ORIGINAL INVESTIGATION

Effect of Amoxicillin-Clavulanate
in Clinically Diagnosed Acute Rhinosinusitis
A Placebo-Controlled, Double-blind, Randomized Trial in General Practice
Heiner C. Bucher, MD, MPH; Peter Tschudi, MD; James Young, PhD; Pierre Periat, MD;
Antje Welge-Lussen, MD; Hansjorg Zust, MD; Christian Schindler, PhD;
for the BASINUS (Basel Sinusitis Study) Investigators

Background: Acute rhinosinusitis is one of the most

common reasons for prescribing antibiotics in primary
care. However, it is not clear whether antibiotics improve the outcome for patients with clinically diagnosed acute rhinosinusitis. We evaluated the effect of a
combination product of amoxicillinpotassium clavulanate on adults with acute rhinosinusitis that was clinically diagnosed in a general practice setting.
Methods: We conducted a randomized, placebocontrolled, double-blind trial with 252 adults recruited at
24 general practices and 2 outpatient clinics. Each patient
had a history of purulent nasal discharge and maxillary or
frontal pain for at least 48 hours. Patients were given amoxicillin, 875 mg, and clavulanic acid, 125 mg, or placebo twice
daily for 6 days. Main outcome measures were time to cure
(primary outcome), number of days during which rhinosinusitis restricted activities at home or work, and frequency of adverse effects (secondary outcomes).

From the Basel Institute for

Clinical Epidemiology
(Drs Bucher and Young),
Medizinische
Universitats-Poliklinik
(Dr Bucher), and
Universitatsklinik fur Hals-,
Nasen- und Ohrenkrankheiten
(Drs Welge-Lussen and Zust),
Kantonsspital Basel; Forum
fur interdisziplinare
Hausarztmedizin (Drs Tschudi
and Periat) and Institut fur
Sozial- und Praventivmedizin
(Dr Schindler), Universitat Basel,
Basel, Switzerland. A complete
list of the BASINUS Trial
Investigators appears at the end
of this article. Dr Bucher has
received honorarium for
presentations
and financial support for
participation in scientific
meetings from GlaxoSmithKline.

Results: The adjusted hazard ratio for the effect of amoxicillin-clavulanate was 0.99 (95% confidence interval [CI],
0.68-1.45) on time to cure and 1.28 (95% CI, 0.80-2.05)
in the prespecified subgroup of patients with a positive rhinoscopy result. At 7 days the mean difference between
amoxicillin-clavulanate and placebo was 0.29 (95% CI,
0.93 to 0.34) in the number of days with restrictions due
to rhinosinusitis and 0.60 (95% CI, 1.41 to 0.21) in patients with a positive rhinoscopy result. At 7 days patients who took amoxicillin-clavulanate were more likely
to have diarrhea (odds ratio, 3.89; 95% CI, 2.09-7.25).
Conclusions: Adult patients in general practice with
clinically diagnosed acute rhinosinusitis experience no
advantage with antibiotic treatment with amoxicillinclavulanate and are more likely to experience adverse
effects.

Arch Intern Med. 2003;163:1793-1798

CUTE RHINOSINUSITIS is one

of the most common diagnoses and most frequent

reasons for prescribing antibiotics in general practice.1,2 Although most cases of acute rhinosinusitis in primary care are caused by
an uncomplicated viral infection, antibiotics are frequently prescribed.3 One reason for this overuse of antibiotics is the lack
of a simple diagnostic test in primary care
that allows physicians to accurately differentiate between acute viral and bacterial rhinosinusitis. Acute bacterial rhinosinusitis is a secondary infection that
results from ostia obstruction and impaired mucous clearance caused by an upper respiratory tract infection. Additional diagnostic tests, such as sonography,
cranial x-ray examinations, and computed tomography, are useful,4 but these
tests have intermediate specificities for the
diagnosis of acute bacterial rhinosinusitis, are not immediately available in gen-

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1793

eral practice, and add additional costs to

the diagnosis and treatment of a common condition. Thus, misclassification of
acute viral rhinosinusitis is an important
reason for overuse of antibiotics in general practice. This overuse contributes to
the emergence and spread of antibioticresistant bacteria.5
Evidence on the effectiveness of antibiotic treatment for acute rhinosinusitis in
primary care is limited. A meta-analysis of
randomized, placebo-controlled trials for the
treatment of acute rhinosinusitis found a
higher likelihood of cure in patients treated
with antibiotics.6 However, this analysis included trials in which patients were recruited using diagnostic criteria that are not
applicable in general practice.7,8
We conducted a randomized, placebo-controlled, double-blind trial of antibiotic treatment with a combination
product of amoxicillinpotassium clavulanate in adults with suspected acute bacterial rhinosinusitis. Patients were in-

