CHAPTER 2 PRUDENT USE IN HUMAN
Over-the-counter (OTC) antibiotics
2.26 In the United
Kingdom at present, generally speaking, systemic antibiotics (i.e.
taken internally, as opposed to "topical") are licensed
as "POM": i.e. prescription-only medicines, available
only on prescription from a doctor, dentist or veterinary surgeon
(not from a nurse-prescriber). There is however a general trend
to deregulate medicines, moving them from POM to "P"
(pharmacy); and there is discussion of treating antibiotics in
2.27 The RCGP believe
that there is pressure for OTC antibiotics from consumers and
from industry. However they have no doubt that OTC availability
would mean more use, and they consider it possible that this would
mean more resistance. Therefore, "We do not think it is a
good idea" (Q 306).
Neither does Professor Petrie (Q 659). The ABPI are "generally
opposed" to OTC antibiotics, with the possible exception
of treatments for uncomplicated lower urinary tract infection
(cystitis) (p 177, Q 338). They object because pharmacists
do not have the necessary training or suitable premises for the
confidential consultations which would sometimes be needed to
advise customers on the right choice of medicine, nor access to
the microbiology services which would sometimes be needed for
diagnosis; and because the imprudent use which contributes to
resistance would probably increase.
2.28 Professor Finch
(p 186, QQ 364-376), who is a member of the Committee
on Safety of Medicines and co-chairman of a BSAC working party
on OTC antibiotics, told us that the pressure to deregulate the
supply of antibiotics comes not just from industry, but from the
regulators themselves, in particular at EU level. He explained
that what is under consideration is not a free-for-all, but OTC
supply of single doses or short courses for particular indications.
In his view, much depends on what drugs are to be deregulated,
and for what conditions; he too identified cystitis as one which
"seems to be reasonable at first view", along with minor
infections of the skin or eye.
It would be necessary to give pharmacists robust guidelines, possibly
access to medical records, and perhaps a surveillance role. OTC
antibiotics would make commercial sense only if they resulted
in increased use; but this would not necessarily mean more resistance,
and might even mean less, if P medicines with a lower tendency
to induce resistance took market share from POM drugs with a higher
tendency. He concludes that more research and consideration is
needed before any major change.
2.29 One systemic antimicrobial
is already available OTC in the United Kingdom: the antifungal
fluconazole, sold in a one-capsule course for Candida vaginitis.
In Spain and Greece fluconazole is available OTC, and seems to
have given rise to significant resistance. According to Professor
Finch, "In the United Kingdom there is no evidence to date
that the use in the community of a single capsule for Candida
vaginitis is associated with resistance" (Q 375);
but this may be because no survey has been undertaken. According
to Dr David Denning of the University of Manchester
(p 402), fluconazole-resistance in Candida is now common,
but the causes are "not known entirely"; any effects
of OTC supply are "not being studied".
2.30 The Department
of Health drew to our attention the concern of the Medical Devices
Agency about wound dressings which incorporate antibiotics (p 345).
Under EU law and the Medical Devices Regulations, there is no
provision for such dressings to be POM, and they have therefore
been available OTC since 1995. The Agency are concerned that uncontrolled
use will give rise to resistance. However they have no evidence
yet that this is happening; and they have received little support
from other Member States "because many antibiotics are already
available OTC in a number of EU countries and there seems to be
general acceptance of this practice". As to actual OTC antibiotics,
however, the Department are confident that they can hold the line.
The Chief Medical Officer, Sir Kenneth Calman, has raised the
issue with his EU counterparts (Q 757); he considers a ministerial
decision to permit OTC availability "very unlikely"
(Q 794). Under EU law, any medicine may be confined to the
POM category if it presents "danger to health" if used
without supervision; and Sir Kenneth assured us that "health"
for this purpose included public health (p 371).
undergraduate, postgraduate and vocational
2.31 The undergraduate
medical curriculum is crowded, and several witnesses told us that
it tends to devote little time to antimicrobial therapy (e.g.
Petrie, McGavock Q 681though Professor Finch disagrees,
p 187). This
would be understandable, since oral antimicrobials are relatively
easy to prescribe, being relatively non-toxic and unlikely to
harm the patient directly. As the AMM put it, "antibacterials
are victims of their own success". They point out that "antimicrobials
are the only class of drugs the prescription of which can have
adverse consequences outside individual recipients"i.e.
the selection of resistant strains. They recommend, "priority
should be given by the medical profession, universities and the
General Medical Council to ensuring that a definitive slot on
antibacterial use is in all curricula, and that this includes
not only technicalities of antibacterials but puts their use into
sociological and world contexts" (p 10). Implementing
this recommendation would of course involve taking time from other
subjects, whose advocates would no doubt make their case with
2.32 In medicine as
in other walks of life, one of the most effective forms of professional
development is participation in teaching. In Oxfordshire, Dr Mayon-White
reports, "the teaching and training practices tend to prescribe
less of the expensive antibioticsand indeed fewer antibiotics
overallthan the non-teaching, non-training practices"
(Q 158, cp Davey p 155 and Q 250). In the context
of prescribing, another effective form of professional development
is participation in the process of creating local formularies
and policies (Petrie Q 679).
