DH - 4047165 - The Path of Least Resistance Synopsis)

THE PATH OF LEAST RESISTANCE SYNOPSIS
Standing Medical Advisory Committee Sub-Group on Antimicrobial Resistance
INTRODUCTION
In July 1997, the Chief Medical Officer asked the Standing Medical Advisory Committee (SMAC) to examine the issue of antimicrobial resistance in relation to medical prescribing. SMAC responded by setting up an interdisciplinary Sub-Group with the following Terms of Reference:
BOX 1. TERMS OF REFERENCE

In the light of the increasing clinical importance of resistance to antimicrobial drugs, to: q identify the major and emerging problems of antimicrobial resistance in clinical practice q identify clinical practices that may predispose to the development of resistance q identify practices in antimicrobial use that might help to limit the development and spread of resistance q identify priorities for changing practice in the use of antimicrobial agents q advise on how such changes might most effectively be achieved for both professionals and the public
Membership of the Sub-Group included cross-representation from the Standing Advisory Committees for Dentistry, Pharmacy, Nursing and Midwifery and consumer, veterinary medicine and pharmaceutical industry representation. The main report, of which this is the synopsis, reviews the problem at several levels: Case-studies explore day-to-day antimicrobial prescribing problems faced by doctors. The basis and impact of resistance are reviewed. Aspects of antimicrobial use and misuse that exacerbate resistance are identified, together with strategies to conserve the usefulness of antimicrobial agents. Recommendations are made. These recognise that the decisions concerning antimicrobial prescribing are often complex, and are as much about minimising harm as about maximising benefit.
Introduction
Methods for implementation of the recommendations are reviewed. The Report does not claim to address all the issues, or to make recommendations that will solve all the problems associated with antimicrobial use. Nevertheless, key areas are identified where innovative approaches may lessen a problem that affects us all. This Synopsis presents the key points from the main Report. It follows the same section numbering as the main Report to ease cross-referral. The main Report also contains a full set of references and a glossary of terms. In introducing the Report, it may be helpful to draw attention to specific features that distinguish antimicrobial therapy from all other forms of medicinal treatment. The majority of the population will take antimicrobial agents at some time or other in their lives. Apart from simple analgesics, no other drugs are in such widespread use. The efficacy of an antimicrobial in any individual patient is affected by its previous use in other individuals, which may have selected for resistance to the drug. This does not apply to any other kind of medicine: taking a drug to lower blood pressure in the wrong dose, or unnecessarily, may be deleterious for that individual, but it will not affect the efficacy of the medication for others. There is probably no other area of prescribing in which patients expectations, and doctors perceptions of those expectations, play such a role in determining whether or not to prescribe. Any strategy to reduce unnecessary prescribing cannot be targeted only at professionals. It must also address the needs of the consumer for clear information about the risks and benefits of antimicrobial agents and about the circumstances in which it is appropriate for the doctor not to prescribe. Resistance is a natural evolutionary result of exposing microbes to antimicrobials. A realistic expectation would be that reducing inappropriate prescribing would prevent the situation deteriorating further. While certain clinical prescribing practices exacerbate the development of resistance, it is much less clear that changing those practices 4
FIRST
SECOND
THIRD
FOURTH
The Path of Least Resistance
will achieve a decline in the prevalence of resistance. Unrealistic expectations should not be generated by the recommendations in this Report. The part played by veterinary prescribing in the development of antimicrobial resistance in human pathogens is important with some (although not all) pathogens. This is the subject of review by the Governments Advisory Committee on the Microbiological Safety of Food. Debate over the relative contributions of medical and veterinary prescribing to the development of antimicrobial resistance in human pathogens must not be allowed to delay the implementation of initiatives to improve clinical prescribing practices. The use of antimicrobials as animal growth promoters is distinct from veterinary prescribing and is not performed under veterinary supervision. Its role in the selection of resistance is a major concern, especially its potential to generate resistance to antibiotics which are under development for use in humans. It is important to recognise that our best efforts, in this country, to minimise resistance may be frustrated by a lack of comparable initiatives abroad. Some early and demonstrable successes in modifying clinical prescribing practice in the UK may provide a helpful model for others. Good antimicrobial prescribing will have other beneficial effects in particular, a reduction in the incidence of adverse effects. Adverse effects are always unwelcome, but an adverse event arising from an unnecessary prescription is doubly so.
FIFTH
SIXTH
SEVENTH
FINALLY
The recommendations in this Report are directed towards ensuring that best practice in antimicrobial prescribing becomes routine practice. This will require a willingness, on the part of health care professionals and the public alike, to treat antimicrobials as a valuable and non-renewable resource, to be treasured and conserved in everyones interest.
Introduction
RECOMMENDATIONS
There is a huge literature on antimicrobial resistance in relation to clinical prescribing. Not all of it is soundly evidence-based and many fundamental questions have not been addressed. Hence, the Sub-Group has not attempted to produce an exhaustive set of recommendations for minimising the development of antimicrobial resistance in every clinical situation. Rather, since the aim of this Report is to make a genuine difference, we have taken the pragmatic approach of concentrating on recommendations where the pay-back in terms of potential benefit seems to us, on the evidence currently available, likely to be greatest. Thus, we have concentrated on recommendations related to prescribing for the most commonly encountered conditions and on proposals for developing support systems that help prescribers make evidence-based decisions and which involve patients and carers in the decision-making process. In the light of research on behavioural change, the Report proposes a co-ordinated approach with various incentives ranging from educational programmes, through organisational changes, to financial inducements to industry. The recommendations are presented in a framework which is addressed to policy and decision makers including industry and to prescribers and the public. Within that framework, there are recommendations aimed at helping general medical practitioners (who undertake 80% of all antimicrobial prescribing) make a real difference to the development of resistance, by optimising their own prescribing practices.
PRESCRIBING IN THE COMMUNITY

Patients with minor infections mostly present to general practitioners (GPs); consequently, 80% of UK human antimicrobial prescribing is in the community. This Report, therefore, concentrates on community prescribing of antimicrobials. We recommend that there should be a national Campaign on Antibiotic Treatment (CAT) in primary care on the theme of Four things you can do to make a difference.
BOX 2. FOUR THINGS YOU CAN DO:

q no prescribing of antibiotics for simple coughs and colds q no prescribing of antibiotics for viral sore throats q limit prescribing for uncomplicated cystitis to three days in otherwise fit women q limit prescribing of antibiotics over the telephone to exceptional cases
In making recommendations aimed at influencing doctors prescribing habits, we acknowledge the importance and influence of patients expectations and demands on the decision-making process. We see these as two sides of the same coin; modifying patients expectations, through a process of public education, will make it easier for GPs to adhere to the recommendations. Hence, we recommend that the CAT must be matched by a National Advice to the Public (NAP) campaign aimed at supporting the initiative in primary care. A key feature of the NAP campaign should be to highlight the benefits of cherishing and preserving your normal bacterial flora. We recommend that further support for appropriate prescribing in primary care be provided by developing and promulgating evidence-based national guidelines for the management of certain infections, under the aegis of the National Institute for Clinical Excellence. Guidelines would aim to minimise unnecessary antimicrobial use, and to ensure that, when needed, the most appropriate antimicrobial and regimen is prescribed, so as to ensure the best possible clinical outcome and reduce the risk of resistance developing. We recommend that such national guidelines be adapted for local use during the development of Health Improvement Plans. Health Authorities will need to co-ordinate ideas on guideline development and use with Primary Care Groups/Local Health Groups and with local microbiological and epidemiological advice. The best of guidelines are of no value if they are not used. To make the incorporation of the guidelines into everyday practice as effort-free as possible, we recommend that they should be integrated within computerised decisionmaking support systems. A number of these are under development and some are currently being piloted in general practice. The guidelines should also be promulgated widely through the medical literature.
Recommendations
PRESCRIBING IN HOSPITALS
Hospital prescribing accounts for only about 20% of all human prescribing of antimicrobials in the UK. Nevertheless, resistance problems are greatest in hospitals, reflecting the facts that (i) the prescribing is concentrated in a small locale, intensifying selection pressure for resistance, (ii) many hospitalised patients have severe underlying diseases that render them susceptible to infection by otherwise harmless opportunist pathogens that have been adept at acquiring resistance and (iii) the high concentration of susceptible patients facilitates the spread of infection. Thus, prescribing in hospitals poses some different issues from those in primary care. However, hospital clinicians would benefit as much as GPs from the availability of computer-aided decisionsupport systems, into which suitably adapted national prescribing guidelines could be integrated. IT for clinical use tends not to be as well developed in hospitals as in primary care, although systems are being developed. Therefore, we recommend that studies be undertaken in selected hospitals to develop and test one or more prototype decision-support systems. To be fully effective, these computer-based advisory systems should include information from local antimicrobial sensitivity profiles. These, in turn, should feed into regional and national surveillance databases.
PRESCRIBING GUIDELINES
We recommend that local prescribing information should, wherever possible, be harmonised with that in the British National Formulary (BNF) and other formularies. Guidelines and formularies should also take account of the proposed national evidence-based guidelines to be produced under the aegis of the National Institute for Clinical Excellence. All local prescribing guidelines should take their cue from these national guidelines to avoid re-invention of the wheel. We recommend that all such local guidelines should include, as a minimum, certain standard items of information on drug, regimen and duration.
EDUCATION
The development of guidelines and their widescale introduction into clinical practice will have important and beneficial spin-offs for the education of health care professionals involved in antimicrobial prescribing. We recommend that greater emphasis than hitherto should be placed on teaching about antimicrobial prescribing in medical and dental schools, as well as in the undergraduate curricula for pharmacists and nurses. We recommend also that teaching about antimicrobials should be better integrated with teaching about the infections for which they are used. This enhanced emphasis on education in antimicrobial use should be carried over into continuing medical, dental and professional education and development. Similar concepts apply in the field of veterinary medicine. The whole population, not just those destined to become health care professionals, would benefit from enhanced education about the benefits and disadvantages of antimicrobials. We recommend that, in addition to health education material aimed at adults, teaching about antibiotics should be included as part of the health education in the National Curriculum.
SURVEILLANCE OF RESISTANCE
Effective surveillance is critical to understanding and controlling the spread of resistance. Not only does surveillance monitor the existing situation, it allows the effects of interventions to be tested. We recommend that a strategic system for surveillance of antimicrobial resistance should be developed as swiftly as possible, and that this should cover the whole of the UK. Discussions to develop such a system are taking place between the Public Health Laboratory Service (PHLS), the British Society for Antimicrobial Chemotherapy and various parties in Scotland and Ireland. It is vital that the system being developed is adequately funded, also that PHLS and NHS microbiology laboratories, whose routine data will be collected, are adequately staffed and resourced to provide high-quality information and we so recommend.
RESEARCH
National and local surveillance will give invaluable guidance to the many Health Service and University projects needed to investigate the drivers of
Recommendations
resistance and the effects of interventions. Aside from these studies, more basic research is needed on the mechanisms of antimicrobial resistance and their spread. We recommend that research into antimicrobial resistance should become a high priority for all funding bodies concerned with health care and biomedical research. We note, with grave concern, the downgrading of medical microbiology as an academic speciality in many teaching hospitals, including several with distinguished records of work on antimicrobial resistance.
HYGIENE, INFECTION CONTROL AND CROSS-INFECTION