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cluded in the trial based on clinical diagnostic criteria

that are applicable in general practice. We designed a trial
that reflects, to the greatest possible extent, a routine approach to patients with uncomplicated acute rhinosinusitis in general practice.
METHODS
PATIENTS AND SETTING
Patients were recruited during the 4 winter seasons (November 1 to April 30) of 1997 to 2001 from 24 general practices in
Basel, Switzerland, and surroundings and in the internal medicine and otolaryngology outpatient clinics of the University Hospital Basel. Outpatient clinics were only allowed to treat walk-in
patients or patients who had not been referred. The inclusion
criteria were a history of repeated purulent nasal discharge and
maxillary or frontal unilateral or bilateral pain for at least 48
hours but less than 1 month and presence of pus under rhinoscopy. Exclusion criteria were younger than 18 years, an upper respiratory tract infection or use of antibiotics for any reason within the previous 4 weeks, an upper respiratory tract
infection or intermittent fever that persisted for more than 4
weeks, pathologic features or malformation of nasal cavities or
the pharynx, immunosuppressive treatment, human immunodeficiency virus infection, allergy to amoxicillin-clavulanate,
pregnancy or breastfeeding, or no fluency in one of the national languages.
After the first winter season, only 43 of 106 patients who
fulfilled the first 2 inclusion criteria and consented to participate in the trial had a positive rhinoscopy result. We therefore
decided to recruit patients without pus under rhinoscopy but
to continue rhinoscopy with all those recruited. In 2000 a patient in the placebo group experienced a brain abscess. After
this, all patients with a C-reactive protein (CRP) level greater
than 100 mg/L were excluded from the trial (none), and patients with a CRP level between 50 and 99 mg/L were reassessed at day 3 (3 patients) and excluded if clinical worsening
was noted or the CRP level had increased to higher than 100
mg/L (none).

exclusion criteria were approved by the ethics committee of the

University Hospital Basel.
A radiograph (occipitomental view) of the maxillary and
frontal sinus was obtained for each patient. Radiographs were
made either in the private practice or by referral to our hospital. General practitioners and their technical staff were instructed by a radiology technician from our hospital to standardize radiographic technique. Two radiologists who were
masked to the groups independently assessed each radiograph. We used fluid levels or complete opacity as a positive
indicator for acute rhinosinusitis.9 Agreement between radiologists was only moderate for this criterion (=0.59). A blood
specimen for white blood cell count (reference range, 350010000/L) and CRP level (reference range, 10 mg/L) was obtained. All specimens were analyzed at the laboratory of the University Hospital Basel.
RANDOMIZATION AND
INTERVENTION
We used stratified randomization, with the general practice or
outpatient clinic as the stratification unit and patients randomized in blocks of 6. A computer random-number generator was
used, and the allocation sequence was performed by a statistician who was not involved in the final analysis. The randomization code was kept at the 24-hour emergency call center in
Basel. Operators had to immediately advise the principal investigator of every case for which the code was broken. Patients were consecutively enrolled, and we required study physicians to record the reason why eligible patients were not
recruited.
Patients were randomly assigned to receive either amoxicillin, 875 mg, and clavulanic acid, 125 mg, twice daily for 6
days, or placebo. Tablets of equal size, color, and taste were
provided in identical, numbered containers by GlaxoSmithKline (Munchenbuchsee, Switzerland). All patients received decongestant therapy with a xylometazolin hydrochloride spray
(Otrivin; Novartis, Berne, Switzerland) and acetaminophen tablets of 500 mg (Panadol; GlaxoSmithKline Switzerland), with
a maximal dose of 3 g/d. Concomitant therapy with steam inhalation was allowed.