2.33 Not every doctor
can be a trainer or policy-maker; and various ways have been found
to deliver professional development to the wider medical community.
Dr Jeremy Grimshaw of the Health Services Research Unit at
the University of Aberdeen gave us an overview drawn from the
findings of the Cochrane Collaboration on Effective Professional
Practice, of which he is the co-ordinating editor (Q 672).
He indicated that there are no "magic bullets"; which
interventions are most effective at changing behaviour depends
on the behaviour in question, and on the context (e.g. hospital
or general practice), and best results are obtained by intervening
in several ways at once. Dr Grimshaw's findings may be crudely
summarised as follows:
(i) Passive dissemination,
using literature and lectures: in itself, ineffective;
(ii) Interactive workshops:
(iii) Audit and feedback:
effective, though the changes achieved may be modest;
(iv) Educational outreach,
whereby trainers visit professionals individually: "very
(v) Local opinion leaders
raising standards by example: "much touted", but requires
further research (Q 683).
We have received further evidence
about (iii) and (iv), as follows.
Audit and feedback
2.34 GPs may already
opt to receive detailed information ("PACT" data) on
their own prescribing from the PPA; and some may have access to
additional information from their own IT system. The AMM, who
recommend wider use of formularies and policies, call for these
to be supported by audit (p 10).
They acknowledge that audit is especially difficult in the isolated
conditions of general practice; on the other hand, GPs are ahead
of hospitals in computerising their records of diagnosis and prescription.
They acknowledge that the cost to the NHS of the staff and IT
required for a proper system of audit would be high; and they
assess the impact, even after 5-10 years, as "Some effect,
but not major". Professor Petrie is an advocate of audit
(Q 663): "By doing audit of what people are doing, you
can get the `outliers' and bring them into the middle group of
prescribers voluntarily. If you start going out with guns and
statutory controls, people hide." Box 4 gives examples
of good practice in this area which have come to our notice.
|PRESCRIBING AUDIT AND FEEDBACK: EXAMPLES OF GOOD PRACTICE
|Dr McGavock told us about COMPASSComputerised On-line Monthly Prescribing Analysed for Science and Stewardship (p 281, Q 635). COMPASS is an evidence-based, computerised prescribing interrogation system, run by the Drug Utilisation Research Unit of The Queen's University, Belfast. "COMPASS compares each practice's prescribing every month in Northern Ireland against best practice and it then prints a clear report showing the ways in which the doctors did prescribe and recommends changes to improve the quality of their prescribing". For a cost of £2 per copy, COMPASS typically identifies possible savings of 15 per cent. "COMPASS is taken to every practice annually by the Area Prescribing Advisers, for detailed discussion, but fundholding practices often request this document quarterly, to drive their cost-effectiveness efforts. COMPASS has saved over £11m in Northern Ireland in the past three years, but could save up to £25m annually, if fully utilised, with a striking improvement in the quality of medical treatment". In the first quarter of 1997, 60 non-fund-holding GPs saved £1.23m using COMPASS, backed up with lectures and visits. Dr McGavock finds the results of COMPASS overall "disappointing". He believes that, if it is to change behaviour significantly, such a system requires to be backed up by educational outreach, and by some direct "incentive", e.g. such that a proportion of the money saved on drugs is returned to the practice (QQ 638, 684).
|Dr Mayon-White told us (p 111) that Oxfordshire Health Authority has begun a programme to improve antibiotic use in general practice. Guidelines have been issued to GPs, recommending first-choice empirical treatments for various infections. The guidelines are supported by prescription monitoring; results are fed back to GPs in general by means of a newsletter, and to individual practices through visits by the Authority's Medical Adviser.
2.35 Dr Grimshaw defined
educational outreach thus: "This is where you have a professional,
often a pharmacist, going to visit a general practice or hospital
to give a number of very selective messages about good prescribing
behaviour, which often use the marketing techniques of the pharmaceutical
industry, to try and identify the specific barriers to the behaviour
they want to happen, and modify their message based on these barriers
and reinforce that message throughout that contact". He mentioned
that the Department of Health is currently funding a large-scale
trial of this method, expected to report in 1999 (QQ 672,
683). The USA is ahead of the United Kingdom in this field: see
|EDUCATIONAL OUTREACH IN THE USA
|Dr Jerry Avorn of Harvard Medical School is a world expert on educational outreach. His approach is modelled on that of the pharmaceutical industry. 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 United Kingdom, 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.
|Dr Ben Schwartz, of the Centers for Communicable Disease Control and Prevention (CDC) in Atlanta, has worked on educating community physicians and their patients, with a view to controlling the rise of penicillin-resistant pneumococcus. 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; question-and-answer 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 resistance.