Not all problems merit the ubiquitous more research needed recommendation. In some cases the solutions are well known; it is implementation that is faulty or deficient. This is true for certain aspects of infection control. In hospitals, guidance is available to be followed. At its heart is the issue of attention to cleanliness and hygiene in all their manifestations. These extend from the thoroughness of the work done by cleaning staff to simple handwashing by health care professionals in contact with patients. The issue of infection control, although intimately bound up with problems of antimicrobial resistance, particularly in hospitals and other health care environments, was outside the Terms of Reference of our Sub-Group. Nevertheless, we believe that it is so fundamental to preventing the spread of resistant organisms, not only in hospitals but also in the community, that we recommend consideration be given to producing guidance on infection control in the community, especially in nursing and residential homes. This may need to await clarification of the roles and responsibilities of Health and Local Authorities in the control of infection.
VETERINARY AND AGRICULTURAL USE

Antimicrobials are used under veterinary supervision for the treatment and prophylaxis of infection in animals. Some agents are also used, without this supervision, as growth promoters. These aspects were, strictly, outside our remit although our Sub-Group had cross-representation from the Advisory Committee on the Microbiological Safety of Food, whose Working Group on Microbial Antibiotic Resistance in Relation to Food Safety is expected to report later this year. Nevertheless, we recognise that the use of antimicrobials in
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animals has a profound influence on the development of antimicrobial resistance in human pathogens and our general recommendation would be that the use of antibiotics in veterinary practice should be guided by the same principles as those for prescribing in humans namely, they should be used only for clinical conditions where their use is likely to provide a genuine health benefit. We recommend that alternative means of animal husbandry be developed so that the use of antimicrobials as growth promoters can be discontinued.
IMPLICATIONS FOR INDUSTRY

If our recommendations are followed, they should have the effect, inter alia, of reducing antibiotic usage. There may be financial implications for the pharmaceutical industry, upon whose profitability the development of new antibiotics depends. Therefore, we recommend that consideration be given by the appropriate bodies to finding ways through pricing and other mechanisms of ensuring that investment in the development of new antibiotics remains commercially viable for the industry. In addition, we recommend that industry should be encouraged to undertake studies of optimum prescribing regimens for new antimicrobials, for each of their indications and in adults and children as appropriate. This evidence-based information should be included in the Summary of Product Characteristics (SPC) for each product as set out in the product licence and the product data sheet. We recommend that the licensing authorities should have due regard to an antimicrobials potential to select for resistance as well as to its efficacy and safety.
INTERNATIONAL CO-OPERATION
In the field of antibiotic prescribing, this country cannot consider itself an island. International prescribing practices have a major influence on the development and spread of antimicrobial-resistant organisms and their genes. Resistant organisms in Europe enjoy as much freedom of movement only in larger numbers as their human hosts. Hence, we recommend that every effort is made by the Government to raise the profile of antimicrobial resistance as a major public health issue meriting priority action from all Member States of the European Union.
Recommendations
11
EXPECTATIONS
We wish to emphasise that our Report should not generate unrealistic expectations. Even stopping altogether the prescribing of certain antimicrobials may not lead to an appreciable reduction in the levels of resistance to those drugs, even over a period of several years. However, we hope to achieve a slowing of the rate at which resistance develops. This may buy a few more years of therapeutic usefulness for certain antimicrobials, until such time, hopefully, as they may be replaced by new and novel compounds. Different considerations may then apply, so as to build in, from the outset, safeguards to minimise the development of resistance.
NATIONAL STRATEGY
Our aim has been to produce recommendations that can constitute the first phase of a national strategy for minimising the development of antimicrobial resistance. We recommend, as part of this phase, the establishment of a small National Steering Group (NSG) charged with ensuring that these recommendations are implemented and their effects, on prescribing practice and on the development of resistance, are monitored. The NSG, which might need to establish a small number of expert groups to take forward specific aspects of the recommendations, should report to the Chief Medical Officer within a year on progress with and lessons learned from implementing Phase 1 of the strategy. Thereafter, the CMO may wish to consider asking SMAC to reconvene this Sub-Group, in order to provide a suitable interdisciplinary forum for the development of the next phase of the strategy, building on the results of various pilot and other studies to evaluate the effectiveness of the recommendations in this Report.
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Figure 1 Recommendations for the professions and the public: CATNAP
Recommendations
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LOOKING INTO THE ABYSS
KEY POINTS
q Antibiotics enable huge advances in medicine q Antibiotic use selects for resistant bacteria q Resistant bacteria accumulate and spread q Resistance increases clinical complications, lengthens hospital stay and adds cost q Development of new antibiotics is slow, expensive and cannot be guaranteed q With more resistance and few new antimicrobial agents, modern medicine is threatened For two generations, antimicrobial agents have altered expectations of life and death. The fever hospitals and tuberculosis sanatoria have gone. In the early 1930s, deaths from sepsis after childbirth in the UK were 100120 per 100,000 births; after antibiotics were introduced this rate fell to almost zero. Antimicrobials have enabled operations and treatments such as transplantation to be undertaken that were previously unthinkable because they exposed the patient to a huge infection risk. Unfortunately however, antimicrobial use exerts an inevitable Darwinian selection for resistance. Once selected, resistant bacteria spread or transfer their resistances to other bacteria. The result has been erosion of antimicrobial efficacy, putting the past half-centurys medical progress at risk. Until recently, man kept ahead and new antimicrobials were developed faster than bacteria developed resistance. Gradually, though, a change occurred: while the 1950s and 60s saw the discovery of numerous new classes of antimicrobials, the 1980s and 90s yielded only relative improvements within classes. Now, in the closing years of the century, micro-organisms are getting ahead, and therapeutic options are narrowing. In the UK there are bacteria resistant to many antimicrobials. Elsewhere the situation is often worse. In Japan, strains of Staphylococcus aureus and Pseudomonas aeruginosa are resistant to all established antimicrobials. There is every reason to fear that such pathogens will be imported to the UK, or will evolve independently here. The spread of resistance threatens a return to darker times, when surgery was restricted to simple operations on the otherwise healthy, and when organ 14
transplants, joint replacements and immunosuppressive therapies were unthinkable. Even when resistance does not prevent effective therapy, it adds cost. The initial antimicrobials must be replaced with agents that are more expensive or have undesirable side-effects. More generally, patients whose therapy proves inappropriate as a result of resistance are more likely to experience complications . In one study, reoperation, abscess formation and wound infection were all commoner in those surgical patients who received inappropriate therapy.
Figure 2 Complications (%) after appropriate and inappropriate therapy in surgical peritonitis
The threats to health posed by antimicrobial resistance are: q Some conditions may become untreatable q Empirical treatment may be inappropriate and time may be lost in critically ill patients q Length of hospital stay, antimicrobial use, morbidity, mortality and costs may be increased q More toxic, less effective or more expensive alternative drugs may have to be used.
Looking into the abyss
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ANTIMICROBIAL AGENTS
The range of antimicrobial agents available and their activities are summarised in this section of the main Report, to which the reader is referred. The terms antimicrobial agent and antimicrobial are used in this Report principally to encompass antibiotics (substances produced by micro-organisms that selectively destry or inhibit other micro-organisms) and chemically produced antibacterial drugs, and also to include, where appropriate, antiviral and antifungal agents.
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5
KEY POINTS
BASIS OF RESISTANCE
q Darwinian selection q Antimicrobial agents kill sensitive organisms, resistant ones survive q Sensitive organisms may become resistant by mutation q Resistances can transfer among different organisms q Some species are inherently resistant and are selected by antimicrobial agents q Bacteria accumulate multiple resistances to unrelated antibiotics
The great principle of antimicrobial resistance is Survival of the Fittest. Antimicrobials kill susceptible bacteria but resistant ones survive to infect other patients. At the same time, advances in medicine enlarge the pool of patients susceptible to infection by organisms that historically were harmless, but which are adept at developing resistance. Resistance can arise via mutation, gene transfer or by the selection of inherently resistant species. The importance of these processes varies with the organism, the antimicrobial agent and the clinical setting. Figure 3 Mechanisms of antimicrobial resistance The antimicrobial, drawn as a bullet, heads towards its target. Resistance may arise (i) if it is inactivated before it reaches the target, (ii) if the bacterial cell becomes impermeable, (iii) if the cell becomes able to pump the antibiotic back out, (iv) if the target is altered so that it no longer recognises the antimicrobial, or (v) if the bacterium acquires an alternative metabolic pathway, by-passing the site of action.
Basis of resistance
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BOX 3. MULTI-RESISTANCE
Organisms resistant to one antimicrobial are more likely to be resistant to unrelated agents. It is not the methicillin resistance of methicillinresistant Staphylococcus aureus ( MRSA) that matters; rather, that many MRSA are also resistant to alternative drugs. Likewise, the vancomycin resistance of increasing numbers of enterococci would not matter if many enterococci were not already resistant to all other drugs.
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DOES USE OF ANTIMICROBIAL AGENTS CAUSE RESISTANCE?
KEY POINTS
q Resistance has repeatedly emerged to new drugs after clinical use q Most resistance occurs in countries and units where use is heaviest q Resistance may be selected in the target organism during therapy q Resistant commensal body flora may also emerge during therapy q Evidence linking antimicrobial use in man and resistance is clear and overwhelming, but mostly circumstantial Key facts are: i) Acquired resistance is absent from bacteria ante-dating the antimicrobial era. The only resistances seen are those inherent to particular species. ii) Introduction of new antimicrobials has been followed repeatedly by resistance. The time scale has varied, reflecting the complexity of the evolution, but the pattern is constant. iii) Resistance often develops in the normal bacterial flora of individuals receiving antimicrobial therapy. If a further infection arises from this flora, it is more likely to be resistant than in patients who have not received prior therapy. iv) Resistance is greatest in countries and hospital units where antimicrobial use is heaviest. The clearest example is the excess of resistance in intensive care units
Does antimicrobial use cause resistance?
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7
KEY POINTS
TO PRESCRIBE OR NOT TO PRESCRIBE?
q In many common infections the decision to prescribe is finely balanced q Infections are often viral and unaffected by antibiotics q Decisions to prescribe are influenced by patientsexpectations q Patients believe that antimicrobials will work for them q Unnecessary or marginal use exacerbates the selection of resistance q Reducing unnecessary antibiotic use must involve health care workers, patients and the pharmaceutical industry
Microbial pathogens are increasingly resistant to the available drugs. However, the anxious parent and the unwell adult continue to expect the doctor to prescribe a pill to cure their ill. GPs, hospital physicians, surgeons, paediatricians, or obstetricians continue to prescribe antibiotics, sometimes for inappropriate indications, in inappropriate doses, for inappropriate lengths of time. Why is this so, and how can it be changed? The unnecessary prescription and consumption of antimicrobials is everyones responsibility. Effective treatment of infectious disease can only be preserved through a determination on the part of policy makers, manufacturers, prescribers and consumers to minimise unnecessary consumption. There may be difficult clinical decisions, as exemplified in Boxes 5-8, but there are also circumstances when prescription of an antimicrobial is clearly wrong. A patient with a common cold should not receive an antibiotic and women with uncomplicated cystitis should not receive antibiotics for more than three days.
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BOX 4. THE ANTIMICROBIAL TUG OF WAR

