Introduction

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. The

research questions in this evidence report are:

1. Given a clinical diagnosis of acute bacterial

rhinosinusitis, what are the comparative

efficacies of the antibiotics in resolving

symptoms and preventing complications or

recurrence? 

1a. Is there evidence that duration of

antibiotic treatment in acute bacterial

rhinosinusitis affects efficacy?

2. What adverse effects are reported for

antibiotics used for acute bacterial

rhinosinusitis?

3. How does the introduction of the

pneumococcal vaccine affect the resistance

patterns of pneumococcus and the treatment

decisions in acute bacterial rhinosinusitis?

Methods

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. 

Inclusion Criteria

• 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.

Exclusion criteria

• 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.

Evidence Report/Technology Assessment

Number 124

Update on Acute Bacterial Rhinosinusitis

Summary

Authors: Ip S, Fu L, Balk E, Chew P, DeVine D, Lau J

Agency for Healthcare Research and Quality

Advancing Excellence in Health Care • www.ahrq.gov

Agency for Healthcare Research and Quality Evidence-Based

Practice
2

Meta-analysis

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

effects model.

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. 

Results

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

amoxicillin.

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 amoxicillinclavulanate. 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 amoxicillinclavulanate, 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 amoxicillinclavulanate 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

bacterial sinusitis.

Discussion

• 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.

Limitations

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. A

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.

Future Research

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.

Availability of the 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. It is expected to be available in summer 2005. At that

time, 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.

In addition, Internet users will be able to access the report and

this summary online through AHRQ’s Web site at

www.ahrq.gov.

Suggested Citation

Ip S, Fu L, Balk E, Chew P, DeVine D, Lau J. Update on

Acute Bacterial Rhinosinusitis. Summary, Evidence

Report/Technology Assessment No. 124. (Prepared by the

Tufts-New England Medical Center Evidence-based Practice

Center under Contract No. 290-02-0022.) AHRQ Publication

No. 05-E020-1. Rockville, MD: Agency for Healthcare

Research and Quality. June 2005.

References

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.[see comment]. 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 Pub. No. 05-E020-1

June 2005

ISSN 1530-440X