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Vol. 162 No. 3, February 11, 2002 |
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Review Article |
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Antibiotics for Common Respiratory Tract Infections in Adults
J. V. Hirschmann, MD
Arch Intern Med. 2002;162:256-264.
ABSTRACT
A thorough review of the published information indicates that antibiotics
rarely benefit acute bronchitis, exacerbations of asthma and chronic bronchitis,
acute pharyngitis, and acute sinusitis, although they are commonly prescribed
for these illnesses. Rather than prescribing them for these conditions, practitioners
should explain to their patients that antibiotics, which have numerous adverse
effects, will not hasten resolution of their symptoms, which will often respond
to other medications. Most patients will accept this approach if the clinician
addresses their concerns, shows a personal interest in them, discusses the
expected course of the ailment, and explains the treatment.
INTRODUCTION
More than 100 years ago, William Osler1
wrote, "A desire to take medicine is, perhaps, the great feature which distinguishes
man from animals." Currently, people have an especial taste for antibiotics,
which constitute about 1 of every 7 outpatient prescriptions in the United
States.2 Among adults nearly one half of prescriptions
are for common respiratory tract infectionsbronchitis, pharyngitis,
sinusitis, and upper respiratory tract infections (otherwise unspecified).3 When seeking medical care for conditions labeled as
upper respiratory tract infections, bronchitis, and even the common cold,3-4 50% to 70% of adults receive an antibiotic
prescription, especially if the clinician believes that the patient expects
it.5
This prescriptive promiscuity, which increasingly involves newer agents
with broader antimicrobial activity than the older preparations,2
largely explains the escalating antibiotic resistance of common bacterial
respiratory pathogens in the community.6 In
the selective pressure of indiscriminate antimicrobial use, susceptible bacteria
succumb; with competition for nutrients and mucosal sites of residence diminished,
resistant organisms thrive and proliferate. Consequently, Haemophilus influenzae and Moraxella catarrhalis are now widely resistant to ampicillin. In some areas, many infections
with group A streptococci no longer respond to erythromycin and other macrolides,
and penicillin is increasingly inactive against Streptococcus
pneumoniae, a most worrisome development since few other effective
agents exist. These bleak trends have led some infectious disease experts
to the gloomy prediction of a "postantibiotic" era; a return to conditions
that prevailed before the discovery of antimicrobial agents, with no efficacious
therapy for many serious bacterial infections.7
Some hope emerges, however, from studies demonstrating that aggressive efforts
to diminish the use of antibiotics to which organisms are insensitive may
allow susceptible strains to reemerge as the dominant isolates.8-9
In Finland, for example, a campaign to restrict macrolides led to a decrease
in erythromycin resistance among group A streptococci.8
A thoughtful approach to reducing the incidence of drug resistance is for
clinicians not only to refrain from giving antibiotics for obvious viral diseases,
such as the common cold, where they are clearly ineffectual, but also to examine
their use in other respiratory tract infections for which they are commonly
prescribed. In adults, such ailments include acute bronchitis, exacerbations
of asthma and chronic bronchitis, pharyngitis, and acute sinusitis. This article
derives data from a MEDLINE search of the English-language literature on topics
of "acute bronchitis," "asthma," "chronic bronchitis," "acute pharyngitis,"
and "acute sinusitis" from 1966-2000, and a review of the pertinent material
in the Cochrane Library as of 2001. It focuses primarily on the evidence from
randomized, controlled trials, especially, when possible, on recent studies
that reflect contemporary conditions.
ACUTE BRONCHITIS
Clinically, acute bronchitis is a recent, commonly productive cough
without evident pneumonia. It lasts approximately 2 weeks in 20% of patients,
3 weeks in 30%, 4 weeks in 30%, and longer in 20%.10
Typically, 3 to 4 weeks elapse from its onset until patients resume all usual
daily activities.11 Diverse viruses presumably
cause most acute bronchitis.12-13 Mycoplasma pneumoniae14
and Chlamydia pneumoniae15
are each present in about 5% of cases.16-20
Some have proposed that respiratory bacteria such as Moraxella (Branhamella) catarrhalis, S pneumoniae, and H influenzae produce acute bronchitis
or superinfect an originally viral condition.21
Since these organisms commonly inhabit upper airways of healthy adults,22-24 their significance
as isolates is unclear. No criteria for sputum culture findings distinguish
innocent airway colonization from invasiveness, if, indeed, such a process
occurs. Thus, the concept of "bacterial bronchitis" from these microbes remains
unproven.