What stimulates prescribing ? Prescribers Failing to prescribe may lead to clinical complications or litigation Applying rules learned as a student which may no longer be appropriate Clinical judgement Scientific and promotional literature A prescription is an easy way to end a consultation Patients Patients expectations drive prescribing Many patients expect a script Belief that they need an antibiotic to stop a cold going to their chest Anxiety over sick children Nurses May not fully appreciate the risks associated with inappropriate use of antimicrobials What inhibits prescribing ? Prescribers Advice from specialists in microbiology and infectious disease, who discourage excessive prescribing Good basic training on risks and benefits of antimicrobial treatment
Patients Some patients are averse to prescription, and seek reassurance that they will recover without an antibiotic
Nurses See the problems associated with over-prescription resistance, wardclosures, antibiotic-associated diarrhoea and try to educate prescribing colleagues and patients Pharmacists Particularly in hospitals, have an important role in controlling prescribing and identifying inappropriate prescribing Pharmaceutical industry Wants to ensure long product life
Pharmacists Often first community contact; may advise that a prescription is necessary Pharmaceutical industry Wants to sell its products
To prescribe or not to prescribe?
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This is the antimicrobial tug of war, and what is required is action that will ensure that every prescription is justified, is of the appropriate drug, dose and regimen, and is reassessed in the light of clinical response and microbiological results, if necessary. Prescription of an antibiotic should be seen as a serious step, similar to the prescription of steroids or any other potentially hazardous medicament.
BOX 5. THE PAINFUL EAR

Acute otitis media (AOM infection of the middle ear) is common in childhood. A child with AOM is distressed, unhappy and febrile. The parents are concerned and eager for the GP to act. The GP may feel under pressure to prescribe. It is easy to write the prescription and see the family leave satisfied. When the symptoms improve this is attributed to the antibiotic, reinforcing the cycle of expectation. A GP will see many children with AOM each year and most will receive an antibiotic. Reviews on AOM suggest that the benefit of routine antimicrobial use is unproved or modest. A proportion of children do benefit but it is difficult to predict which ones. Countries with lower rates of antibiotic prescribing for AOM do not have any increase in the number of complications compared with those where a prescription is usual. Even if antibiotics are prescribed, there is debate about the appropriate length of treatment: three and ten day courses were equally effective in one study. Antibiotics are probably unnecessary in AOM. Reassurance, time and adequate pain relief are required. If antibiotics are prescribed, the course should be limited to three days.
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BOX 6. THE SORE THROAT

Sore throats are common, particularly in children. Most are viral and can be left to run their course without antibiotics. Indeed, recurrence and relapse may be more common in those who have had early treatment with antibiotics. Nevertheless, the GP can come under considerable pressure to prescribe an antibiotic for a sore throat. A recent study showed that patients with sore throats were more likely to leave the consultation satisfied if they received a prescription. However, they were no more likely to be satisfied at the end of the illness. Those who received antibiotics were more likely to return for treatment in future attacks and were more likely to believe in the efficacy of antibiotics. A minority of sore throats are caused by a bacterium, Streptococcus pyogenes. It is not easy to distinguish a streptococcal sore throat from a sore throat caused by viral infection. Streptococcus pyogenes can lead to local abscesses and, rarely, to kidney problems and rheumatic fever. Therefore, many doctors prescribe antibiotics for a sore throat with the intention of preventing the consequences of Streptococcus pyogenes infection. Sore throats should not be treated with antibiotics, unless there is good evidence that they are caused by Streptococcus pyogenes.
BOX 7 SINUSITIS
Several studies, including randomised controlled trials, have shown antibiotics to be effective in proven acute sinusitis. Most of these studies have used ten day courses of antibiotics. One comparative study showed that three days of antibiotics were as effective as ten days. Recent overviews of the treatment of acute sinusitis-like symptoms in adults in the primary care setting suggest that there is no benefit from antibiotic treatment. The adult with sinusitis-like symptomsin primary care does not need immediate antibiotics. In proven acute sinusitis three days of antibiotics are as effective as ten.
To prescribe or not to prescribe?
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BOX 8 CYSTITIS
Each year about one woman in 20 will present to her GP with symptoms of cystitis; about half of these women will have an infection (defined by the presence of a significant number of bacteria in the urine). Most of these infections in otherwise healthy women are caused by coliform bacteria. Uncomplicated cystitis can be treated empirically with trimethoprim. If resistance is common locally, the medical microbiologist can advise on an appropriate alternative. Several studies have shown that a three day course of treatment is as effective as a five or seven day course. Limiting the prescription of antibiotics for uncomplicated cystitis in otherwise healthy women to three days reduces selection pressure for resistance.
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WHERE ARE ANTIMICROBIAL AGENTS USED?
KEY POINTS
q 50% of antibiotic use in the UK is in man, 50% in animals q 80% of human use is in the community q 50% of community use is in respiratory tract infection, 15% in urinary tract infection q Considerable local and regional variation exists in levels of community prescribing q In hospitals, antimicrobial agents account for 1030% of the drugs budget
COMMUNITY PRESCRIBING
About 50 million prescriptions for antibiotics are dispensed in England every year an average of one prescription per person per year. Most human antibiotic prescribing in the UK (80%) is of oral antibiotics in the community. About half of this community use is in respiratory tract infection (RTI), with a further one-sixth in urinary tract infection (UTI). Most community antimicrobial prescribing is by GPs, but dentists account for about 7%. Usage is subject to approximately two-fold variation between Districts with the lowest and highest prescribing, with no obvious explanation.
PRESCRIBING IN HOSPITALS
Although hospital prescribing accounts for only 20% of human usage, it is of key importance because it is concentrated in a small population brought together in a confined environment. Also hospitals with high populations of immunocompromised patients are fertile breeding grounds for opportunist bacteria that are adept at accumulating resistance. Audits at a teaching hospital trust showed that 2025% of patients had received an antibiotic within the previous 24 h, with a range from 40 to 50% in ICU to less than 10% in ENT surgery. As in the community, most prescribing is for RTI.
Where are antimicrobial agents used?
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Figure 4 Hospital and community use of some antimicrobial agents

