Impact of First-Line vs Second-Line Antibiotics for the
Treatment of Acute Uncomplicated Sinusitis
Jay F. Piccirillo, MD; Douglas E. Mager, BS; Mark E. Frisse, MD, MS,
MBA; Robert H. Brophy, MD, MS; Andrew Goggin, MD
Context Studies suggest little benefit in relief of acute sinusitis
symptoms from the use of newer and more expensive (second-line) antibiotics
instead of older and less expensive (first-line) antibiotics. However,
researchers have failed to include development of complications and cost of
care in their analyses.
Objective To compare the effectiveness and cost of first-line with
second-line antibiotics for the treatment of acute uncomplicated sinusitis in
adults.
Design, Setting, and
Patients Retrospective cohort
study using a pharmaceutical database containing demographic, clinical (International Classification of Diseases, Ninth
Revision), treatment, and charge information for 29 102 adults
with a diagnosis of acute sinusitis receiving initial antibiotic treatment
between July 1, 1996, and June 30, 1997.
Main Outcome
Measures Absence of additional
claim for an antibiotic in the 28 days after the initial antibiotic, presence
of a claim for a second antibiotic, serious complications of sinusitis, and
direct charges and use for the acute sinusitis treatment.
Results There were 17 different antibiotics prescribed in this study. The
majority (59.5%) of patients received 1 of the first-line antibiotics. The
overall success rate was 90.4% (95% confidence interval [CI], 90.0%-90.8%). The
success rate for the 17 329 patients who received a first-line antibiotic
was 90.1% and for the 11 773 patients who received a second-line
antibiotic was 90.8%, a difference of 0.7% (95% CI, 0.01%-1.40%; P<.05). There were 2 cases of
periorbital cellulitis, one in each treatment group. The average total direct
charge for patients receiving a first-line antibiotic was $68.98 and a
second-line antibiotic was $135.17, a difference of $66.19 (95% CI,
$64.95-$67.43; P<.001). This
difference was due entirely to the difference in charge of antibiotics and not
other charges, such as professional fees, laboratory tests, or emergency
department visits.
Conclusions Patients treated with a first-line antibiotic for acute
uncomplicated sinusitis did not have clinically significant differences in
outcomes vs those treated with a second-line antibiotic. However, cost of care
was significantly higher for patients treated with a second-line antibiotic.
JAMA. 2001;286:1849-1856
Sinusitis is associated with significant
morbidity, anxiety, reduced quality of life, lost time from work, and treatment
expense. It is estimated that approximately 35 million US residents have some
form of sinusitis, and in 1996 the direct cost of this disorder in the United
States was more than $3.3 billion.1 McCaig and Hughes2 analyzed National
Ambulatory Medical Care Surveys (NAMCS) data and found that acute and chronic
sinusitis was the fifth most common diagnosis for which antibiotics were
prescribed and also found an increasing trend of office visits between the
years 1980 and 1992. In 1992 alone, sinusitis accounted for 12% of all recorded
antibiotic prescriptions. There was a trend over time toward increased use of
more expensive broad-spectrum antibiotics and decreased use of less expensive
narrow-spectrum antibiotics. Ironically, this trend to prescribe more expensive
antibiotics with a broader spectrum of action occurs despite evidence that
about two thirds of patients with acute sinusitis improve or are cured without
any antibiotics.3, 4
Antibiotic selection for initial management of
acute sinusitis is controversial, and there is much variation in clinical
practice.5-8
Recommendations for antibiotics for initial treatment of acute sinusitis vary
between older less expensive antibiotics (eg, amoxicillin and
trimethoprim-sulfamethoxazole)9, 10 and newer more
expensive drugs with a broader antimicrobial spectrum (eg, clarithromycin,
amoxicillin and clavulanate, and cefuroxime).11-14 The recent
Evidence-Based Practice Center report1 and the American
College of Physicians-American Society of Internal Medicine Position Papers15, 16 both state that the
most cost-effective way to manage acute sinusitis in the community is to
initially use symptomatic treatment only (eg, decongestants, nasal steroids).
Further treatment, including the use of antibiotics,17, 18 should be guided by
clinical criteria, such as type, duration, and severity of symptoms.19
In the ambulatory care setting, the epidemic emergence
and spread of resistant bacteria are a major problem.20 Bacterial
proliferation is thought to occur as a result of the increasing use of
antibiotics, especially in the treatment of viral acute respiratory tract
infection. The increase in resistant bacteria has led to the recognition of the
need for more prudent use of antibiotics by limiting use to the treatment of bacterial
infections.21, 22 Spontaneous
resolution of symptoms, without antibiotics, occurs within 2 weeks in the
majority of patients with acute sinusitis. And although the natural history and
clinical course of acute sinusitis are quite favorable, serious sequelae and
complications (eg, meningitis, brain abscess) do occasionally occur.23, 24
The goal of this study was to use a large and
comprehensive pharmaceutical database to compare the effectiveness of
first-line and second-line antibiotics for the treatment of acute uncomplicated
sinusitis. The primary end point was the clinical response to initial treatment
with an antibiotic. The secondary end points were the development of serious
complications and cost of care. The implication of this research is that if
there is no difference in clinical response and development of complications
between patients treated with first-line antibiotics compared with those
treated with second-line antibiotics, then the least expensive (ie, first-line)
antibiotics should be chosen. Because of the large size of the database and the
inclusion of accurate clinical and charge data, all 3 important end points were
studied. The findings from this study will assist in the management of patients
with acute uncomplicated sinusitis.