Eight placebo-controlled, double-blind trials have evaluated antimicrobial
therapy.10, 25-31
The entry criterion was productive cough, with or without purulence, for less
than 2 weeks. The average age was about 35 to 45 years, and all studies enrolled
cigarette smokers unless they had chronic bronchitis. Fewer than 10% were
febrile (temperatures >38°C).26-27,31
Outcomes generally included duration of cough, feeling sick, time off work,
and sputum production or purulence. In 4 studies, antibiotics conferred no
significant advantage.10, 28-30
In the 4 trials favoring antimicrobials, the differences, though statistically
significant, were typically small and clinically unimportant.
This overview is misleading because these studies vary considerably
in quality and size. Defects include small numbers of participants,25-26,28-29 high
drop-out rates,25 incomplete data collection,25-26 clinically meaningless outcome criteria,25 failure to enroll consecutive patients,28
and inappropriate statistical evaluation, such as numerous analyses uncorrected
for multiple comparisons.26 Three investigations
had numerous participants and reasonable methodological rigor. In one involving
91 patients, 25% with serologic evidence of M pneumoniae infection, erythromycin produced no advantage in duration of cough
or chest congestion, improved well-being, and antitussive use, although the
antibiotic recipients missed 1 day less of work.27
In another, with 158 patients, doxycycline did not significantly shorten the
duration of productive or nocturnal cough, feeling ill, or impaired daily
activity.31 With doxycycline, daytime cough
disappeared 1.5 days faster, although it lasted at least 12 days in each group.
In patients older than 55 years, cough lasted 4 days less in doxycycline recipients
than in the placebo group, and those with frequent coughing who felt ill at
entry returned to normal daily activities 2 days sooner with doxycycline administration.
These differences, however, occurred in subgroups defined after the trial
ended and emerged from numerous statistical analyses uncorrected for multiple
comparisons. The largest trial investigated 212 patients with cough and purulent
sputum; doxycycline did not reduce daytime or nocturnal cough, purulent sputum,
and time "off-color" or off work.30 Pneumonia
was rare (2%), irrespective of the treatment.
In conclusion, although about 70% to 90% of patients seen for acute
bronchitis receive antibiotics,16, 32-33
published trials demonstrate no clinically important benefit, even in those
with purulent sputum. Four systematic reviews,34-37
one37 including results from an unpublished
trial, concur in concluding that antibiotics are not warranted for acute bronchitis.
Instead of prescribing antibiotics, clinicians should explain that cough persists
for 2 to 4 weeks, occasionally longer, and that sputum purulence is unimportant
unless other features, such as high fever and chills, suggest pneumonia, which
is a rare complication. An antitussive agent, such as dextromethorphan, may
relieve symptoms,38 and inhaled bronchodilators
help some patients, especially with dyspnea, wheezing, or severe cough.39-40
ASTHMA EXACERBATIONS
Asthma denotes episodic, reversible airway obstruction, usually defined
as reduced airflow improved by inhaled bronchodilators. Exacerbations are
characterized by increased dyspnea, wheezing, and cough, which is often productive.
Microorganisms provoke some attacks: viruses in at least 10% to 55% of patients,41-44 M pneumoniae in less than 5%,44-45
and C pneumoniae in 5% to 10%.46-48
Investigations have not convincingly incriminated respiratory bacteria such
as S pneumoniae.44
One study examined putative "infective" asthmaexacerbations with features
suggesting a bacterial process, including altered sputum volume or color,
radiographically defined sinusitis, nasal congestion or drainage, pharyngitis,
and fever.49 Twenty-seven patients with asthma
and 12 healthy controls underwent transtracheal aspirates to obtain uncontaminated
lower respiratory tract secretions. Samples from both groups were sterile
or yielded only sparse growth, primarily bacteria of low virulence, such as
coagulase-negative staphylococci.
Despite no evidence for bacterial infections in exacerbations, 20% to
50% of patients receive antimicrobials,41, 50-52
a treatment examined in 1 double-blind trial.53
All 60 hospitalized participants received systemic corticosteroids and bronchodilators
for their 71 episodes and randomly received amoxicillin or placebo. This antibiotic
improved no outcome measure, including cough severity, dyspnea, wheezing,
spirometrically measured airflow, and hospital stay.