ANTIMICROBIAL AGENTS Total Systemic Antibiotics Broad spectrum penicillins Med/narrow-spectrum penicillin Tetracyclines + combinations Cephalosporins + combinations Trimethoprim combinations Fluoroquinolones Nitrofurantoin Nalidixic acid Fusidic acid Aminoglycosides Chloramphenicol + combinations Rifampicin/rifamycin Other -lactams Glycopeptides RETAIL (COMMUNITY) (kg) 385600 160406 59800 45900 35900 10900 10300 742 588 354 109 25 12 9 9 HOSPITAL (kg) 80900 25556 17200 1600 15100 3500 3600 45 59 454 5300 88 14 527 493
Data kindly provided by IMS Health UK, Maxims Database
Figure 5 The pyramids of antimicrobial use and selection for antimicrobial resistance
Most prescribing of antimicrobials (80%) takes place in the community; 20% of prescribing is for small numbers of patients, often in specialised hospital units. Both intense pressure in a small number of hospitalised patients and less intense selection pressure in large numbers of patients in the community cause problems with resistance. 26
THE EXTENT OF BACTERIAL RESISTANCE IN THE UK
S. aureus MethS MRSA Enterococci -haem. streps S. pneumoniae Viridans streps E. coli Klebsiella spp Enterobacter Pseudomonas Acinetobacter N. meningitidis N. gonorrhoeae H. influenzae M. tuberculosis
q q 7 r 7 7 q q 7! q r 7 7
r q r 7 7 7 7 q! 7! q r r 7
r q 7 r r r r r r 7! 7 r r 7
7 7 q 7 7 7 q q q q r 7 7
7 q q 7 7 7 q q q q q r 7
7 q q q 7 7 7 7! q
7 q 7 7 7 7! 7 r 7 7
7 q q 7 q q q q 7 7 7
7! 7!
q q q 7 7 7 7
r r 7 r r r
7! 7! 7 7! 7! 7 7 7
7 q r !
Inherently resistant. Acquired resistance in <20% of isolates. Acquired resistance in >20% of isolates. Acquired resistance unknown, or virtually so. Resistance emerges readily by mutation.
NB: This table has many simplifications and ignores variation within antimicrobial classes; it aims to give only an overall, broad-brush picture.
The extent of bacterial resistance in the UK
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CURRENT RESISTANCE PROBLEMS IN THE UK AND WORLD-WIDE
KEY POINTS
q Resistance is accumulating world-wide in many bacteria q The UK situation is not as bad as that in many countries, but the trend is to more resistance q A major problem in the UK is methicillin-resistant Staphylococcus aureus (MRSA) q Other major problems include pneumococci, enterococci and hospital gram-negative opportunists q Resistance is emerging in viruses and fungi
STAPHYLOCOCCUS AUREUS
When penicillin was introduced in l944, over 95% of Staphylococcus aureus isolates were susceptible, but this proportion has since shrunk to 10%. The introduction of -lactamase-stable penicillins (e.g. methicillin and flucloxacillin) in the early l960s was swiftly followed by the emergence of the first methicillin-resistant Staphylococcus aureus (MRSA). Subsequently, a series of epidemic MRSA(EMRSA) strains have evolved and spread, some locally, others internationally. Many are resistant to a number of antibiotics, with only glycopeptides (vancomycin and teicoplanin) remaining active. Recently there have been reports of MRSAwith intermediate resistance to vancomycin and teicoplanin. These are resistant to all available antimicrobials and, unlike other organisms where pan-resistance is seen, have considerable pathogenicity for those not severely immunocompromised.
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Figure 6 Proportion (%) of Staphylococcus aureus isolates from blood and CSF that were resistant to methicillin, 198997
ENTEROCOCCI
Enterococci are a part of the normal human gut flora, where they are harmless. They have little virulence but can cause infection in patients whose health is impaired, particularly in specialised hospital settings (eg renal dialysis and bone marrow transplant units). Serious infections are extremely difficult to treat because of resistance. Enterococci are intrinsically resistant to quinolones and cephalosporins and clinical use of these agents may explain the rising importance of enterococci. In addition, enterococci readily gain resistance to other antimicrobials. Recent concern has centred on the emergence and spread of enterococci with resistance to the glycopeptides (vancomycin and teicoplanin) (Figure 7). Many glycopeptide-resistant enterococci (GRE) are resistant to all established antimicrobials, forcing clinicians to use untested agents or combinations with no guarantee of success.
Current resistance problems in the UK and world-wide
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Figure 7 Number of hospitals submitting enterocococci resistant to glycopeptides to the PHLS Antibiotic Reference Unit: England and Wales, 198796
STREPTOCOCCUS PNEUMONIAE
Streptococcus pneumoniae is most important as a cause of communityacquired pneumonia, which may lead to bacteraemia. It is also a frequent cause of otitis media and is one of the commonest causes of bacterial meningitis. Historically, Streptococcus pneumoniae was exquisitely susceptible to penicillin, which could be used in most pneumococcal infections, including meningitis. Macrolides (eg erythromycin), tetracyclines and co-trimoxazole were alternatives in respiratory tract infection, whereas several cephalosporins and meropenem were and are alternatives in meningitis. Pneumococci with low-level penicillin resistance were recorded in the late l960s and some with high-level resistance began to be seen in the late l970s. These are now increasing, both in frequency and in the level of their resistance (Figure 8). There is also concern about the risk of importation of resistant strains from those countries (eg Spain) where the rate of resistance is much higher.
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Figure 8 Prevalence of resistance in pneumococci from blood and CSF in England and Wales, 198995. YEAR 1989 1990 1991 1992 1993 1994 1995 1996 1997 PREVALENCE (%) OF RESISTANCE PENICILLIN G ERYTHROMYCIN 0.3 3.3 0.5 5.1 0.7 6.4 1.9 8.6 1.7 10.8 2.5 11.2 2.9 10.9 3.7 9.9 7.5 11.8
HOSPITAL-ACQUIRED GRAM-NEGATIVE OPPORTUNISTS

Many different gram-negative bacteria can cause opportunistic infection in immunocompromised patients. The organisms most often involved include members of the genera Escherichia, Klebsiella, Proteus, Enterobacter and Acinetobacter. Escherichia coli is also the commonest cause of cystitis in the community. Resistance to many antibiotics is increasing in these pathogens, notably to cephalosporins, quinolones and trimethoprim.
ENTERIC PATHOGENS SALMONELLA

Several bacterial genera are important in food poisoning. At present multiple drug resistance is a major problem in Salmonella, particularly Salmonella typhimurium, where an important recent factor was epidemic spread of multi-resistant Salmonella typhimurium DT 104 in bovines and its increasing recovery from man.
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Figure 9 Isolation of Salmonella typhimurium DT 104 from man, 198296
CAMPYLOBACTER SPECIES
These organisms, which are the commonest cause of bacterial gastrointestinal infection, can cause severe food poisoning requiring antibiotic treatment. Macrolides and ciprofloxacin are used. Emerging resistance to ciprofloxacin is a concern.
NEISSERIA GONORRHOEAE
Sulphonamides were effective against gonorrhoea on introduction in 1937 and almost invariably ineffective by 1944. Penicillin resistance was slower to emerge, but the agents activity has been gradually eroded, with higher doses being needed. Strains that produce -lactamases (penicillin-degrading enzymes) were first detected in 1974 in gonococci from the Far East and from West Africa. These penicillin-destroying strains are rare in the UK. Ciprofloxacin is very effective against penicillin-resistant isolates and is now used for this purpose in the UK and elsewhere, but this is resulting in a slow increase in the proportion of frankly resistant strains.
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NEISSERIA MENINGITIDIS
This organism is the commonest cause of bacterial meningitis. Frank penicillin resistance is not yet a problem, but the proportion of isolates with decreased susceptibility increased from <1% in 1985/6 to 14% in 1995/6.
MYCOBACTERIUM TUBERCULOSIS
Tuberculosis (TB) remains the commonest bacterial cause of morbidity and mortality world-wide, with nearly 8 million new cases and 3 million deaths annually, mostly in developing countries. A steady decline in clinical cases in the developed world ceased or reversed in the mid-l980s. Tuberculosis is treated with combinations of three or four agents for at least 6 months. Monotherapy leads rapidly to resistance by selecting spontaneous mutants. Even with combination therapy, resistance emerges when there is poor concordance by the patient, incorrect dosage or malabsorption of the drugs. Resistance is a major problem in many developing countries and may be imported into the UK.
FUNGAL INFECTION
Fungal infections are assuming a greater importance, largely because of their increasing incidence in patients with AIDS, transplant recipients, neutropenic cancer patients and debilitated intensive care patients. In the 1980s there was an 11-fold rise in the incidence of disseminated candidosis among patients admitted to hospitals in the USA. The rise in the number of serious fungal infections has resulted in an increase in the use of antifungal agents. This has contributed to the emergence of resistance to a number of important compounds. In recent years, resistance to azole antifungals (eg fluconazole) has become a significant problem in several groups of patients, particularly those with AIDS.
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VIRAL INFECTION
Resistance has been documented to virtually all the antiviral drugs available in the UK. Resistance generally accrues by step-wise mutation, and often leads to a virus with reduced susceptibility rather than one with frank clinical resistance. Combination therapy may militate against the development of resistance in HIV, but the risk cannot be discounted.
What next for antimicrobial resistance ?

FIRST, it seems inevitable that vancomycin-intermediate MRSAwill spread. Worse, gene exchange occurs between staphylococci and enterococci and it is likely that the high-level glycopeptide resistance of enterococci will spread to MRSA. Its spread to pneumococci is also possible. The consequences would be severe: glycopeptides are the drugs of last resort against many serious grampositive pathogens (eg resistant pneumococci in meningitis). SECOND, it is also common to see gram-negative bacteria susceptible only to the carbapenems, imipenem and meropenem. Unfortunately, carbapenem resistance is now seen increasingly in hospital opportunists such as Pseudomonas aeruginosa and Acinetobacter. OTHER RESISTANCES to be feared include those in species that have, thus far, remained remarkably susceptible. Obvious risks are penicillin resistance in Neisseria meningitidis and Streptococcus pyogenes. Penicillin resistance in Streptococcus pyogenes is remarkable by its continued absence. This species, once the most feared of hospital wound pathogens, has remained exquisitely sensitive to penicillin since the 1940s. Nevertheless, gene exchange occurs between Streptococcus pyogenes and staphylococci and there is a risk that -lactamase production may spread from the latter to the former.
In short, evolution hasnt finished yet ...
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AREAS OF CLINICAL PRACTICE WHERE ANTIMICROBIAL RESISTANCE HAS, OR IS LIKELY TO HAVE, THE GREATEST IMPACT
KEY POINTS
q Resistance is greatest where antimicrobial use is heaviest q Major problem areas in hospitals include ICUs, transplant units q Key patient groups include the immunocompromised q Resistance is also rising in common community pathogens
Resistance is most frequent where there are large numbers of susceptible patients. These are also the situations where antimicrobial chemotherapy is most essential. Nevertheless, the consequences of resistance are not restricted to specialised units but are also seen in general in-patients and in the community.
INTENSIVE CARE UNITS

