Evidence Report/Technology Assessment 

Number 124 

Update on Acute Bacterial Rhinosinusitis 

Prepared for: 

Agency for Healthcare Research and Quality 

U.S. Department of Health and Human Services 

540 Gaither Road 

Rockville, MD 20850 

www.ahrq.gov 

Contract No. 290-02-0022 

Prepared by: 

Tufts-New England Medical Center EPC, Boston, Massachusetts 

Investigators 

Stanley Ip, MD 

Linda Fu, MD 

Ethan Balk, MD, MPH 

Priscilla Chew, MPH 

Deirdre DeVine, MLitt 

Joseph Lau, MD 

AHRQ Publication No. 05-E020-2 

June 2005
ii 

This document is in the public domain and may be used and reprinted without permission except 

those copyrighted materials noted for which further reproduction is prohibited without the 

specific permission of copyright holders. 

Suggested Citation: 

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

Evidence Report/Technology Assessment No. 124. (Prepared by Tufts-New England Medical 

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

No. 05-E020-2. Rockville, MD: Agency for Healthcare Research and Quality. June 2005. 
iii 

Preface 

The Agency for Healthcare Research and Quality (AHRQ), through its Evidence-Based 

Practice Centers (EPCs), sponsors the development of evidence reports and technology 

assessments to assist public-and private-sector organizations in their efforts to improve the 

quality of health care in the United States. The reports and assessments provide organizations 

with comprehensive, science-based information on common, costly medical conditions and on 

new health care technologies. The EPCs systematically review the relevant scientific literature 

on topics assigned to them by AHRQ and conduct additional analyses when appropriate prior to 

developing their reports and assessments. 

 To bring the broadest range of experts into the development of the evidence reports and 

health technology assessments, AHRQ encourages the EPCs to form partnerships and enter into 

collaborations with other medical and research organizations. The EPCs work with these partner 

organizations to ensure that the evidence reports and technology assessments they produce will 

become building blocks for health care quality and improvement projects throughout the Nation. 

The reports undergo peer review prior to their release. 

 AHRQ expects that the EPC evidence reports and technology assessments will inform 

individual health plans, providers, and purchasers as well as the health care system as a whole by 

providing important information to help improve health care quality. 

 We welcome written comments on this evidence report. They may be sent to: Director, 

Center for Outcomes and Evidence, Agency for Healthcare Research and Quality, 540 Gaither 

Road, Rockville, MD 20850, or by email to epc.ahrq.gov. 

Carolyn M. Clancy, MD 

Director 

Agency for Healthcare Research and Quality 

Kenneth S. Fink, M.D., M.G.A., M.P.H. 

Director, EPC Program 

Agency for Healthcare Research and Quality 

Jean Slutsky, P.A., M.S.P.H. 

Director, Center for Outcomes and Evidence 

Agency for Healthcare Research and Quality 

Carmen Kelly, PharmD 

EPC Program Task Order Officer 

Agency for Healthcare Research and Quality 

The authors of this report are responsible for its content. Statements in the report should not be 

construed as endorsement by the Agency for Healthcare Research and Quality or the U.S. 

Department of Health and Human Services of a particular drug, device, test, treatment, or other 

clinical service. 
iv 

Acknowledgments 

We would like to acknowledge with appreciation the following members of the Technical Expert 

Panel for their advice and consultation to the Evidence-based Practice Center during preparation 

of this report. 

Technical Expert Panel 

Michael Barza, MD 

Director 

Department of Medicine 

Caritas Carney Hospital 

Dorchester, Massachusetts 

Michael Benninger, MD, FACS 

Cummings-Brush Chair in Surgical Education 

Chairman 

Department of Otolaryngology - Head & Neck Surgery 

Henry Ford Hospital 

Detroit, Michigan 

Larry Culpepper, MD, MPH 

Chairman of Family Medicine 

Boston University Medical Center 

Boston, Massachusetts 

Ellen Wald, MD 

Chief of Allergy, Asthma, and Infectious Disease 

Department of Pediatrics 

Children’s Hospital of Pittsburgh 

Pittsburgh, Pennsylvania 
v 

Structured Abstract 

Context. Our last report on the treatment of acute bacterial sinusitis was published in 1999. 

Since then, many more trials were published comparing different antibiotics not found in the 

previous report. In addition, universal pneumococcal vaccination was introduced in the pediatric 

population. It is of interest to examine the effects of these new developments on the treatment of 

acute bacterial rhinosinusitis. 

Objectives. To perform a systematic review of the literature published since 1997 on 

comparisons of antibiotics in the treatment of acute bacterial rhinosinusitis, to summarize the 

adverse events and note any reported impact of pneumococcal vaccine on the treatment of acute 

bacterial rhinosinusitis. 

Data Sources. We searched the MEDLINE® database and bibliographies of selected reviews. 

Additional studies were provided by technical experts. 

Study Selection. English-language, comparative trials of antibiotics for the treatment of acute 

bacterial rhinosinusitis in both adult and pediatric populations were included. Studies of sinusitis 

with complications or that included both subjects with sinusitis and subjects with other 

respiratory tract infections were excluded. 

Data Extraction. We extracted information about the study design, demographics, eligibility 

criteria, antibiotic dosing regimens, outcome measures, including dropouts, and adverse events. 

Based on these data, studies were graded for quality. 

Data Synthesis. Thirty-nine randomized controlled trials from 1997 to 2004 met the inclusion 

criteria for this report. With the exception of 5 studies that did not provide the information, all 

studies were either funded by pharmaceutical companies or had authors associated with the 

pharmaceutical industry. Only one study exclusively evaluated pediatric population. The trials 

evaluated pencillins, cephalosporins, macrolides, azalides, ketolides, quinolones, carbapenems 

and tetracyclines. In 5 placebo-controlled trials, antibiotics were more effective than placebo, 

reducing the risk of clinical failure by about 25-30 percent 7 to 14 days after treament initiation. 

Compared to amoxicillin/clavulanate, treatment with cephalosporins result in about 3.5 more 

clinical failures per 100 patients at 10-25 days after treatment initiation. There was no consistent 

difference observed when comparing amoxcillin-clavulanate, cephalosporins and quinolones to 

the group encompassing macrolides, azalides and ketolide. 

Eight studies that evaluated different treatment durations generally found no differences in 

efficacy outcomes between the shorter and longer duration therapies. 

Thirty-four of the comparative trials and five additional non-comparative studies 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 

large variation in the adverse event rates within the same antibiotic class. Overall, the most 

common adverse events involved the gastrointestinal and the nervous system (such as headache). 

We did not identify any article in our literature search that directly addressed the impact of 

pneumococcal vaccine on the treatment of acute bacterial rhinosinusitis. 
vi 

Conclusions. About two-thirds of the patients with acute rhinosinusitis receiving placebos 

recovered without antibiotics. Antibiotics are superior to placebo in the treatment of 

rhinosinusitis. Amoxicillin/clavulanate is more effective than the cephalosporin class of 

antibiotics in the treatment of sinusitis only in the short-term follow up, with an absolute risk 

difference of about 3.5 percent. 

There are only a few studies that specifically examined the effect of different treatment 

duration on outcome efficacy; they generally found no difference between shorter and longer 

duration of treatment. It is not possible to compare the rates of adverse events across different 

antibiotic classes. Severe adverse events in general are uncommon; they occurred in up to about 

3.5 percent of patients in all classes of antibiotics. 

As of September 2004, there have not been any published studies examining the effect of the 

pneumococcal vaccine on the treatment of acute sinusitis. 

A minority of studies were placebo controlled. In addition, from a health care cost 

standpoint, there were very few comparative studies between newer antibiotics and older 

inexpensive ones (like amoxicillin and trimethoprim/sulfamethoxazole). 

 

 

 

 

 

 

 
vii 

Contents 

Evidence Report 

 

Chapter 1. Introduction...................................................................................... 3

 Research questions.......................................................................................... 3

Chapter 2. Methods........................................................................................................... 5

 Definitions.................................................................................................... 5

 Search Strategy and Retrieval.............................................................................................. 5

 Inclusion and Exclusion Criteria............................................................................................ 6

 Adverse Events Data Extraction........................................................................... 6

 Methodological Quality Grading.......................................................................... 6

 Meta-Analysis.............................................................................................. 7

 Peer Review Process....................................................................................... 8

Chapter 3. Results...................................................................................................................... 9

 Results of Meta-analyses.................................................................................... 9

 Research Question 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?......................................................................... 9

 1a. Is there evidence that duration of antibiotic treatment in acute bacterial 

 rhinosinusitis affects efficacy?................................................................ 21

 Research Question 2: What adverse effects are reported for antibiotics used for acute 

 bacterial rhinosinusitis?................................................................................ 24

 Research Question 3: How does the introduction of the pneumococcal vaccine affect 

 the resistance patterns of pneumococcus and the treatment decisions in acute bacterial 

 rhinosinusitis?........................................................................................... 36

Chapter 4. Conclusions and Discussion............................................................ 37

 Limitations...................................................................................................... 37

 Future Research............................................................................................... 38

References and Included Studies...................................................................... 39

 References................................................................................................... 39

 Bibliography................................................................................................ 40

List of Excluded Studies............................................................................................. 43

Tables 

Table 1. Placebo-controlled antibiotic trials for the treatment of acute bacterial 

rhinosinusitis from 7/1997 to 8/2004......................................................... 11 

Table 2. Antibiotic-comparison trials for the treatment of acute bacterial 

rhinosinusitis from 7/1997 to8/2004........................................................ 12 
viii 

Tables 

Table 3. Randomized controlled trials of antibiotics in treatment of sinusitis from 

7/1997 to 8/2004.............................................................................. 18

Table 4. Comparison of antibiotics/placebo in the randomized controlled trials: 

each trial contributes 1 or more comparisons to the table................................ 19

Table 5. Per-protocol meta-analyses of treatment failure & recurrence with different 

antibiotics......................................................................................... 20

Table 6. Comparison of different durations of treatment in sinusitis............................... 22

Table 7. Summary ranges of percent of patients experiencing adverse events with placebo 

and each antibiotic................................................................................. 26

Table 8. Adverse events for placebo and penicillins, N (%)....................................... 28

Table 9. Adverse events for cephalosporins and faropenem, N (%)................................. 30

Table 10. Adverse events for macrolides, azalides and ketolide, N (%)........................... 32

Table 11. Adverse events for quinolones, N (%)........................................................ 34

Appendixes 

Appendixes A: Search Strategies 

Appendixes B: Data Extraction Form 

Appendixes C: Evidence Tables 

Appendixes D: Peer Reviewers

Appendixes and Evidence Tables are provided electronically at 

http://www.ahrq.gov/clinic/tp/rhinouptp.htm
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.

3
www.ahrq.gov

AHRQ Pub. No. 05-E020-1

June 2005

ISSN 1530-440X
3

Chapter 1. Introduction 

 The Tufts-New England Medical Center (Tufts-NEMC) Evidence-based Practice Center 

(EPC), under a contract from the Agency for Healthcare Research and Quality (AHRQ), 

produced the original evidence report on the Diagnosis and Treatment of Acute Bacterial 

Rhinosinusitis (March 1999).1 Key points from the report relevant to this review are: 

• About two-thirds of the patients receiving placebos recovered without antibiotics. 

• Antibiotics are significantly more effective than placebo for treating acute bacterial 

sinusitis, reducing the clinical failure rate by one-half (risk ratio [RR], 0.54; 95 percent 

confidence interval [CI], 0.37 to 0.79). Patients are cured more quickly and more often 

when treated with antibiotics compared with no treatment. 

• Amoxicillin and folate inhibitors were as efficacious as the newer and more expensive 

antibiotics. 

• About 4 percent of the patients in the amoxicillin arms of the clinical trials withdrew as a 

result of side effects, but this percent did not differ statistically from that in patients 

treated with other antibiotics. 

 The EPC Program periodically seeks updates of evidence reports when justified by current 

scientific evidence. In the intervening 6 years since the original report, newer antibiotics have 

been introduced and universal pneumococcal vaccination implemented in care of the pediatric 

population. To examine the effects of these developments on the treatment of acute bacterial 

sinusitis, the Tufts-NEMC EPC reviewed the literature published since the last report for the 

research questions listed below. Our objective was to identify and analyze evidence from 

comparative studies on the antibiotic efficacies in the treatment of acute bacterial sinusitis. 

Research Questions 

 In 2004, after consultation with our panel of technical experts, we developed the following 

research questions for this report: 

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? 

5

Chapter 2. Methodology 

 The Tufts-NEMC EPC conducted a systematic review of the literature published since 1997 

to summarize the evidence and we performed meta-analysis on comparative drug trials if there 

were 3 or more studies in the same grouping. We held meetings and teleconferences with 

technical expert representatives from three science partners (the American Academy of Family 

Physicians, American Academy of Otolaryngology-Head and Neck Surgery, and American 

Academy of Pediatrics) to refine the three research questions addressed in this evidence report. 

To answer the question on comparative efficacies of the antibiotics and the effect of different 

treatment durations on acute bacterial sinusitis, we sought only published results from 

randomized controlled trials. For the question on adverse events, we examined the reported 

adverse event data in these trials. For the question on pneumococcal vaccine’s effect on 

treatment decision in acute sinusitis, we looked for published articles that directly addressed this 

question. 

Definitions 

As in the original evidence report, we have focused this update on acute uncomplicated 

bacterial sinusitis. Sinusitis is defined as clinical signs and symptoms of inflammation of the 

paranasal sinuses and nasal passages (including: nasal congestion/discharge, nasal mucosa 

hyperemia, cough, fever, craniofacial pain/tenderness, periorbital edema, headache, toothache, 

earache, hyposmia/anosmia, halitosis, malaise, opacities/mucosal thickening/air-fluid level of the 

sinuses on standard films and/or CT scan, and positive sinus culture). Rhinosinusitis is included 

in this grouping. Acute duration is defined as having signs and symptoms of less than 30 days’ 

duration. Uncomplicated sinusitis is defined as the lack of clinically evident neurological, soft 

tissue or other complications present prior to treatment initiation. Treatment failure is defined as 

the lack of improvement or worsening in signs and symptoms by the end of therapy. Recurrence

includes persistent or relapsed disease assessed after a period of at least one week following the 

end of therapy. Some studies reported clinical success rate rather than clinical failure rate. In 

such instances, the clinical failure rate is calculated as: 100 percent clinical success rate. 

Search Strategy and Retrieval 

 We searched MEDLINE® using a broad search strategy covering the period from January 

1997 to September 2004. The search terms were: “sinusitis,” “rhinosinusitis,” “anti-bacterial 

agents” and other relevant terms. See Appendix A. We limited search results to human and 

English-language studies. Studies of any age group were included. 

 For the question on pneumococcal vaccine and sinusitis, the search terms were: “vaccines”, 

“pneumococcal vaccine”, “sinusitis” and “rhinosinusitis”. 

 Additional sources of published articles were provided by members of the Technical Expert 

Panel (TEP), and also sought from reference lists of selected review articles and meta-analyses. 
6

Inclusion Criteria 

Studies that 

• included subjects with acute rhinosinusitis 

• included subjects with acute exacerbation of chronic sinusitis 

• included any age group, in any country 

• were based in primary care and/or specialty clinics 

• included at least 10 subjects in each treatment arm 

• addressed component(s) of the Research Questions: efficacy of antibiotics, antibiotic 

treatment duration, antibiotic adverse effects, pneumococcal vaccine effect on resistance 

patterns 

• were randomized, comparative trials (5 non-comparative studies were included in the 

review of adverse events only) 

 

Exclusion Criteria 

Studies that 

• included only patients with chronic sinusitis without acute exacerbation 

• included other respiratory infections in addition to acute rhinosinusitis 

Adverse Events Data Extraction 

 Adverse event data were extracted from the antibiotic comparison studies obtained via the 

defined search strategy. In addition, we abstracted data from non-comparative antibiotic studies 

that included safety analyses. We did not seek out the adverse event data collected by the 

pharmaceutical companies. For each study we recorded 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. In addition, 

any other adverse events occurring in at least 2% of study subjects were also extracted. For 

antibiotics with two or more studies, we calculated a median and weighted mean percentage of 

study subjects experiencing at least one adverse event. 

Methodological Quality Grading 

 We used a 3-category grading system (A, B, C) to denote the methodological quality of each 

study. This grading system has been used in most of the previous evidence reports from the 

Tufts-NEMC EPC as well as in evidence-based clinical practice guidelines.2

 For this report, we 

have slightly modified the grading system to take into account the percentage of dropout in the 

study. This system defines a generic grading system that is applicable to varying study designs 

including randomized controlled trials, cohort, and case-control studies: 
7

A Category A studies have the least bias and results are considered valid. A study that 

adheres mostly to the commonly held concepts of high quality including the following: a 

formal randomized study; clear description of the population, setting, interventions and 

comparison groups; sufficient power (arbitrarily defined as minimum sample size of 30 

subjects per treatment arm); clear description of the intervention used; appropriate 

comparator; appropriate measurement of outcomes; appropriate statistical and analytic 

methods and reporting; double-blinding; no reporting errors; less than 10% dropout; clear 

reporting of dropouts; and no obvious bias. 

B Category B studies are susceptible to some bias, but not sufficiently so as to invalidate 

the results. They do not meet all the criteria in category A because they have some 

deficiencies, but none likely to cause major bias. The study may be missing information, 

making it difficult to assess limitations and potential problems. 

C Category C studies have significant bias that may invalidate the results. These studies 

have serious errors in design, analysis or reporting, have large amounts of missing 

information, or discrepancies in reporting. Specific criteria included large (>20%) or 

unequal dropout rate, large discrepancy in baseline and final numbers of subjects, unclear 

duration or numbers of subjects, missing baseline data, or irreconcilable apparent 

differences between data in figures, tables, and text. 

 Two investigators independently reviewed each primary study for methodological quality 

according to this grading system. Discrepancies in assigned grade between investigators were 

resolved via discussion and consensus. In addition to applying this grading system to each study, 

additional comments relating to potential sources of bias and other study limitations were noted 

and recorded during data extraction. Such comments are included in the evidence tables. 

Meta-Analysis 

 Based on the available data, meta-analysis of primary studies was possible only for Research 

Question 1 regarding the comparative efficacies of antibiotics in the treatment of acute bacterial 

rhinosinusitis. Table 4 in chapter 3 shows the number of comparisons between the various 

antibiotics that were obtained by our search strategy. Meta-analysis was possible for the 

following comparisons: 

1. antibiotics with placebo for treatment failure 

2. cephalosporins with amoxicillin/clavulanate for treatment failure and recurrence 

3. the combined category of macrolides/azalides/ketolides with amoxicillin/clavulanate 

for treatment failure and recurrence 

4. quinolones with amoxicillin/clavulanate for treatment failure and recurrence 

5. macrolides/azalides/ketolides with cephalosporins for treatment failure and 

recurrence 

6. quinolones with cephalosporins for treatment failure and recurrence 

7. quinolones with macrolides for treatment failure and recurrence 

 We calculated risk ratios and risk differences for each of these comparisons. All metaanalyses were performed using a random effects model. Similar to our previous report, 
8

cumulative meta-analyses ordered by methodological quality of the studies were used to explore 

possible treatment effect trends as studies with lower quality scores were added to studies with 

higher quality scores. We used a three level quality score (from A to C) in this meta-analysis. 

 Several studies reported intention-to-treat data in addition to per-protocol data. However, 

because intention-to-treat data were not uniformly defined and less common, all meta-analyses 

were reported using per-protocol data. Some studies included multiple study arms comparing 

different doses of the same antibiotic. Chi-square analyses were used to determine the presence 

of heterogeneity in treatment outcome between different doses of the same antibiotic. To avoid 

arbitrarily selecting one treatment dose, multiple study arms evaluating the same antibiotic were 

combined for meta-analyses. 

 A few studies reported rates of microbiological treatment failure. However, because no more 

than 2 to 3 such studies were available for each comparison, we did not perform meta-analysis 

on microbiological treatment results. 

Peer Review Process 

 The EPC requested nominations for potential external reviewers from the members of the 

Technical Expert Panel, which included the original individuals appointed to the first Panel in 

1998 by the American Academy of Family Physicians, American Academy of OtolaryngologyHead and Neck Surgery, and American Academy of Pediatrics. The EPC also directly contacted 

researchers in the field inviting them to peer review. We provided material to reviewers, 

including the draft evidence report, guidance on the review process, and a structured evaluation 

form for collecting feedback from reviewers. We collated responses received from reviewers and 

made these available the EPC evidence review team. We then produced a structured summary 

report of the reviewers’ comments and the responses made by the EPC review team for review 

by the AHRQ Task Order Officer. 
9

Chapter 3. Results 

 From MEDLINE® we identified 704 citations for potential inclusion. Upon screening the 

abstracts, 87 articles were retrieved for full-text screening. A total of 39 studies ultimately 

qualified for inclusion in this update. 

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? 

 We identified a total of 39 randomized controlled trials including 15,739 patients from 

1997 to 2004 that studied antibiotic comparisons in treatment of acute bacterial sinusitis (Tables 

1 & 2). With the exception of 5 studies that did not provide the information, all the studies were 

either funded by pharmaceutical companies or had authors associated with the pharmaceutical 

industry. Twelve of the studies consisted of subjects from the United States. Ten out of 39 

studies included subjects less than 18 years old. No study was explicitly restricted to the pediatric 

population, although one study consisted only of subjects whose age ranged from 6 months to 17 

years. Sample size of the studies ranged from 40 to 1,798. Of 13,220 patients whose per-protocol 

results were reported in the studies, less than 3 percent received placebo. All studies stated 

explicit requirements of clinical signs and symptoms of acute sinusitis for entry into the studies. 

In addition, 33 studies included results from either radiography or computed tomography (CT) 

scan of the sinuses as part of their eligibility criteria. Four studies are considered to be superior in 

methodological, reporting and data quality (A). Twenty-two studies are considered moderate (B) 

and nineteen studies low quality (C). The low quality studies often had limitations due to high 

dropout rate and incomplete reporting of data. 

 The antibiotics studied are listed in Tables 1 & 2. The classes of antibiotics studied consist of 

penicillins, cephalosporins, macrolides, azalides, ketolides, quinolones, carbapenems and 

tetracyclines. There are a total of 112 comparisons reported in the 39 trials (Table 4); 7 compare 

antibiotics to placebos; 5 compare various antibiotics (including 2 placebos) to amoxicillin, 22 

compare various antibiotics (including 1 placebo) to amoxicillin/ clavulanate; 10 compare 

various antibiotics to cefuroxime. In contrast to the previous evidence report, there was no 

comparison against trimethoprim/sulfamethoxazole. 

 Duration of treatment varied between 3 days and 4 weeks. Twenty-six of the studies included 

at least one antibiotic that was prescribed for 10 days. Primary outcome assessment took place 

anywhere from 3 days to more than 4 weeks after the initiation of treatment. 

Results of Meta-analyses 

 We performed 13 different meta-analyses to answer Research Question 1 regarding the 

comparative efficacy of different antibiotics on treatment failure and recurrence rates (Table 5). 

All meta-analyses were reported using per-protocol data from the primary studies. Meta-analyses 

were also performed substituting per-protocol data with modified intention-to-treat data available 

in 5 studies; results were similar and are not reported here. None of the cumulative meta-analyses 

ordered by study methodological quality demonstrated any alteration of treatment effect trend by 

the addition of studies with lower quality scores to those with higher quality scores. As a result, 

studies of all methodological quality are included in these meta-analyses. 
10

Placebo-controlled trials. There were 5 trials (7 comparisons, total of 780 enrolled patients) 

comparing antibiotics to placebo. All of these trials recruited patients from a primary care 

setting. Four of the 5 trials used an antibiotic in the penicillin class, while the fifth trial 

compared azithromycin to placebo. Overall, antibiotics were more effective than placebo, 

reducing the risk of clinical failure by about 25% to 30% 7 to 14 days after treatment initiation 

(risk ratio [RR] 0.69, 95% confidence interval [CI] 0.53-0.89, Table 5). Nevertheless, symptoms 

improved or were cured in 65% of patients without any antibiotic treatment at all (95% CI 40-

91%). 

Antibiotic comparison trials. Five studies, involving a total of 3033 patients, compared various 

quinolones to cefuroxime. Except for one study, all antibiotics were given for 10 days. In the 

four studies that reported data for outcome assessment between 11 to 26 days after initiation of 

treatment, there was a non-statistically significant trend suggesting that quinolones were superior 

to cefuroxime in reducing clinical failure (RR 0.68, 95% CI 0.44 to 1.04). 

 There were four studies involving a total of 2765 patients, which showed that 

amoxicillin/clavulanate, when compared to antibiotics in the cephalosporin class, was 41% more 

effective in reducing clinical failure 10 to 25 days after treatment initiation (RR 1.41, 95% CI 

1.08 to 1.82). In absolute terms, this means treating 100 patients with antibiotics in the 

cephalosporin class will lead to 3.5 more failures (95% CI 0.9 to 6.0) as compared to 

amoxicillin/clavulanate. However, data from four studies involving a total of 2797 patients did 

not show a significant difference in recurrence rates between amoxicillin-clavulanate and 

cephalosporins (RR 1.10, 95% CI 0.83 to 1.45) 24-45 days after treatment initiation. 