In conclusion, without pneumonia, a rare complication, neither obtaining
sputum cultures nor prescribing antibiotics is appropriate. Instead, patients
should receive bronchodilators and systemic corticosteroids to relieve airway
inflammation and obstruction, as authoritative US and British guidelines recommend.54-55 Neither endorses antibiotic use for
uncomplicated exacerbations.
EXACERBATIONS OF CHRONIC BRONCHITIS
Clinically defined, chronic bronchitis is sputum production on most
days for at least 3 months annually for 2 consecutive years.56
Patients are usually current or prior cigarette smokers. Most studies characterize
exacerbations by 1 or more of these features: purulent phlegm or increased
dyspnea, cough, or sputum volume. Investigations implicate viruses in approximately
20% to 50% of attacks,57 C pneumoniae in about 5%58-59
(although by serologic examination rather than culture findings), and M pneumoniae in less than 1%.60-61
Whether respiratory tract bacteria, which chronically colonize many
patients' airways, are pathogenic remains controversial. In most investigations,
sputum cultures yield S pneumoniae and H influenzae from about 30% to 50% of patients during purulent exacerbations.61-67
Two careful prospective studies discovered no significant increase in the
number of patients whose sputum grew these organisms during exacerbations
when compared with periods of remission,60-61
and neither the presence nor density of these bacteria consistently correlates
with sputum purulence or the development of exacerbations.60-61,68-69 M catarrhalis is present in about 5% to 15% of exacerbations,
but usually with S pneumoniae and H influenzae, not as a pure isolate.65-67 Haemophilus parainfluenzae, common in chronic bronchitis,
does not increase during attacks.70 Other bacteria
identifiable by routine culture findings could explain few, if any, episodes:
protected brush samples from bronchoscopy during exacerbations in both outpatient
and hospital settings yielded significant growth from the lower respiratory
tract in only about 50% of cases, the isolates being primarily those already
discussed.66-67
Studies on the serologic and pathologic changes that occur in exacerbations
of chronic bronchitis also fail to provide convincing evidence of a bacterial
cause.71 Another approach to elucidate the
role of bacteria is to examine the double-blind, placebo-controlled antibiotic
trials in treating exacerbations. Of 11 such investigations,62-64,72-79
8 show no statistically significant benefit.63-64,72-74,76, 78-79
Unfortunately, these studies vary considerably in quality, size, and outcome
criteria, including many subjective ones. A meta-analysis found 6 trials,
2 favoring antimicrobials, that used peak expiratory flow rate as an objective
end point and discovered a 10.75 L/min greater improvement in the antibiotic
group.80 Since the patients' average peak expiratory
flow rate was approximately 200 L/min, this result represents about a 5% difference,
a finding that is clinically and physiologically inconsequential.71
The best study supporting antibiotic therapy investigated 173 patients
with 362 exacerbations77 defined by increased
dyspnea, sputum volume, or sputum purulence. Overall, success was significantly
greater in those receiving antibiotics (68%) than placebo (55%) and failures
were fewer (10% vs 19%). For exacerbations with only 1 feature, antibiotics
conferred no clinical advantage, and, with 2 features, it was marginal. With
all 3 criteria present, about 40% of exacerbations, antibiotics recipients
had greater success (63% vs 43%) and less deterioration (14% vs 30%), although
whether these differences were statistically significant is unstated. Another
large study, involving 278 patients, however, demonstrated no benefit for
amoxicillin vs placebo.78 Both trials concur
that antimicrobials are not beneficial in mild attacks. Why these 2 studies
otherwise disagree is unclear, but potential explanations include differing
entry criteria, patient populations, disease severity, and outcome assessments.
Another dissimilarity is that the latter study eliminated patients with fever
or suspected pneumonia, while 29% of subjects in the study favoring antibiotics
reported fever. If some of these patients had pneumonia, a point impossible
to ascertain because chest radiographs were not obtained, the benefit for
antibiotics is not surprising. The latter trial also excluded patients taking
oral corticosteroids, while in the one favoring antibiotics, about 40% of
participants received them, but in no systematic assignment, dose, or duration.
A disproportionate number of patients receiving these agents in high doses
in the various groups might account for some of the differences in outcome.