Resistance is most common in patients receiving mechanical ventilation and in university or teaching hospitals. Intensive care and similar units present special problems. Ventilator-associated pneumonia due to antimicrobialresistant bacteria often follows prior antimicrobial exposure and is a particularly important problem. Heavy antimicrobial use probably lies behind the high rates of antimicrobial resistance in ICUs. Furthermore, ICU patients often require invasive support activities which increase the risk of infection, demanding more antimicrobial treatment and exacerbating the risk of selecting resistance.
Areas of clinical practice where antimicrobial resistance...
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ADMISSIONS WARDS
Over the last decade there has been a 50% increase in emergency admissions to general hospitals in the UK. General hospitals increasingly accept emergency patients on an admissions ward, where a pre-registration house physician makes a diagnosis, orders investigations, and prescribes treatment. Most of these patients have medical rather than surgical problems and so are admitted under physicians. Infection is often considered, but may be difficult to diagnose. The diagnosis of infection relies on microbiological investigation. Meanwhile the junior doctor has to decide whether to prescribe empirically. This provides many opportunities for inappropriate or unnecessary antimicrobial prescribing.
IMMUNOCOMPROMISE
Immunocompromised patients may present with difficult-to-diagnose or occult infections. They are vulnerable to a wide range of opportunist infections and often require urgent empirical treatment, without the opportunity to take appropriate microbiological samples. Broad-spectrum antibiotics are used, selecting for broad resistance.
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WHAT PRACTICES BY CLINICIANS AND THE PUBLIC PREDISPOSE TO THE DEVELOPMENT OF ANTIMICROBIAL RESISTANCE ?
KEY POINTS
q Some antimicrobials are more selective than others for resistance q Selection varies with the dosage and duration of therapy q Unnecessary antimicrobial use selects resistance without any gain q Unnecessary use includes over-long prophylaxis and therapy of infections that are trivial, self-limiting, or viral q Public expectations of A pill for every ill encourage over-prescribing
Spread of resistant bacteria is aided by: i) ii) iii) iv) v) crowding of children and the elderly increased travel increased bed-efficiencyin hospitals increased hospital throughput antimicrobial use
Health care practitioners and the public both carry a responsibility. Claims that the entire responsibility lies elsewhere with veterinary antimicrobial use do not withstand scrutiny, since resistance is widespread to antimicrobials used only in man. This is not to absolve veterinary use it is a major driver of resistance among enteric pathogens and, maybe, enterococci but it is important to stress that the whole responsibility cannot be passed to another group. Ultimately, resistance is an inevitable consequence of use, as microorganisms are selected in an environment of antimicrobials. Nevertheless the practices of prescribers and consumers affect the rate of this evolution. Key factors are:
What are the practices by clinicians...
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ANTIMICROBIAL USED
Some antimicrobials are more prone to select resistance than others, either by encouraging overgrowth of an undesirable flora (eg yeasts or Clostridium difficile) or by favouring resistant mutants within the original infection. Oral cephalosporins and clindamycin are both associated with selection of Clostridium difficile; fusidic acid and rifampicin notoriously select resistant mutants in their target species, as do cephalosporins with Enterobacter and Citrobacter spp.
REGIMEN
Dosage and duration of therapy are key factors in modulating selection pressure. Regimens vary greatly from hospital to hospital and practice to practice, often with no underlying rationale. A review of prescribing guidelines showed that simple information such as dose, frequency and total length of course was often missing.
BOX 9. ANTIMICROBIAL GUIDELINES SHOULD:

q be evidence-based q be dated q contain information on the antimicrobial, dose, frequency and length of course q indicate the strength of the evidence for the recommendation q show local variation from national recommendations Necessary antimicrobial use whether prophylactic, empirical or therapeutic exerts selection for resistance. The question is always whether the gain outweighs the risk; whether the choice of antimicrobial maximises the benefit and minimises the risk. Unnecessary use exerts selection pressure with no gain.
PRESCRIBING UNNECESSARILY OR INAPPROPRIATELY

Antimicrobials are prescribed unnecessarily and empirically for trivial complaints where no treatment is necessary, or where culture and sensitivity 38
results could safely be awaited. The use of empirical antimicrobials in community upper respiratory tract infections is a key concern, since 50% of clinical antimicrobial usage is for infections at this site and 70% of infections are viral. A survey of 21,400 patient encounters revealed that over 80% of patients were prescribed an antimicrobial for upper RTI, including 7080% not actually seen by the doctor. Even where the diagnosis was coryza (common cold), 42% of patients were prescribed an antimicrobial.
PROPHYLAXIS
Prophylactic antimicrobial use, ie use to prevent infection, carries a selection risk, whether the use is warranted or not. This risk is increased where the prophylaxis is prolonged. In most cases effective surgical prophylaxis can be achieved with one or two doses at operation, yet prophylaxis is sometimes continued for several days, without any evidence of need.
EMPIRICAL THERAPY
Empirical antibacterial therapy should be given when bacterial infection is suspected, and poses a sufficient health risk to demand immediate treatment. Clear examples include fever of unknown origin in neutropenic patients, pneumonia, meningitis and tuberculosis. In reality, empirical therapy is used far more widely. In community practice, microbiological examination of specimens is rarely undertaken before initiating therapy and, in hospitals, therapy that begins empirically remains so owing to difficulty in obtaining a specimen or disinclination to do so. The specific problems with empirical therapy are: it is often given to patients who do not have bacterial infections; inappropriate antimicrobials may be selected; it is common to use broad-spectrum agents or combinations. Where warranted, empirical regimens should be based on knowledge of the likely pathogens and their antimicrobial susceptibilities. This depends on access to good LOCAL surveillance data.
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PUBLIC BEHAVIOUR AND SOCIAL CHANGE

Public behaviour and changing lifestyles impact on the resistance problem. Excessive prescribing of antimicrobials for trivial and non-bacterial infections in primary care partly reflects consumer pressure. Patients should be encouraged to take control of their own health care but, without appropriate advice, this may lead to increased demand for inappropriate treatment such as antimicrobials for colds, flu or sore throats. Failure to prescribe may lead to dissatisfaction, yet this usage augments the overall selection for resistance. GPs can over-estimate patients expectations. In one study, a quarter of patients received antimicrobials when they stated that, before the consultation, they had not wanted antimicrobials. TRAVEL Many countries have greater rates of antimicrobial resistance than the UK. These may reflect greater prescribing, poorer control of infection and over-thecounter availability of antimicrobials. Laws on patents and pharmaceutical quality are absent or not enforced in some developing countries, where antimicrobial agents are often sold by the single tablet, leading to frequent underdosage. The UK is not isolated from these problems. Resistant bacteria may enter with visitors or returning travellers, or be imported by those who come for medical treatment. LONG-TERM CARE FACILITIES Increasing numbers of elderly people often in poor health live in nursing homes and other long-term care facilities (LTCFs). The role of these as reservoirs for resistant bacteria is an increasing concern, with MRSA the main problem organism. Elderly patients increasingly are shuttled between LTCFs and hospitals, with the risk of MRSA being transferred and of its spreading within LTCFs, where control-of-infection measures are mostly minimal.
DAY-CARE FACILITIES Crowded day-care facilities for children facilitate the spread of colonisation and infection. The role of modern child-care systems, combined with international travel, is illustrated by the spread of multidrug-resistant pneumococci in Iceland. From l989 to l993, the incidence of penicillin-resistant
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pneumococci rose swiftly, from being virtually unknown to 20% of all pneumococci isolated. This reflected the spread of a resistant strain previously prevalent in Spain. It seems that children were colonised by the strain whilst on holiday and that it then spread among them in child-care facilities, which most attend.
VETERINARY ANTIMICROBIAL USE AND THE EMERGENCE OF RESISTANCE

Disease is inevitable in farm and companion animals. Moreover, healthy animals can be carriers and asymptomatic excretors of pathogens. Antimicrobial resistance rates vary with the animal species, the type of husbandry, environmental pressure, the standard of stockmanship and the patterns in trade. Antimicrobial use in animals has been proposed as a factor in the emergence of resistance in human pathogens. Resistant bacteria selected in animals may be transferred to man via the food chain, or may transfer their resistance genes to human pathogens. TYPES OF ANTIMICROBIAL USAGE IN ANIMALS The main reasons for antimicrobial use in animals are therapy, prophylaxis and, in farm animals only, performance enhancement (growth promotion). Therapy involves individual animals or defined groups with identified disease. Its justification is not difficult; disease can cause death or morbidity. Prophylaxis aims to contain the spread of infection in herds or flocks. Following diagnosis of illness in one or more of the members of a herd or flock, the whole herd may be treated to prevent spread. Performance enhancement (growth promoting) is the most contentious usage. Antimicrobials improve the productivity of healthy animals by increasing growth rate, feed conversion or yield. They are given continuously at sub-therapeutic doses, usually as feed additives or, occasionally, by addition to the drinking water. Antimicrobials that are used in man cannot be used as growth promoters in the UK. Nevertheless there is concern that: growth promoters may select cross-resistance to antibiotics used in man antibiotics for human use are now being sought among classes previously used only as growth promoters; it is feared that the prior use of the agents as growth promoters may have undermined their activity even before they become available for human use.
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These concerns are echoed world-wide: in 1994 the WHO Scientific Working Group on the Monitoring and Management of Bacterial Resistance to Antimicrobial Agents recommended that the unnecessary antimicrobial use for prophylaxis in food animals should be discouraged, and that antimicrobials should not be used as a substitute for adequate hygiene in animal husbandry. To this we would add the desirability of phasing out use as growth promoters.
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PREVENTING THE DEVELOPMENT OF ANTIMICROBIAL RESISTANCE
KEY POINTS
q Without a guarantee of new antimicrobials, conservation of present agents is desirable q Careful antimicrobial use should slow the emergence of new resistance q Reduced use may but cannot be guaranteed to reduce present resistance q Prevention of spread of resistant strains is also critical, especially for MRSA
SHOULD RESISTANCE DECLINE IF ANTIMICROBIAL USE IS RESTRICTED?

