Evidence Report/Technology Assessment: Number 124
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Under its Evidence-based Practice Program, the Agency for Healthcare Research and Quality (AHRQ) is developing scientific information for other agencies and organizations on which to base clinical guidelines, performance measures, and other quality improvement tools. Contractor institutions review all relevant scientific literature on assigned clinical care topics and produce evidence reports and technology assessments, conduct research on methodologies and the effectiveness of their implementation, and participate in technical assistance activities.
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Introduction / Methods / Results / Discussion / Future Research / Availability of Full Report / References
Authors: Ip S, Fu L, Balk E, Chew P, DeVine D, Lau J
This is an update of the original evidence
report, Diagnosis and Treatment of Acute Bacterial
Rhinosinusitis, published in March 1999 by the
Agency for Health Care Policy and Research.1
Our objective is to summarize and analyze
comparative studies on the antibiotic efficacies in
the treatment of acute bacterial sinusitis.
research questions in this evidence report are:
- Given a clinical diagnosis of acute bacterial rhinosinusitis, what are the comparative efficacies of the antibiotics in resolving symptoms and preventing complications or recurrence?
- Is there evidence that duration of antibiotic treatment in acute bacterial rhinosinusitis affects efficacy?
- What adverse effects are reported for antibiotics used for acute bacterial rhinosinusitis?
- How does the introduction of the pneumococcal vaccine affect the resistance patterns of pneumococcus and the treatment decisions in acute bacterial rhinosinusitis?
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Acute bacterial rhinosinusitis is defined by
clinical signs and symptoms of inflammation of
sinuses and nasal passages of less than 30 days.
Cure, improvement, and treatment failure
definitions are based on the original reports.
Studies of subjects with either acute sinusitis or
acute exacerbation of chronic sinusitis were
included. Studies of sinusitis with complications,
those that exclusively evaluated chronic sinusitis
and studies of acute sinusitis along with other
respiratory infections were excluded.
- Pertinent to the research questions.
- Included subjects with acute rhinosinusitis or acute exacerbation of chronic sinusitis.
- Any age group.
- Included at least 10 subjects in each arm.
- Comparative studies for the evaluation of antibiotic efficacy (Non-comparative studies were included in the review of adverse events only).
- Reported clinical and/or radiological and/or microbiological failures.
- Studies that included only patients with chronic sinusitis.
- Studies that included other upper respiratory infections in addition to acute sinusitis.
Search Strategy and Retrievals
We searched MEDLINE® using a broad
search strategy covering the period from 1997 to
September 2004. The search terms were:
"sinusitis," "rhinosinusitis," "anti-bacterial agents,"
"anti-infective agents" and other relevant terms.
We limited the search results to human studies
and English-language studies. We conducted a
separate search using terms such as "vaccines" and
"pneumococcal vaccine" to look for studies to
address the question of pneumococcal vaccine
and sinusitis. This separate search identified a
total of 273 abstracts for screening. None of these
qualified for inclusion in this update. We also
sought additional articles by reviewing reference
lists of selected review articles and meta-analyses
and contacting members of the Technical Expert
Panel. We did not seek unpublished studies.
We constructed an antibiotic comparative matrix to assess
the feasibility of performing meta-analyses of clinical failure.
We determined that it would be feasible to compare the
efficacy of antibiotics with placebo, as well as four different
antibiotic classes with each other. Comparisons were made
between amoxicillin-clavulanate, cephalosporins, quinolones
and the combined category of macrolides, azalides and ketolide.
We calculated the risk ratios and risk differences for clinical
failure. All meta-analyses were performed using a random
Adverse Events Data Extraction
Adverse event data were extracted from the antibiotic
comparison studies that met the inclusion criteria. In addition,
adverse event data were also taken from non-comparative
antibiotic studies that reported this data. We abstracted for each
study the percentage of subjects who experienced at least one
adverse event, the percentage who withdrew from a study due
to adverse events, the percentage with severe adverse events and
the percentage who experienced gastrointestinal, central
nervous system, skin/extremity and/or cardiovascular events.