The issue of corticosteroids illuminates the crux of treating exacerbations:
namely, the goal. Patients primarily seek therapy not for altered sputum volume
or color but for diminished exercise capacity and increased dyspnea.77 Treatment should relieve these symptoms and prevent
severe respiratory compromise, the most common reason for hospitalization,81 by reducing bronchial inflammation and airflow obstruction.
Systemic corticosteroids achieve this goal by resolving bronchoconstriction
and airway inflammation significantly faster than placebo, both in patients
hospitalized with exacerbations82-84
and in outpatients.85 The outpatient study
showed a striking advantage not only in improving oxygenation and peak expiratory
flow rate, but also in preventing deterioration and hospital admission.85 When patients take systemic corticosteroids for exacerbations,
antimicrobials may provide no further benefit. In the large study that favored
antibiotics overall,77 there was no significant
benefit for those concurrently receiving systemic corticosteroids. In another
trial, among 71 patients treated with prednisolone, those randomly allocated
to antibiotics in addition improved no faster than the placebo group.78 This investigation was small, however, and included
10 patients with asthma.
In conclusion, microbiologic studies provide no conclusive evidence
that bacteria cause exacerbations, and in most investigations, antibiotics
provide no significant benefit. Overall, the preponderance of information
indicates that obtaining sputum cultures and prescribing antimicrobials are
unnecessary both in mild exacerbations and in the more severe episodes, which
should be treated with systemic corticosteroids. This topic warrants further
placebo-controlled, randomized trials, however, to clarify the microbiologic
characteristics of exacerbations and determine whether any subgroups, particularly
with severe disease, benefit from antimicrobial therapy when receiving concurrent
systemic corticosteroids.
ACUTE PHARYNGITIS
Infection with Streptococcus pyogenes causes
about 5% to 10% of adult pharyngitis in general practice86-88
and 35% to 40% in emergency departments.87, 89
Other common causes include other streptococci, viruses, M pneumoniae, and C pneumoniae.88
Infection with Neisseria gonorrhoeae, although usually
asymptomatic,90 constitutes 1% or less of cases.91
Discussions of pharyngitis have focused on treating S pyogenes. Identifying streptococcal pharyngitis by clinical features89, 92-93 is inaccurate; even
when adjusted for disease prevalence,94 the
criteria are insufficiently reliable for confident management decisions.95 Techniques to detect S pyogenes include obtaining pharyngeal culture specimens for everyone or only
those with negative rapid test results that demonstrate group A antigen in
throat swab findings.96 Several strategies
for treating acute pharyngitis have emerged. One is to prescribe penicillin
for all cases, without obtaining any studies.97
Trials examining this approach demonstrate no significant clinical benefit.
In one, involving 528 patients, symptoms resolved no more quickly with penicillin
than placebo.98 Another study randomly assigned
716 patients to 1 of 3 approaches: immediate penicillin, no antibiotics, or
delayed therapypenicillin if symptoms were unimproved after 3 days.99 No significant difference emerged for resolution
of sore throat, time off school or work, or duration of any symptom, except
fever, which abated 1 day sooner with antibiotics.
A second strategy is to treat only those cases of acute pharyngitis
whose cultures are positive for S pyogenes. Several
studies have shown that in this group antibiotics alter the clinical course
little. Sore throat, fever, and cervical lymph node tenderness resolve only
about 1 day sooner than with placebo.100-102
Furthermore, in the trial reporting these outcomes,103
patients receiving antimicrobials did not return to school or work more rapidly
and had no reduction in respiratory tract infections over the subsequent 6
months.
A third approach is to treat patients whose clinical features suggest
streptococcal infection. One double-blind study104
included 561 adult patients with sore throat for less than 7 days who met
at least 3 of the following 4 criteria89: history
of fever, absence of cough, pharyngeal exudate, and swollen anterior cervical
lymph nodes. Symptoms resolved 1.7 days sooner with 7 days of penicillin therapy
than with placebo, and patients resumed usual activities 2 days sooner, but
they did not return to school or work more rapidly. Nausea (40%) and abdominal
pain (25%) were significantly more frequent in the penicillin recipients than
in those receiving placebo (15%), although few discontinued the medications
because of these adverse effects. The more rapid resolution of symptoms occurred
in those with cultures positive for S pyogenes or
when other streptococci were present in at least 3+ growth specimens (into
the third inoculation area on the culture plate).
