General
practice
EAR INFECTION
FROM THE BRITISH MEDICAL JOURNAL
kindly reprinted from my purchased copy
Froom
J, Culpepper L, Grob P, Barteld A, Bowers P, Bridges-Webb
C, et al. Diagnosis and antibiotic treatment of acute
otitis media: report from International Primary Care
Network. BMJ
1990;300:582-6.
Antimicrobials
for acute otitis media? a review from the international
primary care network
Jack
Froom,
professor
of family medicine,a
Larry Culpepper,
professor
of family medicine,b
Max Jacobs,
associate
professor of family medicine,c
Ruut A DeMelker,
professor
of family medicine,c
Larry A Green,
Woodward-Chisholm
chairman of family medicine,d
Louk van Buchem,
otorhinolaryngologist,e
Paul Grob,
professor
of general practice,f
Timothy Heeren,
associate
professor of biostatistics and
epidemiology b
a
State
University of New York, Stony Brook, NY 11794,
USA,
b
Boston
University, Boston, MA 02118, USA,
c
University of
Utrecht, 3584 CG Utrecht, Netherlands,
d
University of
Colorado, Denver, CO 80220, USA,
e
St
Elizabeth Hospital, 500 LC Tilburg,
Netherlands,
f
University of
Surrey, Guildford, Surrey GU2 5YG
Correspondence
to: Professor Larry Culpepper Department of Family
Medicine, Dowling 5 South, 1 Boston Medical Center Place,
Boston, MA 02118-2393, USA.
Introduction
Increasing
worldwide resistance of bacteria to antimicrobial
drugs is
causing a crisis, manifested by higher morbidity,
mortality, and
costs.1
In
1992 the Institute of Medicine in the United
States warned
of the growing threat posed by resistant
bacteria,2
and
in 1994 the Centers for Disease Control in Atlanta
initiated a prevention
strategy,3
linked to a
global plan by the World Health
Organisation.4
Proposed
remedies include development of new
antimicrobials, improved
sanitation, and educating patients not to ask
for
antimicrobials when they are
not useful and physicians to prescribe
them conservatively.5
About 30% of
British children under the age of 3 visit their
general
practitioner for acute otitis media each
year6
and
97% receive
antimicrobials.7
In
America it is the most common reason for
outpatient
antimicrobial use. Because this use has uncertain
benefits, it
merits reconsideration.
Increasing
resistance to antimicrobial agents has been reported
for
the three most common bacterial causes of otitis media
(Streptococcus
pneumoniae,
Haemophilus influenzae, and
Moraxella
catarrhalis),
but
rates differ between countries.8
9 In England and
Wales in 1990-5,
resistance to penicillin by S
pneumoniae increased
from 1.5% to
3.9% and to erythromycin from 2.8% to
8.6%.10
Except in the
Netherlands,
antimicrobials are standard
treatment for acute
otitis media in most developed
countries.7
11 Although
type and
duration vary between countries, generally
ampicillin, amoxycillin, or
co-amoxiclav (amoxycillin-clavulanate) are
preferred,with co-trimoxazole
a low cost alternative.7
In
the Netherlands, treatment of
symptoms without
antimicrobials has been
adopted as routine
initial treatment for otitis media,12
and
this policy is associated
with decreased emergence of resistance among
organisms commonly found
in otitis media.13
14 This approach
also is being adopted in
Iceland.15
Does
treatment improve outcomes?
Seven
randomised blinded studies have compared
antimicrobials with placebo in
patients with acute otitis media (table
1)
).16
17
18
19
20
21
22
23 Comparisons
aredifficult because inclusion criteria,
outcome measures, duration of follow up, and the period
when studies were
conducted are different. Also some studies had
insufficient
power to evaluate small to moderate differences.
Nevertheless,
since results are mixed and no study found large
differences between placebo
and antimicrobial groups, we conclude that the
benefit of
routine antimicrobial use for otitis media, judged
by
either short or long term outcomes, is unproved.