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The MEDLINE® search identified 704 abstracts. After
screening the abstracts, 87 articles were retrieved for further
evaluation. A total of 39 studies ultimately qualified for
inclusion in this update. These trials enrolled 15,739 subjects
from 1997 to 2004 and studied antibiotic comparisons in
treatment of acute bacterial rhinosinusitis. With the exception
of five studies that did not provide the information, all the
studies were either funded by pharmaceutical companies or had
authors associated with the pharmaceutical industries. No study
exclusively evaluated a pediatric population. The classes of
antibiotics studied consist of penicillins, cephalosporins,
macrolides, azalides, ketolides, quinolones, carbapenems and
tetracyclines. There were 22 comparisons with
amoxicillin/clavulanate and only five comparisons with
Overall, antibiotics were more effective than placebo,
reducing the risk of clinical failure by about 25 to 30 percent
within 7 to 14 days after treatment initiation (p<0.01).
However, symptoms improved or were resolved in 65 percent
of patients without any antibiotic treatment at all (95% CI, 40-
91%). Amoxicillin-clavulanate, compared to antibiotics in the
cephalosporin class, was 41 percent more effective in reducing
clinical failure within 10 to 25 days after treatment initiation
(p=0.01). In absolute terms, this means treating 100 patients
with antibiotics in the cephalosporin class will lead to 3.5 more
failures (95% CI, 0.86 to 6) as compared to amoxicillin-clavulanate.
The results 24 to 45 days after treatment initiation,
however, did not show significant difference (p=0.5). There was
no consistent trend observed when comparing amoxicillin-clavulanate,
cephalosporins and quinolones to the group
encompassing macrolides, azalides and ketolides.
There are eight studies that reported data on comparison of
treatment duration with outcome efficacy. One study showed
that 10 days vs. 5 days of amoxicillin-clavulanate 500 mg three
times a day showed a non-significant 28 percent reduction in
clinical failure rate.2 Two studies on 10 days vs. 5 days of
telithromycin showed that the clinical failure rate between the
two treatment durations was comparable.3,4 The studies on
gemifloxacin (5 days vs. 7 days),5 azithromycin (3 days vs. 6
days),6 and gatifloxacin (5 days vs. 10 days)7 showed therapeutic
equivalence of the two durations.
Thirty-four comparative trials and five non-comparative
trials reported adverse events. Descriptions of adverse events
were diverse among studies. It was not possible to make
meaningful comparisons of adverse event rates across different
antibiotic classes given the enormous variation in the reported
rate of adverse events within the same antibiotic class. For
example, the reported rate of diarrhea with amoxicillin-clavulanate
across different studies ranged from under 2 percent
to more than 30 percent. Overall, the most common adverse
events involved the gastrointestinal and the central nervous
system. Severe adverse events were rare, occurring in less than
10 percent of any given study population. We did not identify
any article in our literature search that directly addressed the
effect of pneumococcal vaccine in the treatment of acute
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- About two-thirds of the patients receiving placebos recovered without antibiotics.
- Antibiotic is more effective than placebo.
- Amoxicillin-clavulanate is more effective than cephalosporin in the short-term followup.
- There are no significant differences between other classes of antibiotics.
- There is a lack of studies that compare newer antibiotics with inexpensive ones like amoxicillin and trimethoprim/sulfamethoxazole.
Heterogeneous study population and definitions of clinical
success/failure across studies, studies powered primarily for
non-inferiority rather than superiority, few studies within each
comparison grouping, and the possibility of publication bias all lend limitations to our meta-analyses. Sinus aspirations and
cultures, the gold standard for diagnosing and assessing
bacterial sinusitis were performed in a minority of trials.