 There was no consistent trend observed when comparing amoxicillin/clavulanate, 

cephalosporins or quinolones to the group encompassing macrolides, azalides and ketolides. 
11

Table 1. Placebo-controlled antibiotic trials for the treatment of acute bacterial rhinosinusitis from 7/1997 to 8/2004 Abx: antibiotics; Amox/clav: amoxicillin/clavulanate; bid: twice a day; Pharm: pharmaceutical industry; qd: once a day; qid:, four times a dtid: three times a day; X-ray: sinus radiography; y/o, years old Author Year Country Funding 

# Randomized 

 or Enrolled 

# per Protocol Antibiotic Dose Duration Time of evaluation of 1° outcome (days after start of Rx) Clinical failure rate per protocol Com

124 Amox/Clav 875/125 mg bid 23.4% Bucher 

2003 Switzerland Pharm 252 127 Placebo bid 6 days 14 26% 

1° ocurefor crite

71 Penicillin V 1333 mg bid 28%* Hansen 

2000 Denmark Pharm 139 

62 Placebo 2 tabs bid 

7 days 7 

51.5%* 

*cafrom (29for req

87 84 Azithromycin 500 mg qd 6% Haye 

1998 Norway ND 

82 81 Placebo qd 

3 days 3-5 * 

12.3% 

*Paas toutcSubempauthPha

20 Penicillin V 1320 mg tid 10% 22 Amoxicillin 500 mg tid 13.6% 

Lindbaek 1998 Norway 

Norwegian Research Council 

70 

21 Placebo tid 

10 days 10 

14.3% 

Subshowithtota

88 

Amoxicillin 750 mg x2 or Penicillin V 1500 IU x2 or Doxycyclin 100 mg x2 

Varonen 20.5% 2003 Finland Government & industry 150 

59 Placebo 

7 days 14 

32.2% 

Subabx ray incl
12

Table 2. Antibiotic-comparison trials for the treatment of acute bacterial rhinosinusitis from 7/1997 to 8/2004 Author Year Country Funding 

# Randomized 

 or Enrolled 

# per Protocol Antibiotic Dose Duration 

Time of evaluation of 1°outcome (days after start of Rx) 

Clinical failure rate per protoco

140 108 Cefprozil 500 mg bid 13.9% Adelglass 

1998 a ND Pharm 138 111 Amox/Clav 500/125 mg tid 10 days 11-15 8.1% Adelglass 108 101 Levofloxacin 500 mg qd 4.0% 1998 b ND Pharm 108 89 Clarithromycin 500 mg bid 14 days 16-19 6.7% 

307 267 Levofloxacin 500 mg qd* 11.6% Adelglass 

1999 US Pharm 308 268 Amox/Clav 500/125mg q8h* 10-14 days 12-19 12.7% 

240 189 Telithromycin 800 mg qd 5 days 14.8% 

Buchanan 2003 

Argentina France S. Africa US 

Pharm 116 89 Cefuroxime 250 mg bid 10 days 16-24 18% 

124 Amox/Clav 875/125 mg bid 23.4% 

Bucher 2003 Switzerland Pharm 252 

127 Placebo bid 

6 days 14 

26% 

223 Moxifloxacin 400 mg qd 10.3% Burke 1999 North America Pharm 542 234 Cefuroxime 250 mg bid 10 days 17-31 10.7% 29 Roxithromycin 150 mg bid 6.9% Chatzimanolis 

1998 Greece Pharm 60 27 Amox/clav 500/125 mg tid 10 days minimum ~10-12 11.1% 

136 Azithromycin 500 mg qd 3 days 12.5% 

Clement 1998 ND Pharm 254 74 Amox/clav 500/125 mg tid 10 days 21-28 16.2% 

236 Ciprofloxacin 500 mg bid 10 days 15.7% Clifford 1999 ND Pharm 560 221 Clarithromycin 500 mg bid 14 days 16-19 8.6% 181 5 days 12.7% Ferguson 

2002 

Canada & 8 countries in Europe 

Pharm 423 175 Gemifloxacin 320 mg qd 7 days 18-25 13.1% 
13

Author Year Country Funding 

# Randomized 

 or Enrolled 

# per Protocol Antibiotic Dose Duration 

Time of evaluation of 1°outcome (days after start of Rx) 

Clinical failure rate per protoco

181 5 days 21.6% Gehanno 

2000 France Pharm 433 179 Amox/clav 500 mg tid 10 days 14 15.6% 

585 474 600 mg qd 10.3% 610 481 

Cefdinir 

300 mg bid 12.7% 

Gwaltney 1997 

US Europe ND 

603 491 Amox/clav 500 mg tid 

10 days 17-24 

9% 

93 600 mg qd 5.4% 96 Cefdinir 300 mg bid 10.4% Steurer 2000 

(subgroup of Gwaltney) 1997 

Europe Pharm 569 

106 Amox/clav 500/125 mg tid 10 days 17-25 3.8% 

71 Penicillin V 1333 mg bid 28%* 

Hansen 2000 Denmark Pharm 139 

62 Placebo 2 tabs bid 

7 days 7 

51.5%* 

87 84 Azithromycin 500 mg qd 6% 

Haye 1998 Norway ND 

82 81 Placebo qd 

3 days 3-5 * 

12.3% 

132 Cefuroxime 250 mg bid 50%* 

Henry 1999 a US Pharm 131 

193 clinically assessable Amox/clav 500 mg tid 10 days 36-40 59%* 
14

Author Year Country Funding 

# Randomized 

 or Enrolled 

# per Protocol Antibiotic Dose Duration 

Time of evaluation of 1°outcome (days after start of Rx) 

Clinical failure rate per protoco

252 219 Sparfloxacin 

400 mg qd Day 1; 200 mg qd Days 2-10 

10 days 16.9%** 

Henry 1999 b US Pharm 

252 211 Clarithromycin 500 mg q12h 14 days 

20±3 

16.6%** 

272 3 days 28.3% 271 azithromycin 500 mg qd 6 days 26.6% Henry 2003 US Pharm 941 

251 Amox/clav 500/125 mg tid 10 days 22-36 28.7% 

34 Levofloxacin 300 mg qd 8.8% Jareoncharsri 

2004 Thailand Pharm ND 26 Amox/clav 500/125 mg tid 14 days 21 15.4% 

228 Ciprofloxacin 500 mg bid 13% Johnson 1999 ND Pharm 501 225 Cefuroxime 250 mg bid 10 days 11-18 17% 47 Azithromycin 500 mg qd 3 days 0% 

Klapan 1999 ND ND 100 47 Amox/clav 500/125 mg tid 10 days 10-12 0% 

13 Ciprofloxacin 500 mg bid 0% 

Klein 1998 ND Pharm 83 

19 Cefuroxime 250 mg bid 

≥ 10 days ≥11-17 

26.3% 

223 Moxifloxacin 400 mg qd 7 days 3.1% 

Klossek 2003 8 countries in Europe ND 503 229 Trovafloxacin 200 mg qd 10 days 17-20 7.9% 
15

Author Year Country Funding 

# Randomized 

 or Enrolled 

# per Protocol Antibiotic Dose Duration 

Time of evaluation of 1°outcome (days after start of Rx) 

Clinical failure rate per protoco

10 1 week 50%* 10 2 week 20%* 10 3 week 20%* 

Kultluhan 2002 Turkey ND 

10 

ND 

Amox/clav 1 g bid or Ciprofloxacin 500 mg or Clarithromycin 500 mg bid or Cefuroxime 250 mg bid; Choice of antibiotics depended on maxillary sinus puncture and C&S results. 

4 week 

Day 28 

30%* 

119 98 Levofloxacin 500 mg qd 6.1% Lasko 1998 ND Pharm 117 93 Clarithromycin 500 mg bid 10-14 days 12-19 6.5% 

20 Penicillin V 1320 mg tid 10% 22 Amoxicillin 500 mg tid 13.6% 

Lindbaek 1998 Norway 

Norwegian Research Council 

70 

21 Placebo tid 

10 days 10 

14.3% 

146 5 days 24.7% 140 

Telithromycin 800 mg qd 

Luterman 10 days 27.1% 2003 

US Canada S. Africa Argentina Chile 

Pharm 754 

137 Amox/clav 500/125 mg tid 10 days 

17-24 

25.5% 

122 

Clarithromycin Extended release 

1000 mg qd 14.8% 

Murray 2000 US Canada Pharm 284 

123 

Clarithromycin immediate release 

500 mg bid 

14 days 24-31 

21.1% 
16

Author Year Country Funding 

# Randomized 

 or Enrolled 

# per Protocol Antibiotic Dose Duration 

Time of evaluation of 1°outcome (days after start of Rx) 

Clinical failure rate per protoco

104 Amox/clav 875/125 mg bid 2.9% 

Namyslowski 2002 Poland ND 231 

102 Cefuroxime 500 mg bid 

14 days 15-18 

7.8% 

170 Moxifloxacin 400 mg qd 14% 

Rakkar 2001 US Pharm 475 171 Amox/clav 875 mg bid 10 days 24-31 16% 

123 5 days 8.9% 

Roos 2002 9 countries in Europe ND 341 

133 

Telithromycin 800 mg qd 

10 days 

17-21 

9% 

61 875/125 mg q12h 6.6% Seggev 1998 US Canada Pharm 170 73 Amox/clav 500/125 mg q8h 14 days 16-17 12.3% 137 5 days 25.6% 127 Gatifloxacin 400 mg qd Sher 2002 ND ND 445 10 days 20.5% 

141 Amox/clav 875 mg bid 10 days 

17-24 

28.4% 

211 Moxifloxacin 400 mg am 7 days 3.3% 

Siegert 2000 7 countries in Europe ND 493 225 Cefuroxime 250 mg bid 10 days 14 9.3% 

228 Faropenem daloxate 300 mg bid 11% Siegert 2003 7 countries in Europe Pharm 558 224 Cefuroxime 250 mg bid 7 days 14-23 11.6% 
17

Author Year Country Funding 

# Randomized 

 or Enrolled 

# per Protocol Antibiotic Dose Duration 

Time of evaluation of 1°outcome (days after start of Rx) 

Clinical failure rate per protoco

50 Erythromycin- sulfisoxazole 

Erythromycin component 10 mg/kg/ dose qid 

14 days 4%* 

50 10 days 8%* 50 15 days 8%* 

Simon 1999 US ND 

50 

ND 

Ceftibuten 

9 mg/kg/day, maximum 400 mg/day 

20 days 

17-27 (1 week after end of Rx) 

0%* 

185 171 Cefuroxime 250 mg bid 9%** 

Stefansson 1998 

S. Africa and 7 countries in Europe 

ND 

185 175 Clarithromycin 250 mg bid 

10 days 11-14 and 38-45 

7%** 

134 400 mg qd 17.2% 138 Ceftibuten 200 mg bid 13% Sterkers 1997 France ND 458 

128 Amox/clav 500/125 mg tid 8 days 10 10.9% 

88 

Amoxicillin 750 mg x2 or Penicillin V 1500 IU x2 or Doxycyclin 100 mg x2 

20.5% 

Varonen 2003 Finland Government & industry 150 

59 Placebo 

7 days 14 

32.2% 

613 Ciprofloxacin 500 mg bid 8.8% 

Weis 1998 US Pharm 1414 606 Cefuroxime 250 mg bid 10 days 14-26 9.9% Abx: antibiotics; Amox/clav: amoxicillin/clavulanate; bid: twice a day; C&S: culture and sensitivities; ITT: intention-to-treat analysis; Nstated; Pharm: pharmaceutical industry; qd: once a day; qid: four times a day; Rx: prescription; tid: three times a day; X-ray: sinus radiog
18

Table 3. Randomized controlled trials of antibiotics in treatment of sinusitis from 7/1997 to 8/2004 

Penicillins Cephalosporins Macrolides/ Azalides/Ketolides Others Quinolo

Author Study ID 

Amoxicilli

n 

Amox/ 

clav 

Penicillin 

Cefprozil 

Cefdinir 

Ceftibuten 

Cefuroxime 

Azithromycin 

Clarithromycin 

Erythromycin 

Roxithromycin 

Telithromycin 

Doxycycline 

Faropenem 

Gatifloxacin 

Gemifloxacin 

Ciprofloxacin 

Moxifloxacin 

Adelglass ID 534 x x Adelglass ID 540 x Adelglass ID 490 x Buchanan ID 95931 x x Bucher ID 9 x Burke ID 524 x x Chatzimanolis ID 585 x x Clement ID 583 x x Clifford ID 480 x x Ferguson ID 225 xx Gehanno ID 373 xx Gwaltney ID 648 x xx Hansen ID 97079 x Haye 1998 x Henry ID 10 x xx Henry ID 482 x Henry ID 462 x x Jareoncharsri ID 34 x Johnson ID 491 x x Klapan ID 500 x x Klein ID 599 x x Klossek ID 164 x Lasko ID 530 x Lindbaek 1998 x x Luterman ID 97041 x xx Murray ID 375 xx Namyslowski ID 189 x x Rakkar ID 97064 x x Roos ID 240 xx Seggev ID 563 xx Sher ID 257 x xx Siegert ID 143 x x Siegert ID 415 x x Simon ID 475 Pedi xxx x Stefansson ID 97076 x x Sterkers ID 633 x xx Varonen ID 97080 x x x Weis ID 545 x x Amox/clav: amoxicillin/clavulanate 
19

Table 4. Comparison of antibiotics/placebo in the randomized controlled trials: each trial contributes 1 or more comparisons to 

Penicillins Cephalsporins Macrolides / Azalides / Ketolides Quinolones Oth

Amoxicillin 

Amoxicillin 

clavulanate 

Penicillin 

Cefprozil 

Cefdinir 

Ceftibuten 

Cefuroxime axetil 

Azithromycin 

Clarithromycin 

Erythromycin 

Roxithromycin 

Telithromycin 

Gatifloxacin 

Gemifloxacin 

Ciprofloxacin 

Moxifloxacin 

Levofloxacin 

Sparfloxacin 

Trovafloxacin 

Faropenem 

Amoxicillin 2 Amoxicillin clavulanate Penicillins 2 1 2 2 2 4 1 2 2 1 2 

Penicillin 

Cefprozil Cefdinir 2 Ceftibuten 4 3 

Cephalosporins 

Cefuroxime axetil 1 1 3 2 1 

Azithromycin 1 Clarithromycin 1 1 2 1 Erythromycin Roxithromycin 

Macrolides / 

Azalides/ 

Ketolides 

Telithromycin 2 

Gatifloxacin 1 Gemifloxacin 1 Ciprofloxacin Moxifloxacin 1 Levofloxacin Sparfloxacin 

Quinolones 

Trovafloxacin Faropenem 

Others 

Doxycycline 

Placebo Placebo 
20

Table 5. Per-protocol meta-analyses of treatment failure & recurrence with different antibiotics 

Antibiotics 

Compared Studies Included 

Study Day 

of 

Assessment 

Outcome 

Assessed 

Risk Ratio 

(95%CI)

Risk Difference 

[per 100 people 

treated] (95% CI) 

Antibiotics vs. Placebo 

Bucher 2003*

Hansen 2000 

Haye 1998 

Lindbaek 1998†

Varonen 2003 

14 

7 

10-12 

10 

14 

Treatment 

Failure 

0.69 

(0.53-0.89) -7.47 (-14.26 - -0.68) 

Adelglass 1998 a 

Gwaltney 1997‡

Namyslowski 2002‡

Sterkers 1997‡

11-15 

11-14 

15-18 

10 

Treatment 

Failure 

1.41 

(1.08-1.82) 3.62 (1.03-6.22) 

Cephalosporins 

vs. 

Amoxicillin/clavulanate Adelglass 1998 a 

Gwaltney 1997†

Henry 1999 a 

Sterkers 1997†

24 

31-45 

36-40 

40 

Recurrence 1.10 

(0.83-1.45) 2.37 (-0.75-5.49) 

Chatzimanolis 1998 

Henry 2003 

Klapan 1999 

10-17 

8-15 

10-12 

Treatment 

Failure

0.76 

(0.54-1.08) -1.56 (-4.59-1.48) Macrolides, Azalides 

and Ketolides 

vs. 

Amoxicillin/clavulanate 

Clement 1998 

Henry 2003 

Klapan 1999 

Luterman 2003†

21-28 

22-36 

28 

31-45 

Recurrence 0.95 

(0.79-1.14) -2.34 (-6.45-1.78) 

Adelglass 1999 

Jareoncharsri 2004 

Sher 2002†

12-19 

21 

12-24 

Treatment 

Failure 

0.35 

 (.06-1.9) Quinolones -11.45 (-29.92-7.02) 

vs. 

Amoxicillin/clavulanate Adelglass 1999 

Rakkar 2001 

38-46 

36-56 Recurrence 0.74 (0.34-

1.6) -1.06 (-3.5-1.37) 

Buchanan 2003 

Simon1999§

Stefansson 1998 

16-24 

17-25 

11-13 

Treatment 

Failure 

0.81 

(0.53-1.24) Macrolides, Azalides -1.78 (-5.61-2.06) 

and Ketolides 

vs. 

Cephalosporins 

Buchanan 2003 

Simon 1999§

Stefansson 1998 

31-45 

40-50 

38-45 

Recurrence 1.11 

(0.82-1.51) 1.68 (-3.68-7.05) 

Johnson 1999 

Klein 1998 

Siegert 2000‡

Weis 1998 

11-17 

14-25 

14 

14-26 

Treatment 

Failure 

0.68 

(0.44-1.04) -4.51 (-9.15-0.14) Quinolones 

vs. 

Cephalosporins 

(Cefuroxime) 

Burke 1999 

Johnson 1999 

Klein 1998 

Siegert 2000 

37-41 

24-38 

27-46 

34-41 

Recurrence 0.85 

(0.57-1.27) -1.07 (-3.44-1.29) 

Adelglass 1998 b 

Clifford 1999‡

Henry 1999 b 

Lasko 1998 

16-19 

16-17 

20-23 

12-19 

Treatment 

Failure

1.01 

 (0.59-1.73) Quinolones 0.15 (-5.89-6.19) 

vs. 

Macrolides 

(Clarithromycin) Adelglass 1998 b 

Clifford 1999‡

Henry 1999 b 

42-46 

29-42 

31-45 

Recurrence 0.70 

(0.42-1.15) -4.44 (-8.18 - -0.69) 

* No significant difference was found between combined study arms evaluating antibiotics in the same class (P ≥.05). ‡

 Per-protocol results for this study were significantly different than intent-to-treat results (P <.05). ‡

 Treatment results were significantly different between combined study arms evaluating the same antibiotic class (P 

<.05). 

§ Only studies with days of assessment entirely contained by the specified interval were included. || Results recorded 14 (vs. 7) days after treatment initiation were used. 
21

 1a. Is there evidence that duration of antibiotic treatment in acute 

 bacterial rhinosinusitis affects efficacy? 

 There are eight studies that reported data on comparisons of the effect of treatment duration 

on outcomes (Table 6). One study that compared 10 days with 5 days of amoxicillin/clavulanate 

500 mg tid reported a statistically non-significant 27% reduction in clinical failure rate3. Another 

study of ceftibuten concluded that 20 days of treatment may be more effective than either 10 

days or 15 days regimen (0% failure rate vs. 8% vs. 8%, respectively)4; however, the study did 

not report the actual number of patients who completed the study. Two studies of 10 days vs. 5 

days of telithromycin reported that the clinical failure rate between the two treatment durations 

were comparable.5,6 The studies on gemifloxacin (5 days vs. 7 days)7

, azithromycin (3 days vs. 6 

days)8

 and gatifloxacin (5 days vs. 10 days)9 showed therapeutic equivalence of the 2 durations. 

One study compared nasal smear findings for certain periods after different durations of 

antibiotic treatment and concluded that at least 2 weeks of antibiotics would be an appropriate 

treatment duration for acute maxillary sinusitis because the average nasal smear score (derived 

from number of neutrophils) was significantly different beginning from study day 21 between 

the 7-day-antibiotic group and the other groups. 10
22

Table 6. Comparing different durations of treatment in sinusitis Author Year Country Funding 

# Randomized 

 or Enrolled 

# per Protocol Antibiotic Dose Duration Time of evaluation of 1° outcome (days after start of Rx) Clinical failure rate per protocol Comm

181 5 days 12.7% Ferguson 

2002 

Canada & 

8 countries 

in Europe 

Pharm 423 175 Gemifloxacin 320 mg qd 7 days 18-25 13.1% 

Gehanno 181 5 days 21.6% 2000 France Pharm 433 179 Amox/clav 500 mg tid 10 days 14 15.6% Some 

steroid

272 3 days 28.3% 271 Azithromycin 500 mg qd 6 days 26.6% Henry 2003 US Pharm 941 251 Amox/clav 500/125 mg tid 10 days 22-36 28.7% 

10 1 week 50%* 10 2 week 20%* 10 3 week 20%* 

Kultluhan 2002 Turkey ND 

10 

ND 

Amox/clav 1 g bid or Ciprofloxacin 500 mg or Clarithromycin 500 mg bid or Cefuroxime 250 mg bid; Choice of abx depending on maxillary sinus puncture C&S results. 4 week 

28 

30%* 

*calcurate at assumcomplage ra16-45 of studnasal not cli

146 5 days 24.7% 140 Telithromycin 800 mg qd 10 days 27.1% 

Luterman 2003 

US 

Canada 

S. Africa 

Argentina 

Chile 

Pharm 754 

137 Amox/clav 500/125 mg tid 10 days 

17-24 

25.5% 

Stabiliamox/patiengroup & replaexcludreporte

123 5 days 8.9% 

Roos 2002 

9 countries 

in Europe ND 341 

133 

Telithromycin 800 mg qd 

10 days 

17-21 

9% 

Pts wiknown to telitRx weauthorwith P

137 5 days 25.6% 127 Gatifloxacin 400 mg qd 10 days 20.5% Sher 2002 ND ND 445 141 Amox/clav 875 mg bid 10 days 17-24 28.4% 2 auth

with P
23

Author Year Country Funding 

# Randomized 

 or Enrolled 

# per Protocol Antibiotic Dose Duration Time of evaluation of 1° outcome (days after start of Rx) Clinical failure rate per protocol Comm

50 Erythromycin- sulfisoxazole 

Erythromycin 

component 10 

mg/kg/dose 

qid 

14 days 4%* 

50 10 days 8%* 50 15 days 8%* 

Simon 1999 US ND 

50 

ND 

Ceftibuten 

9 mg/kg/day, 

maximum 400 

mg/day 20 days 

17-27 

(1 week 

after end of 

Rx) 

0%* 

*repordenomstatedsubjec17 yeanot ob

Abx: antibiotics; Amox/clav: amoxicillin/clavulanate; bid: twice a day; C&S: culture and sensitivities; ND: no data or not explicitly stated; Pindustry; qd: once a day; qid: four times a day; Rx: prescription; tid: three times a day; y/o: years old.
24

2. What adverse effects are reported for antibiotics used for acute 

bacterial rhinosinusitis? 

 Thirty-four of the comparative trials and five additional non-comparative trials reported 

adverse events. Descriptions of adverse events were diverse among studies. Almost all reported 

probable treatment-related adverse events, but many of them did not state the criteria for 

determining whether an event was considered likely treatment-related or not. Several studies also 

graded the severity of events; however, no study gave clear criteria for the grading scale. Other 

studies reported serious adverse events only. Few studies differentiated between severe (a 

description of degree) and serious (life-threatening, disabling or requiring prolonged 

hospitalization) events. Virtually all studies examined only short-term adverse events with 

assessment ending at the conclusion of patient follow-up 2 months or less after treatment 

initiation. 

 The overall percentage of subjects who reported at least one adverse event varied from 3% to 

88% (Table 7). In general, an average adverse event rate of 15% to 40% of subjects was 

observed for the different classes of antibiotic. The adverse event rate for placebo was in this 

range, as well. Severe adverse events were rare, occurring in 0 to 7.7% of subjects. Severe 

adverse events included diarrhea, abdominal pain and nausea on amoxicillin/clavulanate; 

abdominal pain, diarrhea, constipation, urticaria, headache/dizziness, loss of 

appetite/disorientation/insomnia and vaginitis/monilia on levofloxacin; headache, asthenia, 

diarrhea, vomiting, dizziness and agitation on moxifloxacin; vaginitis, headache, nausea, 

diarrhea, arthralgia, increased cough and dyspnea on cefuroxime; diaphoresis/rash and loss of 

appetite/disorientation/insomnia on clarithromycin; and increased coagulation test on faropenem. 

Very few specific serious adverse events were reported by studies. Reported serious adverse 

events included diplopia on amoxicillin/clavulanate; myocardial infarction, lumbar disk lesion 

and neuropathy on levofloxacin; asthma on sparfloxacin; allergic reaction, facial/tongue edema, 

hepatitis, asthma and convulsion on gatifloxacin; maxillary antral abscess, convulsions, and 

collapse during local anesthesia on clarithromycin; facial edema on ciprofloxacin; amblyopia, 

ischemic heart disease and maxillary sinus surgery on cefuroxime; and tachycardia on 

moxifloxacin. Discontinuation due to adverse events was uncommon with fewer than 10% of 

subjects removed from any trial due to adverse events. 

 It is difficult to compare the rates of occurrence of particular adverse events by antibiotic 

class given the heterogeneity among studies. Overall, the most common events involved the 

gastrointestinal system, specifically reports of nausea or vomiting, diarrhea and abdominal pain. 

Central nervous system adverse events, mostly complaints of headaches, were also common. 

Some subjects in each antibiotic class reported skin disorders, such as rash and photosensitivity. 

Taste perversion seemed to be a problem specific to clarithromycin administration with 

anywhere between 8% and 21% of study subjects reporting this complaint. 

 Cardiovascular problems were a particular concern to investigators of quinolones given their 

association with prolongation of the QTc interval on electrocardiogram. Nevertheless, cardiacrelated adverse event rates were low with quinolones, as well as for all classes of antibiotics. In 

the study conducted on 10,822 subjects with sinusitis by Faich et al. 11, an independent safety 

committee was convened to search for a link between moxifloxacin and cardiac-related events. 

Investigators asked patients specifically about symptoms suggestive of a possible cardiac event 

such as chest pain or tachycardia; however, electrocardiograms were not routinely collected. The 
25

committee concluded that there was no evidence of increased mortality or detectable treatmentassociated ventricular tachyarrhythmias in that trial. In a study of 253 patients treated with 

sparfloxacin conducted by Garrison et al.12 which did collect electrocardiograms on all patients, 

there was a mean increase in the QTc interval from baseline to day 4 of 0.010±0.024 sec., but no 

cardiovascular adverse events related to this increase. 

 Some women in each antibiotic class experienced vaginal moniliasis. Comparison of the 

rates of moniliasis between classes is problematic as the incidence reported by some studies may 

be under-estimated. Some reports are unclear as to whether they excluded men from the 

denominator in their calculations. Other studies did not specifically report the incidence of 

vaginal moniliasis but the incidence of vaginitis or urogenital complaints. 

