Select Committee on Science and Technology Seventh Report


Visit to the United States of America, 16-21 November 1997
Note by the Chairman

1.    I and three other members of the Sub-Committee, one of our Specialist Advisers and our Clerk visited the USA for five days in November 1997, to meet US and international experts in the field. We did so because the USA has similar problems to the UK, but on a larger scale; many of the world's experts are there; and the US approaches to surveillance and control are different, and might, we thought, carry lessons for the UK.

2.    My companions were Baroness Masham of Ilton; Lord Perry of Walton; Lord Rea; Professor Richard Wise; and Mr Andrew Makower. The travellers cannot praise too highly the many busy people, whose names appear below, who made time to prepare for our visit, to receive us on our travels, and to impart the information and ideas which this note attempts to synthesise. We also wish to place on record our gratitude for the help which we received from HE Sir Christopher Meyer KCMG, HM Ambassador to the USA, Mr Peter Marshall CMG, HM Consul General in Atlanta, Mr Jim Poston, HM Consul General in Boston, and their staffs, and in particular from Mr Roy Forey, Science and Technology Officer at the British Embassy, who accompanied us on our travels.

3.    This note is in two parts. The first deals thematically with aspects of the subject on which the travellers brought home new insights and information, finishing with a list of "take-home messages". The second part is a diary.

4.    The cost of the visit was just under £30,000.


5.    Infectious diseases, and resistance in particular, are rising up the US political scale; this can be measured by examining the budgets approved by Congress. The report by the Institute of Medicine, "Emerging Infections: Microbial threats to health in the US", published in 1992, identified resistance as a major factor in the (re-) emergence of infections; the report evidently made a deep impression, and has largely set the US agenda ever since. Other factors include concerns about biological warfare (Iraq) or terrorism (the Tokyo underground incident); and the presence in the Senate of the transplant surgeon Bill Frist.

6.    Staff of OSTP revealed how the report of the Institute of Medicine led to action at the highest level. It was taken up by the National Science and Technology Council and the inter-agency Committee for International Science and Technology; and their recommendations were embodied in 1996 in a Presidential Directive (roughly equivalent to a White Paper). This established a task force on emerging infections, chaired by CDC and OSTP. The task force has set up a sub-group on resistance, to look at matters including surveillance, animal feed additives, and public and professional education. CDC has made it one of its five priorities to "expand our capacity to respond to urgent health threats", including resistant organisms; has published a strategic plan, "Addressing emerging infectious disease threats: A prevention strategy for the US"; and is organising an International Conference on Emerging Infectious Diseases in March 1998 in Atlanta.

7.    Like the UK, the USA is also very concerned about food poisoning: see below.


8.    NIAID believes that around 2m people acquire infection in US hospitals every year, at a total cost for additional treatment of $4.5bn. More precise costs are hard to come by; but it has been calculated that, in New York City in 1995, there were 13,550 Staphylococcal infections, causing 1,400 deaths and treatment costing $435.5m.

9.    Dr Levin of Emory University pointed out two obstacles to surveillance of hospital infections: outcomes may be obscured bacause the patient is already in poor shape, especially in intensive care; and hospitals may be reluctant to conduct rigorous surveillance, since every infection identified counts against them in any league table.

Vancomycin intermediate-resistant Staphylococcus aureus (VISA)

10.    VISA was first reported in Japan in 1996. In 1997 two cases were reported in the USA: one in a peritoneal dialysis patient, the other in a patient infected repeatedly with MRSA. Both patients were successfully treated.

11.    People at FDA told us that they had been expecting fully vancomycin-resistant Staph aureus (VRSA), and that VISA had come as a surprise. Dr Heyse of NIAID expressed doubt whether the VISA recently identified in the USA was a new development, or something which had existed for some time before being spotted. Dr Jarvis at CDC fears that VISA may be only an intermediate step on the way to VRSA.

12.    CDC, NIH and FDA have been working with the pharmaceutical industry to look for existing drugs, possibly unexploited, which might be effective against VRSA; they have looked at 300 candidates, and shortlisted 10. FDA is standing by to grant accelerated approval. Meanwhile, hospitals are attempting to keep VRE and MRSA apart, to prevent the creation of VISA/VRSA by exchange of genetic material.

