprudent use of antibiotics in animals.

  11.19     The United Kingdom led the world in addressing the threat to human health posed by antibiotic use in farming practices with the Swann Report in 1969. Unfortunately, some of the recommendations of Swann were not acted upon and many believe that, had action been taken then, our present concerns would be much less than they are now, at least as regards the situation in the United Kingdom.

  11.20     Antimicrobials are highly efficacious in animals as they are in man. The aim must be to maintain this potency. We do not go so far as some of our witnesses, who call for a ban on all growth promotion and long-term mass prophylaxis. However, on the evidence before us (paragraphs 3.20-24), we recommend that antibiotic growth promoters such as virginiamycin, which belong to classes of antimicrobial agent used (or proposed to be used) in man and are therefore most likely to contribute to resistance in human medicine, should be phased out, preferably by voluntary agreement between the professions and industries concerned, but by legislation if necessary.

  11.21     Potent agents important to human medicine, such as the fluoroquinolones, deserve extreme economy of use in veterinary practice (paragraphs 3.15-19, 25-26). It is right for large animals and companion animals to receive such agents on an individual basis for short-term therapy; but mass-treatment of herds of pigs and flocks of poultry with such agents cannot be best practice from the point of view of human public health. The veterinary profession must address this problem[78], by introducing rapidly a Code of Practice on when such compounds should be prescribed (e.g. when other agents have failed) and how (e.g. for no longer than necessary); we recommend self-regulation in preference to legislation.

  11.22     Many people have pointed out that, even by comparison with the human scene, surveillance of resistance patterns in animals is very limited, making analysis of the problem along the whole food chain very difficult (paragraph 3.12). We draw this to the attention of MAFF, and of the new Food Standards Agency, since the Minister told us that it will have surveillance as an "important function" (Q 755).

  11.23     The role of farming and veterinary practice in contributing to resistance in human pathogens goes beyond the question of food, since pathogens and resistance genes originating on the farm can reach people by routes other than the food chain - for instance, via contact with companion animals. Departmental and Agency boundaries must not be allowed to prevent the Government from getting a grip on the whole of this issue, in the interests of public health. A single multi-disciplinary Government committee to oversee all aspects of antibiotic use should now be set up, as originally recommended by the Swann Report (paragraph 3.31).

  11.24     We draw to MAFF's attention the evidence of Dr Coles (paragraphs 3.36-41), which suggests that resistance in worms and scab pose a serious and imminent threat to the British sheep farming industry. There is no threat to human health; but, if Dr Coles is right and if nothing is done about it, the economic consequences for farmers in the present state of the industry, and the animal welfare consequences, could be serious.

Infection control

  11.25     Besides being desirable in itself, infection control is particularly important to the fight against resistance in two ways. It reduces the need for treatment and therefore the selective pressure which induces resistance in the first place; and, when resistance arises, it limits the damage by keeping the resistant organism within bounds. In respect of hospitals, the NHS is well equipped with policies for infection control; but we are not convinced that they correspond with the reality of life on the wards. We have had disturbing evidence (paragraphs 4.3-19) of infection control teams under-staffed and under-resourced; of poor standards of basic hygiene (e.g. hand-washing), exacerbated by the contracting-out of cleaning services; of inadequate facilities for isolation; of over-crowding of patients, and of "hot-bedding" with inadequate provision for infection control; and of inadequate control of agency staff, and inadequate training for all staff (including doctors, nurses and ancillary staff, and agency staff) in even the basics of hygiene.

  11.26     The rise of MRSA and other hospital infections has taken place at a time when the Health Services have placed emphasis on patient throughput and economy; this may have led some managers and clinicians to see infection control as a cost and an impediment, rather than a basic component of patient care. The present Government express determination to change the ethos of the Health Services in this respect. As one practical way to do so, 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. The evidence of the cost of hospital-acquired infection (paragraphs 4.30-34) suggests that such a policy will pay for itself quite quickly. In particular, the NHS Executive should assure themselves that every NHS hospital is covered by a properly trained infection control team, as recommended in the Cooke Report.