 Tables 8 to 11 present the specific adverse events reported in each antibiotic class. 
26

Table 7: Summary ranges of percent of patients experiencing adverse events with placebo and each antibiotic 

Gastrointestinal # of 

Studies 

Subjects 

with Adverse 

Events, Overall % 

Nausea/ 

Vomiting Diarrhea Abdominal Pain CNS Skin/ Extr. CV Other† 

PLACEBO 

Placebo 3 3.2-27.1 (18.3,15.6)* 1.2 6.1-6.3 1.2-12.5 

CEPHALOSPORINS 

Cefdinir 1 33.6 2 21 2.3 1.7 Ceftibuten 1 11.8 9.2 Cefprozil 1 16.4 5 7.1 0.7 Cefuroxime 10 9.2-45 (17.7, 22.5)* 1.7-6.6 2-6.2 1.1-2.8 0.8- 5.5 2.9 1.7 Urogenita

2.3-2.9 

CARBAPENEMS 

Faropenem 1 16.8 

PENICILLINS

Amoxicillin/clavulanate 17 7-51.1 (25.6, 30.2)* 1.1-12.1 1.8-32.3 0.8-11.1 0- 2.7 2.5- 5.1 Vaginal moni

3-5.3 

Penicillin 1 18.3 15.5 

MACROLIDES, AZALIDES AND KETOLIDES

Azithromycin 4 4-34.3 (22.6, 29.1)* 4-8 4.2-19.1 3.4-4.2 3 1 Clarithromycin 6 9.7-82.4 (43.9, 42.3)* 4.8-7 5.6-27 3.6-3.7 0-9 0.5 Taste perver

7.7-20.9 

Roxithromycin 1 3.4 3.4 Telithromycin 3 22.2-42.4 (34.5, 35.3)* 3.6-10.6 6-19.9 3.3-4.2 1.5- 5.2 Vaginal moni

2.4 

QUINOLONES 

Ciprofloxacin 4 11.3-46 (38.3, 25.6)* 2.5 1-6 1.5- 6.7 Gatifloxacin 2 14 4.4-11.4 1.4-8 2.8 0.4 Gemifloxacin 1 37 ≥3 ≥3 Levofloxacin 5 8.8-87.9 (22.7, 30.1)* 0-5.6 0.9-2.7 1-1.9 2.8- 6.7 0.3 Moxifloxacin 6 12.2-58.1 (36.6, 18.8)* 1.2-14.1 1.2-9.5 1.9-4.1 1.6- 9.5 1.2- 3.8 1.2 

Nervousne

2.7-3.8 

Whole bod

3.8-9.5 

Sparfloxacin 2 45.6-54.9 (50.3, 50.3)* 4.3-4.8 7.5-23.8 1.6-2 4.3 7.9- 9.5 0 Trovafloxacin 1 32.7 4 1.2 1.6 11.6 
27

Abd: abdominal; CNS: central nervous system (headache or dizziness/vertigo); CV: cardiovascular (palpitations, syncope, arrhythmia, caND: no data; Skin/Extr: skin (photosensitivity, rash, urticaria, eczema flare, etc.) or extremities; *Median and weighted mean percentages reported if ≥2 studies for each antibiotic. †Other adverse events occurring in ≥ 2% of patients in at least 2 studies. 
28

Table 8: Adverse events for placebo and penicillins, N (%) 

Gastrointestinal 

Study 

Subjects 

with 

Adverse 

Events 

Nausea/ 

Vomiting Diarrhea Abd. Pain CNS Skin/ Extr. CV Other†

PLACEBO 

Hansen 2000 2/62 (3.2) 1 (1.6) Haye 1998 15/82 (18.3) 1 (1.2) 5 (6.1) 1 (1.2) Varonen 2003 13/48 (27.1) 3 (6.3) 6 (12.5) 0(0) Fatigue 3 (6.3) 

AMOXICILLIN/CLAVULANATE 

Adelglass 1998 a 53/138 (38.4) 14 (10.1) 35 (25.4) 7 (5.1) Adelglass 1999 146/302 (48.3) 5 (1.7) 35 (11.6) 5 (1.7) Chatzimanolis 1998 7/27 (25.9) 5 (18.5) 3 (11.1) Clement 1998 23/89 (25.8) 1 (1.1) 13 (14.6) 7 (7.9) 0 (0) Gehanno 2000 (Non-comparison study) 

46/433 (10.6) X X X X 

Gwaltney 1997 234/603 (38.8) 9 (1.5) 133 (22.1) 25 (4.1) 16 (2.7) Vaginal moniliasis: 18 (3.0) Henry 2003 || 160/313 (51.1) 38 (12.1) 101 (32.3) Henry 1999 a || 38/131 (29.0) 6 (4.6) 25 (19.1) Vaginitis: 5 (3.8) Jareoncharsri 2004 2/26 (7.7) X X Klapan 1999 5/50 (10) 5 (10.0) 1 (2.0) Luterman 2003§ 101/245 (41.2) 19 (7.8) 58 (23.7) 6 (2.4) 5 (2.0) Vaginal moniliasis: 13 (5.3) Namyslowski 2002 8/115 (7) 3 (2.6) Rakkar 2001 60/237 (25.3) 13 (5.5) 24 (10.1) 2 (0.8) 5 (2.1) 6 (2.5) 

Whole body: 20 (8.4) 

Moniliasis: 15 (6.3) 

Asthenia: 5 (2.1) 

Urogenital: 9 (3.8) 

Elevated LFTs: 11 (4.6) 

Seggev 1998 26/170 (15.3) 4 (2.4) 3 (1.8) 6 (3.5) 2 (1.2) Fungal infection: 10 (5.6) Sher 2002 not reported (4) (14) Vaginitis: (9% of women) Sterkers 1997 16/146 (11) 15 (10.3) 

PENICILLIN 

Hansen 2000 13/71 (18.3) 11 (15.5) 

Numbers reported are for all adverse events, unless only likely drug-related adverse events were reported by a study. Abd: abdominal; CNS: central nervous system (headache or dizziness/vertigo); Skin/Extr: skin (photosensitivity, rash, urticaria, eczema fCV: cardiovascular (palpitations, syncope, arrhythmia, cardiac insufficiency, etc.); X: actual percent not reported 
29

* Denominator not specified, so based on number enrolled, or percentage stated by authors † Only reported for adverse events that occurred in ≥ 2%; see study summaries for less common adverse events. ‡ Estimated from stated odds ratio § Study only reported adverse events that occurred on at least 2 occasions. ||Study only reported adverse events that occurred in more t
30

Table 9: Adverse events for cephalosporins and faropenem, N (%) 

Gastrointestinal 

Study 

Subjects 

with 

Adverse 

Events 

Nausea/ 

Vomiting Diarrhea Abd. Pain CNS Skin/ Extr. CV Other† Stu

Withd

Due to 

Eve

CEFDINIR 

Gwaltney 1997 400/1189 (33.6) 24 (2.0) 250 (21.0) 27 (2.3) 20 (1.7) 27 

CEFIBUTEN 

Sterkers 1997 36/304 (11.8) 28 (9.2) 7 (

CEFPROZIL 

Adelglass 1998 a 23/140 (16.4) 7 (5.0) 10 (7.1) 1 (0.7) 3 (

CEFUROXIME 

Buchanan 2003 20/121 (16.5) 8 (6.6) 6 (5) 2 (1.7) Abnormally low creatinine clearance 2 (Burke 1999 112/274 (40.9) 11 (5.1) 17 (6.2) 3 (1.1) 15 (5.5) 8 (2.9) 

Whole body: 15 (5.5) 

Special senses: 9 

(3.3) 

Urogenital: 8 (2.9) 

6 (

Henry 1999 b 23/132 (17.4) 8 (6.1) Vaginitis 3 (2.3) 2 (Johnson 1999 113/251 (45)* X X X 6 (2Klein 1998 10/28 (34)* X X 1 (2Namyslowski 2002 11/116 (9.5) 3 (2.6) 9 (Siegert 2003 49/273 (17.9) X X 2 (Siegert 2000 88/252 (35.1) 9 (3.6) 15 (6.0) 7 (2.8) 2 (0.8) 11 Stefansson 1998 17/185 (9.2) 13 (7.0) NWeis 1998 81/700 (11.6) 12 (1.7) 14 (2.0) 12 (1.7) 26 

FAROPENEM 

Siegert 2003 46/274 (16.8) X X 7 (

Numbers reported are for all adverse events, unless only likely drug-related adverse events were reported by a study. Abd: abdominal; CNS: central nervous system (headache or dizziness/vertigo); Skin/Extr: skin (photosensitivity, rash, urticaria, eczema fCV: cardiovascular (palpitations, syncope, arrhythmia, cardiac insufficiency, etc.); X: actual percent not reported. 
31

* Denominator not specified, so based on number enrolled, or percentage stated by authors. † Only reported for adverse events that occurred in ≥ 2%; see study summaries for less common adverse events. ‡ Estimated from stated odds ratio § Study only reported adverse events that occurred on at least 2 occasions || Study only reported adverse events that occurred in more than 5% of subjects 
32

Table 10: Adverse events for macrolides, azalides and ketolide, N (%) 

Gastrointestinal 

Study Subjects with Adverse Events Nausea/ 

Vomiting Diarrhea Abd. Pain CNS Skin/ Extr. CV Other†

AZITHROMYCIN 

Clement 1998 29/165 (17.6) 8 (4.8) 7 (4.2) 7 (4.2) 5 (3) 2 (1) Haye 1998 24/87 (27.6) 7 (8) 11 (12.6) 3 (3.4) Henry 2003 || 214/623 (34.3) 50 (8) 119 (19.1) Klapan 1999 2/50 (4) 2 (4) 

CLARITHROMYCIN 

Adelglass 1998 b 88/108 (82.4) 7 (6.5) 6 (5.6) 4 (3.7) 0 (0) 

Taste perversion: 13 

(12.0) 

Fungal infection: 3 (2.8) 

Insomnia: 3 (2.8) 

Clifford 1999 158/278 (56.8) Overall GI: 81 (29.1) Diarrhea: 36 (13.0) 25 (9) Taste perversion: 58 (20.9) Special senses: 60 (21.6) Henry 1999 b 122/252 (48.4) 12 (4.8) 68 (27) 9 (3.6) 1 (0.5) Taste perversion: 22 (8.7) Elevated LFT's or blood glucose: 6 (2.4) Lasko 1998 46/117 (39.3) 39 (33.3) 5 (4.3) Taste perversion: 9 (7.7) Murray 2000 85/283 (30) (7) (7) Taste perversion: (10) Stefansson 1998 18/185 (9.7) 8 (4.3) 

ROXITHROMYCIN 

Chatzimanolis 1998 1/29 (3.4) 1 (3.4) 

TELITHROMYCIN 

Buchanan 2003 56/252 (22.2) 22 (8.7) 15 (6) 7 (2.8) Abnormally low creatinine clearance Luterman 2003|| 211/498 (42.4) 53 (10.6) 99 (19.9) 21 (4.2) 26 (5.2) Vaginal moniliasis: 12 (2.4) Roos 2002 115/333 (34.5) 12 (3.6) 38 (11.4) 11 (3.3) 5 (1.5) Vaginal moniliasis: 8 (2.4) 

Numbers reported are for all adverse events, unless only likely drug-related adverse events were reported by a study. Abd: abdominal; CNS: central nervous system (headache or dizziness/vertigo); Skin/Extr: skin (photosensitivity, rash, urticaria, eczema fCV: cardiovascular (palpitations, syncope, arrhythmia, cardiac insufficiency, etc.); X: actual percent not reported 

* Denominator not specified, so based on number enrolled, or percentage stated by authors † Only reported for adverse events that occurred in ≥ 2%; see study summaries for less common adverse events. ‡ Estimated from stated odds ratio 
33

§ Study only reported adverse events that occurred on at least 2 occasions || Study only reported adverse events that occurred in more than 5% of subjects 
34

Table 11: Adverse events for quinolones, N (%) 

Gastrointestinal 

Study 

Subjects with 

Adverse 

Events 

Nausea/ 

Vomiting Diarrhea Abd. Pain CNS Skin/ Extr. CV Other†

CIPROFLOXACIN 

Clifford 1999 120/282 (42.6) Overall GI: 58 (20.6) Diarrhea: 17 (6.0) 19 (6.7) Taste Perversion: 7 (2.5

Special senses: 14 (5) 

Johnson 1999 115/250 (46)* X X X Klein 1998 10/28 (34)* X X Weis 1998 80/711 (11.3) 18 (2.5) 7 (1) 11 (1.5) 

GATIFLOXACIN 

Sher 2002 ND (11.4) (8) Vaginitis in women: (9) Sher 2002 (noncomparison) 1605/11,476(14) 505 (4.4) 161 (1.4) 321 (2.8) 41 (0.4) 

GEMIFLOXACIN 

Ferguson 2002 (37) (≥3) (≥3) 

LEVOFLOXACIN 

Adelglass 1998 b 94/107 (87.9) 6 (5.6) 1 (0.9) 2 (1.9) 3 (2.8) Adelglass 1999 114/297 (38.4) 0 (0) 4 (1.3) 3 (1) Jareoncharsri 2004 3/34 (8.8) X X X X Lasko 1998 27/119 (22.7) 20 (16.8) 8 (6.7) Sydnor 1998 29/329 (9) 4 (1.2) 9 (2.7) 1 (0.3) 

MOXIFLOXACIN 

Burke 1999 126/263 (47.9) 37 (14.1) 18 (6.8) 5 (1.9) 25 (9.5) 9 (3.4) Whole body: 25 (9.5) Nervousness: 7 (2.7) Gehanno 2003§ 31/255 (12.2) 6 (2.4) 3 (1.2) 6 (2.4) 4 (1.6) 3 (1.2) 3 (1.2) Faich 2004 1793/10,822 (16.6) 827 (8.1) 259 (2.4) 378 (3.5) Whole body: 371 (3.4) Klossek 2003 74/248 (29.8) 3 (1.2) 14 (5.6) 5 (2) 5 (2) Asthenia: 5 (2.0) Rakkar 2001 136/234 (58.1) 33 (14.1) 7 (3) 5 (2.1) 9 (3.8) 9 (3.8) 

Moniliasis 8 (3.4) Nervousness: 9 (3.8) Special senses 7 (3.0) 

Siegert 2000 105/242 (43.3) 17 (7) 23 (9.5) 10 (4.1) 7 (2.9) 

SPARFLOXACIN 

Henry 1999 b 115/252 (45.6) 12 (4.8) 60 (23.8) 4 (1.6) 24 (9.5) Elevated LFT’s or blood glucose: 8 (3.2) Garrison 2000 139/253 (54.9) 11 (4.3) 19 (7.5) 5 (2) 11 (4.3) 20 (7.9) 0 (0) Insomnia: 7 (2.8) 

TROVAFLOXACIN 

Klossek 2003 82/251 (32.7) 10 (4) 3 (1.2) 4 (1.6) 29 (11.6) Asthenia: 6 (2.4) 
35

Numbers reported are for all adverse events, unless only likely drug-related adverse events were reported by a study. Abd: abdominal; CNS: central nervous system (headache or dizziness/vertigo); Skin/Extr: skin (photosensitivity, rash, urticaria, eczema fCV: cardiovascular (palpitations, syncope, arrhythmia, cardiac insufficiency, etc.); X: actual percent not reported 

* Denominator not specified, so based on number enrolled, or percentage stated by authors † Only reported for adverse events that occurred in ≥ 2%; see study summaries for less common adverse events. ‡ Estimated from stated odds ratio 

§ Study only reported adverse events that occurred on at least 2 occasions || Study only reported adverse events that occurred in more than 5% of subjects 
36

3. How does the introduction of the pneumococcal vaccine affect the 

resistance patterns of pneumococcus and the treatment decisions in 

acute bacterial rhinosinusitis?

 We did not identify any article in our literature search that directly addressed this question. 

Streptococcus pneumoniae is one of the most common pathogens identified in acute bacterial 

sinusitis. In the early 2000, a 7-valent pneumococcal conjugate vaccine (PCV7) was approved 

for routine administration to infants and children in United States. In the same year, the 

American Academy of Pediatrics (AAP) recommended routine administration of PCV7 to all 

children 23 months and younger.13 It is therefore, important to monitor the changes in serotypes 

and antibiotic susceptibility of S. pneumoniae as a result of the introduction of PCV7 to the 

population. Furthermore, recommendations for treatment of acute bacterial sinusitis may well 

have to be modified depending on the results of the surveillance. Surveillance data are already 

appearing demonstrating the changing epidemiology of S. pneumoniae serogroups after the 

introduction of PCV7. Data collected from the US Pediatric Multicenter Pneumococcal 

Surveillance Group reported that before the licensure, nonvaccine serogroups accounted for 6% 

of the isolates recovered from children ≤ 24 months old; in 2002, nonvaccine-serogroup isolates 

were 37.6% of the total isolates in this age group. Also, among the isolates of S. Pneumoniae 

belonging to the serogroups contained in PCV7, the proportion that were nonsusceptible to 

penicillin decreased from 54% in 2001 to 43% in 2002.14 Another report reported that rate of 

invasive pneumococcal disease decreased from an average of 24.3 cases per 100,000 persons in 

1998 and 1999 to 17.3 per 100,000 in 2001. The largest decline was in children under two years 

of age. Disease rates also fell for adults. This observation suggests that the use of pneumococcal 

vaccine in children may be reducing the rate of disease in adults as well.15 A randomized 

controlled trial between 1995 and 1999 involving 1,662 infants reported that the heptavalent 

pneumococcal vaccine reduced the number of episodes of acute otitis media by 6% (95% CI -4 

to 16%) and also reduced the number of episodes due to the serotypes contained in the vaccine 

by 57% (95% CI 44 to 67%), whereas the number of episodes due to all other serotypes 

increased by 33%.16 This suggests that the impact of pneumococcal immunization on acute 

sinusitis in adults will also depend on the virulence and resistance patterns of the serotypes that 

replace those contained in the vaccine. 
37

Chapter 4. Conclusions and Discussion 

 This report examined the available evidence from randomized trials on the efficacy of 

antibiotics in patients with acute bacterial rhinosinusitis published since our original report in 

1999. Overall, as in our previous report, antibiotics were found to be superior to placebo in the 

treatment of sinusitis, reducing the risk of clinical failure by almost 30%. Judging from the 

prevalence of comparisons involving amoxicillin/clavulanate, it appears that most investigators 

view this antibiotic as the preferred agent in a comparative drug trial. It is also more effective 

than the cephalosporin class of antibiotics in the treatment of sinusitis, reducing clinical failure 

rate by approximately 40% within 10-25 days after treatment initiation. However, in absolute 

terms, this implies that for every 100 patients treated with a cephalosporin, only about 3.5 more 

clinical failures would occur than in patients treated with amoxicillin/clavulanate. The 

superiority in clinical efficacy of amoxicillin/clavulanate over cephalosporins disappears when 

patients are examined for recurrence 24-45 days after treatment initiation. 

 There are only a few studies that specifically examined the effect of different treatment 

durations on outcome efficacy. In the one study of 10 vs. 5 days of amoxicillin/clavulanate, the 

10-day regimen showed a statistically non-significant reduction of clinical failure by 27% (22% 

of patients failed on 5 days of treatment compared to 16% on 10 days of treatment). Studies on 

telithromycin (10 vs. 5 days), gemifloxacin (7 vs. 5 days), gatifloxacin (10 vs. 5 days) and 

azithromycin (6 vs. 3 days) all showed therapeutic equivalence between the 2 durations. In 

conclusion, most of the studies generally found no difference between shorter and longer 

duration of treatment. 

 It is difficult to compare the rates of adverse events 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% to more than 30%. This may be due to a lack of an agreed definition of 

diarrhea, different study populations, and different reporting criteria. In all classes of antibiotics, 

gastrointestinal disturbances were most common, followed by headaches and skin rashes, as well 

as vaginal moniliasis. Cardiovascular complaints were rare. Severe adverse events in general 

occurred in up to about 3.5% of patients in all classes. 

 As of September 2004, there had not been any published studies examining the effect of the 

pneumococcal vaccine on the treatment of acute sinusitis. Preliminary surveillance data suggests 

a changing epidemiology of Streptococcus pneumoniae as a result of the introduction of the 7-

valent pneumococcal vaccine in the pediatric population. Prevalence of different pneumococcal 

serotypes and their resistance patterns will have to be continually monitored to help guide the 

optimal treatment of acute sinusitis. 

Limitations 

 Heterogeneous study population across studies, different definitions of clinical 

success/failure, studies powered primarily for non-inferiority rather than superiority, relatively 

few studies within each comparison grouping, and the possibility of publication bias all lend 

limitations to our meta-analyses. Different inclusion criteria may also affect the comparability of 

the populations across studies. In some studies, patients were recruited from general practices 

and in others, from otolaryngology practices. In addition to requiring an abnormal sinus 
38

radiograph for study entry, some trials also included C-reactive protein and erythrocyte 

sedimentation rate cut-offs in their inclusion criteria. Definitions of cure ranged from 

symptomatic relief to radiographic resolution to no days with restricted activities at home or 

work. Sinus aspirations and cultures, the gold standard for diagnosing and assessing bacterial 

sinusitis were performed in a minority of trials. 

 Fifteen of 39 studies included in this review explicitly stated the power calculation used to 

determine sample size a priori. Virtually all of these studies were powered to demonstrate noninferiority rather than superiority of one treatment over another. Given that the rate of 

spontaneous clinical resolution of acute bacterial sinusitis is approximately 65% and even higher 

with antibiotics, demonstration of superiority of one treatment over another requires extremely 

large sample sizes. 

 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 has important implications for healthcare cost 

containment. We are unaware of any sound reasons in 2005 why amoxicillin and trimethoprimsulfamethoxazole should not be used in comparative trials in treatment of bacterial sinusitis; 

although, our update did not specifically examine the resistance patterns of various pathogens in 

the last few years to amoxicillin and folate inhibitors. 

Future Research 

 In the future, more studies that incorporate bacteriological data will help characterize the 

changing epidemiology of acute sinusitis. We used per-protocol results for our meta-analyses, as 

these are more consistently reported than intention-to-treat results. To reduce the possibility of 

bias, intention-to-treat population should be uniformly defined across studies and data should be 

collected and reported in addition to per-protocol results. 

Almost all the trials sponsored by pharmaceutical companies concluded that the 

sponsored drug was either superior or therapeutically equivalent to the comparator, thus raising 

the concern that there may be unpublished trials with negative results. This concern can only be 

resolved if results from all drug trials are duly reported. In addition, the pharmaceutical 

companies' research agenda appears to be driven by the desire to compare their products against 

those of their competitors. Such an agenda does not necessarily address clinically important 

issues that are relevant to the management of acute bacterial rhinosinusitis. Such potential bias 

can be addressed if there is funding from government and other independent entities to support 

research, which has as its primary objective the improvement of care of patients with acute 

bacterial rhinosinusitis. 

 Compared to our previous report in 1999, the quality of studies in this field has improved. All 

the studies stated explicit inclusion and exclusion criteria, method of analyses and primary 

outcome measurements. However, in order to make meaningful comparisons across studies; 

there should be general agreement in defining eligibility criteria, clinical success and failure, 

appropriate time of outcome assessment and precise criteria for numerators and denominators in 

the calculation of clinical success or failure rates. 
39

References and Included Studies 

References

1. Lau J, Zucker D, Engels E et al. Diagnosis and 

treeatment of acute bacterial rhinosinusitis. 

Evidence Report/Technology Assessment No. 

9 (Prepared by Tufts-New England Medical 

Center Evidence-based Practice Center under 

Contract 290-97-0019). Rockville, MD, 

Agency for Health Care Policy and Research. 

March 1999. 

2. National Kidney Foundation. K/DOQI clinical 

practice guidelines for chronic kidney disease: 

evaluation, classification, and stratification. 

Kidney Disease Outcome Quality Initiative. 

Am J Kidney Dis2002; 39(2:Suppl 2):Suppl246. 

3. 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. 

4. Simon MW. Treatment of acute sinusitis in 

childhood with ceftibuten. Clin Pediatr 

1999;38(5):269-72. 

5. 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 2003;J82(8):576-80, 82-4, 586 passim. 

6. Roos K, BrunswigPitschner 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. 

7. 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. 

8. 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. 

9. 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. 

10. Kutluhan A, Akdeniz H, Kaya Z et al. The 

treatment duration of acute maxillary sinusitis: 

how long should it be? A nasal smear 

controlled study. Rhinology 2002;40(4):198-

202. 

11. Faich GA, Morganroth J, Whitehouse AB et 

al. Clinical experience with moxifloxacin in 

patients with respiratory tract infections. Ann 

Pharmacother 2004;38(5):749-54. 

12. Garrison N, Spector S, Buffington D et al. 

Sparfloxacin for the treatment of acute 

bacterial maxillary sinusitis documented by 

sinus puncture. Ann Allergy Asthma Immunol 

2000; 84(1):63-71. 

13. American Academy of Pediatrics. Committee 

on Infectious Diseases. Policy statement: 

recommendations for the prevention of 

pneumococcal infections, including the use of 

pneumococcal conjugate vaccine (Prevnar), 

pneumococcal polysaccharide vaccine, and 

antibiotic prophylaxis. Pediatrics 2000;106(2 

Pt 1):362-6. 

14. Kaplan SL, Mason EO, Jr., Wald ER et al. 

Decrease of invasive pneumococcal infections 

in children among 8 children's hospitals in the 

United States after the introduction of the 7-

valent pneumococcal conjugate vaccine.[see 

comment]. Pediatrics 2004;113(3 Pt 1):443-9. 

15. Whitney CG, Farley MM, Hadler J et al. 

Decline in invasive pneumococcal disease 

after the introduction of proteinpolysaccharide conjugate vaccine.[see 

comment]. N Engl J Med 2003;348(18):1737-

46. 

16. Eskola J, Kilpi T, Palmu A et al. Efficacy of a 

pneumococcal conjugate vaccine against acute 

otitis media. N Engl J Med 2001; 344(6):403-

9. 
40 

Bibliography

American Academy of Pediatrics. Committee on Infectious 

Diseases. Policy statement: recommendations for the 

prevention of pneumococcal infections, including the use of 

pneumococcal conjugate vaccine (Prevnar), pneumococcal 

polysaccharide vaccine, and antibiotic prophylaxis. 