CLINICAL EVALUATION
AT BASELINE

END POINTS AND

STATISTICAL ANALYSIS

For each patient, physicians recorded a focused medical history for rhinosinusitis-related symptoms, the number of days
during which rhinosinusitis restricted activities at home or work,
and previous upper respiratory tract infections. They collected clinical data on the presence of pus in the pharynx and
in the medial meatus during rhinoscopy, pain on pressure and
on percussion of the frontal and maxillary sinuses, and body
temperature. Patients completed a questionnaire with questions on rhinosinusitis-related symptoms and adverse effects
from antibiotics (eg, purulent rhinorrhea and sputum, frontal
or maxillary unilateral or bilateral pain, pain on bending, hyposmia or anosmia, fatigue, sleep and mood disorders, abdominal cramps and diarrhea, and vaginal pruritus or discharge).
Patients rated the severity of symptoms on a 10-point, equaldistance scale. The study physicians and the study nurse attended a 3-hour seminar to standardize data collection and the
clinical examination of patients. All study physicians were trained
in rhinoscopy by an otolaryngologist (A.W.-L.) and were shown
how to use a rhinoscope with an integrated light source (the
Heine rhinoscope; Heine Optotechnik, Herrsching, Germany).
One refresher seminar was held during the study. Patients were
informed about the study goals and had to sign an informed
consent form. The study protocol and changes to inclusion and

The primary outcome was time to cure. We used 0 days (since

the previous visit or interview) during which rhinosinusitis restricted activities at home or work as our definition of cure. To
confirm the primary outcome, we repeated our analysis using a
second definition of cure: a rating of 1 on a 10-point, equaldistance scale for the severity of restricted activity at home or work.
Secondary end points were the number of days during
which rhinosinusitis restricted activities at home or work, the
frequency of adverse effects, and the recurrence rate of rhinosinusitis at 28 days. Patients were said to have recurrent rhinosinusitis if they were never cured and felt at least as restricted at day 28 as at baseline. At day 7 physicians performed
a second clinical examination, and patients completed a second questionnaire. Physicians also noted the number of tablets taken. At days 14 and 28, the study nurse interviewed patients by telephone. Patients were always asked the same
questions on rhinosinusitis-related symptoms and adverse effects, plus additional questions on use of other drugs or other
visits to physicians. All study physicians and the study nurse
were blinded to the treatment given to each patient. Data were
entered by the study nurse.
To calculate the sample size, we assumed that 50% of the
recruited patients had acute bacterial rhinosinusitis,10 and the

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spontaneous cure rate for acute bacterial rhinosinusitis at 7 days

was 80%.7 We assumed a 50% increase in the cure rate at 7 days
for patients with acute bacterial rhinosinusitis treated with
amoxicillin-clavulanate (Laurant Kaiser, MD, personal written communication, September 15, 1997)11 and a spontaneous cure rate of 60% at 7 days for patients without acute bacterial rhinosinusitis.12 With a type I error of .05 (2-sided), a power
of 90%, and an estimated 10% dropout rate, the required sample
size was 252.
Our statistical analysis was of the intent-to-treat population and 2 subgroups: those with a positive rhinoscopy result
and those who felt restricted at baseline. The first subgroup was
prespecified when the inclusion criteria were changed. The second subgroup was not anticipated but became of interest when
10% of those recruited said before treatment that rhinosinusitis did not restrict their activities at home or work. Three regression methods were used: Cox proportional hazards regression for time to cure, linear regression for the number of days
with restrictions due to rhinosinusitis, and logistic regression
for the proportion of patients with anticipated adverse effects.
With all methods, models were fit without stepwise procedures and with a small number of prespecified covariates. Each
model included covariates for the severity of the response at
baseline, recruitment before or after the change in inclusion
criteria, open treatment, and use of concomitant medication.
Statistical analysis was performed using SAS statistical software version 8.02 (SAS Institute Inc, Cary, NC). All significant levels and confidence intervals (CIs) given are 2-sided.
RESULTS