Study Population
For this study, we used data from the Express Scripts Patient Treatment Episode
(PTE) registry is a relational database with more than 2.1 million covered
lives from several large health maintenance organizations. The PTE registry
includes integrated medical claims and pharmaceutical data. The study
population included insurance plan members who had an office visit with an
accompanying International Classification of
Diseases, Ninth Revision (ICD-9)
code for acute sinusitis (461.0-461.3, 461.8, or 461.9) between July 1, 1996,
and June 30, 1997, and who also had 60 days of enrollment prior to and 365 days
after the first sinusitis-associated office visit (Table 1).
Subjects were excluded if they were younger than
18 years, had an earlier diagnosis of acute sinusitis in the 60 days prior to
the index office visit, received a prescription for an antibiotic in the 60
days prior to the index office visit for a concurrent infectious disease, or
had received a diagnosis for chronic sinusitis (ICD-9, 473.0-473.9) in the study focus year. Subjects with a
diagnosis of cystic fibrosis, human immunodeficiency virus (HIV) infection, or
any other immunodeficiency were excluded. Subjects with complications of acute
sinusitis, including periorbital cellulitis, orbital cellulitis, meningitis,
and intracranial abscess, prior to the index office visit were also excluded.
Patients who received a prescription for an antibiotic in the 60 days prior to
the index office visit were excluded because the subsequent antibiotic use
during the study period may have been for the comorbid condition and not for
sinusitis. This concurrent use of antibiotic would lead to mislabeling of the
indication for and evaluation of the success of the antibiotic. Finally,
patients for whom no antibiotic was prescribed after the index office visit
were excluded. Given the structure of the database, we could not conclude with
certainty that patients who did not have a claim for an antibiotic did not
receive an antibiotic as an office sample.
Physician Type
The physician type was determined by the physician
type code attached to each office visit claim. Physician type was categorized as primary
care if the code indicated the physician was a primary care or internal
medicine physician, specialist if
the physician was an otolaryngologist, allergist, or pulmonologist, and other was selected for all other physician
types.
Antibiotics
The name and frequency of the antibiotics that were prescribed in association
with the index office visit are listed in Table 2.
The antibiotics are grouped into 2 categories: first line or second line based
on accepted treatment guidelines.1, 9
Sinusitis Classification,
Treatment, and Outcome
The classification of a sinusitis episode was determined retrospectively by the
investigators based on guidelines from the American Academy of
Otolaryngology-Head and Neck Surgery Foundation Inc19 and from previously
published standards.25, 26 Patients with asthma,
allergic rhinitis, or nasal polyps were classified as having comorbidity. The
primary treatment for the index acute sinusitis episode was either a first-line
or second-line antibiotic. Information on adjuvant symptomatic therapy,
consisting of decongestants, antihistamines, nasal steroids, or a combination
of these medications, was also included. The sinusitis episode began with the
first antibiotic prescription in a 6-day window period around the index office
visit (ie, 3 days before and 3 days after).
Treatment success was defined as the absence of
an additional claim for an antibiotic in the 28 days after the initial claim.
Treatment failure was defined as the presence of an additional claim for a
second antibiotic in the first 28 days after the initial claim. Based on
clinical experience and the published literature,1, 14, 27 the investigators
thought that a majority of episodes of additional antibiotics within the 28-day
period represent failure of symptoms to improve. A minority of episodes reflect
the development of an of the episode adverse reaction to the first antibiotic.
Relapse was defined as the presence of a claim for a second antibiotic in the
15- through 28-day period after the initial claim.
Complications of acute sinusitis (ICD-9 code) include orbital cellulitis
(376.01), periorbital cellulitis (682.0), meningitis-bacterial (320.81-320.9),
subdural abscess (324.0), intracranial abscess (324.0), subperiosteal abscess
(730.18, 730.08), orbital abscess (376.01), and cavernous sinus thrombosis
(325). A complication was recorded if a claim containing an ICD-9 code corresponding to 1 of the
conditions listed above was received within the 28-day follow-up period.