Pediatrics 2000 Aug;106(2 Pt 1):362-6. 

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 NovDec;20(6):1115-29. 

Adelglass J, Jones TM, Ruoff G, et al. A multicenter, 

investigator-blinded, randomized comparison of oral 

levofloxacin and oral clarithromycin in the treatment of 

acute bacterial sinusitis. Pharmacotherapy 

1998;18(6):1255-63. 

Adelglass J, DeAbate CA, McElvaine P, et al. Comparison 

of the effectiveness of levofloxacin and 

amoxicillin/clavulanate for the treatment of acute sinusitis 

in adults.[see comment]. Otolaryngol Head Neck Surg 

1999 Mar;120(3):320-7. 

Buchanan PP, Stephens TA, Leroy B. A comparison of the 

efficacy of telithromycin versus cefuroxime axetil in the 

treatment of acute bacterial maxillary sinusitis. Am J 

Rhinol 2003;17(6):369-77. 

Bucher HC, Tschudi P, Young J, et al. Effect of 

amoxicillin/clavulanate in clinically diagnosed acute 

rhinosinusitis: a placebo-controlled, double-blind, 

randomized trial in general practice.[see comment]. Arch 

Intern Med 2003 Aug 11-25;163(15):1793-8. 

Burke T, Villanueva C, Mariano H, Jr., et al. Comparison 

of moxifloxacin and cefuroxime axetil in the treatment of 

acute maxillary sinusitis. Sinusitis Infection Study Group. 

Clin Ther 1999 Oct;21(10):1664-77. 

Chatzimanolis E, Marsan N, Lefatzis D, et al. Comparison 

of roxithromycin with co-amoxiclav in patients with 

sinusitis. J Antimicrob Chemother 1998 Mar;41 Suppl 

B:81-4. 

Clement PA, de Gandt JB. A comparison of the efficacy, 

tolerability and safety of azithromycin and co-amoxiclav in 

the treatment of sinusitis in adults. J Int Med Res 1998 

Mar-Apr;26(2):66-75. 

Clifford K, Huck W, Shan M, et al. Double-blind 

comparative trial of ciprofloxacin versus clarithromycin in 

the treatment of acute bacterial sinusitis. Sinusitis Infection 

Study Group. Ann Otol Rhinol Laryngol 1999 

Apr;108(4):360-7. 

Eskola J, Kilpi T, Palmu A, et al. Efficacy of a 

pneumococcal conjugate vaccine against acute otitis media. 

N Engl J Med 2001 Feb 8;344(6):403-9. 

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 Jul;127(1):1-6. 

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. 

Gwaltney JM, Jr., Savolainen S, Rivas P, et al. 

Comparative effectiveness and safety of cefdinir and 

amoxicillin/clavulanate in treatment of acute communityacquired bacterial sinusitis. Cefdinir Sinusitis Study Group. 

Antimicrobial Agents Chemother 1997 Jul;41(7):1517-20. 

Hansen JG, Schmidt H, Grinsted P. Randomised, double 

blind, placebo controlled trial of penicillin V in the 

treatment of acute maxillary sinusitis in adults in general 

practice. Scand J Prim Health Care 2000 Mar;18(1):44-7. 

Haye R, Lingaas E, Hoivik HO, et al. Azithromycin versus 

placebo in acute infectious rhinitis with clinical symptoms 

but without radiological signs of maxillary sinusitis. Eur J 

Clin Microbiol Infect Dis 1998 May;17(5):309-12. 

Henry DC, Moller DJ, Jr., Adelglass J, et al. Comparison of 

sparfloxacin and clarithromycin in the treatment of acute 

bacterial maxillary sinusitis. Sparfloxacin Multicenter AMS 

Study Group. Clin Ther 1999 Feb;21(2):340-52. 

Henry DC, Sydnor A, Jr., Settipane GA, et al. Comparison 

of cefuroxime axetil and amoxicillin/clavulanate in the 

treatment of acute bacterial sinusitis. Clin Ther 1999 

Jul;21(7):1158-70. 

Henry DC, Riffer E, Sokol WN, et al. Randomized doubleblind 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 

Sep;47(9):2770-4. 

Jareoncharsri P, Bunnag C, Fooanant S, et al. An open 

label, randomized comparative study of levofloxacin and 

amoxicillin/clavulanic acid in the treatment of purulent 

sinusitis in adult Thai patients. Rhinology 2004 

Mar;42(1):23-9. 
41

Johnson PA, Rodriguez HP, Wazen JJ, et al. Ciprofloxacin 

versus cefuroxime axetil in the treatment of acute bacterial 

sinusitis. Sinusitis Infection Study Group. J Otolaryngol 

1999 Feb;28(1):3-12. 

Kaplan SL, Mason EO, Jr., Wald ER, et al. Decrease of 

invasive pneumococcal infections in children among 8 

children's hospitals in the United States after the 

introduction of the 7-valent pneumococcal conjugate 

vaccine.[see comment]. Pediatrics 2004 Mar;113(3 Pt 

1):443-9. 

Klapan I, Culig J, Oreskovic K, et al. Azithromycin versus 

amoxicillin/clavulanate in the treatment of acute sinusitis. 

Am J Otolaryngol 1920;(1):7-11. 

Klein GL, Whalen E, Echols RM, et al. Ciprofloxacin 

versus cefuroxime axetil in the treatment of adult patients 

with acute bacterial sinusitis. J Otolaryngol 1998 

Feb;27(1):10-6. 

Klossek JM, Siegert R, Nikolaidis P, et al. Comparison of 

the efficacy and safety of moxifloxacin and trovafloxacin 

for the treatment of acute, bacterial maxillary sinusitis in 

adults. J Laryngol Otol 2003 Jan;117(1):43-51. 

Kutluhan A, Akdeniz H, Kaya Z, et al. The treatment 

duration of acute maxillary sinusitis: how long should it 

be? A nasal smear controlled study. Rhinology 2002 

Dec;40(4):198-202. 

Lasko B, Lau CY, SaintPierre C, et al. Efficacy and safety 

of oral levofloxacin compared with clarithromycin in the 

treatment of acute sinusitis in adults: a multicentre, doubleblind, randomized study. The Canadian Sinusitis Study 

Group. J Int Med Res 1998 Dec;26(6):281-91. 

Lau J, Zucker D Engels EA Balk E et al. Diagnosis and 

treatment of acute bacterial rhinosinusitis. (Contract 290-

97-0019 to the New England Medical Center). Evidence 

Report/Technology Assessment No.9. Rockville, MD, 

Agency for Health Care Policy and Research. 1999. 

Lindbaek M, Kaastad E, Dolvik S, et al. Antibiotic 

treatment of patients with mucosal thickening in the 

paranasal sinuses, and validation of cut-off points in sinus 

CT. Rhinology 1998 Mar;36(1):7-11. 

Luterman M, Tellier G, Lasko B, et al. 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 Aug;82(8):576-80, 82-4, 

586 passim. 

Murray JJ, Solomon E, McCluskey D, et al. Phase III, 

randomized, double-blind study of clarithromycin 

extended-release and immediate-release formulations in the 

treatment of adult patients with acute maxillary sinusitis. 

Clin Ther 2000 Dec;22(12):1421-32. 

Namyslowski G, Misiolek M, Czecior E, et al. Comparison 

of the efficacy and tolerability of amoxicillin/clavulanic 

acid 875 mg b.i.d. with cefuroxime 500 mg b.i.d. in the 

treatment of chronic and acute exacerbation of chronic 

sinusitis in adults. J Chemother 2002 Oct;14(5):508-17. 

National Kidney Foundation. K/DOQI clinical practice 

guidelines for chronic kidney disease: evaluation, 

classification, and stratification. Kidney Disease Outcome 

Quality Initiative. Am J Kidney Dis 2002 Feb;39(2:Suppl 

2):Suppl-246. 

Rakkar S, Roberts K, Towe BF, et al. Moxifloxacin versus 

amoxicillin clavulanate in the treatment of acute maxillary 

sinusitis: a primary care experience. Int J Clin Pract 2001 

Jun;55(5):309-15. 

Roos K, BrunswigPitschner 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 May;48(2):100-8. 

Seggev JS, Enrique RR, Brandon ML, et al. A combination 

of amoxicillin and clavulanate every 12 hours vs. every 8 

hours for treatment of acute bacterial maxillary sinusitis. 

Arch Otolaryngol Head Neck Surg 1998 Aug;124(8):921-5. 

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 

Feb;24(2):269-81. 

Siegert R, Gehanno P, Nikolaidis P, et al. A comparison of 

the safety and efficacy of moxifloxacin (BAY 12-8039) and 

cefuroxime axetil in the treatment of acute bacterial 

sinusitis in adults. The Sinusitis Study Group. Respir Med 

2000 Apr;94(4):337-44. 

Siegert R, Berg O, Gehanno P, et al. Comparison of the 

efficacy and safety of faropenem daloxate and cefuroxime 

axetil for the treatment of acute bacterial maxillary sinusitis 

in adults. Eur Arch Otorhinolaryngol 2003 

Apr;260(4):186-94. 

Simon MW. Treatment of acute sinusitis in childhood with 

ceftibuten. Clin Pediatr 1999 May;38(5):269-72. 

Stefansson P, Jacovides A, Jablonicky P, et al. Cefuroxime 

axetil versus clarithromycin in the treatment of acute 

maxillary sinusitis. Rhinology 1998 Dec;36(4):173-8. 

Sterkers O. Efficacy and tolerability of ceftibuten versus 

amoxicillin/clavulanate in the treatment of acute sinusitis. 

Chemotherapy 1997 Sep-Oct;43(5):352-7. 

Steurer M, Schenk P. Efficacy and safety of cefdinir in the 

treatment of maxillary sinusitis. Eur Arch 

Otorhinolaryngol 2000;257(3):140-8. 
42

Varonen H, Kunnamo I, Savolainen S, et al. Treatment of 

acute rhinosinusitis diagnosed by clinical criteria or 

ultrasound in primary care. A placebo-controlled 

randomised trial. Scand J Prim Health Care 2003 

Jun;21(2):121-6. 

Weis M, Hendrick K, Tillotson G, et al. Multicenter 

comparative trial of ciprofloxacin versus cefuroxime axetil 

in the treatment of acute rhinosinusitis in a primary care 

setting. Rhinosinusitis Investigation Group. Clin Ther 

1920;(5):921-32. 

Whitney CG, Farley MM, Hadler J, et al. Decline in 

invasive pneumococcal disease after the introduction of 

protein-polysaccharide conjugate vaccine.[see comment]. 

N Engl J Med 2003 May 1;348(18):1737-46. 
43 

List of Excluded Studies

Aitken M, Taylor JA. Prevalence of clinical sinusitis in 

young children followed up by primary care pediatricians. 

Arch Pediatr Adolesc Med 1998 Mar;152(3):244-8. 

Observational cohort study 

Casillas JL, Rico G, RodriguezParga D, et al. Multicenter 

evaluation of the efficacy and safety of gatifloxacin in 

Mexican adult outpatients with respiratory tract infections. 

Adv Ther 2000 Nov;-Dec;17(6):263-71. 

Non-comparative study. 

Dowzicky M, Nadler H, Dorr MB, et al. Comparison of the 

in vitro activity of and pathogen responses to sparfloxacin 

with those of other agents in the treatment of respiratory 

tract, urinary tract, and skin and skin-structure infections. 

Clin Ther 1999 May;21(5):790-805; discussion 789. 

Non-comparative study 

Ficnar B, Huzjak N, Oreskovic K, et al. Azithromycin: 3-

day versus 5-day course in the treatment of respiratory tract 

infections in children. Croatian Azithromycin Study Group. 

J Chemother 1997 Feb;9(1):38-43. 

Mixed population 

Fogarty CM, Kohno S, Buchanan P, et al. Communityacquired respiratory tract infections caused by resistant 

pneumococci: clinical and bacteriological efficacy of the 

ketolide telithromycin. J Antimicrob Chemother 2003 

Apr;51(4):947-55. 

Mixed population 

Kaiser L, Morabia A, Stalder H, et al. Role of 

nasopharyngeal culture in antibiotic prescription for 

patients with common cold or acute sinusitis. Eur J Clin 

Microbiol Infect Dis 1920;(7):445-51. 

Mixed population 

Kakish KS, Mahafza T, Batieha A, et al. Clinical sinusitis 

in children attending primary care centers. Pediatric 

Infectious Disease Journal 2000;19(11):1071-4. 

Observational cohort study 

Kroslak M. Efficacy and acceptability of fusafungine, a 

local treatment for both nose and throat infections, in adult 

patients with upper respiratory tract infections. Curr Med 

Res Opin 2002;18(4):194-200. 

Mixed population 

Lauvau DV, Verbist L. An open, multicentre, comparative 

study of the efficacy and safety of azithromycin and coamoxiclav in the treatment of upper and lower respiratory 

tract infections in children. The Paediatric Azithromycin 

Study Group. J Int Med Res 1997 Sep-Oct;25(5):285-95. 

Not sinusitis 

Lindbaek M, Hjortdahl P. Predictors of duration of acute 

sinusitis episodes treated with antibiotics. Scand J Prim 

Health Care 1998 Mar;16(1):24-9. 

Cohort study 

Ludwig E. Cefixime in the treatment of respiratory and 

urinary tract infections. Chemotherapy 1998 Sep;44 Suppl 

1:31-4. 

Mixed population, non-comparative study 

Medeiros EA. Treatment of adults with communityacquired respiratory tract infections: results of a 

multicentric clinical trial with gatifloxacin. Braz J Infect 

Dis 2002 Aug;6(4):149-56. 

Non-comparative study 

Mira E, Benazzo M. A multicenter study on the clinical 

efficacy and safety of roxithromycin in the treatment of 

ear-nose-throat infections: comparison with 

amoxicillin/clavulanic acid. J Chemother 2001 

Dec;13(6):621-7. 

Mixed population 

Mosges R, Spaeth J, Berger K, et al. Topical treatment of 

rhinosinusitis with fusafungine nasal spray. A double-blind, 

placebo-controlled, parallel-group study in 20 patients. 

Arzneimittel-Forschung 2002;52(12):877-83. 

Not sinusitis 

Ng DK, Chow PY, Leung L, et al. A randomized controlled 

trial of azithromycin and amoxicillin/clavulanate in the 

management of subacute childhood rhinosinusitis. J 

Paediatr Child Health 2000 Aug;36(4):378-81. 

Chronic sinusitis 

Nicholson SC, High KP, Gothelf S, et al. Gatifloxacin in 

community-based treatment of acute respiratory tract 

infections in the elderly. Diagn Microbiol Infect Dis 2002 

Sep;44(1):109-16. 

Non-comparative study
A-1

Appendix A: Search Strategies 

Ovid: Search from MEDLINE ® 

< 1966 to September Week 2 2004> 

Sinusitis Update 

# Search History Results

1 rhinosinus$.tw. 1103 

2 sinusitis.tw. 6979 

3 exp Sinusitis/ 9502 

4 or/1-3 11736 

5 (upper adj6 respirat$).tw. 9698 

6 Infect$.tw. 643403 

7 sinus$.tw. 74358 

8 6 and (5 or 7) 9665 

9 4 or 8 19042 

10 limit 9 to human 17756 

11 limit 10 to english language 12205 

12 In Vitro/ 327623 

13 11 not 12 12162 

14 196$.yr. 888556 

15 197$.yr. 2410634

16 198$.yr. 3208775

17 (1991$ or 1992$ or 1993$ or 1994$ or 1995$ or 1996$).yr. 2480047

18 13 not (or/14-17) 5737 

19 exp ANTIMICROBIAL CATIONIC PEPTIDES/ 2756 

20 exp Anti-Infective Agents/ 815121 

21 exp Anti-Bacterial Agents/ 324676 

22 trimethoprim.mp. 11682 

23 Amdinocillin.mp. 523 

24 alamethicin.mp. 490 

25 amikacin.mp. 4730 

26 amphotericin.mp. 12324 
A-2

# Search History Results

27 ampicillin.mp. 17897 

28 amoxicillin.mp. 8189 

29 anisomycin.mp. 1232 

30 ANTIMYCIN.mp. 3401 

31 aurodox.mp. 31 

32 azithromycin.mp. 2513 

33 azlocillin.mp. 724 

34 aztreonam.mp. 1982 

35 bacitracin.mp. 2443 

36 bambermycin$.mp. 92 

37 Bongkrekic.mp. 302 

38 brefeldin.mp. 2693 

39 butirosin sulfate.mp. 61 

40 calcimycin.mp. 11117 

41 candicidin.mp. 241 

42 capreomycin sulfate.mp. 137 

43 carbenicillin.mp. 2899 

44 carfecillin.mp. 37 

45 cefaclor.mp. 1398 

46 exp Cefadroxil/ 394 

47 Cefadroxil.mp. 529 

48 exp Cefamandole/ 1907 

49 Cefamandole.mp. 1544 

50 cefazolin.mp. 2933 

51 cefixime.mp. 883 

52 cefmenoxime.mp. 480 

53 cefmetazole.mp. 542 

54 cefonicid.mp. 234 

55 cefoperazone.mp. 1774 

56 cefotaxime.mp. 6872 

57 cefotetan.mp. 652 
A-3

# Search History Results

58 cefotiam.mp. 592 

59 cefoxitin.mp. 2981 

60 cefsulodin.mp. 554 

61 ceftazidime.mp. 4564 

62 ceftizoxime.mp. 1325 

63 ceftriaxone.mp. 4735 

64 cefuroxime.mp. 2722 

65 Cephacetrile.mp. 156 

66 Cephalexin.mp. 2489 

67 cephaloglycin.mp. 119 

68 Cephaloridine.mp. 1967 

69 exp Cephalosporins/ 29060 

70 cephalothin.mp. 3513 

71 Cephamycins.mp. 1391 

72 cephapirin.mp. 306 

73 cephradine.mp. 721 

74 Chloramphenicol.mp. 28895 

75 chlortetracycline.mp. 2203 

76 citrinin.mp. 318 

77 clarithromycin.mp. 4329 

78 Clavulanic Acid$.mp. 3306 

79 clindamycin.mp. 5827 

80 Cloxacillin.mp. 1869 

81 colistin.mp. 1648 

82 cyclacillin.mp. 103 

83 dactinomycin.mp. 16697 

84 daptomycin.mp. 286 

85 demeclocycline.mp. 653 

86 dibekacin.mp. 518 

87 dicloxacillin.mp. 690 

88 dihydrostreptomycin sulfate.mp. 639 
A-4

# Search History Results

89 distamycins.mp. 672 

90 doxycycline.mp. 5949 

91 echinomycin.mp. 178 

92 edeine.mp. 116 

93 enviomycin.mp. 69 

94 Erythromycin.mp. 15895 

95 Erythromycin Estolate.mp. 190 

96 Erythromycin Ethylsuccinate.mp. 505 

97 filipin.mp. 808 

98 floxacillin.mp. 421 

99 fosfomycin.mp. 1341 

100 framycetin.mp. 268 

101 fusidic acid.mp. 1464 

102 Gentamicin$.mp. 18514 

103 gramicidin.mp. 2713 

104 hygromycin b.mp. 901 

105 imipenem.mp. 4800 

106 josamycin.mp. 550 

107 Kanamycin.mp. 8823 

108 kitasamycin.mp. 45 

109 exp Lactams/ 78059 

110 Lactams.mp. 7122 

111 lasalocid.mp. 728 

112 Leucomycins.mp. 1703 

113 Lincomycin.mp. 2387 

114 lymecycline.mp. 105 

115 mepartricin.mp. 92 

116 methacycline.mp. 360 

117 methicillin.mp. 8925 

118 mezlocillin.mp. 990 

119 mikamycin.mp. 23 
A-5

# Search History Results

120 minocycline.mp. 2908 

121 miocamycin.mp. 291 

122 moxalactam.mp. 1455 

123 mupirocin.mp. 679 

124 mycobacillin.mp. 49 

125 nafcillin.mp. 680 

126 natamycin.mp. 502 

127 nebramycin.mp. 101 

128 Neomycin.mp. 8741 

129 netilmicin.mp. 1578 

130 netropsin.mp. 557 

131 nigericin.mp. 1575 

132 nisin.mp. 771 

133 novobiocin.mp. 2049 

134 nystatin.mp. 3316 

135 Oleandomycin.mp. 794 

136 Oligomycins.mp. 2565 

137 oxacillin.mp. 2863 

138 oxytetracycline.mp. 3880 

139 paromomycin.mp. 979 

140 penicillanic acid.mp. 1524 

141 penicillic acid.mp. 153 

142 exp Penicillins/ 48539 

143 penicillin.mp. 29069 

144 piperacillin.mp. 3081 

145 pivampicillin.mp. 308 

146 polymyxin$.mp. 5058 

147 pristinamycin.mp. 291 

148 prodigiosin.mp. 315 

149 ribostamycin.mp. 131 

150 Rifabutin.mp. 806 
A-6

# Search History Results

151 rifamycin$.mp. 1518 

152 ristocetin.mp. 2162 

153 rolitetracycline.mp. 262 

154 roxarsone.mp. 78 

155 roxithromycin.mp. 955 

156 rutamycin.mp. 73 

157 sirolimus.mp. 3153 

158 Sisomicin.mp. 678 

159 spectinomycin.mp. 1697 

160 spiramycin.mp. 915 

161 exp Streptogramins/ 1072 

162 Streptogramin$.mp. 742 

163 Streptomycin.mp. 13591 

164 Streptovaricin.mp. 123 

165 sulbactam.mp. 1677 

166 sulbenicillin.mp. 165 

167 talampicillin.mp. 103 

168 teicoplanin.mp. 1915 

169 tetracycline.mp. 22308 

170 thiamphenicol.mp. 609 

171 thiostrepton.mp. 311 

172 ticarcillin.mp. 1650 

173 tobramycin.mp. 4593 

174 troleandomycin.mp. 648 

175 tunicamycin.mp. 3618 

176 tylosin.mp. 887 

177 tyrocidine.mp. 170 

178 Tyrothricin.mp. 507 

179 valinomycin.mp. 3665 

180 vancomycin.mp. 10205 

181 vernamycin.mp. 19 
A-7

# Search History Results

182 Virginiamycin.mp. 1099 

183 cycloserine.mp. 1546 

184 rifampin.mp. 12623 

185 viomycin.mp. 441 

186 Amoxicillin-Potassium Clavulanate Combination.mp. 1184 

187 antitreponemal.mp. 89 

188 ethambutol.mp. 3654 

189 ethionamide.mp. 989 

190 iproniazid.mp. 938 

191 isoniazid.mp. 11012 

192 prothionamide.mp. 223 

193 pyrazinamide.mp. 2312 

194 thioacetazone.mp. 391 

195 p-aminosalicylic acid.mp. 470 

196 Thalidomide.mp. 3133 

197 Acedapsone.mp. 42 

198 Clofazimine.mp. 985 

199 Dapsone.mp. 4057 

200 Ethionamide.mp. 989 

201 Sulfameter.mp. 50 

202 telithromycin.mp. 366 

203 exp ciprofloxacin/ 6711 

204 ciprofloxacin.mp. 10454 

205 exp fluroquinolones/ 0 

206 fluroquino$.mp. 24 

207 Trimethoprim-Sulfamethoxazole.mp. 6168 

208 or/19-207 873109 

209 18 and 208 1391 

210 

limit 209 to (addresses or bibliography or biography or case reports or 

congresses or consensus development conference or consensus development 

conference, nih or dictionary or directory or editorial or festschrift or 

government publications or guideline or interview or lectures or legal cases or 

687 
A-8

# Search History Results

legislation or letter or meta analysis or news or newspaper article or patient 

education handout or periodical index or practice guideline or "review" or 

review, academic or "review literature" or review, multicase or "review of 

reported cases" or review, tutorial) 

211 209 not 210 704 

212 from 211 keep 1 1 
A-9

Ovid MEDLINE(R) 

<1966 to September Week 3 2004> 

Pneumococcal Vaccine 

# Search History Results 

1 exp vaccines/ 97637 

2 vaccin$.mp. 139243 

3 1 or 2 142925 

4 exp Pneumonia/ 46421 

5 pneumo$.tw. 108436 

6 4 or 5 126474 

7 3 and 6 5881 

8 exp pneumococcal vaccines/ 1599 

9 7 or 8 6054 

10 limit 9 to human 4797 

11 limit 10 to "all child (0 to 18 years)" 2297 

12 10 not 11 2500 

13 limit 12 to "all adult (19 plus years)" 1220 

14 10 not 13 3577 

15 limit 14 to english language 3055 

16 

limit 15 to (addresses or bibliography or biography or case reports or 

congresses or consensus development conference or consensus development 

conference, nih or dictionary or directory or editorial or festschrift or 

government publications or guideline or interview or lectures or legal cases 

or legislation or letter or meta analysis or news or newspaper article or 

patient education handout or periodical index or practice guideline or 

"review" or review, academic or "review literature" or review, multicase or 

"review of reported cases" or review, tutorial) 