Summary points
Bacterial
resistance to
antimicrobials is responsible
for increasing morbidity, mortality, and costs
The most frequent use of
antimicrobials in the United
States is for otitis media
Evidence from randomised, placebo controlled trials that
routine use of
antimicrobials decreases the
duration and severity of symptoms and prevents
complications is weak
Treatment of acute otitis media differs worldwide, and
careful use of
antimicrobials in the
Netherlands and Iceland seems to have reduced rates of
resistance among organisms without compromising outcomes
The management of acute otitis media needs reassessing
A recent meta-analysis concluded that one child out of
seven benefits from
treatment,24
but
only four of the 33 studies included had placebo or
no medication groups,16
19
21
19 and no
justification was given for
excluding severalmethodologically sound placebo
controlled
studies.18
20
22 In contrast,
after reviewing 50 trials,
Claessen et al judged that methodological flaws
precluded making
recommendations.26
Does
treatment prevent complications?
Although
preventing mastoiditis and meningitis is a rationale
for
antimicrobial treatment, little evidence exists that
routine treatment is
effective for this purpose. Mastoiditis, a commonly
reported complication of
otitis media in the preantimicrobial era, is
now
uncommon. It is uncertain, however, whether the
decrease is related to
antimicrobial treatment, changes in clinical course
and
organism virulence, or increased host resistance.
Also, uncomplicated
otitis media often might not have come to medical
attention in
the era before
antimicrobials, increasing
the relative rate of
reported complications.
Questions
related to the routine use of
antimicrobials
for acute otitis media
* Are the course of and outcomes after acute otitis media
improved by antimicrobial treatment?
* Do
antimicrobials prevent
complications of acute otitis media?
* Which children are at high risk of poor outcomes after
acute otitis media? Do they benefit from
antimicrobials?
* If
antimicrobials are used, are
the optimum type and duration of administration known?
* Have management options, other than routine antimicrobial
administration, been widely used and with what results?
* Does decreased use of
antimicrobials for acute
otitis media influence the development of antimicrobial
resistance?
Selective use of
antimicrobials might yield the
same benefit as routine use.
In the Netherlands, among 4860 consecutive patients
with acute
otitis media who were not given
antimicrobials, only
two
experienced mastoiditis; both responded to treatment
with oral
antimicrobial as outpatients.27
Justification
for routine antimicrobial treatment of
otitis media to prevent meningitis is equally weak.
None of the
4860 patients developed meningitis. Kilpi et al
reported that
positive blood cultures in children with bacterial
meningitis were
equally common in those treated and not treated
with
antimicrobials before
admission (77% and 78%).28
Even
when otitis media
and meningitis coexist, they are likely to result
from a common
upper respiratory infection with haematogenous
spread, rather
than direct spread from ear to meninges.29
It
therefore
remains uncertain whether either routine or
selective antimicrobial
treatment prevents the complications of mastoiditis
and
meningitis.
Do
children at high risk benefit from
antimicrobials?
Adverse
consequences of otitis media include lack of
bacteriological or clinical
resolution, recurrent infection, persistent
effusion, hearing loss,
adenoidectomy, and insertion of a tympanostomy
tube . No study
has addressed whether antimicrobial treatment
decreases the
frequency of these in all or some of those with
known risk
factors.
The most
important risk factors for poor outcome are young
age and attendance
at day care centres. In a study of two groups
of
children infected with S
pneumoniae, comparable by
sex, age at first
attack, and frequency of earlier attacks, more
penicillin resistant
strains were isolated in those under 18 months
(P=0.003).30
Decreased rates
of bacteriological or clinical
resolution7
22
31 and increased
rates ofrecurrence,32
adenoidectomy,
and insertion of a
tympanostomy tube33
are
other consequences reported in children under
2 years old.