Although penicillin is unhelpful for patients whose cultures specifically
fail to grow streptococci,100, 103, 105
some pathogens, such as M pneumoniae and C pneumoniae, are susceptible to macrolides but not penicillin. Two
trials testing erythromycin when throat cultures grew no S pyogenes, however, showed no important clinical advantage over placebo.86, 106
An argument for detecting and treating streptococcal pharyngitis is
to prevent its complications, including the immunologic sequelae of acute
rheumatic fever (ARF), especially carditis, acute poststreptococcal glomerulonephritis,
and the suppurative disorders, primarily peritonsillar abscesses. The efficacy
of treating streptococcal pharyngitis to prevent acute poststreptococcal glomerulonephritis
is unknown,107 although some observations suggest
a benefit in epidemics of streptococcal pyoderma.108
In industrialized countries, acute poststreptococcal glomerulonephritis is
quite uncommon following streptococcal pharyngitis: a study among Scottish
children in the 1970s estimated that it occurred in about 1 of 17 000
cases of untreated patients.109 It is even
rarer in adults, its frequency and severity are declining,110
and, even if antibiotics were effective, enormous numbers of patients would
require treatment to prevent 1 case.
The role of antibiotics in averting peritonsillar abscesses is also
uncertain. In a study of 434 untreated patients with sore throat, 1 occurred
(0.2%).111-112 In the trial that
used clinical criteria for treatment,104 3
(1.7%) of 177 patients given placebo developed this complication. Fortunately,
the implications of this infection are currently considerably less alarming
than before; nearly all cases satisfactorily respond to outpatient therapyneedle
aspiration of the abscess under local anesthesia and antibiotics. Hospitalization
and tonsillectomy are rarely necessary.113
Studies from the mid 20th century, mostly in military personnel, demonstrated
that antibiotics prevent ARF,114 providing
the rationale for the strategy of detecting and treating streptococcal pharyngitis
that has prevailed for decades. Authoritative recommendations from prestigious
organizations95, 115 and most experts
still endorse this approach, based on the conviction that continued adherence
to it remains necessary to control ARF. Some investigators,114, 116
however, have argued that in nations, such as the United States, Great Britain,
and Australia, where it is rare, this policy is no longer appropriate, considering
its costs (eg, time spent seeing patients with pharyngitis, tests to detect
streptococci, antibiotics) and the potential therapeutic complications, ranging
from minor adverse effects to fatal anaphylaxis, estimated to occur in about
1 to 2 of 100 000 penicillin recipients.117
Certainly, ARF is very rare in many countries. Outbreaks in the United States
during the mid 1980s occasioned concern about a resurgence of the disease96; although focal increases occurred; however, no nationwide
rise developed. Instead its frequency continued a decline118-119
that began before the antibiotic era, presumably attributable to 3 factors:
better public health, especially reduced household size, which diminishes
spread of streptococci; antibiotic administration; and, probably the most
important factor in recent decades, decreased prevalence of "rheumatogenic"
streptococcal strains likely to cause ARF.120
The current risk of adult ARF following untreated streptococcal pharyngitis
is unknown, but the estimated incidence among Scottish children during the
late 1970s, when its frequency equaled that in US children, was about 1 in
40 000.121 Since the rate among adults
even when the disease was more common was about one fifth of that in children122-123 and its occurrence is now lower
than 2 decades ago, the current probability is considerably less. Whatever
the actual risk, enormous numbers of adults with streptococcal pharyngitis
would require antibiotics to prevent a single case of ARF, and 3 times as
many to prevent carditis, which occurs in about one third of adults with ARF.124
In conclusion, controlled trials do not support the policy of prescribing
antibiotics to all adults with pharyngitis. Instead, most patients should
receive antipyretics, reassurance, and information about the disease's natural
history: it lasts about 5 days after consultation, and in almost 40% of patients,
symptoms persist even longer.111 For those
who fulfill at least 3 of 4 clinical criteria, it is unclear whether the modest
clinical benefits outweigh the adverse effects for most patients, but 1 reasonable
approach is to offer a 7-day course of oral penicillin to those with more
severe symptoms. Using antibiotics to prevent acute poststreptococcal glomerulonephritis
and peritonsillar abscesses following streptococcal pharyngitis is unjustified
because these complications are rare and the benefit of therapy is uncertain.