1125 

17 15 not 16 1930 

18 limit 17 to yr=1996-2004 1129 

19 exp ANTIMICROBIAL CATIONIC PEPTIDES/ 2763 

20 exp Anti-Infective Agents/ 815813 

21 exp Anti-Bacterial Agents/ 324881 

22 trimethoprim.mp. 11684 

23 Amdinocillin.mp. 523 
A-10

# Search History Results 

24 alamethicin.mp. 490 

25 amikacin.mp. 4731 

26 amphotericin.mp. 12332 

27 ampicillin.mp. 17907 

28 amoxicillin.mp. 8194 

29 anisomycin.mp. 1232 

30 ANTIMYCIN.mp. 3405 

31 aurodox.mp. 31 

32 azithromycin.mp. 2519 

33 azlocillin.mp. 724 

34 aztreonam.mp. 1982 

35 bacitracin.mp. 2445 

36 bambermycin$.mp. 92 

37 Bongkrekic.mp. 302 

38 brefeldin.mp. 2695 

39 butirosin sulfate.mp. 61 

40 calcimycin.mp. 11122 

41 candicidin.mp. 242 

42 capreomycin sulfate.mp. 137 

43 carbenicillin.mp. 2899 

44 carfecillin.mp. 37 

45 cefaclor.mp. 1399 

46 exp Cefadroxil/ 394 

47 Cefadroxil.mp. 529 

48 exp Cefamandole/ 1907 

49 Cefamandole.mp. 1544 

50 cefazolin.mp. 2933 

51 cefixime.mp. 883 

52 cefmenoxime.mp. 480 

53 cefmetazole.mp. 542 

54 cefonicid.mp. 234 
A-11

# Search History Results 

55 cefoperazone.mp. 1774 

56 cefotaxime.mp. 6872 

57 cefotetan.mp. 652 

58 cefotiam.mp. 592 

59 cefoxitin.mp. 2981 

60 cefsulodin.mp. 554 

61 ceftazidime.mp. 4566 

62 ceftizoxime.mp. 1325 

63 ceftriaxone.mp. 4740 

64 cefuroxime.mp. 2724 

65 Cephacetrile.mp. 156 

66 Cephalexin.mp. 2491 

67 cephaloglycin.mp. 119 

68 Cephaloridine.mp. 1967 

69 exp Cephalosporins/ 29070 

70 cephalothin.mp. 3513 

71 Cephamycins.mp. 1391 

72 cephapirin.mp. 306 

73 cephradine.mp. 721 

74 Chloramphenicol.mp. 28903 

75 chlortetracycline.mp. 2204 

76 citrinin.mp. 318 

77 clarithromycin.mp. 4333 

78 Clavulanic Acid$.mp. 3306 

79 clindamycin.mp. 5828 

80 Cloxacillin.mp. 1869 

81 colistin.mp. 1648 

82 cyclacillin.mp. 103 

83 dactinomycin.mp. 16699 

84 daptomycin.mp. 286 

85 demeclocycline.mp. 653 
A-12

# Search History Results 

86 dibekacin.mp. 518 

87 dicloxacillin.mp. 690 

88 dihydrostreptomycin sulfate.mp. 639 

89 distamycins.mp. 672 

90 doxycycline.mp. 5954 

91 echinomycin.mp. 178 

92 edeine.mp. 116 

93 enviomycin.mp. 69 

94 Erythromycin.mp. 15904 

95 Erythromycin Estolate.mp. 190 

96 Erythromycin Ethylsuccinate.mp. 505 

97 filipin.mp. 809 

98 floxacillin.mp. 421 

99 fosfomycin.mp. 1341 

100 framycetin.mp. 268 

101 fusidic acid.mp. 1464 

102 Gentamicin$.mp. 18524 

103 gramicidin.mp. 2717 

104 hygromycin b.mp. 901 

105 imipenem.mp. 4800 

106 josamycin.mp. 550 

107 Kanamycin.mp. 8824 

108 kitasamycin.mp. 45 

109 exp Lactams/ 78094 

110 Lactams.mp. 7130 

111 lasalocid.mp. 729 

112 Leucomycins.mp. 1703 

113 Lincomycin.mp. 2388 

114 lymecycline.mp. 106 

115 mepartricin.mp. 92 

116 methacycline.mp. 360 
A-13

# Search History Results 

117 methicillin.mp. 8933 

118 mezlocillin.mp. 990 

119 mikamycin.mp. 23 

120 minocycline.mp. 2908 

121 miocamycin.mp. 291 

122 moxalactam.mp. 1455 

123 mupirocin.mp. 679 

124 mycobacillin.mp. 49 

125 nafcillin.mp. 680 

126 natamycin.mp. 502 

127 nebramycin.mp. 101 

128 Neomycin.mp. 8747 

129 netilmicin.mp. 1578 

130 netropsin.mp. 558 

131 nigericin.mp. 1575 

132 nisin.mp. 771 

133 novobiocin.mp. 2050 

134 nystatin.mp. 3316 

135 Oleandomycin.mp. 794 

136 Oligomycins.mp. 2567 

137 oxacillin.mp. 2864 

138 oxytetracycline.mp. 3882 

139 paromomycin.mp. 981 

140 penicillanic acid.mp. 1526 

141 penicillic acid.mp. 153 

142 exp Penicillins/ 48564 

143 penicillin.mp. 29083 

144 piperacillin.mp. 3082 

145 pivampicillin.mp. 308 

146 polymyxin$.mp. 5059 

147 pristinamycin.mp. 292 
A-14

# Search History Results 

148 prodigiosin.mp. 316 

149 ribostamycin.mp. 131 

150 Rifabutin.mp. 807 

151 rifamycin$.mp. 1519 

152 ristocetin.mp. 2162 

153 rolitetracycline.mp. 262 

154 roxarsone.mp. 79 

155 roxithromycin.mp. 956 

156 rutamycin.mp. 73 

157 sirolimus.mp. 3173 

158 Sisomicin.mp. 678 

159 spectinomycin.mp. 1697 

160 spiramycin.mp. 915 

161 exp Streptogramins/ 1074 

162 Streptogramin$.mp. 742 

163 Streptomycin.mp. 13593 

164 Streptovaricin.mp. 123 

165 sulbactam.mp. 1678 

166 sulbenicillin.mp. 165 

167 talampicillin.mp. 103 

168 teicoplanin.mp. 1916 

169 tetracycline.mp. 22315 

170 thiamphenicol.mp. 609 

171 thiostrepton.mp. 311 

172 ticarcillin.mp. 1650 

173 tobramycin.mp. 4594 

174 troleandomycin.mp. 650 

175 tunicamycin.mp. 3618 

176 tylosin.mp. 889 

177 tyrocidine.mp. 170 

178 Tyrothricin.mp. 507 
A-15

# Search History Results 

179 valinomycin.mp. 3666 

180 vancomycin.mp. 10208 

181 vernamycin.mp. 19 

182 Virginiamycin.mp. 1101 

183 cycloserine.mp. 1547 

184 rifampin.mp. 12633 

185 viomycin.mp. 441 

186 Amoxicillin-Potassium Clavulanate Combination.mp. 1184 

187 antitreponemal.mp. 89 

188 ethambutol.mp. 3655 

189 ethionamide.mp. 989 

190 iproniazid.mp. 938 

191 isoniazid.mp. 11017 

192 prothionamide.mp. 223 

193 pyrazinamide.mp. 2313 

194 thioacetazone.mp. 391 

195 p-aminosalicylic acid.mp. 471 

196 Thalidomide.mp. 3140 

197 Acedapsone.mp. 42 

198 Clofazimine.mp. 987 

199 Dapsone.mp. 4058 

200 Ethionamide.mp. 989 

201 Sulfameter.mp. 50 

202 telithromycin.mp. 368 

203 exp ciprofloxacin/ 6719 

204 ciprofloxacin.mp. 10462 

205 exp fluroquinolones/ 0 

206 fluroquino$.mp. 24 

207 Trimethoprim-Sulfamethoxazole.mp. 6169 

208 or/19-207 873848 

209 18 and 208 273 
A-16

# Search History Results 

210 rhinosinus$.tw. 1103 

211 sinusitis.tw. 6984 

212 exp Sinusitis/ 9506 

213 or/210-212 11742 

214 (upper adj6 respirat$).tw. 9703 

215 Infect$.tw. 644056 

216 sinus$.tw. 74408 

217 215 and (214 or 216) 9675 

218 213 or 217 19055 

219 limit 218 to human 17767 

220 limit 219 to english language 12215 

221 In Vitro/ 327772 

222 220 not 221 12172 

223 196$.yr. 888556 

224 197$.yr. 2410634 

225 198$.yr. 3208776 

226 (1991$ or 1992$ or 1993$ or 1994$ or 1995$ or 1996$).yr. 2480055 

227 222 not (or/223-226) 5747 

228 exp ANTIMICROBIAL CATIONIC PEPTIDES/ 2763 

229 exp Anti-Infective Agents/ 815813 

230 exp Anti-Bacterial Agents/ 324881 

231 trimethoprim.mp. 11684 

232 Amdinocillin.mp. 523 

233 alamethicin.mp. 490 

234 amikacin.mp. 4731 

235 amphotericin.mp. 12332 

236 ampicillin.mp. 17907 

237 amoxicillin.mp. 8194 

238 anisomycin.mp. 1232 

239 ANTIMYCIN.mp. 3405 

240 aurodox.mp. 31 
A-17

# Search History Results 

241 azithromycin.mp. 2519 

242 azlocillin.mp. 724 

243 aztreonam.mp. 1982 

244 bacitracin.mp. 2445 

245 bambermycin$.mp. 92 

246 Bongkrekic.mp. 302 

247 brefeldin.mp. 2695 

248 butirosin sulfate.mp. 61 

249 calcimycin.mp. 11122 

250 candicidin.mp. 242 

251 capreomycin sulfate.mp. 137 

252 carbenicillin.mp. 2899 

253 carfecillin.mp. 37 

254 cefaclor.mp. 1399 

255 exp Cefadroxil/ 394 

256 Cefadroxil.mp. 529 

257 exp Cefamandole/ 1907 

258 Cefamandole.mp. 1544 

259 cefazolin.mp. 2933 

260 cefixime.mp. 883 

261 cefmenoxime.mp. 480 

262 cefmetazole.mp. 542 

263 cefonicid.mp. 234 

264 cefoperazone.mp. 1774 

265 cefotaxime.mp. 6872 

266 cefotetan.mp. 652 

267 cefotiam.mp. 592 

268 cefoxitin.mp. 2981 

269 cefsulodin.mp. 554 

270 ceftazidime.mp. 4566 

271 ceftizoxime.mp. 1325 
A-18

# Search History Results 

272 ceftriaxone.mp. 4740 

273 cefuroxime.mp. 2724 

274 Cephacetrile.mp. 156 

275 Cephalexin.mp. 2491 

276 cephaloglycin.mp. 119 

277 Cephaloridine.mp. 1967 

278 exp Cephalosporins/ 29070 

279 cephalothin.mp. 3513 

280 Cephamycins.mp. 1391 

281 cephapirin.mp. 306 

282 cephradine.mp. 721 

283 Chloramphenicol.mp. 28903 

284 chlortetracycline.mp. 2204 

285 citrinin.mp. 318 

286 clarithromycin.mp. 4333 

287 Clavulanic Acid$.mp. 3306 

288 clindamycin.mp. 5828 

289 Cloxacillin.mp. 1869 

290 colistin.mp. 1648 

291 cyclacillin.mp. 103 

292 dactinomycin.mp. 16699 

293 daptomycin.mp. 286 

294 demeclocycline.mp. 653 

295 dibekacin.mp. 518 

296 dicloxacillin.mp. 690 

297 dihydrostreptomycin sulfate.mp. 639 

298 distamycins.mp. 672 

299 doxycycline.mp. 5954 

300 echinomycin.mp. 178 

301 edeine.mp. 116 

302 enviomycin.mp. 69 
A-19

# Search History Results 

303 Erythromycin.mp. 15904 

304 Erythromycin Estolate.mp. 190 

305 Erythromycin Ethylsuccinate.mp. 505 

306 filipin.mp. 809 

307 floxacillin.mp. 421 

308 fosfomycin.mp. 1341 

309 framycetin.mp. 268 

310 fusidic acid.mp. 1464 

311 Gentamicin$.mp. 18524 

312 gramicidin.mp. 2717 

313 hygromycin b.mp. 901 

314 imipenem.mp. 4800 

315 josamycin.mp. 550 

316 Kanamycin.mp. 8824 

317 kitasamycin.mp. 45 

318 exp Lactams/ 78094 

319 Lactams.mp. 7130 

320 lasalocid.mp. 729 

321 Leucomycins.mp. 1703 

322 Lincomycin.mp. 2388 

323 lymecycline.mp. 106 

324 mepartricin.mp. 92 

325 methacycline.mp. 360 

326 methicillin.mp. 8933 

327 mezlocillin.mp. 990 

328 mikamycin.mp. 23 

329 minocycline.mp. 2908 

330 miocamycin.mp. 291 

331 moxalactam.mp. 1455 

332 mupirocin.mp. 679 

333 mycobacillin.mp. 49 
A-20

# Search History Results 

334 nafcillin.mp. 680 

335 natamycin.mp. 502 

336 nebramycin.mp. 101 

337 Neomycin.mp. 8747 

338 netilmicin.mp. 1578 

339 netropsin.mp. 558 

340 nigericin.mp. 1575 

341 nisin.mp. 771 

342 novobiocin.mp. 2050 

343 nystatin.mp. 3316 

344 Oleandomycin.mp. 794 

345 Oligomycins.mp. 2567 

346 oxacillin.mp. 2864 

347 oxytetracycline.mp. 3882 

348 paromomycin.mp. 981 

349 penicillanic acid.mp. 1526 

350 penicillic acid.mp. 153 

351 exp Penicillins/ 48564 

352 penicillin.mp. 29083 

353 piperacillin.mp. 3082 

354 pivampicillin.mp. 308 

355 polymyxin$.mp. 5059 

356 pristinamycin.mp. 292 

357 prodigiosin.mp. 316 

358 ribostamycin.mp. 131 

359 Rifabutin.mp. 807 

360 rifamycin$.mp. 1519 

361 ristocetin.mp. 2162 

362 rolitetracycline.mp. 262 

363 roxarsone.mp. 79 

364 roxithromycin.mp. 956 
A-21

# Search History Results 

365 rutamycin.mp. 73 

366 sirolimus.mp. 3173 

367 Sisomicin.mp. 678 

368 spectinomycin.mp. 1697 

369 spiramycin.mp. 915 

370 exp Streptogramins/ 1074 

371 Streptogramin$.mp. 742 

372 Streptomycin.mp. 13593 

373 Streptovaricin.mp. 123 

374 sulbactam.mp. 1678 

375 sulbenicillin.mp. 165 

376 talampicillin.mp. 103 

377 teicoplanin.mp. 1916 

378 tetracycline.mp. 22315 

379 thiamphenicol.mp. 609 

380 thiostrepton.mp. 311 

381 ticarcillin.mp. 1650 

382 tobramycin.mp. 4594 

383 troleandomycin.mp. 650 

384 tunicamycin.mp. 3618 

385 tylosin.mp. 889 

386 tyrocidine.mp. 170 

387 Tyrothricin.mp. 507 

388 valinomycin.mp. 3666 

389 vancomycin.mp. 10208 

390 vernamycin.mp. 19 

391 Virginiamycin.mp. 1101 

392 cycloserine.mp. 1547 

393 rifampin.mp. 12633 

394 viomycin.mp. 441 

395 Amoxicillin-Potassium Clavulanate Combination.mp. 1184 
A-22

# Search History Results 

396 antitreponemal.mp. 89 

397 ethambutol.mp. 3655 

398 ethionamide.mp. 989 

399 iproniazid.mp. 938 

400 isoniazid.mp. 11017 

401 prothionamide.mp. 223 

402 pyrazinamide.mp. 2313 

403 thioacetazone.mp. 391 

404 p-aminosalicylic acid.mp. 471 

405 Thalidomide.mp. 3140 

406 Acedapsone.mp. 42 

407 Clofazimine.mp. 987 

408 Dapsone.mp. 4058 

409 Ethionamide.mp. 989 

410 Sulfameter.mp. 50 

411 telithromycin.mp. 368 

412 exp ciprofloxacin/ 6719 

413 ciprofloxacin.mp. 10462 

414 exp fluroquinolones/ 0 

415 fluroquino$.mp. 24 

416 Trimethoprim-Sulfamethoxazole.mp. 6169 

417 or/228-416 873848 

418 227 and 417 1394 

419 

limit 418 to (addresses or bibliography or biography or case reports or 

congresses or consensus development conference or consensus development 

conference, nih or dictionary or directory or editorial or festschrift or 

government publications or guideline or interview or lectures or legal cases 

or legislation or letter or meta analysis or news or newspaper article or 

patient education handout or periodical index or practice guideline or 

"review" or review, academic or "review literature" or review, multicase or 

"review of reported cases" or review, tutorial) 

689 

420 418 not 419 705 

421 209 not 420 262 
A-23

# Search History Results 

422 from 421 keep 1 1 
B-1

Appendix B: Data Extraction Form 

Extraction Form 

Name Year ID# 

Stated Purpose of the Study: 

Population & Setting: 

X patients from? # of (ENT?, Primary care?) centers in ? country from ? study years. 

Drug1 group (n=): Mean age (range)= N yrs (J-K) Males= N (M%) 

Drug2 group (n=): Mean age (range)= N yrs (J-K) Males= N (M%) 

Inclusion Criteria:

≥X y.o. in outpatient? setting with Si/Sx of acute sinusitis/acute exacerbation of chronic sinusitis (based 

on ?) of X duration AND radiologic signs (air-fluid levels?, opacification? or mucosal thickening≥6mm?) 

Exclusion Criteria: ? 

Study Design: Randomized (? method of randomization and concealment), double / not blinded (list 

method of masking), multi-center? trial. ? if pre-stratified by center. 

Treatments: Drug 1 X mg D for X days 

 Drug 2 X mg D for Y days 

Outcome: (Primary) End of study? (X weeks after enrollment) 

 (Secondary) End of therapy? (Y weeks after enrollment) 

Stated definitions of success and failure... 

Results: ? enrolled and randomized. X/Y in Drug1group and A/B in Drug2 group were evaluated for 

clinical efficacy (intent to treat analysis / per protocol analysis). X/Y in Drug1 group and A/B in Drug2 

group were excluded for reasons including: ? 

1. Clinical Failure: (Primary) X/Y in Drug1 group and A/B in Drug2 group failed. (Secondary) 

X/Y in Drug1 group and A/B in Drug2 group failed.

2. Microbiological Failure: Most common pathogens isolated at baseline: A, B, C. Determined 

by sinus aspiration? at baseline and X weeks after treatment. X/Y in Drug1 group and A/B in 

Drug2 group failed. 

Adverse Events: Adverse events occurred in X/Y in Drug1 group (nausea=#, diarrhea=#, other=#), and 

A/B in Drug2 goup (nausea=#, diarrhea=#, other=#). Discontinuation due to major adverse events 

occurred in X/Y in Drug1 group (symptoms causing d/c) and A/B in Drug2 group (symptoms). 

Funding: ? 

Comments: Use of adjuvant therapy? Compliance with study medications is? 
C-1

Appendix C: Evidence Tables 

Adelglass et al. 1998 ID 534 

Stated Purpose of the Study: To compare the efficacy and tolerability of cefprozil with 

amoxicillin/clavulanate in the treatment of adults with severe acute bacterial sinusitis 

Population & Setting: 278 patients from multi-center enrolled in the study, study years not 

specified. Patients were stratified according to the severity of disease before randomization. 

Baseline statistics: 

Cefprozil 140 Mean age 36.9 Males 42% 

Amox/Clav 138 Mean age 37 Males 50% 

Inclusion criteria: ≥ 13 y/o; signs and symptoms of acute sinusitis; abnormal sinus x-ray, 

women of childbearing potential were required to have a negative pregnancy test on enrollment, 

be using an acceptable method of contraception, and not be lactating 

Exclusion criteria: hx of hypersensitivity to beta-lactam abx; abx within 24 h of study entry, 

long-acting parenteral PCN within 2 weeks of enrollment; see paper for others 

Study design: Multicenter, open-label study. To achieve balance in the severity of signs and 

symptoms, the eligible patients were stratified according to the severity of disease before 

randomization. Method of randomization not explicitly stated. 

Treatments: 

Cefprozil 500 mg twice a day for 10 days 

Amox/Clav 500/125 mg three times a day for 10 days 

Outcome: 

Primary – clinical response satisfactory (either cure or improvement, based on a clinical score) or 

unsatisfactory, assessed on days 11 – 15 (after the initiation of treatment) 

Secondary – assessment for relapse 2 weeks after the end of therapy 

Sinus cultures were not performed as part of the study. 

See paper for subgroup analysis for “severe sinusitis.” 

Results: 

278 patients randomized into 2 groups (cefprozil 140; amox/clav 138) 

219 assessable for efficacy (cefprozil 108; amox/clav 111) 

Clinical failure – Cefprozil 15/108 (13.9%); Amox/Clav 9/111 (8.1%) 

2-week post treatment follow up Failure – Cefprozil 18/100 (18%); Amox/Clav 16/99 (16.2%) 

Adverse events: 

At least one event cefprozil 23/140 (16.4%) amox/clav 53/138 (38.4%) 

Diarrhea 10/140 (7.1%) 35/138 (25.4%) 

Nausea 4/140 (2.9%) 12/138 (8.7%) 

Rash 1/140 (0.7%) 7/138 (5.1%) 

See table VII in paper for others. 

3 patients treated with cefprozil and 9 patients treated with amox/clav discontinued treatment 

because of adverse events, most commonly diarrhea (cefprozil 2; amox/clav 7). 

Funding: Bristol-Myers Squibb 

Comments: 
C-2

Adelglass et al. 1998 ID 540 

Stated Purpose of the Study: To compare the clinical efficacy and safety of oral levofloxacin 

once daily for 14 days with those of oral clarithromycin twice daily for 14 days in patients with 

acute bacterial sinusitis 

Population & Setting: 

216 patients from 20 sites were randomized into 2 groups (108 in each group). 

Levofloxacin 101 mean age (range) 41.1 (18-83) males 58.4% 

Clarithromycin 89 mean age (range) 38.8 (19-68) males 70.8% 

Inclusion criteria: ≥ 18 y/o; radiograph supported dx of acute bacterial sinusitis (see paper for 

details regarding clinical criteria); x-ray showed opacification, air-fluid level, and/or mucosal 

thickening of ≥ 5 mm; see paper for others 

Exclusion criteria: chronic sinusitis (presence of current signs/symptoms for > 4 weeks or > 2 

episodes of acute sinusitis within the past 12 months); calculated creatinine clearance ≤ 50 

ml/min; nasal steroids and others (see paper) 

Study design: randomized, single (investigator) – blinded, parallel group study; subject 

randomization list was computer-generated and stratified by site; equal numbers of subjects were 

assigned to each treatment group; 

Treatments: 

Levofloxacin oral 500 mg once daily in AM for 14 days 

Clarithromycin oral 500 mg twice a day for 14 days 

Outcome: 

Primary: clinical response 2-5 days post treatment; clinical success was defined as cure or 

improvement 

Secondary: relapse rate assessed one month after therapy 

Results: 

216 patients were randomized; 190 evaluable. 4/101 in Levofloxacin group withdrew due to 

symptomatic failure; 5/89 in Clarithromycin group withdrew (4 due to symptomatic failure; 1 for 

other reasons) 

Reported clinical failure rate: Levofloxacin 4/101 (4%) Clarithromycin 6/89 (6.7%) 

ITT analysis: Levofloxacin 8/108 (7.4%) Clarithromycin 17/108 (15.7%) 

One month after therapy relapse rate: Levofloxacin 4/97 (4.1%) Clarithromycin 6/83 (7.2%) 

Adverse events: 

2 serious events in Levofloxacin group, lumbar disk lesion and neuropathy, not felt to be 

treatment related by investigator 

 Levofloxacin (n=107) Clarithromycin (n=108) 

At least one adverse event 94 (87.9%) 89 (82.4%) 

Drug-related adverse event 15 (14%) 25 (23.1%) 

Abdominal pain 2 (1.9%) 4 (3.7%) 

Dizziness 3 (2.8%) 0 

Nausea 6 (5.6%) 7 (6.5%) 

Diarrhea 1 (0.9%) 6 (5.6%) 
C-3

Insomnia 1 (0.9%) 3 (2.8%) 

Taste perversion 1 (0.9%) 13 (12%) 

Fungal infection 2 (1.9%) 3 (2.8%) 

See table 3 in paper for rest. 

Funding: Ortho-McNeil Pharmaceutical 

Comments: 
C-4

Adelglass et al. 1999 ID 490 

Stated Purpose of the Study: To compare the efficacy and safety of levofloxacin 500 mg 

orally once daily for 10-14 days with those of amox/clav 500/125 mg orally 3 times daily for 10-14 

days in treating acute sinusitis in adult outpatients. 

Population & Setting: 615 patients from 28 centers in US enrolled in the study. 307 randomly 

assigned to levofloxacin and 308 to amox/clav. Patients were enrolled by both office-based 

primary care physicians and otolaryngologists, study years not specified. 

Baseline statistics: 

Levofloxacin 306 Mean age (range) 39.2 (18-85) Males 37.6% 

Amox/Clav 309 Mean age (range) 38.6 (18-84) Males 35.6% 

Inclusion criteria: ≥ 18 y/o; female and male outpatients with 2/5 typical signs and symptoms 

of acute sinusitis (see paper for details); radiographic evidence including air-fluid level, 

opacification, or ≥ 4 mm mucosal thickening of at least 1 sinus on sinus x-ray, CT, or sinus scope 

Exclusion criteria: hx of hypersensitivity to beta-lactam abx levofloxacin or any quinolone; 

chronic sinusitis > 4 weeks, pregnancy (or inability to r/o pregnancy), breast feeding, calculated 

creatinine clearance of ≤ 20 mL/min, see paper for others 

Study design: Multicenter, open-label study. Method of randomization not explicitly stated. 

Treatments: 

for patients with normal renal function, Levofloxacin 500 mg once daily for 10 – 14 days; 

for patients with creatinine clearance of 50 mL/min, an initial loading dose of levofloxacin 500 mg 

followed by 500 mg every 48 hours; 

Amox/Clav 500/125 mg every 8 hours for 10 – 14 days, dosage was adjusted in accordance with 

package insert instructions for patients with renal impairment. 

Duration of therapy could extend beyond 14 days if medically justified; the decision to extend 

therapy was made between days 10 and 14 of therapy. 

Outcome: 

Primary – clinical response satisfactory (either cure or improvement, based on a clinical score) 

or failure, assessed on 2-5 days post therapy; clinical success rate was calculated based on the 

number of evaluable patients 

Secondary – assessment for relapse 28 - 32 days after the end of therapy 

Sinus cultures were not performed as part of the study. 