PATIENT ENROLLMENT
AND CHARACTERISTICS
In total, 1565 patients were eligible (Figure 1). The main
reason for not participating in the trial was refused consent (441 patients: 220 definitely wanted antibiotics, 74
definitely did not want antibiotics, and 147 refused consent for other reasons). We enrolled 252 patients, and
249 (98.8%) completed the trial. One patient was randomized but never took any medication, 1 medical record was lost, and 1 patient in the placebo group had a
severe complication. Eleven patients (8.8%) in the amoxicillin-clavulanate group and 19 patients in the placebo
group (14.9%) received open antibiotic therapy. Of these
patients, 5 received open amoxicillin-clavulanate (2 patients in the intervention and 3 patients in the placebo
group); the remaining patients received antibiotics chosen by their treating physician. Thirty-nine (15.5%) of
251 patients took fewer tablets than instructed, and of
these patients 24 (61.5%) were receiving antibiotics. Compliance with the interview schedule was good: at day 7,
93.6% of all visits were within 1 day of the scheduled
date, and at days 14 and 28, 89.2% and 94.8%, respectively, of the interviews were within 1 day of the scheduled dates.
The 2 groups were similar in terms of sex, age, number of days with rhinosinusitis-related symptoms, and
clinical findings for pus under rhinoscopy and in the epipharynx, occipitomental x-ray films with fluid levels or
complete opacity, laboratory variables (CRP, leukocytes, and neutrophils), and the additional use of concomitant medication (Table 1). More than 50% of participants were women. The median number of days with

1565 Eligible Patients

1313 Not Randomized
439 Did Not Meet Inclusion Criteria
441 Refused Consent
433 Were Not Included for Other
Reasons
252 Randomized

125 Were Allocated to

AmoxicillinPotassium
Clavulanate

127 Were Allocated to Placebo

1 Never Started Treatment

124 Were Available for Analysis
122 on Day 7
124 on Day 14
11 Had Open Treatment

124 Completed Trial (Day 28)

127 Were Available for Analysis

125 on Day 7
126 on Day 14
19 Had Open Treatment
1 Had Serious Adverse Events
1 Was Lost to Follow-up
125 Completed Trial (Day 28)

Figure 1. Trial profile. Reasons for nonparticipation included the following:

not meeting inclusion criteria for 439 eligible patients (antibiotic treatment in
the previous 4 weeks, 105; chronic sinusitis, 58; recurrent infection in the
previous 4 weeks, 51; immunosuppression such as human
immunodeficiency virus, 26; pathologic findings of sinus or cavum nasi, 12;
allergic to amoxicillinpotassium clavulanate combination product, 66; age
younger than 18 years, 32; pregnancy or breastfeeding, 23; and no fluency in
national languages, 66); refused consent for 441 (wanted antibiotics, 220;
did not want antibiotics, 74; and refused consent for other reasons, 147); or
other reasons for 433 (comorbidity, organizational reasons, expected
nonadherence).

rhinosinusitis-related symptoms was 5 days in the amoxicillin-clavulanate group and 4 days in the placebo group.
In the 2 groups, 65.3% and 66.9% of patients had pus at
rhinoscopy, respectively.
PRIMARY OUTCOME
We found no difference in the time to cure between the
amoxicillin-clavulanate and placebo groups (Figure 2).
At 1 week, 29.8% and 30.7% in the amoxicillin-clavulanate
and placebo groups were cured and at 2 weeks, the corresponding figures were 76.6% and 74.0%, respectively.
In the Cox proportional analysis, with adjustment for severity of restrictions at baseline, modification of the inclusion criteria, open treatment, and concomitant medication with steam inhalation, the hazard ratio for the effect
of antibiotic treatment on time to cure was 0.99 (95%
CI, 0.68-1.45) (Table 2). In patients with a positive rhinoscopy result, the hazard ratio for time to cure was 1.28
(95% CI, 0.80-2.05), and in patients who reported restrictions at baseline, the hazard ratio was 1.23 (95% CI,
0.81-1.87). We used 0 days (since the previous interview) with restrictions due to rhinosinusitis as a definition of cure. With cure alternatively defined as a rating
of 1 on a 10-point, equal-distance scale for degree of restriction at home or work, hazards ratios for the effect
of antibiotic treatment on time to cure were 1.03 (95%
CI, 0.71-1.50) for all patients, 1.40 (95% CI, 0.88-2.25)
for those with a positive rhinoscopy result, and 1.22 (95%
CI, 0.81-1.85) for those restricted at baseline. For both