Methicillin-resistant Staphylococcus aureus (MRSA)

13.    The proportion of MRSA among strains of Staph aureus in large US teaching hospitals rose from 8 per cent in 1986 to 40 per cent in 1992. In New York City in 1995 the proportion was 50 per cent. We heard remarkably little about it, indicating perhaps that it is now simply a fact of life in US hospitals.

14.    MRSA is not notifiable in the USA.

Vancomycin-resistant enterococcus (VRE)

15.    VRE is much more of a problem in US hospitals than in the UK; but Dr Levy of Tufts University pointed out that, as MRSA increases, so does the use of vancomycin, bringing VRE in its wake. The proportion of US hospital-acquired enterococci found in non-critical care units and reported as resistant to vancomycin rose from 4.9 per cent in 1993 to 9.1 per cent in 1994. In intensive care units, where vancomycin use and resistance are higher, VRE as a proportion of all E rose from 11.5 per cent to 13.6 per cent over the same period. VRE has also risen as a proportion of all US hospital infections, from 0.3 per cent in 1989 to 7.9 per cent in 1993.

16.    A few States have made VRE notifiable.


Multi-drug resistant tuberculosis (MDR-TB)

17.    TB is unusual among infectious diseases: the mycobacteria multiply relatively slowly, so the incubation period and the courses of treatment required are exceptionally long. These factors affect control and compliance, and therefore affect resistance. Resistance in TB first arises by spontaneous random mutation of the mycobacterium; it is then fostered by selective pressure induced by poor prescribing and non-compliance with therapy.

18.    Around the world, TB is on the increase, and MDR-TB is a global problem: a recent WHO report has identified several "hot zones", mainly in Eastern Europe and South America. In the USA, total TB rose from 22,200 cases in 1985 to 26,700 cases in 1992, but has since fallen back to 21,337 cases in 1996; however in some areas (e.g. Washington DC) it is still rising, for a range of reasons. In the early '90s, the USA suffered several mini-epidemics of MDR-TB: the worst was in New York, where at its height MDR-TB accounted for 15 per cent of all TB, concentrated particularly among homeless persons, prisoners and people with HIV. MDR-TB now accounts for 2 per cent of all TB in the USA; one case in two among people aged 25-44 is associated with HIV.

19.    MDR-TB carries a high mortality, and is much more difficult and expensive to treat than susceptible TB. Dr Ginsberg of NIAID told us that multi-drug resistance raises the cost per case from $200 to $200,000: most of this is accounted for by expensive drugs and long stays in hospital. From 1993 to 1996, the number and proportion of US cases of MDR-TB decreased, but at a cost: New York City alone spent $175m over 4 years. The principal means of control has been "directly-observed therapy" (DOT), whereby patients are followed up for the whole of a long course of treatment, and are supervised every time they take their medicine. DOT has been a success in the USA; but Dr Brennan at FDA told us that China has practised DOT since 1988 and still seems to have plenty of MDR-TB.

20.    Dr Ginsberg does not consider the casebook closed. Whereas in 1991 MDR-TB was reported in only 13 States, it is now found in 42; and "There are still physicians out there who don't know the appropriate therapy". If political will falters and funding for public health measures falls away again, NIAID expect the problem to return. Dr Miller of CDC drew the moral: maintaining a proper public health infrastructure is much cheaper than managing the consequences of running it down.

21.    UK and US scientists are working together to combat TB. Scientists at the Sanger Centre (funded by the Wellcome Trust) and the Institute for Genomic Research (funded by NIAID) are sequencing the TB genome; and the USA, the UK and France are contributing to a WHO working group on a vaccine against TB, which people at NIH regard as crucial to long-term success against this disease. (The BCG vaccine familiar in the UK is not recommended for use in the USA: it is regarded as ineffective and unnecessary, and it compromises a diagnostic technique widely used in the USA.)

22.    In contrast, the pharmaceutical industry shows little interest in TB: the market is generally felt to be insufficient to justify developing new drugs; and firms with established drugs (e.g. quinolones) which might be effective against TB are reluctant to try them. We received three slightly different explanations for this reluctance. People at NIH put it down to fear that the long courses required for TB would throw up new side-effects; Dr Goldberger at FDA put it down to fear that a drug which became known as a TB drug would fall out of favour for other, more lucrative indications; Dr Siegfried at PhRMA reckoned that any drug which purported to be effective against resistant strains would be labelled so restrictively, at FDA's behest, that the market would be too small.