Direct Charges and Utilization
Direct charges and utilization were determined for the index episode of
sinusitis and the 28-day follow-up period. All medical claims for charges and
services attached to the ICD-9
acute sinusitis code claim were included in the direct charges and utilization
analyses. Direct prescription charges for each patient were calculated by
summing the charges for all of the study antibiotic drugs used by a patient in
the 28-day period.
Statistical Analysis
The analysis of treatment effectiveness first proceeded with an analysis of the
relationship between cogent demographic and clinical subgroups (ie, existence
of comorbidity) and category of antibiotic use (first-line or second-line) and
rate of the outcome event (success of antibiotic treatment). A t test, 2 test, and analysis of variance (ANOVA) were performed
to test the statistical significance of the observed relationships. To adjust
for inflated P values due to
multiple comparisons in the ANOVA, the Bonferonni correction was used.
Two-tailed tests of significance were used and P<.05
was selected for the level of statistical significance. Stepwise logistic
regression analysis was used to assess the impact of treatment on outcome while
controlling for the impact of baseline demographic and clinical factors.
Results are presented as differences in outcome
between treatment groups, and 95% confidence intervals (CIs) are used to
indicate the precision of the observed differences. Due to the extremely large
number of patients contained within the database and the observational nature
of the study, sample size calculations and determination of power to detect a
clinically meaningful difference were not performed prior to the start of this
study. All analyses were performed using SAS software, version 6.12 (SAS
Institute, Cary, NC).
Unfortunately, multiple logistic regression
techniques cannot discriminate between the effects of treatment and the effects
of baseline features if these features are related to both treatment selection
and outcome.28, 29 In an attempt to
control for significant factors related to treatment and outcome, Rubin28, 29 proposed the use of
propensity score technology. Propensity scores adjust for significant
characteristics of the patient or provider that are related to the choice of a
particular treatment (eg, antibiotic) and outcome. In this study, multivariable
analysis was used to determine the factors related to the use of antibiotics
(first line vs second line) and propensity scores were used to allow for a more
valid comparison of the effectiveness of these 2 groups of antibiotics.
The propensity scores analysis was performed by
examining in a stepwise multivariable logistic regression analysis the
association between cogent baseline demographic and clinical variables and the
decision to prescribe a first-line or second-line antibiotic. The independent
variables were selected based on significance in the univariate analyses (P<.01) and included age, physician
type, use of symptomatic therapy, and concurrent existence of comorbidity
diagnosis. The reference level for the dependent variable was the use of
first-line antibiotic treatment. The logistic regression analysis was used to
determine the probability of first-line vs second-line antibiotic treatment
(ie, propensity score). The c
statistic associated with the logistic regression model of antibiotic category
was 0.552. The propensity score was then divided into quintiles with the
highest quintile describing those subjects most likely to receive first-line
antibiotics. As a validation of the propensity score, the prevalence of all
independent variables was calculated by treatment class and quintile. In this
study, the prevalence of our independent variables was consistent between
treatment classes within each quintile. Because of variation in treatment not
controlled for in the propensity scores analysis (eg, patient preference), a
significant number of subjects within each quintile did not receive the
treatment suggested by the propensity score. This variation in treatment within
each propensity quintile allowed for the comparison of success rates between
subjects who received first-line antibiotics and those who received second-line
antibiotics (ie, treatment effectiveness).
Description of the Population
The study population of 29 102 adults with an ICD-9 diagnosis code of acute sinusitis was drawn from a
larger sample of 88 403 subjects. The largest numbers of patients were
excluded either because they did not have a claim for receiving an antibiotic
during the episode period (17 627) or had received an antibiotic during
the 60-day preperiod (12 092) (Table 1).
The use of office antibiotic samples is 1 reason a patient with a diagnosis of
acute sinusitis may not have an associated claims record for an antibiotic
prescription.
Distribution of First-Line and
Second-Line Antibiotics
The list of 17 different antibiotics that the study subjects received and the
frequency of use is shown in Table 2.
The antibiotics are divided into first-line and second-line therapy.
Amoxicillin was the most frequently prescribed (39.6%),
trimethoprim-sulfamethoxazole was the second most frequently prescribed
(15.9%), and clarithromycin was the third most frequently prescribed (9.8%).
The majority of patients (59.5%) received 1 of the first-line antibiotic
agents. Surprisingly, a large number of patients (32%) received 1 of the
antibiotics that are not approved for the treatment of sinusitis by the US Food
and Drug Administration (FDA).
There was large variation in the frequency of
antibiotic prescriptions throughout the year. As expected, the number of
antibiotic prescriptions was greatest between the months of November and March.
The frequency of antibiotic prescriptions throughout the year was similar
between first- and second-line antibiotics.
Relationship Between Patient
and Provider Characteristics and Treatment
The relationship between patient and provider characteristics and use of first-
or second-line antibiotic is shown in Table 3.