Almost all the studies that were sponsored by pharmaceutical
companies concluded that the sponsored drug was either
superior or therapeutically equivalent to the comparator. In
actuality, virtually all the studies demonstrate non-inferiority
only. It is possible that there may be unpublished trials with
negative results. This could be a continual limitation if
mandatory registration of drug trials is not implemented.
notable omission compared to our previous report is the lack of
comparative studies between newer expensive antibiotics and
older inexpensive ones (like amoxicillin and
trimethoprim/sulfamethoxazole). This is an important issue to
be addressed for health care cost containment.
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Future trials should incorporate bacteriologic data to help
characterize the changing epidemiology of acute bacterial
rhinosinusitis. In order to make meaningful comparisons across
studies, there should be general agreement in defining
inclusion/exclusion criteria, clinical success/failure, and the
appropriate time of outcome assessment. To reduce the
possibility of bias, the intent-to-treat population should be
uniformly defined across studies and data should be collected
and reported in addition to per-protocol results. Also, results
from all drug trials should be duly reported. Prevalence of
different pneumococcal serotypes and their resistance patterns
will have to be continually monitored to help guide the optimal
treatment of acute bacterial rhinosinusitis.
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Availability of Full Report
The full evidence report from which this summary was taken
was prepared for the Agency for Healthcare Research and
Quality (AHRQ) by the Tufts-New England Medical Center
Evidence-based Practice Center under Contract No. 290-02-0022. Printed copies may be obtained free of charge from the
AHRQ Publications Clearinghouse by calling 800-358-9295.
Requesters should ask for Evidence Report/Technology
Assessment No. 124, Update on Acute Bacterial Rhinosinusitis.
The Evidence Report is also online on the National Library of Medicine Bookshelf, or can be downloaded as a PDF File (680 KB). Plugin Software Help.
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1. Lau J, Zucker DR, Engels EA, et al. Diagnosis and treatment of acute bacterial rhinosinusitis. Evidence Report/Technology Assessment No. 9. (Prepared by Tufts-New England Medical Center under Contract 290-97-0019.) AHCPR Publication No. 99-E016. Rockville, MD: Agency for Health Care Policy and Research. March 1999.
2. Gehanno P, Beauvillain C, Bobin S, et al. Short therapy with amoxicillin-clavulanate and corticosteroids in acute sinusitis: results of a multicentre study in adults. Scand J Infect Dis 2000;32(6):679-84.
3. Luterman M, Tellier G, Lasko B, Leroy B. Efficacy and tolerability of telithromycin for 5 or 10 days vs. amoxicillin/clavulanic acid for 10 days in acute maxillary sinusitis. Ear Nose Throat J 2003;82(8):576-80, 82-4, 586 passim.
4. Roos K, Brunswig-Pitschner C, Kostrica R, et al. Efficacy and tolerability of once-daily therapy with telithromycin for 5 or 10 days for the treatment of acute maxillary sinusitis. Chemotherapy 2002;48(2):100-8.
5. Ferguson BJ, Anon J, Poole MD, et al. Short treatment durations for acute bacterial rhinosinusitis: five days of gemifloxacin versus 7 days of gemifloxacin. Otolaryngol Head Neck Surg 2002;127(1):1-6.
6. Henry DC, Riffer E, Sokol WN, Chaudry NI, Swanson RN. Randomized double-blind study comparing 3- and 6-day regimens of azithromycin with a 10-day amoxicillin-clavulanate regimen for treatment of acute bacterial sinusitis. Antimicrobial Agents Chemother 2003;47(9):2770-4.
7. Sher LD, McAdoo MA, Bettis RB, et al. A multicenter, randomized, investigator-blinded study of 5- and 10-day gatifloxacin versus 10-day amoxicillin/clavulanate in patients with acute bacterial sinusitis. Clin Ther 2002;24(2):269-81.
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AHRQ Publication Number 05-E020-1
Current as of June 2005