Whilst the relationship between antimicrobial use and the emergence of resistance is clear, if circumstantial, its corollary that resistance should decline if use is restricted is much less certain. Studies of disused antimicrobials are useful since they examine agents where direct selection is no longer significant and where no active steps are being taken to reduce resistance. Neither streptomycin nor chloramphenicol has been used against Enterobacteriaceae for over 25 years. Yet, a recent survey in London found that 20% of Escherichia. coli isolates remained resistant to streptomycin and chloramphenicol resistance occurred in 510% of isolates. These studies show how difficult it is to displace accumulated resistance.
DO GOOD PRESCRIBING PRACTICES PREVENT OR SLOW DEVELOPMENT OF RESISTANCE?

Intensive control or monitoring of prescribing has been accompanied by an increase in susceptibility in a few institutions. Co-operative multicentre studies are needed to assess fully the value of control measures. One investigation from Finland has caused much comment. An increase
Preventing the development of antimicrobial resistance
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was noted in resistance to macrolides amongst Streptococcus pyogenes isolates in Finland through the late 1980s and early 1990s. Nationwide recommendations calling for a reduction in macrolide use were introduced. Macrolide prescriptions and the incidence of erythromycin resistance among Streptococcus pyogenes isolates halved over the next 3 years. A causal relationship was assumed, but this is arguable, not least because the incidence of macrolide resistance increased in pneumococci in the same period. Although reducing antimicrobial use may not reduce rates of resistance, it should limit the rate at which new resistance accumulates, and this may be critical.
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DEVELOPMENT OF NEW ANTIMICROBIAL AGENTS
KEY POINTS
q Antimicrobial research is more efficient than previously q New antimicrobials are under development, but success cannot be guaranteed q Development cost is high (350 m) and patent life brief (17 years) q Anti-infectives are not amongst the most profitable pharmaceuticals q Vaccines may be an answer to pneumococci, but little advance against other key pathogens q Little progress achieved in developing non-antimicrobial treatments of infection
NEW STRATEGIES IN ANTIMICROBIAL DEVELOPMENT

Despite the recent dearth of new antimicrobials there are several promising factors for antimicrobial development, on a 10-year view: the new science of genomics may yield new families of antimicrobials methods of synthesising new candidate drugs have become vastly more efficient methods of screening antimicrobial activity have been improved These strategies may (although this is not certain) yield whole new families of antimicrobials towards the end of the next decade. However, even if this optimism is warranted, there will be a window with resistance accumulating and a dearth of new antimicrobials. Furthermore, it is virtually certain that resistance will develop to any new compounds, therefore good prescribing habits will help preserve their value when they appear.
Development of new antimicrobials
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15 PROMOTING GOOD PRACTICE

KEY POINTS
We need: q Faster diagnosis to allow identification of those patients needing antimicrobial therapy q Faster susceptibility testing to allow better-tailored therapy q Guidelines for theraby of common infections q Computer-assisted antimicrobial prescribing q Better surveillance as background to empirical therapy and to monitor effects of interventions to alter antimicrobial usage patterns q Better communication of resistance surveillance data to GPs and in hospitals q Better control of infection to stop spread of resistant bacteria q Education of prescribers, health care staff and consumers q Greater public awareness of antimicrobial resistance q A higher profile for research on the epidemiology and bases of resistance
From the preceding sections of this synopsis, it is clear that: Resistance is increasing to many antimicrobials and in many species We face the prospect of having no useful antimicrobials for some infections Development of new antimicrobials is in progress, but will take time and success cannot be guaranteed Careful antimicrobial use, and prevention of cross-infection, can minimise the emergence and accumulation of resistance Once resistance has accumulated, it cannot readily be displaced The recommendations that we make are based on these premises.
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KEY POINTS
PROMOTING BETTER PRESCRIBING
Improved prescribing can be encouraged by: q evidence-based guidelines for prescribing (or not prescribing) q computer-assisted systems to aid antimicrobial choice and to help the physician and patient avoid an antimicrobial when it is not needed q swifter microbiological diagnosis to minimise inappropriate therapy
BOX 10. BETTER PRESCRIBING

q Stop unnecessary antimicrobial use eg viral upper respiratory tract infection q Shorten unnecessarily long courses eg cystitis; surgical prophylaxis q Avoid inappropriate broad-spectrum antibiotics eg ciprofloxacin for URTI q Avoid inappropriate repeat prescriptions without microbiological confirmation eg repeat courses q Further research into inappropriate prescribing
GUIDELINES FOR ANTIMICROBIAL USE

The huge variation and incompleteness of current prescribing guidelines in many centres has already been noted. Evidence-based guidelines are urgently needed for antimicrobial use, particularly for the treatment of common conditions in the community. Local guidelines should take their cue from these national guidelines to avoid re-invention of the wheel. Guidelines should be sufficiently flexible to accommodate regional and local differences in the prevalence of antimicrobial resistance, especially in hospitals. Such differences would be informed by an antimicrobial resistance surveillance programme.
Promoting better prescribing
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It is not suggested that there should, say, be a national standard regimen for UTI; rather, that there should be a series of potential regimens, designed to optimise success and minimise the emergence of resistance, with the choice between these based on local circumstances.
COMPUTER-ASSISTED PRESCRIBING (or non-prescribing!)

Improved prescribing can potentially be encouraged by computer-based advisory systems. Systems are being developed, piloted and used. They are designed to enable clinicians to augment their clinical decision-making skills rather than to replace or control them and to use locally derived data (with respect to the epidemiology of resistance) to guide the selection of drugs. Potential for the use of such systems exists in primary care, where there is likely to be less local variation in pathogen prevalence and resistance, as well as in hospitals. Use of these systems deserves urgent investigation. Prescribing guidelines should be incorporated into the computer-aided decision-support systems, improving their availability and implementation. If the computer systems can be made relevant to both the prescriber and the patient this will assist in their interaction and help the prescriber to explain why a prescription may not be necessary.
IMPROVING EMPIRICAL THERAPY THROUGH SWIFTER DIAGNOSIS

Empirical therapy is often given when only a few patients the minority with bacterial infections are likely to benefit. Simple pathogen detection tests can be introduced into GPs surgeries and are valuable if they give an instant result, identifying those who may benefit from antimicrobial theraby. Examples include dipsticks and leucocyte esterase tests to identify UTI. A rapid antigen-detection test for Streptococcus pyogenes led to a reduction in the proportion of culture-negative patients with sore throats who were given antimicrobials from 53% to 32%. The savings on antimicrobial costs offset the costs of the tests, irrespective of any long-term gain achieved by reducing antimicrobial usage.
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ROLE OF THE MEDICAL MICROBIOLOGIST

All major acute hospitals in the UK are served by departments of medical microbiology, under the direction of a medically qualified consultant microbiologist. Most medical microbiologists have close links with their hospital and GP colleagues and collect information on the susceptibility patterns of their local bacterial isolates. Many departments provide prescribing information for use in hospitals and general practice, based upon these local patterns. The local medical microbiology department also can offer advice on infection control matters. As GPs undertake increasing numbers of procedures in their surgeries, it is especially important to ensure that responsible and thorough infection control advice is provided. The diagnostic facilities of the local laboratory can assist in the rational choice of antimicrobials by advising on the submission of specimens. Some laboratories have guidelines as to whether, for example, sputum should be examined from all patients who have a respiratory tract infection, or only those patients in whom previous therapy has failed. It is vital that hospital doctors and GPs form strong links with their medical microbiology colleagues in the battle against antimicrobial resistance, with the aim of optimising prescribing patterns.
IMPROVING MEDICAL EDUCATION

Education on antimicrobials and resistance often takes place in the early pre-clinical years of medical and dental training and is divorced from clinical situations where students are exposed to prescribing decisions. There is a paucity of experts available to teach antimicrobial prescribing in the context of clinical medicine and microbiology and this is less than ideal. Greater exposure of medical and dental students, house staff and postgraduates in all specialities to the issues of antimicrobial prescribing, and the threat posed by antimicrobial resistance, is desirable.
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COMMUNICATION
Data on local rates of pathogen prevalence and resistance are often poorly disseminated from the laboratory to physicians, both within hospitals and in the community. This information should be the key to the choice of therapy and better communication is essential.
ROLE OF HEALTH CARE PROFESSIONALS, OTHER THAN MEDICAL PRESCRIBERS

Although doctors are responsible for most antimicrobial prescribing, other professionals also have a role. The roles of dentists, nurses and pharmacists are described below. In hospitals and community care facilities ALL staff have a role in controlling cleanliness and hygiene, which impact hugely on the transmission of infection and on the need for antimicrobial chemotherapy. DENTISTS Dentists are prescribers, albeit for only a small fraction of total antimicrobial usage. Dental practice is significant for certain antimicrobials which dentists prescribe frequently, eg metronidazole. NURSES Nurses should be familiar with prescribing protocols so that they can alert doctors, when for example, antimicrobials are being prescribed for excessively long periods. Nurses help patients to understand the nature of their illness and the actions and side-effects of medications. They are in an excellent position to maximise concordance and to educate patients. They may be able to identify those individuals and families in whom concordance is likely to be a problem and where single-dose therapy is desirable if available. Most of all, nurses have a key role in the prevention and control of infection, especially in hospitals. PHARMACISTS The pharmacist is frequently the point of contact for the patient when a prescription is collected and thus can help educate the public about concordance. Within the community, the role of the pharmacist in providing services to nursing homes is developing, and is one where pharmacists could
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have an important role in influencing change in the prescribing of antimicrobials. Hospital pharmacists are involved in a number of key areas. They are well qualified to advise prescribers on choice and change of agent as well as suitable routes and durations of therapy. Pharmacists commonly have an input into the education of junior hospital doctors about prescribing. They may also be able to help in the enforcement of prescribing policies. VETERINARY SURGEONS Veterinary surgeons have a responsibility to use antimicrobials prudently. We recommend that the use of antimicrobials in veterinary practice should be guided by the same principles as in human prescribing viz antimicrobials should be used only where their use is likely to yield a specific health benefit.
PUBLIC EXPECTATIONS AND ATTITUDES TO ANTIMICROBIALS