The relationship between the first-line vs second-line antibiotic use was
approximately the same for men (59.2% vs 40.8%) as for women (59.7% vs 40.3%).
The mean age was approximately the same within the 2 antibiotics groups
(first-line, 38.1 vs second-line, 38.9).
The use of first-line and second-line
antibiotics was different based on physician type (primary care vs specialty),
use of adjuvant symptomatic therapy, and presence of concurrent diagnosis
comorbidity. Primary care physicians were more likely to prescribe first-line
antibiotics (60.3%) while specialists were more likely to prescribe second-line
antibiotics (63.5%). Patients who received adjuvant symptomatic therapy were
more likely to receive first-line antibiotics. Patients who had comorbidity
were also more likely to receive second-line antibiotics.
Treatment Outcomes
The overall treatment outcomes and outcomes according to patient
characteristics and antibiotic group are shown in Table 4.
The overall success rate was 90.4%, (95% CI, 90.0%-90.8%), failure rate was
3.4%, and relapse rate was 6.3%. Men had a statistically significantly higher
success rate than women (91.9% vs 89.6%; difference, 2.3%; 95% CI, 1.6%-3.0%; P<.001) and lower relapse rate (4.9% vs
6.9%) than women. The mean age of the patients classified as a success was
statistically significantly lower than the mean age of the patients classified
as a failure (38.3 vs 39.5 years; difference 1.1 years; 95% CI, 0.7-1.5; P<.001). Patients who had a concurrent
diagnosis of a comorbid ailment had a significantly lower success rate than
those patients without a comorbid ailment (85.1% vs 90.6%; difference, 5.5%;
95% CI, 3.8%-7.2%; P<.001).
The success rate for the 17 329 patients
who had received first-line antibiotics was 90.1%, and for the 11 773
patients who received a second-line antibiotic, it was 90.8%, a difference of
0.7% (95% CI, 0.0%-1.4%; P<.05).
Among patients who received first-line antibiotics, the relapse rate was 3.3%
and for patients who received second-line antibiotics, the rate was 3.5%. Given
this small absolute difference in success rates between patients treated with a
first-line vs a second-line antibiotic, 131 patients must be treated with a
second-line antibiotic to obtain 1 additional cure had all 29 102 patients
received a first-line antibiotic.
Direct Charges
The average total direct charges and breakdown of charges by setting according
to antibiotic class are shown in Table 5.
As can be seen, the average total direct charges for patients who received
first-line antibiotics was $68.98 while the amount for patients who received
second-line therapy was $135.17. The difference in charges was $66.19 (95% CI,
$64.95-$67.43; P<.001). Based
on the average charges for patients treated with first-line and second-line
antibiotics, an additional $8737 per success is spent when a second-line
antibiotic is chosen rather than a first-line antibiotic. As shown in the
breakdown of charges, this large difference is due entirely to differences in
the cost of prescription therapy and not for other services, such as
professional visits, tests, laboratory or pathology, medical or surgical, or
emergency department visits.
Propensity Scores Analysis
In Table 6,
the results of propensity scores analysis are shown. As described in the
"Methods" section, the propensity scores analysis used logistic
regression analysis to divide the patients into quintiles based on the
propensity to receive a particular category of antibiotic (eg, first-line or
second-line). The probability that a patient would receive a first-line
antibiotic (as opposed to second-line antibiotic) increased from quintile 1 to
quintile 5. Success, failure, and relapse rates for patients treated with
first-line and second-line antibiotics were determined within each quintile
group. Average direct charges for patients receiving first-line and second-line
antibiotics were compared within quintile group and are also presented in Table 6.
There is no consistent pattern of difference in
success, failure, or relapse rates between first-line and second-line
antibiotics across the different quintiles. With the exception of the second
quintile, the success rates between first-line and second-line antibiotics are
not statistically different within each quintile. However, within each
quintile, the average direct charges are very different between patients
receiving first-line or second-line therapy. In each quintile, patients who
received first-line therapy had a statistically significant lower average
charge.
Complication Rates
There were 2 patients who developed a complication of acute sinusitis in the
28-day follow-up period. In both cases, the complication was periorbital
cellulitis. One patient had received a first-line antibiotic while the other
received second-line therapy.
In this study, patients with acute uncomplicated
sinusitis were prescribed a wide range of different antibiotics, many without
FDA approval for use in acute sinusitis. The overall success rate was quite
high and there was no clinically significant difference in success rates among
patients treated with first-line and second-line antibiotics. Two patients
developed periorbital cellulitis, one in each treatment group. There were
significant differences in average charges between patients treated with first-line
antibiotics vs patients treated with second-line antibiotics. This large
difference in charge was due entirely to the category of antibiotic. The
results of this study have a direct effect on the care of patients with acute
uncomplicated sinusitis.