Most authorities continue to recommend detecting and treating streptococcal
pharyngitis to prevent ARF, but in industrialized nations this policy seems
outdated. Certainly, however, it remains warranted in those with prior ARF,
along with secondary prophylaxis, to prevent recurrent attacks; in epidemics
of ARF or in locales where it remains endemic; and in scarlet fever, for which
antibiotics provide substantial benefit.125
ACUTE SINUSITIS
Diagnosing bacterial sinusitis is unreliable without sampling sinus
contents by surgery or needle aspiration. Computed tomography demonstrates
that nearly 90% of patients with the common cold have radiological evidence
of sinus disease that usually resolves or markedly improves in 2 to 3 weeks.126 It is thus an acute rhinosinusitis, and many patients
with presumed bacterial infection actually have uncomplicated viral disorders.
Most cases of bacterial sinusitis, however, probably follow such infections,
which obstruct sinus ostia and impair mucociliary clearance. Bacteria colonizing
the nasopharynx apparently enter the normally sterile sinuses and, entrapped,
provoke inflammation.127 The most frequent
isolates from needle aspirations, constituting about 60% to 90% of bacteria
recovered, are S pneumoniae and H influenzae.127-128 Viruses
are detectable by culture findings in about 15%,127
rhinoviruses by reverse transcription polymerase chain reaction in 40%.129
Clinicians suspect acute sinusitis when colds or influenza-like illnesses
persist for several days, accompanied by nasal congestion, maxillary toothache,
sinus discomfort or tenderness, purulent nasal discharge, fever, and headache
or facial pain, often worsened on bending forward.127, 130-133
In 1 study, clinical findings independently associated with abnormalities,
suggesting sinusitis on plain radiographs, included maxillary toothache, visible
purulent nasal secretions, history of colored nasal discharge, poor response
to decongestants, and altered transillumination.130
Predicting the presence or absence of radiographic changes by clinical criteria
was excellent at the extremes: sinus radiograph findings were abnormal in
9% of patients with no criterion present, 81% with 4, and 92% with all 5 criteria.
With 1, 2, or 3 predictors, however, the probabilities were 21%, 40%, and
63%, respectively, making clinical diagnosis more difficult in these common
settings. Moreover, radiographic changes do not reliably identify bacterial
sinusitis: only about 60% of patients with abnormal radiograph results have
positive culture findings from sinus needle aspiration.127
Other studies find no consistently reliable clinical criteria to identify
acute sinusitis, including fever, which occurs in 10% to 15% of cases.130, 132, 134 Several investigations131-134
have also shown that only 45% to 70% of patients with clinically suspected
sinusitis have radiographic or needle aspiration evidence of it, and only
30% to 40% have a bacterial infection.
For the 60% to 70% of patients having no bacteria in suspected acute
sinusitis, antimicrobials presumably confer no benefit. Moreover, given the
pathogenesis, promoting sinus drainage by relieving ostial obstruction may
be more important than antibacterial therapy. Six double-blind, placebo-controlled
trials evaluated antibiotics in acute sinusitis.131, 135-139
Four showed no benefit.131, 135, 138-139
The studies conflict for unclear reasons, but examining the 3 best trialsthose
with numerous participants and clearly delineated entry and outcome criteriais
illuminating. One supported antibiotics,131
2 did not.135, 137 One, using computed
tomographic criteria of fluid levels or total sinus opacification, randomly
gave 130 patients amoxicillin, penicillin, or placebo.131
Those receiving antibiotics recovered significantly faster: symptoms lasted
a median of 9 days for amoxicillin, 11 days for penicillin, and 17 days for
placebo. (In 70 patients with identical clinical features, but with only mucosal
thickening on computed tomographic scan, antibiotics were no better than placebo,
but the numbers in each group were small.139)
Another trial randomized 214 patients with abnormal plain radiograph results
to amoxicillin or placebo.135 No benefit for
antibiotic therapy emerged. The third study used clinical criteria: 3 major
symptoms (preceding cold or influenza, purulent nasal discharge, maxillary
sinus pain on bending forward) or 2 major symptoms plus 1 other complaint
(predominant unilateral maxillary pain, toothache, or pain when chewing).137 The trial randomized 192 patients to placebo or
doxycycline; the antibiotic provided no advantage.
One possible explanation for these discrepant results is that computed
tomographic criteria in the first study identified patients more likely to
have bacterial infection than the radiographic or clinical criteria of the
other 2 trials. Another difference, however, is that the latter studies explicitly
prescribed xylometazoline nasal drops (which cause vasoconstriction, reducing
mucosal edema) and steam inhalation, while the first neither required nasal
decongestants nor specified their type or frequency of use. Since relief of
ostial obstruction probably hastens improvement, antibiotics may add nothing
to aggressive therapy that decreases mucosal edema.