  11.27     While we do not go so far as to recommend a national task force against MRSA, we found what the Department of Health had to say on this subject complacent (paragraphs 4.35-37). Levels of MRSA in this country are low by international standards, but they are rising. The more MRSA circulates, the more vancomycin must be used to treat it, bringing closer the prospect of VRSA which in the words of the PHLS would be "catastrophic" (p 44, Q 95). We recommend that the NHS should set itself targets for controlling MRSA in hospitals, and publish its achievements.

  11.28     As Dr Winyard himself acknowledged (Q 811), infection control beyond the hospital is an area of particular weakness (paragraphs 4.20-25). This is especially true of nursing and residential homes, which can act as reservoirs of MRSA and other resistant organisms which are carried back into hospitals again and again. As a step towards improving the situation, we recommend that, once the current review of the Public Health (Control of Disease) Act 1984 is concluded, the NHS should draw up national standards and guidelines for community infection control management, along the lines of the Cooke Report for hospitals. These should include a requirement that every district health authority should have at least one community infection control nurse. Such an exercise might also usefully include the special factors affecting prisons (paragraph 4.29).

  11.29     We draw to the attention of those responsible for the review of the Public Health (Control of Disease) Act 1984 Dr Mayon-White's evidence (paragraph 4.26) as to shortcomings of the provisions for compulsory medical examination and detention in hospital, and the case for a more humane regime, and for extending the legislation to provide also for supervised treatment at home.

Surveillance

  11.30     Surveillance—the collection of microbiological data for comparison, analysis and feedback—is vital to the fight against resistance. It supports prudent prescribing, by tracking the rise of resistance, and informing local formularies and policies accordingly; and it supports infection control, by giving warning of areas of weakness. In both areas, it allows practice to be evaluated by revealing its effects on local rates of resistance and infection.

  11.31     The PHLS were admirably frank with us about the shortcomings of their surveillance, especially in the area of denominator information (paragraphs 10.9-10). We recommend that the NHS R&D Directorate should support microbiological surveillance among the population at large, with a view to improving denominator information, as a legitimate call on the NHS R&D Budget. This is just the sort of public health research which we had in mind in 1988 when we first recommended that there should be a NHS R&D Budget.[79] The MRC and the medical charities should also be prepared to support such work.

  11.32     It is astonishing that the Departmental subvention for the PHLS is falling (paragraph 5.14), at a time when surveillance of infectious disease and particularly resistant disease has become so important. The Department of Health must reconsider these cuts.

  11.33     We draw to the attention of those responsible for the review of the notification provisions of the Public Health (Control of Disease) Act 1984 the proposals of our witnesses (paragraphs 5.2-6) for reporting of diseases by causative organism, and for mandatory reporting of certain resistances. Any increase in the burden of reporting placed on hospital laboratories will have resource implications which the NHS must face; and it must be matched by an improvement in the level of feedback from the PHLS.

  11.34     We recommend that Health Ministers assure themselves that liaison between the PHLS and its analogues in Scotland (especially in the context of impending Devolution) and Northern Ireland is as close as possible (paragraphs 5.7-9). In particular, Ministers should set a deadline for full compatibility of definitions and data-collection.

  11.35     We draw to the attention of those responsible for the NHS Information Technology Strategy the scope for IT to facilitate surveillance of disease and resistance (paragraph 5.10), particularly by speeding up exchange of compatible data locally, nationally and internationally, and by permitting links to be made between microbiological data and clinical data of prescribing and outcomes, subject to the necessary safeguards for confidentiality of patient-specific information.

  11.36     We congratulate the PHLS and the NHS on the establishment of the Nosocomial Infection National Surveillance System (NINSS) (paragraphs 5.11-13). The usefulness of NINSS will be much enhanced if it can be linked with data on the use of antimicrobials. We recommend that the NHS should examine the ICARE Project run by the US Centers for Communicable Disease Control and Prevention (CDC), and consider the possibility of setting up something similar, possibly in partnership with CDC.