The findings of this study agree with those of
de Bock et al,9 who performed a
meta-analysis of 16 randomized controlled trials of antibiotic treatments for
3358 patients with acute sinusitis. They found 14 different antibiotic
combinations used in these 16 studies. The overall clinical cure rate (defined
as complete recovery with absence of all signs and symptoms) was 69%, success
rate (defined as either clinical cure or clinical improvement) was 92%, and the
adverse event rate was 2.4%. However, one study30 included in the
meta-analysis demonstrated the superiority of cefpodoxime, an antibiotic stable
in the presence of -lactamase enzymes,
to cefaclor, an antibiotic that is not stable. de Brock et al concluded that
nearly all antibiotics were of comparable effectiveness and therefore price
alone could dictate choice of antibiotic treatment. They also acknowledged the
self-limited nature of acute uncomplicated sinusitis. In another study, de Bock
et al31 used data from
clinical trials to develop a cost-effectiveness model to determine which
treatment strategy was preferred in acute sinusitis. They concluded that
postponing antibiotics for 1 week and thereby prescribing them selectively
rather than prescribing them immediately was the most cost-effective strategy.
Williams et al32 performed a
meta-analysis of 32 trials involving 7330 subjects on the role of antibiotics
for acute sinusitis confirmed by radiograph or sinus aspiration. Of the 32
trials, 5 compared antibiotic with no antibiotic use. Compared with no
antibiotic, penicillin improved clinical cure (relative risk [RR], 1.72; 95%
CI, 1.00-2.96) while amoxicillin did not (RR, 2.06; 95% CI, 0.65-6.53). Garbutt
et al33 conducted a
randomized placebo-controlled trial of the effectiveness of antibiotics for 188
patients between the ages of 1 and 18 years with clinically diagnosed acute
sinusitis. Neither amoxicillin nor amoxicillin-clavulanate offered any clinical
benefit compared with placebo.
The findings of this study generally agree with
the recent recommendations of the American College of Physicians-American
Society of Internal Medicine Clinical Practice Guideline15, 16 and the Agency for
Health Care Policy and Research report on the diagnosis and treatment of acute
bacterial rhinosinusitis.1 Both the guideline and
the report state that symptomatic treatment and reassurance is the preferred
initial management strategy for patients with mild symptoms. Antibiotics should
be reserved for patients with moderately severe symptoms that have lasted more
than 7 days and for those with severe symptoms, regardless of duration of
illness. Indiscriminate use of antibiotics in ambulatory practice has
contributed to the emergence and spread of antibiotic-resistance bacteria,21, 22 allergic reactions,
and drug-drug interactions. Antibiotics with the most narrow spectrum and are
active against the likely pathogens, Streptococcus
pneumoniae and Haemophilus influenzae,
should be used.16 The duration
of antibiotic use will also effect the development of resistance, and a
recently published study34 suggests that
short-course high-dose amoxicillin therapy may minimize the impact of
antibiotic use on the spread of resistant pneumococci. These recommendations
are based on the fact that most cases of acute, community-acquired sinusitis
are preceded by viral upper respiratory tract infections and only 0.2% to 2% of
viral infections are complicated by bacterial sinusitis.35, 36
The analysis of the effectiveness of different
treatments from an observational database is challenging due to the potential
for bias and confounding, both of which are more likely to occur in
observational research than in controlled clinical trials.37 In this study,
potential sources of error included the inability to classify the severity of
the index sinusitis episode, the variation in the treatment patterns of
physicians regardless of the severity of illness of the patient, associated
comorbidities, and seasonal patterns. These factors may be related both to the
choice of antibiotics and the success of treatment. Using propensity scores
analysis to control for features that were related to the use of a particular
type of antibiotic, there was no significant difference in success rates for
patients treated with first-line or second-line antibiotics. However, the large
differences in charges between patients receiving first-line and second-line
antibiotics remained.
There are several limitations to this research.
First, the cohort was defined based on the ICD-9
code assigned at the time of office visit. The accuracy of this diagnosis was
not confirmed, and it is possible that patients with other conditions, such as
viral upper respiratory illness, may be included in this study. In fact, given
the higher success rate observed in this study than in studies in which the
diagnosis of acute bacterial sinusitis is confirmed4, 38, 39 suggests that
patients with viral illness were included in this study. We were unable to
estimate the magnitude of this misclassification in this study, although van
Buchem et al4 found that
approximately 45% of 488 patients presenting to general practitioners with
symptoms suggestive of acute maxillary sinusitis had normal sinus radiographs.
Furthermore, it is possible, although unlikely, that physicians used first-line
antibiotics for patients suspected of viral illness while reserving second-line
therapy for patients suspected of bacterial sinusitis. If this selective use of
antibiotics did occur, then it is possible that a true antibiotic treatment
effect was missed. Unfortunately, in this study, we were unable to investigate
the outcomes of patients who did not receive an antibiotic because we could not
be certain that those patients for whom an antibiotic claim was not attached to
an office visit claim had not in fact received an office antibiotic sample.