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1.00

Table 1. Characteristics of Randomized Patients

0.75

Proportion Not Cured

Characteristic

AmoxicillinPotassium
Clavulanate

Antibiotic
Placebo

Placebo

No. of patients
124
127
No. (%) of women
67 (54.0)
69 (54.3)
Age, mean (SD), y
37 (13)
37 (13)
Symptoms at baseline,
median No. of days
(quartiles)
Rhinosinusitis-related
5.0 (3.0-7.0)
4.0 (3.0-7.0)
symptoms
Putrid discharge
4.0 (2.0-7.0)
3.0 (2.0-6.0)
Cranial pain
3.0 (2.0-5.0)
3.0 (2.0-5.0)
Clinical findings at baseline,
No. (%) of patients
Positive rhinoscopy
81 (65.3)
85 (66.9)
result
Pus in epipharynx
20 (16.1)
32 (25.2)
X-ray examination
at baseline, No. (%)
of patients*
Normal sinus
50 (40.3)
57 (44.9)
Sinus with fluid levels
28 (22.5)
25 (19.7)
Sinus with complete
8 (6.5)
10 (7.9)
opacity
Laboratory parameters at
baseline, median (range)
C-reactive protein,
10 (5-214)
13 (5-177)
mg/L
Leukocytes, cells/L 8600 (3700-14 700) 8100 (3900-17 300)
Neutrophils, %
5.3 (1.6-10.4)
5.3 (0-11.9)
Concomitant medication
during trial, No. (%)
of patients
Steam inhalation
7 (5.6)
16 (12.6)
Nonsteroidal anti
10 (8.0)
12 (8.9)
inflammatory drugs
*Independent agreement by 2 radiologists.

definitions of cure, there was no evidence of correlation

between time and the Schoenfeld residuals for treatment, which suggests that a proportional hazards assumption was appropriate.
SECONDARY OUTCOMES
At 7 and 14 days, there was no statistically significant difference between amoxicillin-clavulanate and placebo in
the mean days of restrictions due to rhinosinusitis in neither the intent-to-treat population nor our subgroups. At
7 days patients with a positive rhinoscopy result had a
mean difference of 0.60 days of restrictions due to rhinosinusitis (95% CI, 1.41 to 0.21), and patients restricted at baseline had a mean difference of 0.60 days
(95% CI, 1.25 to 0.06). Two patients (1.6%) in the
amoxicillin-clavulanate group and 5 patients (4.0%) in
the placebo group had recurrent rhinosinusitis at 28 days.
At 7 and 14 days, diarrhea was significantly more
likely in the amoxicillin-clavulanate group than in the
placebo group, with odds ratios of 3.89 (95% CI, 2.097.25) and 1.71 (95% CI, 0.91-3.23) at 7 and 14 days, respectively (Table 3). Other prespecified adverse effects (abdominal pain and vaginal discharge or pruritus)

0.50

0.25

0.00
0

14

21

28

Day

Figure 2. Time to cure for patients treated with amoxicillinpotassium

clavulanate combination product or placebo, with cure defined as 0 days
(since the previous interview) during which rhinosinusitis restricted activities
at home or work.

seemed more likely in the amoxicillin-clavulanate group,

but these odds ratios were not statistically significant.
There were 4 adverse events of moderate or severe intensity that were thought to be drug related: 2 in the
amoxicillin-clavulanate group (diarrhea) and 2 in the placebo group (diarrhea and vomiting). In the placebo group,
there was 1 serious disease-related adverse event. After
2 weeks of symptomatic treatment, the patient was then
treated for 1 week with amoxicillin-clavulanate (1 g twice
daily) but experienced a brain abscess caused by an amoxicillin-clavulanatesensitive strain of Streptococcus milleri. The patient was operated on and recovered but has
a frontal syndrome. There were 2 additional serious adverse events in the placebo group, 1 myocardial infarction and 1 severe depressive episode; both were thought
to be neither disease nor drug related.
COMMENT

In this randomized controlled trial in general practice,

we were unable to show that antibiotic treatment with
amoxicillin-clavulanate improves time to cure in adults
with clinically diagnosed acute rhinosinusitis. We also
found no difference in the number of days during which
rhinosinusitis restricted activities at home or work. Patients treated with antibiotics tended to report more adverse effects, particularly diarrhea, during the first week.
Our study has several limitations. First, time to cure
could be insensitive to any treatment difference, because there were only 2 measurements during the period when cure typically takes place (within 14 days).
We decided not to use patient diaries, because we believed that patients might not complete these at the prespecified time points. In practice, this limitation is unlikely to affect the findings of our study. Any appreciable
difference in the rate of cure between amoxicillinclavulanate and placebo should have been seen at either
7 or 14 days but was not. Second, the prevalence of acute
bacterial rhinosinusitis is likely to have been lower in our
trial than anticipated. The inclusion criteria of our trial
had to be modified, because we could not recruit enough
patients with a positive rhinoscopy result. The study phy-