Over-prescribing of antimicrobials partly reflects public expectation. If campaigns to reduce prescribing are aimed only at health care professionals, then these professionals will be left facing dissatisfied patients or carers, not all of whom take refusal to prescribe kindly. We therefore propose a National Advice to the Public (NAP) campaign, to run concurrently with the efforts to reduce and rationalise prescribing. Since most inappropriate community use of antimicrobials is for upper RTI, this usage should be targeted, with key messages that: Patients should not expect antimicrobials for trivial infections GPs may give post-dated prescriptions when the need for an antimicrobial is doubtful Antimicrobials are magic bullets invaluable but not to be taken lightly Taking antimicrobials unnecessarily does you no good and damages them for everyone else For serious infections eg meningitis swift antimicrobial therapy is essential
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Various ways of communicating these messages could be envisaged, from simple slogan-based advertising:
Antimicrobials cure serious diseases not colds, coughs and wheezes... Save them for when its important
through billboard advertising, and on to patient information leaflets such as those produced in America by the Alliance for the Prudent Use of Antibiotics. These messages should also be communicated in schools, with information on antimicrobials included in health education, maybe as part of the National Curriculum. It is highly desirable that children are taught the difference between bacteria, which antibiotics kill, and viruses, which they do not kill. The failure of many adults, and of the national press, to make this distinction is an obstacle to understanding the problem of resistance. Those who design school curricula should consider including antimicrobial resistance as an eloquent demonstration of evolution in action and of evolution with very direct consequences for mankind.
CHERISHING YOUR FLORA THE BENEFICIAL NATURE OF BACTERIA

The normal human microflora comprises more bacteria than there have ever been people upon the planet. The microflora has a role in the metabolism of nutrients, vitamins, drugs, endogenous hormones and carcinogens. This role is poorly understood, but probably largely beneficial. Furthermore, the microflora is probably protective against invasion by pathogens. Unnecessary insults to the normal microflora through the injudicious use of antibiotics can lead to adverse health outcomes. These may be transient and self-limiting, such as the diarrhoea that may accompany a course of antibiotics, but more serious problems may also arise (eg pseudomembranous colitis). The role of our normal resident microflora is now beginning to be understood, and with understanding comes a realisation that we should be cherishing our normal bacterial flora.
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SURVEILLANCE OF RESISTANCE
To measure the public health impact of antimicrobial resistance and of interventions to minimise antimicrobial usage, requires close surveillance. The PHLS, in liaison with the British Society for Antimicrobial Chemotherapy and other interested parties, is developing a multi-faceted national surveillance scheme. It is critical that this receives support, both financially and in terms of encouragement to laboratories to participate. Alert organism reporting and reference laboratory activities will identify unusual resistances deserving priority work, but will provide minimal denominator data. Sentinel laboratory surveys and those where isolates are collected centrally will provide high quality microbiology and quantitative measurement of levels of resistance, but with small sample sizes. Collection of routine data will provide mass information, suitable for relation to prescribing and population denominators, but will be based on routine susceptibility tests, which are poorly standardised in the UK. Collectively, however, these activities will validate each other to give a comprehensive picture. The sentinel laboratory and ad hoc studies will test the quality of the routine data, whilst the appearance of trends (or unexpected results) in the routine data will advise the choice of organisms demanding enhanced surveillance.
Surveillance of resistance
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RESEARCH ON RESISTANCE AND ON NEW ANTIMICROBIALS
KEY POINTS
q Research on resistance has been unfashionable and underfunded q Research is key to the development of new antimicrobials q Research is key to understanding how to preserve the value of current antimicrobials
Whilst the problem of resistance is clear, there are many aspects on which our understanding is limited. Consequently, there is much scope for useful research.
BOX 11. ASPECTS MERITING FURTHER RESEARCH

q q q q q q q q q q Factors driving resistance Mathematical modelling of resistance Geographical information systems Basic research on mechanisms of resistance Links between prescribing and resistance at individual and population levels Beliefs concerning antimicrobial use, their influence on demand and concordance Factors leading to inappropriate prescribing The role of social change, particularly day-care of the elderly and children Computerised decision-support systems Investment versus restriction in antimicrobial use
ANTIMICROBIAL DEVELOPMENT
The thrust of this Report is upon the conservation of present antimicrobials. Past resistance problems have been overcome (if only temporarily) by the development of new antimicrobials. In recent years, the pharmaceutical
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industry has developed vastly more efficient systems for seeking new antimicrobials. These strategies will, hopefully, yield new generations of antimicrobials by the end of the next decade. It is vital that research on new antimicrobials is encouraged and not made uneconomic. If the recommendations of this Report are followed, they should reduce overall antimicrobial usage. As a result there may be financial implications for the pharmaceutical industry, upon whose profitability the development of new antimicrobials depends. Consideration may, therefore, need to be given to finding ways, through pricing and other mechanisms (eg, extended patents), of making investment in the development of new antimicrobials commercially attractive.
Research on resistance and on new antimicrobials
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KEY POINTS
CHANGING PRACTICE
q A national strategy aimed at the professional and the public is required q This should be supported by the development of surveillance, education and decision support systems
Although the Terms of Reference of the Sub-Group were to concentrate on changing professional activities in order to reduce antimicrobial resistance (Box 1), change management cannot be undertaken in isolation. The overall culture and organisation in which professionals work has to be addressed at local and national levels. This includes modifying patient expectations. There have been many attempts to identify strategies for changing professional behaviour and some general lessons have emerged. Change needs to be carefully planned and all essential protagonists need to be identified, as well as the associated barriers. Specific interventions need to be implemented for each obstacle. The whole process must be co-ordinated and progress evaluated.
CREATING A SUPPORTIVE ENVIRONMENT FOR CHANGE