Information about the use of office antibiotic sample or adjuvant therapy
samples was not obtained, and this failure could have led to underreporting of
medication use.
The clinical severity of sinusitis is defined by
the frequency and severity of symptoms, past history of response to
antibiotics, recent use of antibiotics, severity of structural abnormalities
within the nasal cavity, severity of abnormalities as defined by computed
tomography, presence of concomitant diseases such as allergic rhinitis, nasal
polyps, and asthma, and use of tobacco products or exposure to nasal irritants.
Some, but not all, of these features were captured by the ICD-9 coding available for this study.
Important clinical features of the patient not included in this study affected
the accuracy of the prognostic stratification obtained through the propensity
analysis. Imprecision in the definition of clinical severity will decrease the
ability to detect true clinical effects of first-line and second-line
antibiotics. Differences in clinical severity may explain the differences in
the use of first-line and second-line antibiotics between primary care and
speciality physicians. The patients who seek care from a specialist may, in one
or more ways, be more ill than patients who seek care from a primary care
physician.
There are no widely agreed on standard ways, at
present, to assess treatment success, failure, or relapse for acute sinusitis.
For most patients, the main effect of acute sinusitis is the production of
symptoms that decrease quality of life, interfere with work or school, and may,
in rare circumstances, result in hospitalization. The ideal outcome measure
would incorporate patient-based measures of disease-specific functional status
and quality of life.40, 41 All outcome measures
used in this study (success, failure, cost of care, and complications) were
derived from claim records contained within the PTE database. No measures of
symptoms, functional status, or quality of life were used. Although these
outcome measures are clinically important, the authors do not believe that the
incorporation of these measures in this study would undermine the central
conclusions. Since sinusitis symptoms usually persist over a matter of weeks
with gradual diminution over time, an analysis that reflected the impact of
symptoms over time (eg, life table or Kaplan-Meier analysis) would be better
than relying on a one-time snapshot of clinical response.
In conclusion, it appears that there is no
incremental clinical benefit of newer, more expensive second-line antibiotics
over older less expensive first-line antibiotics for patients with acute
uncomplicated sinusitis. Due to the higher expense and potential for the
development of resistant bacteria, physicians should avoid prescribing
second-line antibiotics as the initial antibiotic treatment. Health departments,
physician specialty organizations, managed care organizations, pharmacy
benefits managers, and industry should promote recommendations for the use of
narrow-spectrum, less expensive antibiotics (eg, amoxicillin,
trimethoprim/sulfamethoxazole, or erythromycin) rather than broader-spectrum,
more expensive antibiotics. It seems that there is a significant opportunity to
improve patient care and decrease costs through more judicious use and
selection of antibiotics.
Author/Article Information
Author Affiliations: Division of
Clinical Outcomes Research, Department of Otolaryngology-Head and Neck Surgery
(Dr Piccirillo), Washington University School of Medicine, St Louis, Mo (Dr
Brophy); Express Scripts Inc, Maryland Heights, Mo (Drs Frisse and Goggin and
Mr Mager).
Corresponding Author and Reprints:
Jay F. Piccirillo, MD, Department of Otolaryngology-Head and Neck Surgery,
Washington University School of Medicine, Campus Box 8115, 660 S Euclid Ave, St
Louis, MO 63110 (e-mail: [log in to unmask]).
Author Contributions: As principal investigator, Dr Piccirillo had full access to all
of the data and takes full responsibility for the integrity of the data and the
accuracy of the data analysis.
Study concept and design: Piccirillo, Mager, Frisse, Brophy, Goggin.
Acquisition of data: Piccirillo, Mager.
Analysis and interpretation of
data: Piccirillo, Mager,
Brophy.
Drafting of the manuscript: Piccirillo, Mager, Brophy, Goggin.
Critical revision of the
manuscript for important intellectual content: Piccirillo, Mager, Frisse, Brophy.
Statistical expertise: Piccirillo, Mager, Brophy.
Obtained funding: Frisse.
Administrative, technical, or
material support: Frisse, Brophy
Study supervision: Frisse, Goggin.
Funding/Support: This research was supported by Express Scripts Inc, St Louis, Mo,
an independent pharmacy benefits manager. As such, Express Scripts Inc research
programs are not obligated to any health care provider or pharmaceutical
company.
Acknowledgment: We thank Edward L. Spitznagel, Jr, PhD, Professor of Mathematics,
Washington University in St Louis for his statistical assistance. Throughout
the research process several other Express Scripts Inc employees were involved
in this project. During the design and conduct of the study, the coauthors had
several meetings with Larry Adamovic, project manager, who assisted with
planning the project. Yakov Svirnovskiy, Dolly Mathew, and Christine Terry
worked on patient identification, data collection, data integrity, and other
issues related to data quality assurance. Brenda Motheral provided research
feedback and edited the first draft of the manuscript. Fred Teitelbaum, PhD,
provided input on manuscript preparation and provided approval on the final
manuscript.