Results: 

615 patients randomized into 2 groups (levofloxacin 307; amox/clav 308) 

535 evaluable for efficacy (levofloxacin 267; amox/clav 268) 

Reported Clinical failure – Levofloxacin 31/267 (11.6%); 

 Amox/Clav 34/268 (12.7%) 

4 week post treatment follow up Relapse – Levofloxacin 5/233 (2.1%) 

 Amox/Clav 9/231 (3.9%) 

Adverse events: Levofloxacin Amox/Clav 

Adverse event 114/297 (38.4%) 146/302 (48.3%) 

Diarrhea 4/297 (1.3%) 35/302 (11.6%) 

Abdominal Pain 3/297 (1%) 5/302 (1.7%) 

Flatulence 1/297 (0.3%) 4/302 (1.3%) 
C-5

Vomiting 0 5/302 (1.7%) 

Vaginitis 2 (1.1% of women) 8 (4.1% of women) 

Genital moniliasis 2 (0.7% of women) 10 (3.3% of women) 

11/297 (3.7%) patients treated with levofloxacin and 16/302 (5.3%) patients treated with 

amox/clav discontinued treatment because of adverse events. 

In the levofloxacin group, those who discontinued because of adverse events included 4 patients 

with urticaria, rash or pruritus; 4 patients with GI adverse events; and 1 patient with astheniadizziness and symptoms of influenze. In the amo/clav group, all discontinued for GI adverse 

events except for one instance of fatigue. 

No serious drug-related events or deaths occurred during the study 

Funding: R. W. Johnson Pharmaceutical Research Institute 

Comments: 
C-6

Buchanan et al. 2003 ID 91698 

Stated Purpose of the Study: To establish the clinical equivalence of 800 mg of telithromycin 

once daily for 5 days with 250 mg of cefuroxime axetil twice daily for 10 days in the treatment of 

patients with acute bacterial maxillary sinusitis (ABMS) 

Populaton and Setting: 385 subjects were randomized in 73 sites in 4 countries: Argentina 

(3), France (6), South Africa (9), and the United States (55). Study took place from 4/2000 to 

11/2000. 

Telithromycin group = 240 Median age = 40 Males= 42% 

Cefuroxime group= 116 Median age = 40.5 Males= 41% 

Inclusion criteria: ≥ 18 y/o and consent for sinus puncture (US only); ≥ 13 y/o and consent for 

sinus endoscopy (at non-US sites); for females, postmenopausal for at least one year or 

surgically unable to bear children or a normal menses within 1 month of study entry, plus a 

negative pregnancy test and agreement to use contraceptive; ABMS as evidenced by clinical and 

radiological findings (see paper for details); gram stain or microbiological results of sinus 

specimens 

Exclusion criteria: > 3 episodes of sinusitis requiring abx within the previous 12 months; hx of 

sinusitis > 28 days; suspicion of sphenoidal sinusitis requiring treatment other than oral abx; 

nosocomial sinusitis and others (see paper) 

Study design: multicenter, multinational, randomized, double-blind, active-controlled trial; 

method of randomization, not stated. 

Treatments: Patients were randomized in a 2:1 ratio 

Telithromycin - 2 x 400 mg capsules in am for 5 days and 2 matched placebo capsules in evening 

from days 1-5 and 2 matched placebo capsules in am and pm from days 6-10. 

Cefuroxime Axetil - 2 x 125 mg capsules in am and pm for 10 days. 

Outcome: 

Primary Outcome: Clinical cure is assessed by study investigators, it is defined by return to 

preinfection state, with no ABMS-related signs and symptoms present, as determined on a scale 

of 0-3 in which 0=absent, 1=mild, and 3= severe, supplemented by a sinus x-ray/CT scan 

confirming no worsening or the presence of only those residual symptoms indicative of a normal 

course of clearance in the infection process, with no requirement for additional abx. Test of Cure 

visit took place at days 16-24 after the 1st day of abx. 

Secondary Outcome: Late post therapy visit (days 31-45 after the 1st day of abx) 

Results: 

Clinical failure: Telithromycin 28/189 (14.8%); Cefuroxime 16/89 (18%) 

Microbiological failure: Telithromycin 20/132 pathogens (15.2%); 

Cefuroxime 11/61 pathogens (18%) 

Secondary Outcome at late post therapy visit: Clinical Failure: Telithromycin 35/174 (20.1%); 

Cefuroxime 18/82 (22%) 

Adverse events: 

Adverse events possibly related to study medications: telithromycin 56/252; cefuroxime 20/121; 

Most frequent in telithromycin: nausea 6.7%, diarrhea 6%, dizziness 2.8%, vomiting 2% 

Most frequent in cefuroxime: nausea 4.1%, diarrhea 5%, vomiting 2.5% 

Most common “clinically noteworthy abnormal lab value” was abnormally low creatinine clearance 

in both groups. 
C-7

2 cefuroxime patients experienced one or more adverse event known to have a potential for 

association with prolonged QTc (palpitations, arrhythmia, syncope, vertigo and cardiac 

insufficiency) 

Discontinuation rates due to adverse events were 2% for telithromycin and 1.7% for cefuroxime. 

Funding: Aventis Pharmaceuticals 

Comments: 
C-8

Bucher et al. 2003 ID 9 

Stated Purpose of the Study: To evaluate the effect of a amox/clav on adults with clinically 

diagnosed acute rhinosinusitis in a general practice setting 

Population & Setting: 252 patients from 24 general practices in Switzerland over 4 winter 

seasons (November to April, 1997-2001) were randomized. 

Amox/clav 124 mean age 37 males 46% 

Placebo 127 mean age 37 males 45.7% 

Inclusion criteria: hx of repeated purulent nasal d/c and maxillary or frontal unilateral or 

bilateral pain for at least 48 hours but < 1 month and presence or absence (see paper) of pus 

under rhinoscopy 

Exclusion criteria: < 18 y/o; URI or abx within the previous 4 weeks; after year 2000, pts with 

CRP > 100 mg/L; pts with CRP between 50 and 99 mg/L were reassessed at day 3 (3 pts) and 

excluded if clinical worsening was noted or the CRP level had increased to > 100 mg/L (none); 

see paper for rest of details 

Study design: randomized, placebo-controlled, double-blind trial; 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; patients were consecutively 

enrolled; study physicians were required to record the reason why eligible patients were not 

recruited 

Treatments: 

Amox/Clav 875/125 mg twice daily for 6 days 

Placebo matching tablets for 6 days 

All patients received decongestant therapy with xylometazolin hydrochloride spray and 

acetaminophen 500 mg tablet, with a maximal dose of 3 g/day 

Outcome: 

Primary outcome was time to cure. 

Definition of cure = zero days (since the previous visit or interview) during which rhinosinusitis 

restricted activities at home or work 

Results: 252 randomized, 1 randomized but never took any medication, 249 completed the trial 

(see Figure 1 in paper for details) 

Calculated Failure rate (100% - reported cure rate) at 1 week: amox/clav 70.2% 

 Placebo 69.3% 

Calculated Failure rate (100% - reported cure rate) at 2 weeks: amox/clav 23.4% 

 Placebo 26% 

In 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) 

Reported Relapse rate at 28 days amox/clav 2/124 (1.6%) 

 Placebo 5/125 (4%) 
C-9

Adverse events: 

At 7 and 14 days was significantly more likely in the amon/clav group than in the placebo group, 

with odds ratio of 3.89 (95% CI, 2.09 – 7.25) and 1.71 (95% CI, 0.91 – 3.23) at 7 and 14 days, 

respectively. 

4 adverse events of moderate or severe intensity that were thought to be drug related: 2 in the 

amox/clav 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 amox/clav (1 g twice daily) 

but experienced a brain abscess caused by an amox/clav sensitive 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. 

Funding: GlaxoSmithKline, Swiss Academy of the Medical Sciences, Astra Klinik Fonds 

University Hospital Basel, and Forum fur interdisziplinare Hausarztmedizin, University of Basel. 

Comments: 
C-10

Burke et al. 1999 ID 524 

Stated Purpose of the study: To compare the efficacy and safety of Moxifloxacin with those 

of Cefuroxime axetil for the treatment of community-acquired acute sinusitis. 

Population & Setting: 

542 patients from 48 clinical sites (primary care, allergists, infectious disease) in North America. 

Unknown study years. 

Moxifloxacin group (n=223): Mean Age (range) = 40 yrs (18-76) Males= 84 (38%) 

Cefuroxime axetil group (n=234): Mean age (range) = 39 yrs (18-78) Males=94 (40%) 

Inclusion Criteria:

≥18 y/o with acute sinusitis (based on having at least 2 of the following: nasal congestion, postnasal drainage, frequent coughing/throat clearing, frontal headache, malar tenderness/pain and 

purulent nasal discharge) of 1-4 weeks duration AND radiologic signs of sinusitis (air-fluid levels, 

opacification or mucosal thickening≥6mm). 

Exclusion Criteria:

More than 2 episodes of acute sinusitis within the previous 12 months despite therapy; allergy to 

carboxyquinolones or ß-lactams; history of carboxyqinolone therapy or of sinus surgery; 

pregnancy, nursing or not using contraception; inability to take oral medications; bacteremia or 

meningitis; received investigational drugs during the preceding 30 days; requiring concomitant 

systemic antimicrobial therapy with non-study drugs; hepatic or renal insufficiency; 

immunocompromise; prolonged QTc interval or taking medications that prolong QTc; received an 

antimicrobial agent within 24 hours of enrollment, unless treatment failure. 

Study Design: Randomized (by block-design random code, with unknown concealment 

method), double-blinded (medications encapsulated in gelatin), multi-center trial. Unknown if 

prestratified by center. 

Treatment: 1) Moxifloxacin 400 mg QD + matched placebo QD for 10 days 

 2) Cefuroxime axetil 250 mg PO BID for 10 days 

Outcome: (Primary) End of therapy (7-21 days after therapy) 

(Secondary) Follow up (27-31 days after therapy) 

Resolution: Resolution or improvement of clinical Si/Sx and radiographic findings and no 

additional antibiotics required. 

Failure: No change, worsening or reappearance of infection and need for additional antibiotics. 

Indeterminate: Clinical response could not be determined. 

Results: 542 enrolled and randomized. 223 in the moxifloxacin group and 234 in the cefuroxime 

axetil group were evaluated for clinical efficacy (per protocol analysis). 44 in the moxifloxacin 

group and 41 in the cefuroxime axetil group were excluded (for reasons including insufficient 

duration of therapy and entry criteria violation). Rates of and reasons for ineligibility stated to be 

similar between treatment arms. 

Clinical Failure: (Primary) 23/223 (10.3%) in the moxifloxacin group and 25/234 (10.7%) in the 

cefuroxime axetil group failed. (Secondary) 3/184 in the moxifloxacin group and 5/202 in the 

cefuroxime axetil group relapsed.

Adverse Events: Adverse events were experience by 126/263 in the moxifloxacin group and 

112/274 in the cefuroxime axetil group. Discontinuation due to adverse events occurred in 

15/263 in the moxifloxacin group and 6/274 in the cefuroxime axetil group (P=.04). Severe drugrelated adverse events occurred in 7 (3%) of patients taking moxifloxacin (2 headache, 1 
C-11

asthenia, 1 diarrhea, 1 vomiting, 1 dizziness and 1 agitation) and 10 (4%) of patients taking 

cefuroxime (5 headache, 2 nausea 1 diarrhea, 1 arthralgia, 1 increased cough, 1 dyspnea). 

 Moxifloxacin (n=263) Cefuroxime (n=274)

Any drug-related AE 96 (37%) 70 (26%) 

Nervousness 7 2 

Asthenia 5 4 

Dizziness 13 7 

Headache 12 8 

Nausea 28 11 

Diarrhea 18 17 

Vomiting 9 3 

Abdominal pain 5 3 

Skin and Appendages 9 8 

Special senses 3 9 

Urogenital 3 8 

Funding: Bayer 

Comments: Use of decongestants and antihistamines were “standardized by each study 

center.” Steroid use was prohibited unless the patient had already been receiving treatment prior 

to study entry. Compliance of ≥80% of study medication administered required for inclusion in 

analysis.
C-12

Chatzimanolis et al. 1998 ID 585 

Stated Purpose of the Study: To compare the clinical efficacy and tolerability of 

roxithromycin and amox/clav, given in the conventional doses used in respiratory tract infections, 

in acute or recurrent sinusitis 

Population & Setting: 60 patients with acute or recurrent sinusitis were enrolled in Greece. 

Roxithromycin 31 mean age (range) 39 (18-70) males 54.8% 

Amox/clav 29 mean age (range) 37 (18-70) males 58.6% 

Inclusion criteria: recurrent or acute sinusitis; diagnosis of sinusitis was mainly documented 

by clinical and endoscopy findings, bacteriology and x-ray; > 18 y/o of either sex; 

Exclusion criteria: not stated 

Study design: open, randomized study 

Treatments: 

Roxithromycin 150 mg oral twice a day for at least 10 days 

Amox/Clav 500/125 mg oral thrice a day for at least 10 days 

Outcome: Clinical response was assessed within 48 hours after the end of treatment. 

Results: 60 patients enrolled, 56 patients evaluated for efficacy and safety 

For roxithromycin, treatment lasted 10 -14 days (mean 11 days) 

For amox/clav, treatment lasted 10 – 15 days (mean 12 days) 

Calculated Clinical Failure Rate post-treatment (100% - reported satisfactory case rate in 

clinically assessable population): 2/29 (6.9%) in roxithromycin; 3/27 (11.1%) in amox/clav 

Microbiological failure: 2 in roxithromycin and 3 in amox/clav out of a total of 48 patients 

(combined roxithromycin and amox/clav) Unable to calculate actual rate as denominators for 

antibiotics were not reported. 

Adverse events: 

 Roxithromycin n=29 Amox/Clav n=27 

GI 1 (3.4%) 7 (25.9%) 

3 patients from Amox/Clav had discontinuation of medication 2° to adverse event?) 

Funding: Hoechst Marion Roussel 

Comments: 
C-13

Clement & de Gandt 1998 ID 583 

Stated Purpose of the Study: To compare azithromycin with amox/clav in the treatment of 

acute sinusitis

Population & Setting: 

254 patients from 38 ENT clinics in unknown country (authors are from Belgium), Unknown study 

years. 

Azithromycin group (n=158): Mean age (range) = 42.1 yrs (unknown range) Males=61 

(37%) 

Co-amoxiclav group (n=82): Mean age (range) = 38.7 yrs (unknown range) Males= 38 

(47.2%) 

Inclusion Criteria:

Adults of any age with acute ethmoidal or maxillary sinusitis (based on a scoring system 

described in the study) for an unspecified duration AND endoscopic evidence of pus from a sinus 

ostium AND unspecified CT scan evidence. 

Exclusion Criteria:

Chronic sinusitis; suspected fungal sinusitis; allergy to macrolides or ß-lactams; infection 

requiring IV antibiotics; immunocompromise; pregnancy/nursing; receiving ergot derivatives, 

digoxin, cyclosporine or phenytoin; received investigational drugs during the preceding month 

Study Design: Randomized (unknown method of randomization or concealment), not blinded, 

multi-center trial. Unknown if prestratified by center. 

Treatment: 1) Azithromycin 500 mg PO qd for 3 days 

 2) Co-amoxiclav 500/125 mg PO TID for 10 days 

Outcome (Primary): Follow up (21-28 days after enrollment) 

Response rate was based on clinical scoring system 0-21. 

Cure: score=0, Improvement: score=1-20, Failure: score=21 

Results: 254 enrolled and randomized. 136 in azithromycin group and 74 in co-amoxiclav group 

were evaluated for clinical efficacy (per protocol analysis). 7 in azithromycin group (lost to follow 

up) and 7 in co-amoxiclav group (lost to follow up, premature discontinuation of treatment due to 

lack of efficacy or adverse event) were excluded. 

1. Clinical Failure: 17/136(12.5%) in azithromycin group and 12/74(16.2%) in coamoxiclav group had no response (includes failure and relapse). 17/136 in azithromycin 

group and 10/74 in co-amoxiclav group had improvement but not cure. 

2. Microbiological Failure: Most common pathogens isolated at baseline: S. 

pneumoniae, H. influenzae and S. aureus. Presumed persistence determined by 

presence of purulent discharge at day 21-28 only for those patients from whom 

pathogens were isolated at baseline by endoscopy of the ostia. 5/52 in azithromycin 

group and 5/31 in co-amoxiclav group had presumed persistence of infection. 

Adverse Events: Discontinuation due to adverse events occurred in 0/165 in azithromycin 

group and 2/89 in co-amoxiclav group. 

 Azithromycin (n=165) Co-amoxiclav (n=89)

# reporting drug-related AE 29 23 

Drug related AE 24 19 

Abdominal pain 7 7 
C-14

Diarrhea 7 13 

Nausea 8 1 

CNS (headache/vertigo) 5 0 

Severe AE 5 3 

Study withdrawal due to AE 0 2 

Funding: Pfizer, Belgium 

Comments: 133 patients used adjuvant therapy (vasoconstrictors, mucolytics and 

corticosteroids). Compliance with study medications is unknown. 
C-15

Clifford et al. 1999 ID 480 

Stated Purpose of the Study: To compare the efficacy and safety of a 10-day oral treatment 

course of ciprofloxacin to those of 14-day therapy with clarithromycin for the management of 

adults with acute maxillary sinusitis or acute exacerbations of chronic sinusitis 

Population & Setting: 560 patients enrolled at 19 clinical sites 

Ciprofloxacin 236 (efficacy-valid population) mean age (range) 40.4 (18-74) males 38% 

Clarithromycin 221 (efficacy-valid population) mean age (range) 41 (18-76) males 44% 

Inclusion criteria: ≥ 18 y/o; primary dx of clinically (see paper for details) and radiologically 

documented acute sinusitis of ≤ 4 weeks duration; x-ray: opacification, or ≥ 6 mm of mucosal 

thickening or air-fluid level; 

Exclusion criteria: inability to take oral medications; symptoms > 4 weeks (chronic sinusitis); 

unwillingness to undergo a sinus aspiration; need for concomitant anti-bacterial agents during the 

study period; baseline creatinine ≥ 3 mg/dL; terfenadine or astemizole during the study period; 

nasal or oral steroids; abx within 5 days of enrollment unless the patient was a treatment failure 

or had received only 1 or 2 doses of the abx; see paper for rest 

Study design: prospective, randomized, double-blind, multicenter comparative trial; patients 

were randomly assigned to 1 of 2 treatment groups by means of a block design random code 

computer-generated at Bayer; study drugs were encapsulated in opaque gelatin capsules for 

blinding purposes. 

Treatments: 

Ciprofloxacin 2x250 mg twice a day for 10 days; placebo for days 11 to 14 

Clarithromycin 2x250 mg twice a day for 14 days 

Outcome: 

Primary: clinical response 2-3 days post-treatment 

Secondary: follow up at 28 day 

Results: 560 enrolled; 559* included in Intent to treat analysis; 457 valid for efficacy analysis 

Clinical failure rate in efficacy-valid group: ciprofloxacin 37/236 (15.7%) 

 Clarithromycin 19/221 (8.6%) 

Clinical failure rate in Intent to treat group: ciprofloxacin 45/272* (16.5%) 

 Clarithromycin 25/267* (9.4%) 

28-day follow up relapse rate in efficacy-valid group: ciprofloxacin 7/175 (4%) 

 Clarithromycin 18/187 (9.6%) 

28-day follow up relapse rate in Intent to treat group: ciprofloxacin 9/196 (4.6%) 

 Clarithromycin 20/223 (9%) 

Adverse events: 559 valid for safety analysis, 1 was excluded because no study drug (the 

paper did not specify which one) was administered; therefore, calculated rates are based on 560 

 Ciprofloxacin (282) Clarithromycin (278) 

At least 1 adverse event 120 (42.6%) 158 (56.8%) 

At least 1 drug-related event 93 (33%) 133 (48%) 

GI 58 (20.6%) 81 (29.1%) 
C-16

Nervous system 19 (6.7%) 25 (9%) 

Special-senses related 14 (5%) 60 (21.6%) 

Diarrhea 17 (6%) 36 (13%) 

Taste perversion 7 (2.5%) 58 (20.9%) 

Discontinuation 2° to adverse event 9 (3.2%) 9 (3.2%) 

One episode each of arthralgia and tinnitus in the ciprofloxacin group, and 1 episode each of 

peripheral edema, hyperuricemia, and pleural pain in the clarithromycin group were reported as 

unchanged at the final evaluation. 

Funding: Bayer Corporation 

Comments: *Unclear why the denominators in ITT (272+267=539) do not add up to the 

reported 559?
C-17

Faich 2004 ID 20 

REJECTED STUDIES: Adverse Events extraction only

Stated Purpose of the Study: 

Population and Setting: 

18,409 patients from 3,377 family practice and general internist sites in the US and Puerto Rico 

between 4/00-6/00. 

Diagnoses included in the study:

Acute maxillary sinusitis, community acquired pneumonia, acute bacterial exacerbation of chronic 

bronchitis 

Treatment: Moxifloxacin 400 mg QD x 5-10 days (10 days for sinusitis indication) 

Study Design: multicenter, open-label noncomparative surveillance study 

Adverse Events Included in Analyses: Those contactable by phone (70%, 12,854) or office 

visit (27%, 4,908) within 48 hours of treatment completion. 3% (n=645) were lost to follow-up. 

Funding: Bayer Pharmaceuticals Corp. 

Comments: Use of adjuvant therapy is unknown 

Adverse Events: Of the 18,374 safety-validated patients, 3257 (17.7%) had one or more AE. 

No difference in AE rate by gender, race or age. 

Most common reasons for early discontinuation due to AE: 

Reason Number

Nausea 396 

Dizziness 202 

Vomiting 161 

Diarrhea 124 

Headache 81 

Abdominal pain 66 

Rash 64 

Palpitation 48 

Serious adverse events were reported in 168 (0.9%). And 131 (0.7%) were hospitalized. 843 had 

possible cardiac-related events. An independent safety committee concluded there was no 

evidence of increased mortality or treatment-associated ventricular tachyarrhythmias. 6 deaths 

occurred, 5 were deemed not related to study drug and 1 was unlikely related. 

Most common AE deemed probably or possibly drug related by the investigator only in those 

with sinusitis indication: (SEE TABLE 2) 

Reason Number

Any 1793/ 10,822 (16.6%) 

Nausea 729 (6.7%) 

Body as a whole 371 (3.4%) 

Diarrhea 259 (2.4%) 

Dizziness 245 (2.3%) 

Vomiting 143 (1.3%) 

Headache 133 (1.2%) 
C-18

Ferguson et al. 2002 ID 225 

Stated Purpose of the Study: To compare clinical and radiologic efficacy of 2 treatment 

regimens, 5 days vs. 7 days of gemifloxacin therapy, in adults with acute bacterial rhinosinusitis 

Population & Setting: 423 patients from 59 centers in 9 countries ( Belgium, Canada, Estonia, 

Finland, Germany, Ireland, Italy, Lithuania, and the Netherlands) were randomized. 

In ITT analysis 

5-day Gemifloxacin 218 mean age 41.4 males 42.7% 

7-day Gemifloxacin 203 mean age 39.7 males 41.9% 

Inclusion criteria: > 18 y/o; signs and symptoms of acute bacterial rhinosinusitis for at least 7 

but not more than 28 days (see paper for details); radiologic confirmation was required within 72 

hours of randomization (sinus opacification and/or air-fluid level); patients in Germany and 

Lithuania were required to consent to an initial sinus endoscopy/rhinoscopy at study entry 

Exclusion criteria: abx within 7 days before enrollment; signs and symptoms of disseminated 

infection requiring hospitalization or parenteral abx; hypersensitivity to fluoroquinolone abx; 

receipt of an investigational drug in the 30 days before the first dose of study medication; see 

paper for others 

Study design: prospective, double-blind, multicenter, parallel-group study; method of 

randomization not stated 

Treatments: 

Gemifloxacin oral 320 mg once daily for 5 days; matching placebo once daily for study day 6 & 7 

Gemifloxacin oral 320 mg once daily for 7 days 

Outcome: 

Primary: clinical response at follow-up (study days 18-25); success was defined as sustained 

improvement or resolution in signs and symptoms of acute bacterial rhinosinusitis so that no 

additional abx was required 

Secondary: clinical response at end of therapy (study days 9 to 11) 

Results: 423 randomized, 421 received at least 1 dose of study medication and were included 

in the Intent-to-treat (ITT) analysis; 356 were in the completed per-protocol-analysis (181 in 5-day 

group and 175 in 7-day group). 

Calculated clinical failure (100% - reported clinical success rate in per-protocol patients): 

5-day group 12.7% 

7-day group 13.1% 

Calculated clinical failure (100% - reported clinical success rate in ITT population): 

5-day group 16.5% 

7-day group 15.8% 

Data on secondary clinical response at end of therapy (study days 9 to 11) were not 

reported. 

Adverse events: diarrhea, nausea, and rash were the only reported events that occurred in 3% 

of patients or more in either group. 

 5-day group 7-day group 

adverse events while on 33.5% 40.4% 

therapy + 30 days post-therapy 
C-19

Rash 1.4% 5.9% 

Patients withdrawn 2° to adverse events 2/218 (0.9%)* 1/203 (0.5%)** 

*one broken leg injury and one maculopapular rash 

**vertigo 

Funding: GlaxoSmithKline 

Comments: 
C-20

Garrison 2000 ID 438 

REJECTED STUDIES: Adverse events extraction only

Stated Purpose of the Study: Determine the efficacy and safety of sparfloxacin in the 

treatment of AMS, microbiologically documented by maxillary sinus puncture, aspiration and 

culture. 

Population and Setting: 

253 patients in the outpatient setting of unknown specialty type by 21 investigators in the US 

Diagnoses included in the study: Acute maxillary sinusitis

Treatment: Sparfloxacin 400 mg X1 (loading dose) followed by 200 mg QD for a total Rx of 10 

days PLUS nasal decongestant therapy for the first 3 days of antibiotic treatment

Study Design: Open, non-comparative multicenter trial 

Adverse events included in analysis: All 253 patients

Funding: Rhône-Poulenc Rorer Pharmaceuticals Inc. 

Comments: Nasal decongestant administered for the first 3 days of antibiotic treatment 

Adverse Events: One or more adverse events were reported by 139/253 (54.9%). 

Most common AE N, % (of 253 total) 

Headache 33, 13.0% 

Photosensitivity reaction 20, 7.9% 

Diarrhea 19, 7.5% 

Many others with frequency over 2%--see original paper. 

62/253 (24.5%) reported AE “considered by investigator to be possibly or probably related to the 

study medication” (not specified by what criteria considered related). 