In making recommendations aimed at influencing doctors prescribing in primary care, through a national Campaign on Antibiotic Treatment (CAT), we acknowledge the importance of patients expectations in the decisionmaking process. Therefore there must be a concurrent and co-ordinated programme to modify patients expectations through a National Advice to the Public (NAP) campaign of public education. This will help GPs to adhere to the recommendations, all of which relate to unnecessary prescribing. This approach will need to be co-ordinated at a national level, hence the recommendation for a Steering Group, charged with ensuring the implementation and monitoring of the strategy, of which CATNAP is a central feature. Change will also be supported by the production of high quality, evidencebased guidelines. Computer systems will improve access to guidelines and aid their implementation, particularly if the systems can be made relevant to both the prescriber and the patient, assisting in their interaction and helping the 56
prescriber to explain why a prescription may not be necessary. All guidelines will need to be up-to-date and locally relevant; otherwise they risk losing credibility. They need underpinning with information on local antimicrobial sensitivity profiles. These local profiles, in turn, should feed into regional and national surveillance databases. National, regional and local surveillance will provide: i) closure of the audit feedback loop ii) data for the adaptation and revision of guidelines iii) outcome data for studies to identify the drivers of resistance and the effectiveness of interventions to improve antimicrobial prescribing The national strategy for resistance surveillance currently under development between the Public Health Laboratory Service, the British Society for Antimicrobial Chemotherapy, the Scottish Centre for Infection and Environmental Health and the Northern Ireland Department of Health and Social Services, is a key element in the strategy for improving antimicrobial prescribing practices.
Changing practice
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20
INDEPENDENT REVIEW OF THE LITERATURE
As part of the process of preparing our Report the Sub-Group on Antimicrobial Resistance commissioned an independent review of the literature to determine the nature and quality of the evidence that changing prescribing patterns could result in reduction or limitation of the spread of antimicrobial resistance. This literature review aimed: q To assess the evidence that inappropriate use of antibiotics leads to increased levels of antimicrobial resistance q To assess the quality of evidence that antimicrobial resistance levels can effectively be reduced or reversed q To examine the evidence that effective implementation of changes in prescribing practices will result in reduction of antimicrobial resistance levels q To provide independent confirmation, or otherwise, that the conclusions reached in the main report were justified Key conclusions are incorporated into the body of this Synopsis. The full results are available in the Report.
IN CONCLUSION
Antimicrobial prescribing is an activity with roots in many cultures, clinical and lay. It is only through addressing all of those involved that we are likely to find
the path of least resistance
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22 LIST OF RECOMMENDATIONS
PRESCRIBING IN THE COMMUNITY Patients with minor infections There should be a national Campaign mostly present to GPs; on Antibiotic Treatment (CAT) in consequently, 80% of UK human primary care on the theme of: Four prescribing is in the community. things you can do to make a difference This Report therefore concentrates (see Box 2). on community prescribing of The CAT must be matched by a antimicrobial agents. National Advice to the Public (NAP) campaign aimed specifically at supporting the initiative in primary care. A key feature of the NAP campaign should be to highlight the benefits of cherishing and conserving your normal bacterial flora. Further support for appropriate prescribing in primary care should be provided by developing and promulgating evidence-based national guidelines for the management of certain infections, under the aegis of the National Institute for Clinical Excellence. Such national guidelines should be adapted for local use during the development of Health Improvement Plans. To make the incorporation of the guidelines into everyday practice as effort-free as possible they should be integrated within computerised decision-support systems.
List of recommendations
59
FOUR THINGS YOU CAN DO: q no prescribing of antibiotics for simple coughs and colds q no prescribing of antibiotics for viral sore throats q limit prescribing for uncomplicated cystitis to 3 days in otherwise fit women q limit prescribing of antibiotics agents over the telephone to exceptional cases PRESCRIBING IN HOSPITALS Hospital prescribing accounts for c. 20% of human prescribing of antimicrobial agents in the UK; nevertheless, resistance problems are greatest in hospitals and infections may be life-threatening. Although prescribing in hospitals poses some different issues from those in primary care, hospital clinicians would benefit as much as GPs from the availability of computer-aided decisionsupport systems. PRESCRIBING GUIDELINES Prescribing guidelines should be quality, evidence-based documents. They are often the first source of information for inexperienced prescribers. National guidelines, suitably adapted in response to local resistance patterns, could be integrated into decision-support systems.
Studies should be undertaken in selected hospitals to develop and test one or more prototype decisionsupport systems. Systems should include information from local antimicrobial sensitivity profiles; these, in turn, should feed into regional and national surveillance databases.
Local prescribing information should, wherever possible, be harmonised with prescribing information in the British National Formulary (BNF) and other formularies. Guidelines and formularies should also take account of the proposed national evidence-based guidelines to be produced under the aegis of the National Institute for Clinical Excellence. Local prescribing guidelines should take their cue from these national guidelines. All such local guidelines should include, as a minimum, advice on drug dose, frequency and duration.
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INTERNATIONAL CO-OPERATION Resistant bacteria spread between countries, the UK is not isolated from the greater resistance problems that exist in other parts of the world, for example, Southern Europe. SURVEILLANCE OF RESISTANCE Effective surveillance is critical to understanding and controlling the spread of resistance. Not only is surveillance essential for monitoring the existing situation, it allows the effects of interventions to be evaluated. RESEARCH Antimicrobial resistance has been of low priority for Research Councils and scored poorly in the recent Research Assessment Exercise.
Every effort should be made by the Government, in international fora, particularly in the European Union, to raise the profile of antimicrobial resistance as a major public health issue meriting priority action.
A national strategy for resistance surveillance should be developed and implemented as swiftly as possible, covering the whole of the UK.
Research into antimicrobial resistance should become a high priority for all funding bodies concerned with health care and biomedical research.
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EDUCATION The development of guidelines and their widescale introduction into clinical practice will have important and beneficial spin-offs for the education of health care professionals involved in antimicrobial prescribing. The whole population would benefit from enhanced education about the benefits and disadvantages of antimicrobials.
Greater emphasis should be placed on teaching about antimicrobial prescribing in medical and dental schools as well as in the undergraduate curricula for pharmacists and nurses. Teaching about antimicrobials should be better integrated with teaching about the infections for which they are used. This enhanced emphasis on education in antimicrobial use should be carried over into continuing medical, dental and professional education and development. Similar concepts apply in the field of veterinary medicine. In addition to health education material aimed at adults, teaching about antibiotics should be included as part of health education in the National Curriculum.
HYGIENE, INFECTION CONTROL AND CROSS-INFECTION Infection control, although intimately bound up with problems of antimicrobial resistance particularly in health care environments was outside the Terms of Reference of the Sub-Group. Nevertheless, it is fundamental to preventing the spread of resistant organisms, not only in hospitals but also in the community.
Consideration should be given to producing guidance on infection control in the community, especially in nursing and residential homes, similar to that which exists for hospitals.
62
VETERINARY AND AGRICULTURAL USE Antimicrobials are used in therapy and prophylaxis, and as growth promoters/enhancers in animals.
The use of antibiotics in veterinary practice should be guided by the same principles as for human prescribing namely, they should be used only for clinical conditions where their use is likely to provide a genuine health benefit. Alternative means of animal husbandry should be developed so that the use of antibiotics as growth promoters can be discontinued.
IMPLICATIONS FOR INDUSTRY If our recommendations are followed, they should have the effect, inter alia, of reducing antibiotic usage. There may be financial implications for the pharmaceutical industry, upon whose profitability the development of new antibiotics depends.
Consideration should be given by the appropriate bodies to finding ways through pricing and other mechanisms of ensuring that investment in the development of new antibiotics remains commercially viable. Industry should be encouraged to undertake studies of optimum prescribing regimens for new antimicrobial agents, for each indication and in adults and children as appropriate. Licensing authorities should have due regard to an antimicrobial agents potential to select for resistance as well as to its safety and efficacy.
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IMPLEMENTATION OF RECOMMENDATIONS The aim of this Report has been to produce recommendations that can constitute the first phase of a national strategy for minimising the development of antimicrobial resistance. q As part of this phase a small National Steering Group (NSG) should be established, charged with ensuring that these recommendations are implemented and that their effects on prescribing practice and on the development of resistance are monitored. q The NSG, which might need to establish a small number of expert groups to take forward specific aspects of the recommendations, should report to the Chief Medical Officer within a year on progress. q Thereafter the CMO may wish to consider asking SMAC to reconvene this Sub-Group, to provide a suitable inter-disciplinary forum for the development of the next phase of the strategy.
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25
MEMBERS Dr Diana Walford Mrs A Close Dr A Dearmun
MEMBERSHIP OF THE SUB-GROUP

Chairman of Sub-Group: Director of PHLS and SMAC member Nursing Director, Dudley Group of Hospitals and SNMAC member Principal Lecturer Practitioner, Senior Nurse Oxford Brookes University and SNMAC member Professor of Orthopaedic Surgery, Sheffield University and SMAC member Director of Pharmacy, Countess of Chester Hospital and SPAC member General Practitioner, London and SMAC member General Practitioner, Stockton on Tees and SMAC member Professor of Surgery, Sheffield University and SMAC Chairman Professor of Epidemiology and Public Health, Institute of Child Health and SMAC member Consultant Anaesthetist, Bristol Royal Infirmary and SMAC member Consultant Physician, Countess of Chester Hospital and SMAC member
Professor T Duckworth Miss A Ewing Dr J Gilley Dr R Horne Professor A Johnson Professor C Peckham Dr S Willatts Dr G Youngs
CO-OPTED MEMBERS Dr A M Johnston Professor P Littlejohns Miss C Murphy Dr G Patou Dr M Powell

Membership of the Sub-Group
Senior Lecturer, Royal Veterinary College Professor of Public Health, St Georges Hospital Medical School BMAJunior Doctors Committee Vice President, Anti-infectives Development, SmithKline Beecham Pharmaceuticals Medicines Control Agency 65
Dr P Wilkie Professor R Wise
Social Scientist and RCGP Patient Liaison Group Professor of Microbiology, City Hospital, Birmingham
OBSERVERS Dr P Clappison Mr I Cooper Professor B I Duerden Mr R Fenner Dr J Leese Dr K Ridge Dr W Smith SECRETARIAT Ms M Hart Dr DM Livermore Dr J R Weinberg DH (SMAC Secretariat) PHLS (Scientific Secretariat) PHLS (Scientific Secretariat) DH DH and SDAC Representative Deputy Director (Programmes), PHLS DH DH DH and SPAC Representative Welsh Office
66

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THE PATH OF LEAST RESISTANCE SYNOPSIS

Standing Medical Advisory Committee Sub-Group on Antimicrobial Resistance

BOX 1. TERMS OF REFERENCE

The Path of Least Resistance

PRESCRIBING IN THE COMMUNITY

The Path of Least Resistance

BOX 2. FOUR THINGS YOU CAN DO:

The Path of Least Resistance

HYGIENE, INFECTION CONTROL AND CROSS-INFECTION

VETERINARY AND AGRICULTURAL USE

The Path of Least Resistance

IMPLICATIONS FOR INDUSTRY

The Path of Least Resistance

Figure 1 Recommendations for the professions and the public: CATNAP

LOOKING INTO THE ABYSS

Looking into the abyss

The Path of Least Resistance

The Path of Least Resistance

DOES USE OF ANTIMICROBIAL AGENTS CAUSE RESISTANCE?

Does antimicrobial use cause resistance?

TO PRESCRIBE OR NOT TO PRESCRIBE?

The Path of Least Resistance

BOX 4. THE ANTIMICROBIAL TUG OF WAR

To prescribe or not to prescribe?

BOX 5. THE PAINFUL EAR

The Path of Least Resistance

BOX 6. THE SORE THROAT

To prescribe or not to prescribe?

The Path of Least Resistance

WHERE ARE ANTIMICROBIAL AGENTS USED?

Where are antimicrobial agents used?

Figure 4 Hospital and community use of some antimicrobial agents

Data kindly provided by IMS Health UK, Maxims Database

THE EXTENT OF BACTERIAL RESISTANCE IN THE UK

CURRENT RESISTANCE PROBLEMS IN THE UK AND WORLD-WIDE

The Path of Least Resistance

Current resistance problems in the UK and world-wide

The Path of Least Resistance

HOSPITAL-ACQUIRED GRAM-NEGATIVE OPPORTUNISTS

ENTERIC PATHOGENS SALMONELLA

Current resistance problems in the UK and world-wide

Figure 9 Isolation of Salmonella typhimurium DT 104 from man, 198296

The Path of Least Resistance

Current resistance problems in the UK and world-wide

What next for antimicrobial resistance ?

In short, evolution hasnt finished yet ...

The Path of Least Resistance

INTENSIVE CARE UNITS

Areas of clinical practice where antimicrobial resistance...

The Path of Least Resistance

What are the practices by clinicians...

BOX 9. ANTIMICROBIAL GUIDELINES SHOULD:

PRESCRIBING UNNECESSARILY OR INAPPROPRIATELY

What are the practices by clinicians...

PUBLIC BEHAVIOUR AND SOCIAL CHANGE

The Path of Least Resistance

VETERINARY ANTIMICROBIAL USE AND THE EMERGENCE OF RESISTANCE

What are the practices by clinicians...

The Path of Least Resistance

PREVENTING THE DEVELOPMENT OF ANTIMICROBIAL RESISTANCE

SHOULD RESISTANCE DECLINE IF ANTIMICROBIAL USE IS RESTRICTED?

DO GOOD PRESCRIBING PRACTICES PREVENT OR SLOW DEVELOPMENT OF RESISTANCE?