Day care is a
risk factor for poor outcomes, including recurrent
infection,34
admission to
hospital, adenoidectomy, and insertion of a
tympanostomy tube.33
After other
risk factors (age <2 years, white race,
male sex, and history of tonsillitis, enlarged
adenoids, or asthma) were
controlled for, children in day care had a 50%
higher chance
of repeated ear infections than those not in day
care.35
In
a nine country study, children in day care were more
likely to have
a history of poor hearing, tympanostomy tubes,
tonsillectomy, or
adenoidectomy and to be referred to an otolaryngologist
at the initial
visit.36
Other factors
likely to contribute to poor recovery include
multiple
previous episodes,37
bottle
feeding,38
history of
ear infections in
parents or siblings,39
and
use of a dummy.40
Although
exposure to
tobacco smoke has been considered a contributor
to
poor outcome, the evidence is controversial and the
effect weak at
best.41
Although risk
factors are known, no study has shown that
antimicrobial treatment improves outcome in children
at
risk.
What
is the optimal type and duration of administration?
In the nine
country study,
antimicrobials did not improve
outcome at two months,
and no differences in rates of recovery were
found for
either antimicrobial type or duration.7
The
optimum duration of
antimicrobial treatment for otitis media is
uncertain. There is
evidence that two days,42
three
days,43
five
days,44
and
10
days are equally effective. Treatment for more than a
few days might have
little local effect. In a study of antimicrobial
penetrance of
the middle ear, penicillin concentrations decreased
by
about 70% after the second day of treatment (compared
with the first day),
suggesting that penetration depends on
inflammation.45
No
compelling evidence
After
addressing these four questions, we conclude that
existing research offers
no compelling evidence that children with acute
otitis media
routinely given
antimicrobials have a shorter
duration of symptoms,
fewer recurrences, or better long term outcomes
than those who
do not receive them. It also is not clear that
routine
compared with selective use of
antimicrobials prevents
complications.
Thus it is prudent to reconsider routine use
of
antimicrobials for otitis
media and to consider other approaches.
What
are the effects of other management options?
Dutch family
physicians use
antimicrobials for upper
respiratory tract
infections more conservatively than doctors in other
countries (see
box).18
27 A World Health
Organisation study of tonsillitis in 17 European
countries found that 68% of Dutch patients received
antimicrobials compared with
94% in other countries.46
In
1990 the Dutch
College of General Practitioners adopted a guideline
for
treating acute otitis media. It has received
widespread use in the
Netherlands, but its adoption elsewhere requires
consideration
of the current healthcare system, particularly
the
ability of parents to access care for their children
initially and if they
fail to improve after treatment of symptoms.
Dutch
guideline for the treatment of acute otitis
media*12
Patients 2
years and older
* Treatment of symptoms only (paracetamol with or without
decongestant nose drops) for the first three days
* Re-evaluation if symptoms (pain or fever thought to be
due to acute otitis media) continue for three days. At that
time the doctor may continue additional observation or give
an antimicrobial (amoxycillin, or erythromycin if
amoxycillin is contraindicated) for seven days
* Special treatment for tympanic membrane perforation is
not suggested unless it persists for 14 days, at which time
a course of
antimicrobials is suggested
Children
between the ages of 6 months and 2 years
* Management is the same as for those 2 years and older,
except for a mandatory contact (either telephone or visit)
after 24 hours. If there is no improvement doctors may
either start
antimicrobials or wait an
additional 24 hours
* Referral to an otolaryngologist suggested if patients in
this age group appear to be seriously ill or do not improve
after 24 hours of treatment with
antimicrobials
*
An
English translation of the guideline is available from: The
Dutch College of General Practitioners, Domus Medica, PO
Box 323, 3502 GE Utrecht, Netherlands
Has this guideline resulted in more complications in Dutch
children? While no
controlled study has addressed this question, van
Buchem et al found
that only 2.7% of 4860 children given symptomatic
treatment and
no antimicrobial drug developed persistent fever,
pain, or
persistent discharge after three to four days and
only two developed
mastoiditis.27
Compared with
cases in seven other countries where
antimicrobial therapy is virtually universal,
Dutch patients
had similar outcomes at two months.7
Thus
Dutch experience
suggests feasible alternatives to antimicrobial
treatment exist.