23.    However Dr Goldberger knew of some pharmaceutical work in progress. CDC are experimenting with rifamycins; it is possible that this family of drugs may be effective over relatively short courses, which would improve compliance. And some manufacturers are working on drugs specifically for MDR-TB, on immunologic drugs to complement chemotherapy, and on vaccines. Dr Sheldon Morris of FDA told us that Merck Sharp and Dohme are making progress towards a DNA vaccine.


24.    Two special features of HIV are the virus's exceptional rate of mutation, so that resistance to any single drug evolves very quickly; and the exceptional success of activists in attracting resources to research. Of NIAID's 124 research projects in 1996, 50 concerned HIV.

25.    The treatment currently favoured for HIV is "triple therapy", with three antivirals. According to people at PhRMA, even triple therapy gives rise to resistance after a time; and, with only ten drugs to choose from, only three non-overlapping regimens can be tried. However according to Dr Hu at CDC, a mutation which confers resistance to one drug sometimes opens up a target to another. People at NIH consider that the world's best hope for HIV, as for TB, is a vaccine; however according to Dr Livengood of the National Immunization Program this is a long way off.


Penicillin-resistant Streptococcus pneumoniae (PRP)

26.    A major concern in the USA, more than in this country, is the rise in Strep. pneumoniae resistant to penicillins, cephalosporins and other drugs. Unlike hospital infections and TB, Strep. pneumoniae can affect anybody, including the healthy and wealthy; it may only cause a transient middle-ear infection or a cough, but it may also cause pneumonia, bacteraemia or meningitis. Drug-resistant Strep. pneumoniae, as a proportion of all isolates in a survey of US hospitals, rose rapidly from 3.6 per cent in 1987 to 14.5 per cent in 1994 (source: NIAID Profile 1996). In 1995, 23.6 per cent of all Strep. pneumoniae was resistant to penicillin, and a further 14.1 per cent had reduced susceptibility; more recent figures go up to 46 per cent, and even higher in children (source: Dr Heyse, NIAID). The rise in resistance has been matched in the USA by a rise in virulence (i.e. more invasive infections).

27.    A substantial proportion of PRP has multi-drug resistance. According to Dr Schwartz of CDC, 7 per cent of Strep. pneumoniae is resistant to all oral antibiotics, and some strains are susceptible only to vancomycin. Vancomycin-resistant Strep. pneumoniae would be a very serious public health problem.

28.    The rise in PRP in the USA is universally ascribed to over-prescription of antibiotics, particularly for upper respiratory tract infections ("Strep throat"), and for children with otitis media (middle-ear infection), but also for conditions such as acute bronchitis or a common cold where antibiotics are of no use at all. In the UK GPs usually give an ear infection 1-2 days to clear up before prescribing, but in the USA antibiotics are usually given at once. This is partly for fear of litigation, and partly due to pressure from patients and parents: see below. According to Dr Levy, for every case of otitis media where an antibiotic is justified, there are 10 where it is not.

29.    The rise of PRP has prompted a search for a better Strep. pneumoniae vaccine, and a conjugate vaccine is now under trial. Dr Gorbach in Boston observed that an effective Strep vaccine, with the existing Hib vaccine, would all but eliminate bacterial otitis media, and thereby remove the biggest single cause of inappropriate prescribing in the USA.

30.    PRP has recently been made notifiable in several States.


31.    Dr Levy agreed that the infections noted above are the biggest threats to public health in the short term. For the longer term, he drew attention to Neisseria gonorrhoeae: in the USA, resistance to penicillin and tetracycline reached 31.6 per cent in 1995, and strains resistant to fluoroquinolones were found. He also mentioned Klebsiella and Pseudomonas.

Food-borne infections

32.    As in the UK, the principal food-borne infections in the USA are Salmonella, Campylobacter jejuni and Escherichia coli (E. coli). Penta-resistant Salmonella typhimurium DT104 is on the increase; in 1996 it accounted for 33 per cent of Salmonella found in people, and 10.5 per cent in animals.