2.36 One major factor
affecting the prescribing behaviour of GPs is the expectations
of their patientsor
GPs' perception of patients' expectations, which is not necessarily
the same thing. Patients'
expectations are not uniform; according to Dr Grimshaw, they "vary
across different areas, socio-economic groups and cultures"
2.37 It may not be
the case that people in poorer communities have a higher expectation
of receiving antibiotics. Rather, it may be that GPs in such communities
are more pressed for time, and therefore inclined to prescribe
rather than explain. However a GP under pressure of time may do
various things to terminate the consultation besides prescribing.
First, he may simply say No: Dr Grimshaw cited evidence from a
randomised trial that this reduces the likelihood that the patient
will attend again with the same complaint (Q 674). Saying
No is not always easy: Dr Grimshaw recommended training for
GPs in communication skills (p 301). Dr Davey mentioned
two alternative approaches (Q 273): give the patient an information
leaflet; or say, "I do not think you need an antibiotic,
but if you want to get a prescription you can come back any time,
you do not have to make another appointment". Of the latter
approach, he commented, "Most of the people who were given
that option did not come and get the antibiotics". Dr Taylor
of the RCGP mentioned another: a delayed-action prescription,
for use if symptoms persist. "The result of that is that
many patients do not in fact take the prescription" (Q 303);
this strategy is also known to reduce the rate of follow-up appointments.
2.38 Rather than waiting
until the patient is in the surgery, the professions may take
the message of prudent use out to the public at large. The AMM
recommend that the health and education departments, the health
professions and the media should all do more to convey the message
(p 11). Dr Mayon-White similarly calls for public education;
he recommends that health authorities' health education departments
should prepare material for schools, while adult education should
be delivered through the media (QQ 159-163).
2.39 The RCGP observe
that GPs work within, and are to an extent constrained by, a "cultural
framework" (Q 281). A GP who unilaterally defies this
framework may simply lose his patients. However the culture can
be changed, as in the cases of barbiturates and amphetamines.
Changing the culture requires public education and consensus-building,
based on evidence. In this matter, they feel, the evidence will
have to be compelling: "Whether or not, and how far, antibiotic
use for relief of symptoms of self-limiting illness should be
limited should not be a matter for doctors to decide, but the
subject of public policy. In a context in which antibiotics are
much more freely used in agriculture and food production, it seems
unlikely that there would be much public support for such restriction...Antibiotic
use in the United Kingdom is already lower than in many other
European countries; in that context it would be difficult to operate
a more restrictive policy" (p 167). The RCGP observe
that typically the sort of patients who are most insistent on
antibiotics belong to the social groups who are hardest to reach
with educational material (Q 299, cp Petrie Q 677).
bad for you?
2.40 Persuading the
public of the case for reduced use of antibiotics will be much
easier if it can be shown that unnecessary use carries risks not
only to public health in general, but also to the particular patient
2.41 Professor Finch
said (in the context of OTC antibiotics), "It is uncommon
for resistance to arise in an individual receiving an antibiotic
and for this to cause him/her harm" (p 189). (TB is
an exception, as are viruses such as HIV.) However he went on,
"Agents can affect the susceptibility of the bacteria which
make up the normal flora of the skin and gastrointestinal tract.
This in turn could give rise to subsequent infection in an individual".
Dr Ben Schwartz of the US Centers for Communicable Disease
Control and Prevention (CDC) and Dr Michael Bennish of Boston
both believe they can show that previous treatment with antibiotics
is a risk factor for infection with resistant strains. Dr McGavock
cited evidence that, in cases of otitis media, withholding antibiotics
for two to three days reduced the rate of recurrence by four fifths
(QQ 659, 677).
2.42 Dr Davey also
has evidence to support this proposition. "Patients with
resistant organisms are more likely to have received prior antibiotic
therapy than are controls [i.e. patients with susceptible strains
of the same organism]"though, he admits, "Antibiotic
use may just be a marker for patients who are more ill" (p 145).