What
is the effect on antimicrobial resistance?
Antimicrobial
use in children with otitis media results in the
emergence of
resistant organisms in those children and in the
community.
Among children previously given
antimicrobials for
otitis media,
Harrison et al found a rate of ampicillin resistance
in
bacteria in effusions obtained during a subsequent bout
of otitis media
that was three times higher than normal.47
Significant
increases in
resistant strains of H
influenzae,
M
catarrhalis,48
and
S
pneumoniae
49 have been
reported among children with otitis media who have
had previous antimicrobial treatment. Development
and
spread of multiply resistant pneumococci after
treatment for otitis
media have been documented in day care centres and
surrounding
communities,50
including
instances that have led to deaths from
meningitis in children treated previously for
uncomplicated acute otitis
media.51
Although the
organisms that cause otitis media are similar across
countries,52
the
Netherlands has a lower prevalence of resistant
strains than
other European countries. A study in 1989 in the
Netherlands
found that only 3% of 1100 S
pneumoniae cultures
showed
decreased sensitivity to penicillin compared with
more than 10% in
most countries.14
53 Similarly, 4.7%
of non-type B
H
influenzae isolates from
respiratory tract infections were resistant to
amoxycillin—less than the 10% overall rate
in
Europe.13
In Iceland,
penicillin resistant pneumococci appeared in 1988
and
increased to nearly 20% of pneumococcal infections by
1993.54
After a
campaign to decrease antimicrobial use, particularly
for
otitis media, and to control spread of infections in
day care centres,
this rate declined to 16.9% in 1994. The presence
of
resistant pneumococci among carriers who are day care
attendees declined from
20% (21 of 104) in 1992 to 15% (19 of 126) in
1995.15
Nevertheless,
it is not possible to state with certainty
that decreased
use of
antimicrobials results in
decreased resistance in endemic
bacteria.
What
needs to be done?
Research—Placebo
studies indicate that more than 80% of children with
acute otitis media recover without
antimicrobials.
Antimicrobials might be useful
for some of the remainder, but evidence of
benefit is lacking. A trial should be designed to
study
antimicrobial effectiveness in children at high risk
for poor outcomes,
using carefully chosen outcome measures, with
sufficient
numbers of patients for subgroup analyses.
Prevention
of acute otitis media—Sufficient
information exists to support
aggressive encouragement of breast feeding and
avoidance of tobacco
smoke.38
55 There is
insufficient evidence of effectiveness to recommend
pneumococcal vaccine.56
Over 70% of
cases of acute otitis media
are immediately preceded by viral respiratory
infections,31
and
there is convincing evidence that contaminated hands
and surfaces are
more important than airborne respiratory droplets
in
viral transmission.57
58 Campaigns to
encourage day care centres to
increase hand washing by staff and children and the
use
of virocidal agents to wipe surfaces might reduce viral
transmission and subsequent
otitis media.
Treatment
of acute otitis media—Clinicians
should immediately reconsider the
routine use of
antimicrobials for children
with otitis media
and consider treating symptoms with analgesics
and
observation for lack of improvement. Children less
than 2 years old
require frequent re-evaluation if not treated.
Doctors are often
uncertain about the diagnosis of otitis media
7; in
such
circumstances in particular
antimicrobials should be
withheld. If
antimicrobials are used they
should be given for less than 10 days. In
addition doctors should identify modifiable risks
for
poor outcome and work with parents to eliminate them.
The potential
benefits of these actions are profound. They could
reduce costs
without compromising outcomes while reducing the
risk of
bacterial resistance.
Acknowledgements
This paper is dedicated to the memory of Dr Max Jacobs,
whose intellect, wit, and
ability to solve problems internationally made our
collaboration
possible. He died suddenly on 21 December 1996.
Funding: Agency
for Health Care Policy and Research, Grant No.
RO1
HS07035-03.
Conflict of
interest: None.
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