AE related to study drug N, % 

Photosensitivity reaction16 (6.3%) 

Diarrhea 14 (5.5%) 

Headache 11 (4.3%) 

Nausea 11 (4.3%) 

Insomnia 7 (2.8%) 

Dyspepsia 5 (2.0%) 

Pruritis 4 (1.6%) 

Nervousness 3 (1.2%) 

9/253 (3.6%) discontinued study due to AE, 6 were considered related to study medication(4 with 

photosensitivity reaction, 1 with headache and 1 with 1 urticaria). One patient discontinued the 

study prematurely due to a serious adverse event (asthma) that was considered by the 

investigator to be remotely related to study medication. No other patients experienced serious 

adverse events. No cardiovascular AE related to increase in QTc interval. No deaths occurred. 

1 elevated creatinine. 
C-21

Gehanno 2003 ID 41 

REJECTED STUDIES: Adverse events extraction only

Stated Purpose of the Study: Evaluate the efficacy of moxifloxacin for treating acute 

maxillary sinusitis after confirmed failure of empirical antimicrobial therapy and acute sinusitis with 

a higher risk of complications, such as frontal or sphenoidal sinusitis and pansinusitis.

Population and Setting: 

258 patients from 52 ENT centers throughout France between 1/01 to 7/01 

Diagnoses included in the study: Acute maxillary sinusitis after confirmed failure of 

empirical antimicrobial therapy and acute sinusitis with a higher risk of complications such as 

frontal or sphenoidal sinusitis and pansinusitis 

Treatment: Moxifloxacin 400 mg QD x7 days 

Study Design: multi-center, non-comparative study

Adverse events included in analysis: Events that occurred at least 2 times and that 

occurred after the first dose of moxifloxacin until 7-10 days after the last dose were reported. 

Only 255/258 received the study medication. Serious adverse events were followed until 4-5 

weeks after the last dose. 

Adverse Events: 31/255 patients (12.2%) experienced at least 1 adverse event. 

No data on number of patients with serious adverse events, or the number of patients who 

discontinued treatment due to adverse events. 

Events deemed by investigators to be possibly or probably related to moxifloxacin treatment 

Event Number 

Abdominal pain 6 (2.4%) 

Nausea 6 (2.4%) 

Neurosensorial 4 (1.6%) 

Cardiovascular 3 (1.2%) 

 (includes tachycardia) 

Diarrhea 3 (1.2%) 

Musculoskeletal complaints 3 (1.2%) 

 (includes arthralgia) 

Skin/Mucous membrane3 (1.2%) 

 (includes rash) 

Funding: unknown 

Comments: Use of adjuvant therapy is unknown. Corticosteroids were not permitted.
C-22

Gehanno et al. 2000 ID 373 

Stated Purpose of the Study: The efficacy and tolerance of amoxicillin-clavulanate, with and 

without associated short steroid therapy, was evaluated in adults with acute sinusitis. 

Population & Setting: 433 patients recruited from 51 private ENT specialists in France were 

randomized. The study was carried out from 11/1991 to 7/1994. 

In ITT population: 

5-day amox/clav (with or without steroids) 205 mean age 39.1 male 82/205 (40%) 

10-day amox/clav (with or without steroids) 212 mean age 30.5 male 82/212 (39%) 

Inclusion criteria: outpatients ≥ 18 y/o with acute sinusitis (see paper for details) < 10 days; 

opacities with or without air-fluid levels on standard films or computed tomography 

Exclusion criteria: acute sinusitis requiring immediate surgical drainage and acute 

exacerbations of chronic sinusitis; abx or steroids in the 15 days preceding recruitment; see 

paper for others 

Study design: muticenter, randomized, double-blind, placebo-controlled, parallel 

 2x2 factorial arrangement 

Treatments: 

A: Amox/Clav 500 mg three times a day for 5 days, then matching placebo for 5 more days 

B: Amox/Clav 500 mg three times a day for 10 days 

Also, for both group A and B, patients were randomized to receive 8 mg of methylprednisiolone 

three times daily or a matching placebo for study days 1 to 5 

Outcome: 

Primary: primary efficacy was assessed on day 14; success was defined as clinical recovery on 

day 14, with or without radiological normalization 

Results: 

433 randomized, 417 in Intent to treat (ITT) analysis, 360 in per-protocol analysis 

Reported clinical failure rate on day 14, in ITT population: 

5-day group 41/205 (20%) 

10-day group 32/212 (15%) 

Reported clinical failure rate on day 14, in per-protocol population: 

5-day group 39/181 (21.6%) 

10-day group 28/179 (15.6%) 

Reported recurrence rate on day 30 follow up: 

5-day group 11/162 (6.8%) 

10-day group 7/175 (4%) 

Absence of interaction between the duration of treatment by the antibiotic and the adjunctive use 

of methlyprednisolone was verified, permitting separate analysis of each treatment. 

Evaluation at day 14 showed no evidence of a higher rate of recovery in the group treated by 

methylpredinsolone than in the placebo group (actual data not provided). 

Adverse events: 

433 in safety analysis; recorded adverse events were nausea, vomiting, diarrhea, gastric pain, 

skin reactions and Candida superinfection. 
C-23

 5-day (213) 10-day (220) 

patients with adverse events 20 (9.4%) 26 (11.8%) 

discontinuation 2° to adverse events 1 (0.4%) 7(3.2%) 

 steroids (219) no steroids (214) 

patients with adverse events 24 (11%) 22 (10.3%) 

discontinuation 2° to adverse events 5 (2.3%) 3(1.4%) 

Funding: SmithKline Beehcam 

Comments: some patients received both amox/clav and methylprednisolone (see explanation 

in paper), actual data not provided. 
C-24

Gwaltney et al. 1997 ID 648 

Stated Purpose of the Study: To evaluate cefdinir for the treatment of acute communityacquired bacterial sinusitis. 

Population & Setting: 1798 patients in US (1229) and Europe (569) participated 

Cefdinir 600 mg once a day = 585 Median age (range) = 35 (12-83) Males= 44% 

Cefdinir 300 mg twice a day = 610 Median age (range) = 35 (13-88) Males= 43% 

Amox/Clav 500mg thrice a day=603 Median age (range) = 34 (13-79) Males= 45% 

Inclusion criteria: ≥13 y/o; males and females; signs and symptoms of acute sinusitis; had to 

include facial pain and purulent nasal discharge; dx confirmed by x-ray showing disease of the 

maxillary sinus; duration of illness ≤ 4 weeks; see paper for details 

Exclusion criteria: hx of sensitivity to beta lactams, treatment with systemic abx within prior 48 

hours;, significant renal or hepatic disease; requirement of Fe therapy; pregnant or lactating 

Study design: Two (one in US, one in Europe) randomized, Investigator-blinded,multi-center 

trials were conducted. The studies were identical in design, with the exception that admission 

sinus aspiration was optional in US and mandatory in Europe. Patients were randomly assigned 

at each site to one of 3 treatment groups. Medications were dispensed by a third party, and all 

records regarding study medications were kept at a separate site. Patients were instructed to 

withhold details of study medication appearance and dosing schedule. 

Treatments: 

Cefdinir 600 mg once a day for 10 days 

Cefdinir 300 mg twice a day for 10 days 

Amoxicillin/Clavulanate 500 mg three time a day for 10 days 

Outcome: 

Primary: Satisfactory clinical response is defined by cure or improvement, assessed by absence 

or presence of clinical signs and symptoms. Test of cure visit took place 7-14 days post therapy. 

Secondary: rate for continued clinical response with initial success was determined 3 to 5 weeks 

post therapy 

Results: Evaluable patients were defined as those who took ≥ 80% of prescribed medications, 

returned for the test of cure visit (except for failures prior to scheduled visits), and did not take 

non-study systemic abx for other infections. 

Calculated Clinical Failure Rate at 1-3 days post-treatment (100% - reported satisfactory

cases in clinically evaluable population): 

Cefdinir 600 mg once a day 49/474 (10.3%) 

Cefdinir 300 mg twice a day 61/481 (12.7%) 

 Amox/Clav thrice a day 44/491 (9%) 

Calculated Clinical Failure Rate at 3-5 wks post-treatment (100% - reported satisfactory

cases in clinically evaluable population): 

Cefdinir 600 mg once a day 37/379 (9.8%) 

Cefdinir 300 mg twice a day 39//370(10.5%) 

Amox/Clav thrice a day 30/389 (7.7%) 

Calculated Microbiological failure at 7-14 days post therapy (evaluable patients): 

 Cefdinir 600 mg once a day 25/215 

Cefdinir 300 mg twice a day 31/225 (1 
C-25

Amox/Clav thrice a day 28/256 (10.9%) 

Calculated Microbiological failure at 3-5 wks post therapy (evaluable patients): 

Cefdinir 600 mg once a day 10/169 (5.9%) 

Cefdinir 300 mg twice a day 20/167 (12%) 

 Amox/Clav thrice a day 14/203 (6.9%) 

Adverse events: 

Cefdinir once a day 188/582 (32%); Cefdinir twice a day 212/607 (35%); Amox/Clav 234/603 

(39%) experienced at least one side effect (see table 6 in paper). The most frequent adverse 

event is GI related; mild diarrhea occurred in approximately 20% of each group. Diarrhea was the 

most common reason for discontinuation of treatment. 

8/582 (1.4%) patients of the cefdinir OD group and 19/607 (3.1%) patients of the cefdinir BD and 

30/603 (5%) patients of amox/clav groups discontinued treatment because of an adverse event. 

No clinically important alterations in laboratory values were observed for any of the groups. 

Funding: 

Comments: authors Leigh and Tack associated with Parke-Davis 
C-26

Hansen et al. 2000 ID 97079 

Stated Purpose of the Study: To compare the effectiveness of penicillin V and placebo given 

to patients with a dx of acute maxillary sinusitis based on pain in the maxillofacial area combined 

with either raised CRP or ESR. 

Population & Setting: 139 patients from 26 general practices in town and rural areas from 

Denmark. Study took place from 11/1995 to 4/1997. 71 were given PCN and 62 placebo. Median 

age was 37 (quartiles 30 to 46). 33 (25%) were males. Consecutively included only once if they 

fulfilled the inclusion criteria. 

Inclusion criteria: 18-65 years; pain in the maxillofacial area and values of CRP > 10 mg/L or 

ESR > 10 mm/h in males and > 20 mm/h in females. 

Exclusion criteria: known allergy to PCN; pregnancy; breastfeeding; previous maxillary sinus 

surgery; ENT malignancy; DM; rheumatic arthritis; collagen vascular diseases; facial trauma; Rx 

with steroids, probenecid or immunotherapy; abx treatment previous 2 weeks or ongoing Rx; 

Symptoms > 4 weeks. After randomization, excluded if severe side effects, unwilling to continue 

or did not show up for control visit. 

Study design: Randomized (a block randomization was used with 10 dark colored glasses in 

each block containing 5 glasses of PCN and 5 glasses of placebo; each glass contained 28 

tablets; the general practitioner received one block each), double-blind, placebo-controlled. 

Treatments: Penicillin V 1333 mg (2 million IE) twice daily for 7 days. 

 Placebo: 2 tablets twice daily for 7 days. 

Outcome: Pain score after 7 day of treatment (from patient kept diary). Pain score of zero is 

considered a cure. 

Results: After randomization, 2 in placebo and 4 in PCN group were withdrawn because of noncompliance. Another 6, 3 in each group, stopped treatment before day 7, due to lack of effect in 4 

and side effects in 2 treated with PCN. They were included in analyses and registration of side 

effects until they dropped out. 133 patients in final analysis, 71 in PCN group, 62 in placebo. 

Calculated Clinical Failure Rate of PCN at 7 days post initiation of treatment (100% - reported 

percentage of patients with pain score of zero at 7 days multiply by number of patients at 7 days 

divided by number of patients at day zero): 100% - 75%x68/71= 28% 

Calculated Clinical Failure Rate of placebo at 7 days post initiation of treatment (100% - reported 

percentage of patients with pain score of zero at 7 days multiply by number of patients at 7 days 

divided by number of patients at day zero): 100% - 51%x59/62= 51.5% 

See table 1 for original reported data. 

Adverse events: 13 (18%) patients treated with PCN claimed to have side effects – 11 due to 

GI symptoms and 2 with unspecified symptoms – in contradiction to two (3%) patients treated 

with placebo – one with abdominal pain and one with unspecified symptoms (p=0.009). 

Funding: PCN and placebo tablets from Nycomed Amersham, Denmark; financial support from 

Danish Practitioners’ Foundation. 

Comments: calculated results differ from reported results in the abstract (PCN failure 29%, 

placebo failure 63%)? 
C-27

Haye et al. 1998 ID 562 

Stated Purpose of the Study: To compare the efficacy of azithromycin to placebo in the 

treatment of patients with clinical symptoms and signs of acute maxillary sinusitis but without 

radiological evidence of empyema 

Population & Setting: 169 patients recruited from general practices in Norway in the winter 

season were randomized. 

Azithromycin group 87 mean age (range)= 40.2 (21-84) males 20.7% 

Placebo 82 mean age (range)= 43.2 (18-68) males 31.7% 

Inclusion criteria: ≥ 18 y/o; hx of URI; signs and symptoms of acute maxillary sinusitis: 

presence of nasal secretion (purulent at the time of examination) for > 10 days and < 30 days, 

and maxillary sinus tenderness and/or pain of < 30 days’ duration; radiograph should not show 

complete opacity or an air-fluid level, and the mucosal thickness must be < 6 mm, should not 

show frontal or sphenoidal sinusitis 

Exclusion criteria: hx of intolerance to macrolides, azalides, PCN, or lactose; >2 episodes of 

sinusitis in the past 12 months; abx within the preceding 2 weeks; see paper for rest 

Study design: double-blind, double-dummy, parallel-group, multicenter study; computer 

randomized in blocks of six to either of the two treatment groups 

Treatments: 

Azithromycin one 500 mg tablet daily for 3 days 

Matching Placebo one tablet daily for 3 days 

Outcome: Primary outcome not defined. 

Results: 169 patients enrolled in the study; all patients had at least one follow up visit after 

treatment; in patients who did not return for visits on study day 10-12 or study day 23-27, the 

results from the previous visit were carried forward. 

 Azithromycin Placebo 

Reported Failure rate at 3-5 days: 5/84 (6%) 10/81 (12.3%) 

Reported combined failure + relapse rate 

at 10-12 days (counted some patients who 

were not present at this visit but 

were present at the previous visit): 6/86 (7%) 9/81 (11.1%)

Reported combined failure + relapse rate 

at 23-27 days (counted some patients who 

were not present at this visit but 

were present at the previous visits): 9/87 (7%) 10/82 (12.2%) 

Adverse events: 

 Azithromycin (n=87) Placebo (n=82) 

Patients with adverse events 24 (27.6%) 15 (18.3%) 

GI (diarrhea, nausea, abdominal pain) 22 (25.3%) 12 (14.6%) 

One azithromycin related adverse event was considered severe (details not provided). 

No patient in either treatment group discontinued therapy due to an adverse event. 
C-28

Funding: 

Comments: author Odegard associated with Pfizer 

 
C-29

Henry et al. 1999 ID 482 

Stated Purpose of the Study: To compare the efficacy and tolerability of a 10-day regimen of 

sparfloxacin with a 14-day regimen of clarithromycin in patients with well-defined acute maxillary 

sinusitis 

Population & Setting: 504 patients from 61 centers in US participated. 

Sparfloxacin 252 

Clarithromycin 252 

Inclusion criteria: ≥ 18 y/o; dx of acute maxillary sinusitis (AMS) within the previous 2 weeks; 

at least one symptom of AMS and sinus x-ray abnormalities (see paper for details) 

Exclusion criteria: Symptoms of AMS within the previous 4 weeks; chronic sinusitis; systemic 

abx within 7 days before start of study; pregnancy, baseline QTc > 500 msec and others (see 

paper) 

Study design: randomized, double-masked, comparative, multicenter trial. Randomized in a 

1:1 ratio. To preserve masking, patients were provided with cards containing encapsulated study 

medications and placebos. 

Treatments: 

Sparfloxacin arm - 2x 200 mg tablets on day one, followed by 1x 200 mg tablet each am from 

days 2 through 10, plus appropriate am and pm placebos for 14 days 

Clarithromycin arm - 2x 250 mg tablets every 12 hours for 14 days. 

Outcome: Primary: Test of cure occurs on study day 20±3; clinical success is defined by 

number of patients with clinical outcomes of cure plus improvement divided by the total 

population minus the indeterminate cases. 

Secondary: recurrence of infection was assessed on day 38± 7 

Results: 504 enrolled, 430 clinically assessable; primary reasons for exclusion were incorrect dx 

of AMS, normal x-ray at baseline, and non-compliance 

Calculated Clinical Failure Rate (100% - reported clinical success rate* in clinically assessable 

population): 

Sparfloxacin 37/219 (16.9%) 

Clarithromycin 35/211 (16.6%) 

Calculated Clinical Failure Rate in all-treated population (100% - reported clinical success 

rate in all-treated population): 

Sparfloxacin 40/230 (17.4%) 

Clarithromycin 40/224 (17.9%) 

Secondary follow up at 3- 4 weeks after therapy

Calculated Clinical Relapse Rate (100% - reported sustained clinical success rate in clinically 

assessable population): 

Sparfloxacin 52/191 (27.2%) 

Clarithromycin 56/185 (30.3%) 

Calculated Clinical Relapse Rate in all-treated population (100% - reported sustained clinical 

success rate in all-treated population): 

Sparfloxacin 56/197 (28.4%) 

Clarithromycin 61/194 (31.4%) 
C-30

Adverse events: 

 Sparfloxacin Clarithromycin 

 n=252 n=252 

diarrhea 60 (23.8%) 68 (27%) 

photosensitivity 24 (9.5%) 1 (0.45) 

taste perversion 2 (0.8%) 22 (8.7%) 

nausea 12 (4.8%) 12 (4.8%) 

abdominal pain 4 (1.6%) 9 (3.6%) 

flatulence 5 (2%) 4 (1.6%) 

discontinuation 2° to med 11 (4.4%) 14 (5.6%) 

adverse lab values** 8 (3.2%) 6 (2.4%) 

**elevations in lipase, aspartate aminotransferase, alanine aminotransferase or blood glucose 

5 patients in the clarithromycin group experienced serious adverse events, 1 of which (rash) was 

considered to be drug related; 4 of these patients were discontinued from the study. 

Funding: Rhone-Poulenc Rorer

Comments: *clinical success rate is defined by number of patients with clinical outcomes of 

cure plus improvement divided by the total population minus the indeterminate cases
C-31

Henry et al. 2003 ID 10 

Population & Setting: 

941 patients from multiple (unknown number) of centers in the U.S. Unknown study years. 

Azithromycin for 3 days group (n=312): 

Mean age (range) = 40.2 yrs (18-76) Males=123 (39.4%) 

Azithromycin for 6 days group (n=311): 

Mean age (range) = 41.3 yrs (18-80) Males=124 (39.9%) 

Amoxicillin-clavulanate group (n=313): 

Mean age (range) = 42.4 yrs (18-84) Males=134 (42.8%) 

Inclusion Criteria:

≥18 y.o. in outpatient setting with acute sinusitis (based on: purulent nasal discharge or facial 

pain and/or pressure and/or tightness) for 8-27 days duration AND radiologic signs of sinusitis 

(air-fluid levels, opacification or mucosal thickening≥6mm). 

Exclusion Criteria:

History of chronic sinusitis; allergy to penicillins or macrolides; history of sinus surgery; systemic 

anti-histamine treatment; systemic antibiotic treatment for over 24 hours within 2 weeks of 

enrollment. 

Study Design: Randomized (unknown method of randomization or concealment), doubleblinded (amoxicillin-clavulanate given as a suspension to facilitate masking), multicenter trial. 

Unknown if prestratified by center. 

Treatment: 1) Azithromycin 500 mg QD for day 1-3 + matched placebo tab QD day 4-6 + 

matched placebo suspension TID for 10 days 

 2) Azithromycin 500 mg QD for 6 days+ matched placebo suspension TID for 10 

days 

3) Amoxicillin-clavulanate 250/62.5 mg TID for 10 days + matched placebo QD 

for 6 days 

Outcome: (Primary) End of study (22-36 days after enrollment) 

 (Secondary) End of therapy (8-15 days after enrollment) 

Cure: Resolution of Si/Sx, no worsening in radiographic findings and no additional antibiotics 

required. 

Improvement: Partial resolution of Si/Sx and no additional antibiotics required. 

Failure: Persistence of Si/Sx or emergence of new Si/Sx and/or the need for additional antibiotics 

or a change in antimicrobial therapy. 

Results: 941 enrolled and randomized; 298 in azithromycin for 3 days group, 294 in 

azithromycin for 6 days group, and 288 in the amoxicillin-clavulanate group were included in the 

intent to treat analysis for clinical efficacy. 5 in azithromycin for 3 days group, 5 in azithromycin 

for 6 days group, and 6 in the amoxicillin-clavulanate group were excluded due to enrollment by 

an ineligible center. Others excluded for not meeting entry criteria, visits outside the protocolspecified windows or unknown/missing data. 

Clinical Failure: (Primary) 85/298 in azithromycin for 3 days group, 76/294 in azithromycin for 6 

days group, and 82/288 in the amoxicillin-clavulanate group failed. (Secondary) 35/303 in 

azithromycin for 3 days group, 33/298 in azithromycin for 6 days group, and 43/291 in the 

amoxicillin-clavulanate group failed. 
C-32

Adverse Events: (Primary) Adverse events were experience by 97/312 in azithromycin for 3 

days group (nausea=23 diarrhea=53, flatulence=17), 117/311 in azithromycin for 6 days group 

(nausea=27, diarrhea=66, flatulence=11) and 160/313 in the amoxicillin-clavulanate group 

(nausea=38, diarrhea=101, flatulence=6). Discontinuation due to adverse events occurred in 7 in 

azithromycin for 3 days group, 11 in azithromycin for 6 days group and 28 in the amoxicillinclavulanate group. No treatment-related serious adverse events occurred in any treatment arm. 

Funding: Pfizer 

Comments: Compliance is stated as being recorded by investigators (amount taken, reasons 

for missed doses and amount of study medication returned at the end of therapy), but data is not 

shown. Sinus films at the end of therapy compared to baseline showed improvement/resolution 

in 71.7% in azithromycin for 3 days group, 74.2% in azithromycin for 6 days group and 66.2% in 

the amoxicillin-clavulanate group. 
C-33

Henry et al. 1999 ID 462 

Stated Purpose of the Study: To compare the efficacy and tolerability of a 10-day regimen of 

cefuroxime axetil 250 mg twice daily with a 10-day regimen of amoxicillin/clavulanate 500 mg/125 

mg three times daily in adult patients with acute bacterial maxillary sinusitis 

Population & Setting: 263 patients from 9 centers in US participated. 

cefuroxime 132 mean age (range) 40.5 (19-70) males 52% 

amox/clav 131 mean age (range) 39.4 (18-82) males 38% 

Inclusion criteria: men and women ≥ 18 y/o; clinical dx of acute maxillary sinusitis (AMS) 

within the previous 30 days; ≥ 2 of the following symptoms with at least moderate severity: 

rhiniorrhea, nasal congestion, or cough, sinus x-ray: opacification, ≥ 4 mm membrane thickening, 

and/or air-fluid level in 1 or both maxillary sinuses; and others (see paper) 

Exclusion criteria: dx or hx of chronic sinusitis; sinus washout or systemic abx in the previous 

7 days; sinus surgery in the past month, pregnancy, see paper for others 

Study design: randomized, double-masked, multicenter trial. Method of randomization not 

explicitly stated. 

Treatments: 

Cefuroxime 250 mg twice a day plus matched placebo once daily for 10 days 

Amox/Clav 500 mg three times a day for 10 days 

Outcome: 

Primary: Post treatment response and follow-up assessment 26 –30 days after cessation of 

treatment. Satisfactory response comprised of both “cure” and “improvement”. For the outcome to 

be judged satisfactory, no residual opacification or air-fluid level was allowed on sinus x-ray (see 

paper for details). Data on post treatment 1-3 days not shown. 

Results: 263 enrolled, 193 clinically assessable; primary reasons for exclusion were violation of 

selection criteria, failure to complete all required study visits, absence of urine compliance assay, 

and loss to follow-up 

Actual result reads: “A satisfactory clinical response (cure or improvement) in the per-protocol 

analysis at the follow-up assessment was present in 50% and 41% of clinically assessable 

patients treated with cefuroxime axetil and amoxicillin/clavulanate, respectively (P=0.19). Fiftyone cefuroxime axetil patients and 54 amoxicillin/clavulanate patients were judged to be clinical 

failures or had clinical recurrences.” 

Calculated Clinical Failure Rate at follow-up assessment (100% - reported satisfactory case rate 

in clinically assessable population): 

Cefurxoime 100%-50%=50% 

Amox/Clav 100%-41%=59% 

Adverse events: 

 Cefuroxime Amox/Clav 

 n=132 n=131 

patients with ≥ 1 23 (17.4%) 38 (29%) 

drug-related event 

patients with ≥ 1 GI events 15 (11.4%) 30 (22.9%) 

diarrhea 8 (6.1%) 25 (19.1%) 
C-34

nausea 0 6 (4.6%) 

vaginitis 3 (2.3%) 5 (3.8%) 

patients withdrew 2°

adverse event 2 (1.5%) 8 (6.1%) 

Funding: Glaxo Wellcome 

Comments: Table IV heading should specify the data is from a retrospective analyses using an 

overall symptom scoring system for the subset of symptoms published by the IDSA and not from 

the per-protocol analyses. 
C-35

Jareoncharsri et al. 2004 ID 34 

Stated Purpose of the study: To compare the efficacy, safety and antimicrobial activity of 

Levofloxacin with amoxicillin/clavulanic acid in the treatment of purulent sinusitis in adult Thai 

patients.

Population & Setting: 

60 patients from 2 ENT centers in Thailand from 6/98-12/99. 

Overall mean age (range) =35.5 yrs (17-68) Overall Males= 23 (38%) 

Levofloxacin group (n=34) Co-amoxiclav group (n=26) 

Unknown age range and number of males for each group, but demographic characteristics stated 

to be statistically comparable. 