In all studies, symptoms resolved slowly. On average, they began about
2 weeks before entry into the trials, and, however treated, at least 20% to
30% of patients had significant complaints 7 to 10 days later, some persisting
for at least 2 to 3 weeks. In these studies placebo recipients developed no
serious complications, such as subdural empyema or chronic sinusitis.
In conclusion, most patients with putative acute sinusitis have no bacterial
infection, and antibiotics are unhelpful for most patients with suggestive
symptoms, even when suspicious abnormal findings appear on radiographs or
computed tomographic scans. Ordinarily, such tests are unnecessary, impractical,
and expensive. Instead of antibiotics, most patients should receive nasal
drops or sprays (xylometazoline or oxymetazoline), analgesics, and, possibly,
steam inhalations 3 times daily. They should understand that symptoms abate
slowly; complete resolution may require several weeks, but some improvement
usually occurs within a few days. Currently, no clinical criteria reliably
define patients who might benefit from antibiotics, but treatment is certainly
reasonable for those with high fever, systemic toxicity, immune defects, or
features suggesting intracranial or orbital involvement.
ADVERSE EFFECTS
In many trials, drug-related complications were much more common with
antibiotics, as 3 recent studies of acute sinusitis demonstrate. In 1, doxycycline
recipients had a 17% incidence of adverse effects, with 4 (4%) of 98 patients
discontinuing the medication, while only 2% reported complications in the
placebo group, none stopping the agent for that reason.137
In the second trial, adverse effects occurred in 9% in the placebo group vs
28% in the amoxicillin recipients,135 and in
the third study, they developed in 36% of the placebo group compared with
56% receiving amoxicillin and 59% receiving penicillin.133
Recent investigations of pharyngitis, acute bronchitis, and exacerbations
of chronic bronchitis also demonstrated substantially more adverse effects
in those receiving antimicrobials.22, 31, 78, 104
Determining the overall benefits of treating respiratory tract infections,
therefore, requires considering symptoms that antibiotics cause, which may
be less palatable than those from the original disorder. One study, for example,
queried patients about the additional duration of pharyngitis that they would
accept compared with the therapeutic risks.140
They preferred 1.5 to 2.5 days of symptoms to even a 5% chance of a mild penicillin
rash (hives).
ANTIBIOTIC THERAPY AND PATIENT EXPECTATIONS
In a survey, the most common prescribing situation by far that disquieted
English practitioners was respiratory tract infections, and the most troubling
medicines were antibiotics.141 In these difficult
circumstances, patient expectation predominantly dictated whether practitioners
provided medications. Indeed, several studies confirm that people expecting
prescriptions receive them far more frequently than those who do not,5, 142-145
even when clinicians consider medications unjustified.145
The strongest predictor is not the patients' actual attitude, but the practitioners'
judgment of their attitude.5, 144, 146
Physicians often err,5, 144, 146
prescribing medications more often than patients desire142, 144-148
or consider appropriate.142 Moreover, when
patients state that they want antibiotics for respiratory tract infections,
what they often really want is a medicine to relieve their symptoms.149 Indeed, they are frequently mistaken about which
medications are actually antibiotics.149
Clinicians may assume that providing antibiotics makes patients happier.
Satisfaction, however, usually depends not on whether patients receive antibiotics
for respiratory tract infections, even when they expect them,5, 99, 150
but on whether practitioners deal with their concerns,99
show personal interest in them,151 provide
and discuss the diagnosis,5, 151
reassure them that their disease is not serious,152
and explain the treatment.5 Contentment appears
therapeutic: patients with pharyngitis improved faster when satisfied, which
most closely related to feeling that clinicians addressed their concerns.99
Some practitioners may believe that prescribing antimicrobials is quicker
than fulfilling these expectations, although no investigations evaluated the
time involved with these different strategies or the patients' assessment
of such behavior. Two studies of pharyngitis, however, showed that those not
receiving antibiotics were less likely to return for subsequent episodes than
those who did, although both groups were equally satisfied.111, 153
These trials occurred where patients were unlikely to seek other medical care;
rather, they managed their illness by themselves. Physicians who educate patients
in this way may actually reduce their workload.
CONCLUSIONS
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