33.    As noted above, the USA is as concerned about food poisoning as is the UK. The emphasis is different: whereas UK concern is focussed on home-produced meat, in the USA there is equal concern about imported fruit and vegetables. In 1996, the Department of Agriculture introduced Hazard Analysis at Critical Control Points (HACCP) regulations for slaughter-houses and chicken-houses: as someone at NIH put it, this means "microbiology instead of sniffing carcasses". There are proposals to create a unified "plough-to-plate" food safety agency, bringing together responsibilities currently divided between the Department of Agriculture and the FDA; the National Academy of Sciences is to report on this matter in August 1998.

34.    People at NIH stressed the importance of extending epidemiology onto the farm. According to William James, the FSIS has made a start: in 1995 they tested 1,000 animals, and in 1996 2,000. Most of these were casualty animals, and therefore would not normally enter the food chain. However from this year on they intend to sample each year 20,000 animals which would normally enter the food chain.

35.    Many of those whom we met agreed that antibiotics are overused in animal husbandry, and also in arboriculture and aquaculture (fish-farming). See below.


36.    Dr Colley and his colleagues at CDC told us about their work on parasitic infections.

      (i)  Malaria They speculated that the currently fashionable strategy of impregnating bednets may eventually induce resistance.

      (ii)  Human helminths (_)There is no resistance problem yet; but new programmes of targeted mass treatment of children may create one.

      (iii)  Headlice (_)There is anecdotal evidence of resistance, and no public-domain research. Treatment manufacturers blame parents for inadequate treatment.

      (iv)  Vaginitis (_)The USA is experiencing some resistance of Trichomonas vaginalis to metronidazole, which is widely used in UK hospitals as a prophylactic in general abdominal surgery.



37.    There is no shortage of information in the USA about infectious diseases and antimicrobial usage. Hospitals, health management organisations (HMOs) and pharmaceutical companies have plenty of data. However, as in the UK, standards and IT systems are not all compatible; and, unlike the UK, there is no network of national laboratories. Public health laboratories are the responsibility of the State or locality; the States are also responsible for deciding what conditions are notifiable, and their lists are not the same. Federal agencies therefore proceed by encouraging voluntary data-sharing, and convergence of standards around the National Committee for Clinical Laboratory Standards (NCCLS) and of software around WHONET.

38.    A recent Institute of Medicine workshop on surveillance identified two desiderata: data must include locality, since resistance is often due to local phenomena; and it must include clinical outcome. Those we met at the Institute acknowledged that the ideal surveillance system has not been realised anywhere.

39.    At CDC we learned from Mr Jarvis and his colleagues about the National Nosocomial Infection Surveillance (NNIS) system, and about Project ICARE (Intensive Care Antibiotic Resistance Epidemiology). NNIS began in 1970, as a voluntary system to collect demographic and infection data from certain wards in participating hospitals. It now involves 250 hospitals, all of 100 beds or more; it is still expanding, and becoming more representative of the generality of US hospitals. NNIS is confidential; CDC returns to each hospital its own results, in relation to the overall distribution.

40.    ICARE takes NNIS data and adds information about antibiotic usage. It currently involves 40 hospitals, each of which receives a nominal $3-4000 to support data collection; it covers 13 "bug-drug" combinations, chosen for their clinical importance. Like NNIS, ICARE is confidential; CDC returns to each hospital its own results, in relation to the overall distribution. In feeding back results to each hospital, the ICARE team at CDC try to identify interventions which can bring down rates of resistance. "One size doesn't fit all": two hospitals may have equally high levels of MRSA; in one case the cause may turn out to be overuse of cephalosporins, in the other proximity to a nursing home with poor infection control. Dr John McGowan commented that, as a means of tackling resistance, ICARE has the advantage, over general guidelines, of being highly specific and taking full account of local circumstances, including constraints on resources.

41.    One limiting factor for ICARE, admitted by CDC, is the usage data; if pharmacy information exists at all, it is often set up to inform billing rather than to analyse usage. Another, pointed out by Dr McGowan, is the absence of community surveillance, which for some bug-drug combinations would be crucial.

42.    We were most impressed by ICARE, and wondered how the concept might be transplanted to the UK. Without external funds, probably only two or three UK hospitals would be interested. One way forward might be for a few UK hospitals to ask to participate in ICARE itself; alternatively, a free-standing UK project might be supported from the NHS R&D Budget.