Speaking in the context of the successful campaign in Iceland
to bear down on penicillin-resistant pneumococci, he added, "The
message that we need to get across is that most of the bacteria
that live in our bodies do not do us any harm, and if you eliminate
them with antibiotics then you allow the bad guys in" (Q 262;
cp Q 236, pp 146, 154). He went so far as to say, "Germs
are good for you...germs are part of your environment" (Q 274);
he admitted that this is "probably not something that people
2.43 The ABPI observe
that effects on the gut flora are checked as part of the process
of licensing a new antimicrobial. "Whilst it is true that
there are occasional changes in gut flora which are limited to
the duration of treatment, generally speaking you find that the
gut flora returns to normal quickly after the antibiotics are
stopped" (Q 331).
2.44 If antibiotics
do even slight collateral damage, then it would plainly be better
not to use them in situations where they can do no good (e.g.
the minor viral infections which Dr Davey believes account
for more than half of GPs' prescriptionsQ 265). More
difficult are situations where antibiotics do a little good, which
must then be weighed against the possibility of harm. The RCGP
draw attention to the major grey area in general practice: the
use of antibiotics to relieve the symptoms of self-limiting illness
such as sore throat, bronchitis and otitis media. They concede
that there may be a case for limiting use in such cases on public
health grounds, but they insist that such use does have direct
benefit (p 166). The ABPI, on the other hand, regard prescribing
antibiotics for "the majority of sore throats", or for
"a banal, self-limiting, mild condition, e.g. an upper respiratory
tract infection", as "irresponsible" (p 176).
2.45 Tessa Jowell MP,
the Minister for Public Health, was firmly of the view that the
public must not be warned off antibiotics. For her, the issue
crystallised around meningitis: nothing must be said to deter
parents, in particular, from contacting their doctor at once if
they suspected meningitis in their child. She acknowledged that
it was difficult to convey the message of appropriate use of antibiotics
in a way which was balanced and not confusing; but, she insisted,
"We do not want patients to think that antimicrobials are
dangerous for the individual...; they are among the safest medicines"
(Q 759). The Chief Medical Officer suggested that the problem
could be addressed by acknowledging that what was appropriate
varied from case to case: for instance, what was appropriate for
a young child with a fever was not necessarily appropriate for
a middle-aged man with a cold (Q 761).
2.46 It is usual practice
for patients receiving antibiotics to be instructed to "complete
the course". Yet the quality of evidence on which the recommended
duration of antibiotic treatment is based varies, in fact, greatly
from case to case. For some infections, of which tuberculosis
is the most notable example, the type and duration of treatment
needed to cure the patient (and to prevent resistance in those
few patients who are not cured) has been well authenticated by
numerous controlled trials. For others, including the many respiratory
infections, such as bronchitis, pneumonia, sinusitis and otitis
media, which constitute the most frequent occasions of antibiotic
use, the optimum duration of courses of treatment is still surprisingly
ill-founded. International comparisons reveal these uncertainties
vividly, particularly in otitis media, bacterial endocarditis
and urinary tract infection (Griffin p 548). There is certainly
no virtue in completing the course if the infection was not in
fact present in the first place (Davey Q 268), or if the
prescribed course was longer than necessary to cure the infection
and completing the course only prolongs the selective pressure
on the commensal flora.
2.47 Whether or not
the particular recommendations for duration of treatment are well-founded,
however, it is clear that compliance with prescribing recommendations
is hard to achieve and that non-compliance with treatment can
contribute to resistance, especially in the case of tuberculosis
and sexually-transmitted infections. The Royal Pharmaceutical
Society has addressed this problem in a valuable document entitled
From Compliance to Concordance (March 1997). The RCGP observe
that compliance can be encouraged by drug and regimen design,
and by patient information, on which there is recent EU legislation
which they support (p 167). The ABPI are "particularly
keen" on improving compliance by means of new formulations
(p 176, Q 347); and they support the Patient Pack Initiative
on patient information.
The RCGP's memorandum (p 167) said, "In principle...we
would not object to the direct sale of certain antibiotics".
They admitted under oral examination that they would object,
up to the point where the Medicines Control Agency licensed antibiotics
OTC, at which point "We would have to go along with that"
(Q 306). Back
Cp Royal Pharmaceutical Society p 463. Back
Professor David Greenwood, of Nottingham University Hospital,
believes that his department "may be unique" in giving
third-year medical students a two-week module on antimicrobial
therapy (p 410). Back
So do the British Pharmacological Society (p 386). Back
For eloquent accounts of this problem from the front line, see
the evidence of the Osborne Practice in Southsea (p 440)
and Dr John Sterland (p 526). Back
"Doctors tend to overestimate the patient's desire for a
prescription"-RCGP Q 297, cp Grimshaw Q 674. Back
Like all medicines, antibiotics carry risks of direct adverse
side-effects in the individual. Although antibiotics are generally
safe medicines, unwanted effects do occur, mostly trivial but
occasionally life-threatening. Our particular concern, however,
is the relationship of antibiotic treatment to the development
of resistance. Back