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Table 2. The Effect of AmoxicillinPotassium Clavulanate Relative to Placebo on Time to Cure and Mean Difference
at 7 and 14 Days in the Number of Days Where Rhinosinusitis Restricted Activities at Home or Work
No. of Patients
Group
All patients
Patients with pus in rhinoscopy
Patients restricted at baseline

Days Restricted, Mean Difference (95% CI)

Amoxicillin-Clavulanate

Placebo

Time to Cure,
HR (95% CI)*

124
81
116

127
85
111

0.99 (0.68 to 1.45)

1.28 (0.80 to 2.05)
1.23 (0.81 to 1.87)

Day 7

Day 14

0.29 (0.93 to 0.34)

0.60 (1.41 to 0.21)
0.60 (1.25 to 0.06)

0.06 (0.68 to 0.57)

0.61 (1.40 to 0.19)
0.16 (0.82 to 0.50)

Abbreviations: CI, confidence interval; HR, hazards ratio.

*Proportional hazards regression with strata (recruited before or after change in inclusion criteria) and covariates (severity of restriction at baseline, open
treatment, concominant medication, eg, steam inhalation).
Linear regression with covariates (recruited before or after change in inclusion criteria, severity of restriction at baseline, open treatment, concomitant
medication, eg, steam inhalation).

Table 3. The Effect of Treatment With AmoxicillinPotassium Clavulanate Relative to Placebo

on the Proportion of Patients With Adverse Effects at 7 and 14 Days
No. of Patients
Adverse Effect
Diarrhea
Abdominal pain
Vaginal discharge and itching

OR (95% CI) for Adverse Effects*

Amoxicillin-Clavulanate

Placebo

Day 7

Day 14

124
124
67

127
127
69

3.89 (2.09-7.25)
1.66 (0.87-3.14)
1.40 (0.50-3.94)

1.71 (0.91-3.23)
1.60 (0.81-3.15)
2.21 (0.91-5.40)

Abbreviations: CI, confidence interval; OR, odds ratio.

*Logistic regression with covariates (recruited before or after change in inclusion criteria, severity of adverse effect at baseline, open treatment, concomitant
medication, eg, use of nonsteroidal anti-inflammatory drugs).

sicians were experienced, highly motivated general practitioners trained for this trial. A lack of technical skill is
therefore unlikely to be the reason for this slow recruitment. In addition, US guidelines recommend treatment
of acute rhinosinusitis with antibiotics only after 7 days
of symptoms or in patients with severe facial pain irrespective of the duration.13 In our trial, only 32% of patients had a history of 7 days or more of rhinosinusitisrelated symptoms. Therefore, both the necessary
modification of the inclusion criteria and the short duration of symptoms suggest a lower prevalence of bacterial rhinosinusitis than planned, reducing the power
of this trial to detect differences between treatments.
We do not believe that bacterial infection with resistant strains could be an explanation for the negative
findings of this study. Amoxicillin-clavulanate shows excellent activities against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis, the most
common bacteria in upper respiratory tract infection and
acute bacterial rhinosinusitis. In Switzerland, prevalence of penicillin resistance against S pneumoniae is approximately 5% and -lactamase production in H influenzae and M catarrhalis is lower compared with most other
European countries.14
The strengths of our trial are the double-blind design with blinded outcome assessment, a high follow-up rate of more than 98%, and high external validity. We recruited all patients in a general practice setting.
Most of those who refused consent did so because they
had their own opinion about the benefit or otherwise of
antibiotics and explicitly required or declined antibiotics. We used inclusion criteria that are applicable in general practice and correspond with generally accepted pro-