Diagnostic testing

43.    Many of our witnesses in the UK have called for the development of rapid tests for susceptibility and resistance. Dr Shively of FDA told us that there are several rapid susceptibility tests on the market (e.g. Vitek, MicroScan). The Crystal MRSA is an example of a rapid test for identifying MRSA, which uses a fluorescent signal; because it is a single test unit, the cost per test would be higher than using a susceptibility panel.

44.    NIAID's recent "programme announcement" (i.e. call for proposals) on antibiotic resistance includes a challenge to develop rapid tests for susceptibility and resistance. Dr Ginsberg believed that rapid tests based on gene sequencing might still be 5 years away (Dr Gorbach said 10); however in the short term techniques were emerging based on the rate of bacterial growth. Dr Shively showed us the ESP Culture System, used for detecting positive blood cultures and mycobacterial growth in broth cultures; it is based on detecting pressure changes due to gas consumption or gas production when bacteria metabolize. Such systems have potential for being used for TB susceptibility testing. Bacteriophages also present possibilities for diagnosis—though not necessarily for treatment, according to those we met at NIAID.

45.    Dr O'Brien said that, with over 200 resistance genes already, to expect genetic tests for all of them might be unrealistic. Dr Shively suggested that, in any case, having rapid susceptibility test results may not affect how physicians use results. Although "rapid" tests give a faster turnaround time, the results are not available until bacteria in cultures are isolated. Thus "rapid" results are usually not available at the time antimicrobials are prescribed, as many patients are treated empirically. Physicians may not change already prescribed antimicrobials unless the patient fails to get better or has a life-threatening condition.

Hygiene and infection control

46.    We heard little about infection control, perhaps because we visited no hospitals. Dr Heyse of NIAID identified a general "breakdown" in hygiene, infection control and public health programmes. There is a major campaign of public education in hand-washing—though Miss Stoiber of the US Department of Health suggested that this could amount to a form of "victim-blaming", and that other factors such as intensive food production were more important.

Pharmaceutical industry and new drug development

47.    The people we met tended to be realistic about what could be expected from the pharmaceutical industry. Industry has "a different bottom line" from public health services; in the end, its priorities are bound to be market-driven.

48.    It was observed at NIH that most new anti-infectives of recent years were really variations on a theme, rather than wholly novel drugs: e.g. there are 8 variants of vancomycin. Dr Rakowsky at FDA told us that the last new class of drugs, with a new target, came out in 1971. However industry has regained interest in anti-infectives, in the light of rising resistance and new scientific opportunities; and new classes are now under development.

49.    Dr Levy of Tufts is actively researching mechanisms of resistance and new approaches to overcoming it. He mentioned three lines of investigation. First, in a joint venture, he is hoping to apply the tetracyclines (which fell out of general use in the 1970s) to combat MRSA/VRSA. Secondly, his team are looking for new gene targets. Finally, they are exploring "antipathogenesis". This involves agents which do not destroy the bacterium, but render it harmless, e.g. by neutralising toxins; since they apply no selective pressure, they ought not to give rise to resistance. Certain companies are interested.

50.    Dr Levy also mentioned "probiotics", whereby beneficial or harmless bacteria are encouraged to displace pathogens and resistant strains. This approach is being used against malaria and its vectors, and Dr Levy believes that it may offer a substitute for animal growth promoters. Bacteriophages hold no promise for human medicine, he believes, but might have applications in arboriculture.

Commercial surveillance

51.    In the USA, there are commercial companies which conduct disease surveillance and sell their results to pharmaceutical companies, to inform drug development and marketing strategies. As Dr Siegfried of PhRMA pointed out, information which shows that an established drug is slowly losing its effect is bound to be commercially sensitive.


52.    In the long term, the future of both diagnosis and treatment may depend on understanding the genes responsible for infection and resistance. At PhRMA, we were told that industry is researching this area intensively. Several commercial companies have already sequenced the genome of MRSA, but the information is not in the public domain; so NIH are funding a separate non-commercial sequencing project. They are funding a further 11 genome sequencing projects, including TB and the enterococcus, with a total estimated budget of $5m for 1997.

53.    Of NIAID's 124 research projects with a primary emphasis on antimicrobial resistance in 1996, 47 concerned genetic aspects of resistance; but people at NIH said that, though having the data was exciting, it was not yet clear how best to use it. Dr Levin suggested that genomic treatments would be so specific as to be of doubtful commercial viability.