  11.37     We commend the efforts of the BSAC and the PHLS to put resistance surveillance on a more strategic and comprehensive footing (paragraphs 5.18-22). The Government must engage constructively with those involved, and find additional resources. Surveillance depends on many microbiological laboratories in the NHS and the medical schools, as well as those which are part of the PHLS, and we have received evidence that these are generally under-staffed; we recommend that NHS Trusts and universities should examine their priorities in this area.

  11.38     We are concerned at evidence (paragraphs 5.15-17) that clinical academic microbiology, which provides much of the expertise for surveillance, and for infectious disease medicine generally, is currently failing to attract recruits and fill senior posts. The problem is widely acknowledged; it must be addressed by the NHS, the Higher Education Funding Councils, and the heads of medical schools. This may be a special case of a more general problem concerning the pressures placed on clinical academic medicine by the conflicting demands of the Research Assessment Exercise and the ever-growing burdens of teaching, service provision and administration; we have expressed concern about this before, and we do so again.

New drug development

  11.39     We congratulate the British pharmaceutical industry for renewing their efforts to find novel antimicrobials (paragraphs 6.2-4). We wish them success; but results cannot be expected in the short term. Pharmaceutical development is a very lengthy process; drugs at the R&D stage today may not be on the market for several years, during which time resistance to existing drugs could get dramatically worse. The sequencing of complete genomes, such as that of Mycobacterium tuberculosis which was achieved at Hinxton Hall as our enquiry drew to a close, is a great achievement, but only a first step; there are numerous other steps between a gene sequence and a new drug product, including characterisation of the gene products and the trial of many possible drug targets.

  11.40     We commend the EU proposal for an "orphan drug" regime (paragraph 6.6). The Government should respond positively, and should seek to ensure that the scheme gives the pharmaceutical industry a real incentive to work on novel treatments for problem diseases, particularly diseases of the world's poor such as malaria where the market is at present worth relatively little but the cost in human suffering is huge.

Vaccines

  11.41     As more antimicrobials lose their effectiveness, the importance of vaccines grows (see Chapter 7). What is more, like other forms of infection control, vaccines act against resistance at source, by reducing the amount of antimicrobial chemotherapy required and therefore reducing the selective pressure on bacterial populations. We commend the establishment of the Edward Jenner Institute. The numerous agencies committed to research into effective vaccines must keep up the good work. Vaccines effective against malaria, group B meningococcus and HIV, and more effective vaccines against the pneumococcus and TB, would be particularly valuable.

Viruses

  11.42     As new antivirals reach the market (see Chapter 8), the NHS must ensure that they are used prudently from the start, and that changes in susceptibility are monitored. The lessons learned from 50 years of use and abuse of antibacterials must be fully applied.

  11.43     We congratulate the PHLS on establishing the world's first reference laboratory for antiviral resistance, under Dr Deenan Pillay in Birmingham. The PHLS must adequately resource the development of this important field.

International

  11.44     Resistant bacteria do not respect frontiers. The international trade in food of all kinds exposes British shoppers to the consequences of the misuse of antibiotics in farming practice around the world. In the era of mass travel by air, a resistant bacterium of gonorrhoea (for example) may evolve in Bangkok one day and be in Birmingham the next. Public health in the United Kingdom is therefore affected directly, for better or worse, by action or inaction in other parts of the world.

  11.45     We commend the Government, and particularly the Department for International Development, for their exemplary support over recent years for the WHO Division of Emerging Diseases (paragraph 9.4). This support should be maintained, and the United Kingdom Government's example should encourage other nations and agencies to contribute to this vital work. We endorse the resolution on this subject which is to be considered by the World Health Assembly in May; we urge the Assembly to pass it.

  11.46     The United Kingdom has had a good record of support for malaria research, and for the efforts of the WHO to help poor countries to combat this disease (paragraphs 9.6-15). The Government and the grant-awarding bodies must maintain this record.