cedures in general practice. We strictly limited the

inclusion criteria to clinical signs and symptoms known
to generate the highest likelihood ratio for acute bacterial rhinosinusitis when compared with the gold standard of sinus puncture.10 We also collected additional information about laboratory and x-ray data. Only 1 in 4
patients showed fluid levels or complete opacity on
x-ray films, radiologic signs that are most likely associated with bacterial rhinosinusitis.4,9,15 This underlines how
difficult it is to accurately diagnose acute rhinosinusitis
using clinical signs and symptoms.
Patients treated with amoxicillin-clavulanate were
more likely to experience adverse effects such as diarrhea and abdominal pain. Other randomized controlled
trials of antibiotic treatment for acute rhinosinusitis or
for sinusitis-like symptoms report similar findings using different antibiotics.8,11 Three placebo-controlled, randomized trials (all somewhat smaller than the present
study) have evaluated different antibiotics in general practice for the treatment of acute rhinosinusitis. Two trials
included patients based on clinical symptoms for acute
rhinosinusitis in conjunction with either radiologic signs
for maxillary sinusitis or raised values of CRP or erythrocyte sedimentation.7,16 The third trial included patients solely on the basis of clinical signs and symptoms.17 Although these studies used different diagnostic
criteria to identify patients with suspected acute bacterial rhinosinusitis, they all showed no difference in improvement of symptoms or cure rates under treatment
with antibiotics. The present study suggests that adults
with a positive rhinoscopy result who are undergoing antibiotic treatment may have fewer days during which rhinosinusitis restricts their activities at home or work. The

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expected benefit from antibiotic therapy, however, might

be at best moderate and comparable to the treatment with
neuraminidase inhibitors in patients with early symptoms from influenza.18,19 Further studies are needed using better diagnostic tests for acute bacterial rhinosinusitis. These tests might include a refined symptom score
that identifies those severely restricted by rhinosinusitis
or with a prolonged upper respiratory tract infection.
Most patients with acute rhinosinusitis are seen in
general practice. Because of the low specificity of available imaging tests, the costs, and the need to refer patients, most patients with acute rhinosinusitis in general practice do not receive a diagnostic workup that allows
the physician to accurately differentiate between acute
viral and bacterial rhinosinusitis. The decision to treat
with antibiotics is therefore based on clinical diagnostic
criteria or other reasons related to physicians or patients preferences.
CONCLUSIONS

Evidence from the present study suggests that antibiotic

treatment with amoxicillin-clavulanate offers no benefit
for adults with acute rhinosinusitis clinically diagnosed
in general practice. We conclude that antibiotics should
not be given at first to patients with acute rhinosinusitis, and symptomatic treatment is justified. This policy
should help limit the emergence of antibiotic-resistant
strains and reduce costs. Some individual patients profit
from antibiotic therapy. Whether such individuals can
be identified by clinical tests such as rhinoscopy has yet
to be shown.
Accepted for publication October 21, 2002.
BASINUS Investigators: study nurse and manager:
Christa Hugenschmidt; study physicians in general practice: Fritz Ammann, MD, Ruedi Bachmann, MD, Anselm Benz,
MD, Ruedi Burger, MD, Jadi Fabbri, MD, Remigius Faesch,
MD, Peter Flubacher, MD, Josef Forrer, MD, Daniel Gelzer,
MD, Michael Gonon, MD, Alexander Haegeli, MD, Friedrich Hugenschmidt, MD, Ruedi Isler, MD, Hanspeter Lienhardt, MD, Louis Litschgi, MD, Michael Nuscheler, MD, Christian Ott, MD, Pierre Periat, MD, Alexander Ruckstuhl, MD,
Florian Suter, MD, Claude Scheidegger, MD, Alex Schwank,
MD, Andreas Schlumpf, MD, Andreas Stoll, MD, Peter Tschudi, MD, Christoph Waldmann, MD, Jurg Weber, MD, Rolf
Wenger, MD; study physicians at the medical and otolaryngology outpatient clinics: Pia Schneider, MD, Tatiana Spicher, MD, Andreas Zeller, MD; radiologists: Monika Meier,
MD, Thomas Lacina, MD, Ulrike Otto, MD.
This study was supported by grants from GlaxoSmithKline Switzerland, Swiss Academy of the Medical Sciences
(Basel), Astra Klinik Fonds University Hospital Basel, and
Forum fur interdisziplinare Hausarztmedizin, University

of Basel. The Basel Institute for Clinical Epidemiology is

funded by santesuisse (Solothurn) and the Gottfried and
Julia Bangerter-Rhyner-Stiftung (Berne).
We thank the patients who participated in the trial
and Peter Hersberger, PhD, and Wolf Langewitz, MD, for
helping us with the patient recruitment.
Corresponding author and reprints: Heiner C. Bucher,
MD, MPH, Basel Institute for Clinical Epidemiology,
Kantonsspital Basel, Universitatskliniken, CH-4031 Basel,
Switzerland (e-mail: hbucher@uhbs.ch).

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