Prescribing practice

54.    The prescribing practices of individual physicians (GPs) are no less significant a driver of resistance in the USA than in the UK; but in the USA the government has even less control. Who pays the piper calls the tune; in the USA, the government pays for healthcare only for the old (Medicare) and the poor (Medicaid). The rest is paid for by insurers or by the patients themselves; and the government has no locus to regulate practice. FDA has some control over drug use by regulation of labelling: physicians who authorise "off-label" use open themselves to suits for negligence. However, as Dr Rakowsky told us, if labelling were too restrictive, industry would be discouraged from developing drugs at all.

55.    CDC put the level of unnecessary use of antibiotics in the community at 20-50 per cent, and in hospital at 25-45 per cent.

56.    Managed care (see below) is affecting practice, but whether for good or ill was not clear. As Miss Stoiber of the US Department of Health saw it, on the one hand, managed care was squeezing cross-subsidies for local and State public health services; on the other hand, HMOs have a shared interest with public health services in ensuring rational treatment and curbing over-prescribing. Dr Siegfried of PhRMA was less ambivalent: managed care strains the patient's confidence in the doctor, and pressures the doctor to give less time to the patient; both factors favour prescribing over not prescribing. To transpose these arguments from the USA to the UK, for "managed care" read "the NHS internal market".

57.    Everyone we met agreed that achieving rational or "prudent" use of antibiotics depends very largely on education and persuasion of physicians and their patients. Dr Rakowsky pointed to some of the difficulties of educating physicians: antibiotics are beguilingly safe to prescribe in terms of direct risk to the patient—though not in terms of long-term risk to public or indeed individual health; antibiotic use is scantily covered in undergraduate lecture courses, and most subsequent education is from "the guy who gives you the pizza and the pen", the pharmaceutical salesman or "detailman". Dr Siegfried of PhRMA defended the industry: free gifts are out of fashion; the detailman should be seen as an educator; what physicians do with the information is ultimately up to them; and in many cases the detailman must now make his pitch not just to the physician, but to the HMO which imposes on all its physicians a restricted formulary.

58.    Dr Goldberger of FDA drew attention to one common pattern of bad practice. A patient is given a broad-spectrum antibiotic pending diagnosis. Diagnosis then reveals that a narrow-spectrum drug would be appropriate; but the prescription is not changed.

59.    Dr Mark Lipsic, a colleague of Dr Levin from Emory University examined some of the "rules of thumb" which tend to guide doctors prescribing antibiotics:

      (i)  Finish the course This may or may not be good advice, depending on the effect on the commensal flora.

      (ii)  Give several drugs in combination The effectiveness of multi-drug therapies is well attested for TB and HIV.

      (iii)  If the regimen is failing, do not simply add one more drug This is proven.

      (iv)  Give different drugs in rotation The evidence in favour of "drug cycling" is anecdotal; it may in fact be counter-productive.

He showed how practical questions of this sort can be addressed by population biology and mathematical modelling.

60.    Dr John McGowan of Emory University told us how, in May this year, Canada held a national meeting of all those with a stake in the issue, and agreed a national plan to reduce medical use of antibiotics by 23 per cent over 3 years, by concentrating mainly on mis-prescription for upper respiratory tract infections. The government has agreed to fund the plan. "The USA should have done this years ago," said Dr McGowan; so, perhaps, should the UK.

61.    We listened out for stories of resistance rates actually being brought down, and found only three. One is the story of MDR-TB, told above. The second comes from Finland, where use of erythromycin for streptococcal infections rose sharply in the late 1980s, causing a rise in resistance from 5 per cent in 1988 to 19 per cent in 1993. A national warning was issued, with recommendations on alternative drugs. Use of erythromycin fell by half; and by 1996 the rate of resistance was down to 8.6 per cent. The third was told by Dr Gorbach in Boston: one hospital eliminated second and third generation cephalosporins from its formulary, and halved its rate of VRE. Dr Gorbach knew of no other such stories. Dr Bennish of Boston pointed out that the premise of such stories, and of our efforts to control resistance, is that selective pressure is the main driver of resistance. This may not be true in all cases, and removing the selective pressure may only rarely result in the return of susceptible strains.

Pressure from patients

62.    In the USA perhaps even more than in the UK, many patients expect their doctor to prescribe, and will be reluctant to leave the surgery until he has done so. Education must therefore not be confined to the doctor, but must also reach the patient. Several of those we met cited seatbelts, red meat and smoking to show that public attitudes can be changed by campaigns of public health education.