Resources for research and data-collection

  11.47     There is still much that needs to be done to increase understanding of the mechanisms of resistance and the action of antimicrobials and, in the clinical sphere, methods of using agents to best advantage (paragraphs 10.2-14). There are data to be collected on resistance and use (in animals and man), and how to prevent the emergence and spread of resistant pathogens (bacterial, viral, fungal and parasitic); and many educational ventures are required in order to find the most suitable approaches to control the problem.

  11.48     Research in this area evidently falls between a number of stools (paragraphs 10.15-20), receiving inadequate support from the major grant-giving bodies and the NHS R&D Strategy. The grant-awarding bodies and the NHS Executive should reconsider the important public health issues surrounding antimicrobial research, and should give such research an enhanced priority. As in the case of surveillance, we particularly commend this as a suitable area of activity for the NHS R&D Strategy.

  11.49     We note that both the MRC and the Wellcome Trust report a shortage of high-quality research proposals in this area. We challenge the research community to come forward with proposals which, given the increased interest in the field which is already apparent, will fully justify support from the grant-awarding bodies.

  11.50     Although research including surveillance is imperative, it should not take the place of immediate action to improve antibiotic use and prevent the spread of infections.

Information technology

  11.51     Information technology can play a major role in the fight against antimicrobial resistance, in three main areas: audit of antibiotic usage (see above, paragraphs 11.7 and 17), collection and analysis of disease surveillance data (paragraph 11.35), and linkage of the one with the other. The full benefits of IT in this area, as in others, will only be realised when every GP, every hospital ward and infection control team, and every clinical microbiology laboratory, has compatible and interconnected IT. The NHS Executive must work towards this goal, accepting that it will involve considerable cost, and giving a strong lead from the centre to ensure compatibility.

An epidemic in its own right

  11.52     It will be apparent from the above that we take the issue of resistance to antibiotics extremely seriously. The evidence we have received is alarming enough as to the present situation, and even more so as to the prospect for the future. In the long term, science may come to the rescue, with novel antimicrobials and additional vaccines; but in the short term the world is facing what may be described as an epidemic in its own right, and the dire prospect of revisiting the pre-antibiotic era.

  11.53     As things stand, the United Kingdom has much to be grateful for, and a certain amount to be proud of. Rates of resistance here are lower than in most countries, and the health care professions are doing their best to keep them so; and our contribution to the fight against resistant disease in other parts of the world is considerable. But the trend of resistance is upward, and we are not convinced that either Ministers[80], the public or the veterinary and agricultural community have fully grasped the importance of action in the short term. The health care professions may have a better grasp of the problem, but lack the resources to address it vigorously. To the extent that the problem is understood, the fact that it crosses several departmental and disciplinary boundaries is impeding action; hence our recommendation for a multidisciplinary interdepartmental committee as recommended by Swann.

  11.54     We do not wish to overstate the problem, at least as it affects the United Kingdom. This country is facing nothing like the continuing tragedy of malaria in Africa. But food poisoning and hospital-acquired infection are already at levels which cause concern, and, if action is not taken now, it is quite conceivable that VRSA, or further outbreaks of MDR-TB, may arise here, with all the consequences of suffering and expense. The Government clearly desire to develop a strategy to safeguard the effectiveness of antimicrobials; we conclude by urging them to follow this project through along the lines recommended in this report, to back it with resources, and to set themselves and the Health Services challenging targets for real improvement. Antimicrobial resistance is here to stay; but action or inaction now, not only by the Government but by everyone with a stake in public health, will have a real impact on the public health legacy which we pass on to the next generation.


77   Including directly-observed therapy-BMA p 381. Back

78   The evidence of the British Veterinary Association (p 393) suggests that they are already doing so. Back

79   Priorities in Medical Research, 3rd Report 1987-88, HL Paper 54. Back

80   The Chief Medical Officer has made it clear in his annual reports for 1995 and 1996, and in his evidence to us (QQ 756, 765) that he is seized of the problem. Ministers will shortly receive advice on prudent use in human medicine from a sub-committee of the Standing Medical Advisory Committee (Q 759), and on prudent use in animals from the Advisory Committee on Microbiological Safety of Food (see above, Chapter 3). Back


 
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