Financial Disclosure: Dr Piccirillo had served as a consultant to Express Scripts Inc.
1.
Agency for Health Care Policy and Research.
Diagnosis and Treatment of Acute Bacterial
Rhinosinusitis.
Rockville, Md: Agency for Health Care Policy and Research; 1999. Summary,
Evidence Report/Technology Assessment No. 9.99-E015.
2.
McCaig LF, Hughes JM.
Trends in antimicrobial drug prescribing among office-based physicians in the
United States.
JAMA.
1995;273:214-219.
MEDLINE
3.
Mann W, Jonas I.
Untersuchungen zur Spontanheilung der Sinusitis maxillaris [A study of
spontaneous cure of sinusitis (author's translation)].
HNO.
1981;29:92-94.
MEDLINE
4.
van Buchem FL, Knottnerus JA, Schrijnemaekers VJ, Peeters MF.
Primary-care-based randomised placebo-controlled trial of antibiotic treatment
in acute maxillary sinusitis.
Lancet.
1997;349:683-687.
MEDLINE
5.
de Bock GH, Kievit J, Mulder JD.
Acute maxillary sinusitis in general practice: a decision problem.
Scand J Prim Health Care.
1994;12:9-14.
MEDLINE
6.
Williams JW, Holeman DR, Samsa GP, Simel DL.
Randomized controlled trial of 3 vs 10 days of trimethoprim/sulfamethoxazole
for acute maxillary sinusitis.
JAMA.
1995;273:1015-1021.
MEDLINE
7.
Bro F, Mabeck CE.
Variation in use of penicillin for treatment of sinusitis in general practice.
Scand J Prim Health Care.
1988;6:175-178.
MEDLINE
8.
Poole MD.
A focus on acute sinusitis in adults: changes in disease management.
Am J Med.
1999;106:38S-47S.
MEDLINE
9.
de Bock GH, Dekker FW, Stolk J, Springer MP, Kievit J, van Houwelingen JC.
Antimicrobial treatment in acute maxillary sinusitis: a meta-analysis.
J Clin Epidemiol.
1997;50:881-890.
MEDLINE
10.
de Ferranti SD, Ioannidis JP, Lau J, Anninger WV, Barza M.
Are amoxycillin and folate inhibitors as effective as other antibiotics for
acute sinusitis: a meta-analysis.
BMJ.
1998;317:632-637.
MEDLINE
11.
Adelglass J, Bundy JM, Woods R.
Efficacy and tolerability of cefprozil versus amoxicillin/clavulanate for the
treatment of adults with severe sinusitis.
Clin Ther.
1998;20:1115-1129.
MEDLINE
12.
Burke T, Villanueva C, Mariano H Jr, et al, for the Sinusitis Infection Study
Group.
Comparison of moxifloxacin and cefuroxime axetil in the treatment of acute
maxillary sinusitis.
Clin Ther.
1999;21:1664-1677.
MEDLINE
13.
Adelglass J, DeAbate CA, McElvaine P, Fowler CL, LoCocco J, Campbell T.
Comparison of the effectiveness of levofloxacin and amoxicillin-clavulanate for
the treatment of acute sinusitis in adults.
Otolaryngol Head Neck Surg.
1999;120:320-327.
MEDLINE
14.
Sinus and Allergy Health Partnership.
Antimicrobial treatment guidelines for acute bacterial rhinosinusitis.
Otolaryngol Head Neck Surg.
2000;123:5-31.
15.
Hickner JM, Bartlett JG, Besser RE, et al.
Principles of appropriate antibiotic use for acute rhinosinusitis in adults:
background.
Ann Intern Med.
2001;134:498-505.
MEDLINE
16.
Snow V, Mottur-Pilson C, Hickner JM, et al.
Principles of appropriate antibiotic use for acute sinusitis in adults.
Ann Intern Med.
2001;134:495-497.
MEDLINE
17.
Kennedy DW.
Meeting the goals of therapy for sinusitis: conclusion.
Otolaryngol Head Neck Surg.
1990;103:887.
MEDLINE
18.
Williams JW, Simel DL.
Does this patient have sinusitis: diagnosing acute sinusitis by history and
physical examination.
JAMA.
1993;270:1242-1246.
MEDLINE
19.
Lanza DC, Kennedy DW.
Adult rhinosinusitis defined.
Otolaryngol Head Neck Surg.
1997;117:S1-S7.
MEDLINE
20.
Gonzales R, Bartlett JG, Besser RE, et al.
Principles of appropriate antibiotic use for treatment of acute respiratory
infections in adults: background, specific aims, and methods.
Ann Intern Med.
