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.
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.
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.
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
Multi-drug resistant tuberculosis
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
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.
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
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
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.
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
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
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
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 diagnosisthough 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-washingthough 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
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
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.
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
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
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 patientthough 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
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
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.