Pressure from parents

63.    It came out time and again that much of the pressure on US physicians to prescribe antibiotics comes from the parents of poorly children. Even more mothers go out to work in the USA than in the UK, and cannot easily take time off to look after a sick child; and some daycare centres (nurseries) even require a certificate that antibiotics have been taken before a child who has been sick is allowed to return. According to Miss Shoemaker of the American Society for Microbiology, the number of US children under 6 attending daycare has risen to 60 per cent since 1975; over that period, the amount of antibiotics prescribed has tripled, and 20-25 per cent of antibiotics now prescribed in the USA are prescribed for children. Daycare centres are also, of course, an ideal setting for the spread of infection.

64.    All this may carry warnings for the UK, where public policy has for years favoured the out-to-work parent and encouraged childcare outside the home.

Education for prudent use

65.    Dr Levin of Emory University observed that prudent use requires that the patient's immediate perceived need be subordinated to the wider interests of public health. This will only happen if the costs and consequences of imprudent use are better documented than at present, and if it can be shown by evaluation that imprudent use may even harm the patient. He pointed out that cultural factors are sometimes on the side of the angels: for instance, in Italy antibiotics are believed to stunt children's growth.

66.    Dr Levy of Tufts agreed as to the importance of sound cost-benefit analysis. Dr Schwartz of CDC and Dr Bennish of Boston both believe they can show that previous treatment with antibiotics is a risk factor for infection with resistant strains.

67.    Dr Schwartz has worked on educating community physicians and their patients, with a view to controlling the rise of PRP (see above). In focus groups, physicians acknowledged overusing antibiotics by as much as 50 per cent. They blamed pressure from patients, and shortage of consultation time: it is quicker to prescribe, than to explain why a prescription would be inappropriate. Dr Schwartz has therefore produced the following aids for physicians: professional information sheets; a simple patient information leaflet for the waiting room, explaining that unnecessary antibiotics are bad for the patient; a "non-prescription" form; Q&A sheets for parents; and a letter for parents to give to their child-carer. Pilot projects are now under way in five States; CDC is equipping the local health department to train senior doctors to disseminate the concepts and materials to their peers. Evaluation will show whether these approaches reduce inappropriate use, and whether this in turn affects the level of PRP. We asked whether the pharmaceutical industry had been supportive; Dr Schwartz has had practical help from SKB, and other firms have made encouraging noises.

68.    Dr Avorn of Harvard Medical School has also worked on education for prudent use. His approach is modelled on that of the pharmaceutical industry, and not unlike that of Dr Schwartz. He began with focus groups of physicians. These revealed two groups of doctors: some who overprescribe out of ignorance; and others who consciously overprescribe in order to satisfy their patients. For the second group, like Dr Schwartz, he provides "paper placebos". For the first, he sends out "academic detailmen": pharmacists from the medical school who meet physicians one-to-one, on the same basis as salesmen, to talk about prudent prescribing. He has shown that every $1 spent on these actions saves $2 on the drugs bill. His approach has been taken up in various places around the USA; similar approaches have been tried in various parts of the UK, and adopted nationwide in Australia. He acknowledged that some doctors require to be persuaded that prudent use is not just a euphemism for cutting costs at the expense of patient care.

69.    As a location for education of patients, Dr Avorn commended schools; so did Dr Levy. The Alliance for the Prudent Use of Antibiotics, which was set up in 1981 and now has members in 92 countries including a few in the UK, has produced material for schools. APUA also produces patient leaflets, issues a newsletter and organises conferences. It encountered initial hostility from the pharmaceutical industry, but this is wearing off.

70.    The people we met over lunch in Boston disagreed as to the appropriate level of coercion. Dr Gorbach favours control, e.g. by requiring that every prescription for a drug associated with a resistance problem be accompanied by a "chit" giving the reason for prescribing. Dr Medeiros considers that this would restrict professional freedom to a degree unacceptable in the USA; he believes that, if surveillance is thorough and its findings are properly communicated, doctors will moderate their practice voluntarily. Dr Bennish inclines towards Dr Gorbach's position; he considers that Dr Medeiros underestimates the power of pharmaceutical advertising, and he would like to see such advertising controlled.

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