2001;134:479-486.
MEDLINE
21.
Levy SB.
The challenge of antibiotic resistance.
Sci Am.
1998;278:46-53.
MEDLINE
22.
Dowell SF, Butler JC, Giebink GS, et al.
Acute otitis media: management and surveillance in an era of pneumococcal
resistance: a report from the Drug-resistant Streptococcus pneumoniae
Therapeutic Working Group.
Pediatr Infect Dis J.
1999;18:1-9. [published correction appears in Pediatr
Infect Dis J. 1999;18:341].
MEDLINE
23.
Wagenmann M, Naclerio RM.
Complications of sinusitis.
J Allergy Clin Immunol.
1992;90:552-554.
MEDLINE
24.
Mansfield EL, Gianoli GJ.
Intracranial complications of sinusitis.
J La State Med Soc.
1994;146:287-290.
MEDLINE
25.
McCombs JS, Nichol MB.
The use of first and second-line outpatient antibiotics under the Saskatchewan
Drug Plan.
Pharmacoeconomics.
1995;7:543-544.
MEDLINE
26.
Halpern M, Schmier J, Richner R, Togias A.
Antimicrobial treatment patterns, resource utilization, and charges associated
with acute sinusitis in asthma patients.
Am J Health Syst Pharm.
2000;57:875-881.
MEDLINE
27.
Report of the Rhinosinusitis Task Force Committee Meeting.
Otolaryngol Head Neck Surg.
1997;117:S1-S68.
28.
Rubin DB.
Estimating causal effects from large data sets using propensity scores.
Ann Intern Med.
1997;127:757-763.
MEDLINE
29.
Rubin DB, Schenker N.
Multiple imputation in health-care databases: an overview and some
applications.
Stat Med.
1991;10:585-598.
MEDLINE
30.
Gehanno P, Depondt J, Barry B, Simonet M, Dewever H.
Comparison of cefpodoxime proxetil with cefaclor in the treatment of sinusitis.
J Antimicrob Chemother.
1990;26(suppl E):87-91.
MEDLINE
31.
de Bock GH, van Erkel AR, Springer MP, Kievit J.
Antibiotic prescription for acute sinusitis in otherwise healthy adults.
Scand J Prim Health Care.
2001;19:58-63.
MEDLINE
32.
Williams JW Jr, Aguilar C, Makela M, Cornell J, Hollman DR, Chiquette E, Simel
DL.
Antibiotics for acute maxillary sinusitis [Cochrane Review on CD-ROM].
Oxford, England: Update Software; 2001: Issue 3.
33.
Garbutt JM, Goldstein M, Gellman E, Shannon W, Littenberg B.
A randomized, placebo-controlled trial of antimicrobial treatment for children
with clinically diagnosed acute sinusitis.
Pediatrics.
2001;107:619-625.
MEDLINE
34.
Schrag SJ, Pena C, Fernandez J, et al.
Effect of short-course, high-dose amoxicillin therapy on resistant pneumococcal
carriage: a randomized trial.
JAMA.
2001;286:49-56.
ABSTRACT
| FULL TEXT
| PDF
| MEDLINE
35.
Dingle JH, Badger GF, Jordan WS Jr.
Illness in the Home: A Study of 25,000
Illnesses in a Group of Cleveland Families.
Cleveland, Ohio: Press of Case Western Reserve University; 1964:347.
36.
Berg O, Carenfelt C, Rystedt G, Anggard A.
Occurrence of asymptomatic sinusitis in common cold and other acute
ENT-infections.
Rhinology.
1986;24:223-225.
MEDLINE
37.
Horwitz RI, Viscoli CM, Clemens JD, Sadock RT.
Developing improved observational methods for evaluating therapeutic
effectiveness.
Am J Med.
1990;89:630-638.
MEDLINE
38.
Edelstein DR, Avner SE, Chow JM, et al.
Once-a-day therapy for sinusitis: a comparison study of cefixime and
amoxicillin.
Laryngoscope.
1993;103:33-41.
MEDLINE
39.
Lindbaek M, Hjortdahl P, Johnsen UL.
Randomised, double blind, placebo controlled trial of penicillin V and
amoxycillin in treatment of acute sinus infections in adults.
BMJ.
1996;313:325-329.
MEDLINE
40.
Piccirillo JF, Edwards D, Haiduk A, Yonan C, Thawley SE.
Psychometric and clinimetric validity of the 31-item rhinosinusitis outcome
measure (RSOM-31).
Am J Rhinol.
1995;9:297-306.
41.
Benninger MS, Senior BA.
The development of the Rhinosinusitis Disability Index.
Arch Otolaryngol Head Neck Surg.
1997;123:1175-1179.
MEDLINE
Edward E.
Rylander, M.D.
Diplomat American
Board of Family Practice.
Diplomat American
Board of Palliative Medicine.