Inclusion Criteria:

≥16 y.o. in outpatient setting with acute sinusitis/acute exacerbation of chronic sinusitis (based on 

nasal obstruction, purulent nasal discharge or postnasal drip, impairment of sense of smell, foul 

smell and headache) of ≤4 weeks duration AND purulent discharge in the middle meatus or 

maxillary ostium by endoscopy AND abnormal radiologic signs (undefined). 

Exclusion Criteria:

None listed 

Study Design: Randomized (unknown method of randomization or concealment), not blinded, 

multi-center trial. Unknown if prestratified by center. 

Treatment: Levofloxacin 300 mg QD for 14 days 

 Co-amoxiclav 500/125 mgTID for 14 days 

Outcome: (Primary) End of study (day 21 after enrollment)Cure: Resolution of Si/Sx and no 

radiologic evidence of remaining disease 

Improvement: Incomplete resolution of Si/Sx and improvement of radiologic findings 

Relapse: Initial improvement/cure followed by recurrence of Si/Sx 

Failure: Neither clinical nor radiologic improvement is seen 

Results: Unknown number enrolled and randomized. 34 in levofloxacin group and 26 in coamoxiclav group evaluated for clinical efficacy (unknown if intent to treat analysis). Unknown 

number excluded. 

1. Clinical Failure: (Primary) 3/34 in levofloxacin group and 4/26 in co-amoxiclav group 

failed, relapsed or withdrew from therapy.

2. Microbiological Failure: Most common pathogens isolated at baseline: Streptococcus 

species, H. influenzae and Staphylococcus species. Persistence determined by repeated 

isolation of baseline pathogens at day 14 after enrollment. 6/28 in levofloxacin group and 

6/20 had persistence of infection. 

Adverse Events: Adverse events were experience by 3/34 in levofloxacin group (nausea, 

dizziness, abdominal pain and diarrhea) and 2/26 in co-amoxiclav group (nausea, palpitation, 

acute urticaria and bronchospam). All adverse events in both groups were mild and resolved 

spontaneously.

Funding: Daiichi Pharmaceutical Co. 

Comments: Use of adjuvant therapy is unknown. Compliance with study medications is 

unknown. 14 days after enrollment, 62% in levofloxacin group and 62% in co-amoxiclav group 

showed radiological improvement. 
C-36

Johnson et al. 1999 ID 491 

Stated Purpose of the Study: To compare the efficacy and safety of a 10-day oral treatment 

of ciprofloxacin to cefuroxime axetil for the management of adults with acute bacterial sinusitis or 

acute exacerbations of chronic sinusitis 

Population and Setting: 501 (ITT) adults in 17 otolaryngology offices, study years not 

specificed 

Ciprofloxacin 228 mean age (range) 40 (18-72) males 40% 

Cefuroxime 225 mean age (range) 43 (18-85) males 43% 

Inclusion criteria: Primary dx of acute presumed or documented bacterial sinusitis or acute 

exacerbation of chronic bacterial sinusitis of up to 4 weeks’ duration; > 18 y/o; clinical signs and 

symptoms of sinusitis and x-ray confirming maxillary sinusitis; for additional criteria, see paper; 

antral puncture procedure was performed on all patients 

Exclusion criteria: inability to take oral medications, allergy to carboxyquinolones or betalactams; symptom duration > 4 weeks, administration of an antimicrobial agent within 5 days of 

study enrollment was also a reason for exclusion, unless the patient was a treatment failure or 

had received only 1 or 2 doses of the antibiotic, see paper for rest of criteria 

Study design: Prospective, randomized (one of two treatment groups using a block-design 

random code), double-blind, two-arm comparative study 

Treatments:

Ciprofloxacin 500 mg twice a day for 10 days 

Cefuroxime 250 mg twice a day for 10 days 

Outcome: 

Primary - Clinical resolution – resolution based on the resolution or improvement of both clinical 

symptoms and radiography, as well as the physician’s clinical judgment of whether or not 

additional antimicrobial treatment was necessary. Test-of-cure took place 1 – 7 days posttherapy. 

Secondary – follow-up at 2 - 4 week 

Results: 

501 enrolled; 48 disqualified (22 cipro; 26 cefuroxime); 453 were valid for efficacy analysis (228 

cipro; 225 cefuroxime); 

Clinical failure = ciprofloxacin 29/228 (13%); cefuroxime 38/225 (17%) 

Microbiological response; 99 (43%) ciprofloxacin and 90 (40%) cefuroxime had one or more 

causative organisms isolated pre-therapy. 

Microbiological failure = ciprofloxacin 3/92 (3.3%); cefuroxime 5/100 (5%) 

2-4 week follow up: clinical relapse = cipro 16/168 (9.5%) cefuroxime 20/165 (12.1%) 

Adverse events: 

115 (46%) cipro and 113 (45%) cefuroxime treated patients reported at least one treatmentemergent event. 

87 (35%) cipro and 83 (33%) cefuroxime experienced at least one drug-related adverse event. 

Diarrhea, nausea, headache and dizziness were the most common events reported. Premature 

discontinuation of a study drug due to an adverse event was reported in one cipro patient 

(vasodilatation, facial edema and rash) and 6 cefuroxime patients ( 3 rash, 2 diarrhea, 1 dizziness 

and amblyopia). 

Funding: Bayer 
C-37

Klapan et al. 1999 ID 500 

Stated Purpose of the study: To compare the efficacy and tolerability of a 3-day course of 

azithromycin and a 10-day course of amox/clav in the treatment of acute sinusitis in adults

Population & Setting: 

100 patients from unknown number or type of centers possibly in Croatia. Unknown study years. 

Azithromycin group (n=50): Mean age (range) = 33yrs (unknown range) 

Males=40 (80%) 

Amoxicillin/clavulanic acid group (n=50): Mean age (range) = 40yrs (unknown range) 

Males=37 (74%) 

Inclusion Criteria:

≥15 y/o with Si/Sx of acute sinusitis (undefined) of ≤4 weeks duration AND radiologic signs (airfluid levels, opacification or mucosal thickening≥4mm or opacities) AND nasal endoscopy 

(complete obstruction of ostiomeatal complex or partial obstruction with purulent drainage). 

Exclusion Criteria:

Chronic sinusitis; allergy to azithromycin or amoxicillin/clavulanic acid; pregnancy or nursing; viral 

infection; severe hepatic or renal impairment; GI disorder; immunodeficiency; received more than 

1 dose of antibiotic within 7 days of enrollment.

Study Design: Randomized (unknown method of randomization or concealment), not blinded 

trial. 

Treatment: Azithromycin 500 mg PO qd for 3 days 

 Amoxicilllin-clavulanic acid 500/125 mg PO TID for 10 days 

Outcome: (Primary) End of treatment (10-12 days after initiation of treatment) 

 (Secondary) Follow up (4 weeks after initiation of treatment) 

Response rate was based on clinical scoring system 0-3 (based on fever, headache, facial 

tenderness, nasal congestion/discharge, nasal mucosa hyperemia and post-nasal secretions) 

Cured: complete disappearance of signs and symptoms, score≤1 

Improvement: partial disappearance of signs and symptoms without need for further therapy 

Failure: persistence or progression of signs or symptoms requiring further therapy 

Relapse: reappearance of signs or symptoms at 4 weeks 

Results: 100 enrolled and randomized. 47 in azithromycin group and 47 in amoxicillin/clavulanic 

acid group were evaluated for clinical efficacy (per protocol analysis). 3 in azithromycin group 

and 3 in amoxicillin/clavulanic acid group were excluded for reasons including: violation of 

inclusion criteria. 

1. Clinical Failure: 

• (Primary) 0/47 in azithromycin group and 0/47 in amoxicillin/ clavulanic acid 

group had failure or relapse. 3/47 in azithromycin group and 12/47 in 

amoxicillin/clavulanic acid group had improvement. 

• (Secondary) 1/43 in azithromycin group and 4/46 in amoxicillin/clavulanic acid 

group had failure or relapse. 

2. Microbiological Failure: Ostiomeatal sinus aspiration was performed in 70 patients at 

baseline (unknown reason not performed on all patients). Most common pathogens 

isolated at baseline: H. influenzae, S. aureus and S. pneumoniae. No pathogens cultured 

in 33%. Aspiration was repeated after 72 hours from treatment initiation if clinical failure. 

0/23 in azithromycin group and 3/24 in amoxicillin/clavulanic acid group failed (includes 

persistence and relapse). 
C-38

Adverse Events: Adverse events occurred in 2/50 in azithromycin group (nausea=2,

diarrhea=0, other=0), and 5/50 in amoxicillin-clavulanic acid group (nausea=5, diarrhea=1,

other=0). Discontinuation due to adverse events did not occur in either group. 

Funding: Not disclosed 

Comments: Some of the authors are from Pliva d.d. Pharmaceuticals Division, Zagreb, 

Croatia. Compliance with study medications is unknown. 
C-39

Klein et al. 1998 ID 599 

Stated Purpose of the Study: To compare the efficacy and safety of ciprofloxacin to 

cefuroxime in the treatment of adult outpatients with acute bacterial sinusitis or acute 

exacerbation of chronic sinusitis. 

Population & Setting: 

83 patients from a single (unknown type) center in unknown country. Unknown study years. 

Ciprofloxacin group (n=13): Mean age (range) = 46.8yrs (30-75) Males= 6 (46%) 

Cefuroxime axetil group (n=19): Mean age (range) = 44.3yrs (25-71) Males= 4 (21%) 

Inclusion Criteria:

≥18 y.o. with acute sinusitis/acute exacerbation of chronic sinusitis (based on having at least 2 of 

the following: fever, leukocytosis, typical symptoms or physical findings) of ≤4 weeks duration 

AND radiologic signs (air-fluid levels, opacification or mucosal thickening≥6mm). 

Exclusion Criteria:

Frequent, recurrent acute sinusitis; allergy to carboxyquinolones or ß-lactams; pregnancy or 

nursing; inability to undergo sinus aspiration or to take oral medications; bacteremia or meningitis; 

received investigational drugs during the preceding 30 days, or more than 2 doses of an antibiotic 

within 5 days of enrollment unless the patient was a treatment failure; baseline serum 

creatinine≥3.0 mg/dL. 

Study Design: Randomized (computer-generated block-design random code with unknown 

concealment method), double-blinded (study drugs encapsulated in opaque capsules for 

masking), single-center trial 

Treatment: Ciprofloxacin 500 mg PO BID for 10 or more days (range=14-18 days) 

 Cefuroxime axetil 250 mg PO BID for 10 or more days (range=13-18 days) 

Outcome (Primary): End of therapy (1-7 days after treatment) 

 (Secondary): Follow up (2 to 4 week after treatment) 

Resolution: complete resolution of Si/Sx, negative radiography and no further therapy required 

Improvement: decrease in Si/Sx, decreased mucosal thickening and no further therapy required 

Failure: no change, worsening or reappearance of Si/Sx requiring alternative therapy 

Relapse: reappearance of any Si/Sx AND positive sinus x-rays 

Results: 83 enrolled and randomized. 13 in ciprofloxacin group and 19 in cefuroxime axetil 

group were evaluated for clinical efficacy (per protocol analysis). 51 (unknown number in 

ciprofloxacin vs. cefuroxime axetil group) were excluded for reasons including: no pathogen 

isolated and inadequate treatment length. 

1. Clinical Failure: 

• (Primary) 0/13 in ciprofloxacin group and 5/19 in cefuroxime axetil group were 

failed. 8/13 in ciprofloxacin group and 11/19 in cefuroxime axetil group had 

improvement. 

• (Secondary) 3/9 in ciprofloxacin group and 1/9 in cefuroxime axetil group had 

relapse. 

2. Microbiological Failure: Most common pathogens isolated at baseline: H. influenzae 

and Streptococcus species. By sinus aspiration if clinical failure at end of therapy. 

• (Primary) 0 (of unknown number re-cultured) in ciprofloxacin group and 5 (of 

unknown number re-cultured) in cefuroxime axetil group failed. All 5 failures were 

due to super-infection, not persistence of pathogen originally cultured. 

• (Secondary) 0 (of unknown number re-cultured) in ciprofloxacin group and 0 (of 

unknown number re-cultured) in cefuroxime axetil group failed. 
C-40

Adverse Events: Drug-related adverse events were experienced by 10 (45%) of ciprofloxacin 

group and 10 (34%) or cefuroxime axetil group. Most events in both groups were GI related 

(diarrhea, nausea/vomiting and flatulence). Discontinuation due to adverse events occurred in 1 

(rash) in the ciprofloxacin group and 1 (eczema flare) in the cefuroxime axetil group. 

Funding: Bayer 

Comments: Use of decongestants and antihistamines were permitted but not recorded. Onesided 95% CI were calculated for clinical and microbiological efficacy. More subjects in the 

cefuroxime axetil group had multiple organisms cultured at baseline than in the ciprofloxacin 

group. An unknown number of patients were removed from analysis for clinical failure with 

resistant pathogens cultured at end of study. Compliance with study drugs is unknown. 
C-41

Klossek et al. 2003 ID 164 

Stated Purpose of the Study: To compare the efficacy and safety of oral moxifloxacin 400 

mg once daily for 7 days with those of oral trovalfloxacin 200 mg once daily for 10 days in treating 

adult out-patients with acute bacterial rhinosinusitis 

Population & Setting: 503 patients with acute bacterial maxillary sinusitis were randomized. 

Patients were enrolled in 60 centers in 8 countries: Belgium, France, Germany, Great Britain, 

Greece, Lithuania, Spain and Sweden, by both office-based primary care physicians (UK) and 

otolaryngologists (other countries). 

Moxifloxacin 223 mean age 38.8 males 43.9% 

Trovafloxacin 229 mean age 41.9 males 49.3% 

Inclusion criteria: male and female patients ≥ 18 y/o with acute sinusitis (see paper for details) 

and x-ray evidence of air-fluid level, opacification or ≥ 6 mm mucosal thickening. 

Exclusion criteria: chronic sinusitis (symptomatic > 4 weeks), recurrence of > 2 episodes of 

acute sinusitis within the preceding 6 months, patients with hypersensitivity to any quinolone, 

receiving concomitant medication reported to increase the QT interval, and others (see paper) 

Study design: This was a prospective, multinational, multicenter, randomized, double-blind, 

comparative study. Patients were randomly assigned 1:1 to one of two treatment groups using a 

block design computer-generated random code. As randomization was performed by the center, 

each patient within each center was assigned a sequential ascending random number to 

complete a pre-defined block size of four. Matching placebos were used. 

Treatments: 

Moxifloxacin 400 mg once daily for 7 days, matching placebo once daily for days 8-10 

Trovafloxacin 200 mg once daily for 10 days 

Outcome: 

Primary – clinical response 7-10 days after the end of therapy, “clinical resolution” is defined by 

disappearance of signs and symptoms or improvement and no further therapy required 

Secondary – final follow up 3 to 4 weeks after the end of therapy 

Results: Primary efficacy analysis was performed on clinically evaluable patients: confirmed 

clinical and x-ray dx of acute sinusitis, received at least 5 days of therapy (with no other abx 

administered concomitantly), followed the protocol and received post-therapy clinical evaluation 

within 3 to 14 days after ending the study drug therapy 

503 enrolled, 452 valid for efficacy analysis; most common reasons fro exclusion were violation of 

the time schedule for evaluation and insufficient duration of therapy 

Reported clinical failure rate 7-10 days post –therapy:

Moxifloxacin 7/223 (3.1%) 

Trovafloxacin 18/229 (7.9%) 

Microbiological failure rate: 

Moxifloxacin 5/90 (5.6%) 

Trovafloxacin 10/101 (9.9%) 
C-42

Adverse events: 

Drug-related adverse events occurring in ≥ 2% of patients 

Moxifloxacin Trovafloxacin 

 N=248 N= 251 

Dizziness 3 (1.2%) 21 (8.4%) 

Diarrhea 14 (5.6%) 3 (1.2%) 

Nausea 3 (1.2%) 10 (4%) 

Asthenia 5 (2%) 6 (2.4%) 

Vertigo 2 (0.8%) 8 (3.2%) 

Abdominal Pain 5 (2%) 4 (1.6%) 

One or more serious events were reported for 4 moxifloxacin and 2 trovafloxacin-treated patients. 

However, only 2, in one patient of the moxifloxacin group, were considered to be drug-related 

(pruritus and tachycardia) necessitating study drug discontinuation. 5 patients (2%) receiving 

moxifloxacin and 12 (4.8%) of trovafloxacin treated patients discontinued therapy prematurely. 

Early discontinuation was at least in part due to dizziness/vertigo in 6/12 patients who received 

trovafloxacin compared to 1/5 of those in the moxifloxacin group. 

Of the 499 patients evaluated for safety, treatment-emergent adverse events were reported by 74 

(29.8%) of moxifloxacin group and 82 (32.7%) of the trovafloxacin group. 

Funding: not stated 

Comments: authors Arvis & Leberre associated with Bayer Pharma, France 
C-43

Kutluhan et al. 2002 ID 97073 

Stated Purpose of the Study: To determine the most appropriate duration of treatment in 

adult patients with bacterial acute maxillary sinusitis and to investigate whether a linear 

correlation is present between nasal smear findings and symptoms of acute maxillary sinusitis at 

the time of diagnosis and the follow-up period 

Population & Setting: 

Selected group of 40 clinic patients in Turkey enrolled in the study between 1998 and 2001. 

Mean age (range): 29 (16-45) 

Inclusion criteria: bacterial acute maxillary sinusitis diagnosed by maxillary sinus puncture; 

also clinical signs and symptoms (major and minor, see table 1 in paper); x-ray opacification and 

air-fluid level; 

Exclusion criteria: x-ray findings of mucosal thickening or cysts...etc.; acute sinusitis within 

the last 6 months; chronic sinusitis 

Study design: prospective, randomized; method of randomization not stated 

Treatments: 

Group 1 = 10 patients 1 week antibiotic 

Group 2 = 10 patients 2 week antibiotic 

Group 3 = 10 patients 3 week antibiotic 

Group 4 = 10 patients 4 week antibiotic 

Antibiotic choice was made depended on culture and sensitivity results from maxillary sinus 

puncture. 

Amox/Clav 1 g twice a day 

Ciprofloxacin 500 mg (dosing frequency not specified) 

Clarithromycin 500 mg twice a day 

Cefuroxime 250 mg twice a day 

Patients were allowed Paracetamol if needed. 

Outcome: Presence or absence of symptoms at study day 7, 14, 21, 28 and 56 

Results: Total number of patients completed the study was not explicitly stated in the paper.

At day 7 and 14, no reported relapse in any patients. 

At day 28, relapse of the symptoms was noted in 5, 2, 2 and 3 patients in groups 1, 2, 3, and 4. 

Assuming all patients completed the study, the following relapse rate at day 28 can be 

calculated: 

1 week antibiotic 5/10 (50%) 

2 week antibiotic 2/10 (20%) 

3 week antibiotic 2/10 (20%) 

4 week antibiotic 3/10 (30%) 

Adverse events: data not presented 

Funding: 

Comments: Total number of patients completed the study was not explicitly stated in the paper. 

Number of patients with relapse on other study days was not reported. 
C-44

Lasko et al. 1998 ID 530 

Stated Purpose of the Study: This report presents the findings of the first multicenter, 

randomized, double-blind trial in acute sinusitis evaluating the efficacy of levofloxacin compared 

with clarithromycin in the management of acute sinusitis. 

Population & Setting: 236 patients were randomized into 2 groups. 

Levofloxacin 119 Mean age (range) 40.4 (18-83) Males 44.4% 

Clarithromycin 117 Mean age (range) 39.9 (18-78) Males 41.9% 

Inclusion criteria: male and female patients > 18 y/o with clinical symptoms of acute sinusitis 

and positive x-ray of opacification, air fluid level or mucosal thickening ≥ 5 mm, not pregnant, see 

paper for details. 

Exclusion criteria: symptoms > 4 weeks or hx of > 2 episodes of sinusitis within the previous 

year, reaction to quinolone or macrolide abx and others (see paper) 

Study design: multicenter, randomized, double-blind trial; randomization based on a computergenerated randomization schedule; double-blinding was accomplished by encapsulation of 250 

mg tablets of levofloxacin or clarithromycin. 

Treatments: 

Levofloxacin 2x 250 mg capsules in am and matching placebos in pm for 10-14 days 

Clarithromycin 2x 250 mg capsules twice a day for 10-14 days 

Outcome: Primary: Clinical success is defined by “cured” or “improved”. The assessment took 

place 2-5 days after completing therapy. 

Secondary: Patients were assessed for relapse or worsening of symptoms and had a repeat 

sinus x-ray at days 28-32 after completing therapy. 

Results: 236 randomized; 191 evaluable for clinical efficacy; 21 (17.6%) unevaluable in 

Levofloxacin arm, 24 (20.5%) unevaluable in clarithromycin arm; majority of patient were 

excluded either because the admission x-ray was negative or they were lost to follow-up. 

Reported clinical failure rate in evaluable patients: 

Levofloxacin 6/98 (6.1%) 

Clarithromycin 6/93 (6.5%) 

Adverse events: 

 Levofloxacin (n=119) Clarithromycin (n=117) 

All Body Systems 27 (22.7%) 46 (39.3%) 

GI 20 (16.8%) 39 (33.3%) 

CNS (dizziness,headache) 8 (6.7%) 5 (4.3%) 

Taste Perversion 1 (0.8%) 9 (7.7%) 

Loss of appetite, disorientation and insomnia 

 5 (4.2%) 4 (3.4%) 

See table 6 for rest. 

Comparison of laboratory data collected at admission and post therapy demonstrated no 

significant changes in laboratory values. 

Funding: Janssen-Ortho Inc. 

Comments: 
C-45

Lindbæk et al. 1998 ID 586 

Stated Purpose of the Study: To compare the efficacy of penicillin V, amoxicillin and placebo 

given to patients with mucosal thickening on CT without fluid level or total opacification

Population & Setting:

244 patients from 29 family practice centers in Norway. Unknown study years. 

Penicillin V group (n=20): Mean age (range)= 41.2 yrs (unknown range) Males= 8 (40%) 

Amoxicillin group (n=22): Mean age (range)= 37.1 yrs (unknown range) Males= 11 

(50%) 

Placebo (n=21) Mean age (range)= 32.5 yrs (unknown range) Males= 6 (29%) 

Inclusion Criteria:

Patients with clinical Si/Sx of acute sinusitis (based on scoring system including: 

hyposmia/anosmia, unilateral facial pain, pain in upper teeth, pain worsening at bending forward, 

“double sickening,” nasal obstruction, rhinorrhea, sinus pain, malaise, fever and purulent 

secretion) of ≥7 days duration AND paranasal sinus mucosal thickening ≥5mm without air-fluid 

levels or total opacification on CT scan. 

Exclusion Criteria: 

Age≤ 15 years; pregnancy; ongoing antibiotic treatment; immunosuppressive treatment, previous 

sinus/nose surgery; alcohol or drug abuse; rheumatic disease; penicillin allergy; chronic sinusitis; 

high fever; high degree of pain. 

Study Design: Randomized (unknown method of randomization and concealment), double 

blinded to clinician, patient and radiologist (study drugs were all similar-appearing tablets), multicenter trial. Unknown if prestratified by center. 

Treatment: 1) Penicillin V 1320 mg TID for 10 days 

 2) Amoxicillin 500 mg TID for 10 days 

 3) Matched Placebo TID for 10 days 

Outcome: Subjects kept a diary and after 10 days of treatment answered if they thought they 

still had sinusitis. If the answer was no, the diary was stopped (day of cure). The daily diary 

continued until the answer was no until a maximum of 30 days. 

(Primary) Subjective status: After 10 days of treatment, subjects ranked their own condition as 

restored, much better, somewhat better, unimproved or worse. 

(Secondary) Clinical score: Assessed after 10 days of treatment. Maximum value of 4. Summed 

from four visual analogue scales based on subjects’ ranking their own degree of nasal 

obstruction, rhinorrhea, sinus pain and malaise. 

Results: 244 enrolled and 70 randomized. 20 in penicillin V group, 22 in amoxicillin group and 

21 in placebo group were evaluated for clinical efficacy (intent to treat analysis). 7 subjects were 

excluded (unknown from which groups) for reasons including: poor quality CT scans and failure to 

return a diary. 

Clinical Failure: (Primary) 2/20 in penicillin V group, 3/22 in amoxicillin group and 3/21 in 

placebo group failed (includes unimproved and worse). (Secondary) Mean reduction in clinical 

score was 1.1 (95%CI 0.8,1.5) in penicillin V group, 1.1 (0.6-1.6) in amoxicillin group, and 1.0 

(0.7-1.3) in placebo group.

Adverse Events: not reported 

Funding: Norwegian Research Council 
C-46

Comments: Use of nasal decongestants and paracetamol was allowed but not recorded. 

Compliance with study medications is unknown. If a patient asked for another antibiotic after 10 

days because subjective symptoms persisted, (s)he was given amoxicillin 500 mg TID for 10 

days. The median number of days before a patient was no longer feeling ill (Kaplan-Meier plot) 

was 13.5 days in penicillin V group and 10 days in both the amoxicillin and placebo groups. 

 
C-47

Luterman et al. 2003 ID 97041 

Stated Purpose of the Study: To compare the efficacy and safety of 5- and 10-day courses 

of telithromycin with that of a standard 10-day regimen of amoxicillin/clavulanic acid in the 

treatment of acute maxillary sinusitis (AMS). 

Population and Setting: 7/17/98-6/16/99 in 69 centers in US, Canada, S. Africa, Argentina & 

Chile 

Median age (range): 

Group 1: 800 mg telithromycin qd for 5 days : 38 y/o (18-69) 

Group 2: 800 mg telithromycin for 10 days: 39 y/o (18-84) 

Group 3: 500/125 mg amoxicillin/clavulanic tid for 10 days: 38.5 (16-79) 

Inclusion criteria: ≥ 18 y/o with presumed acute maxillary sinusitis (purulent nasal discharge, 

maxillary tenderness...etc.); <28 days Symptoms; sinus x-ray: presence of air-fluid level and/or 

total sinus opacity and/or ≥6 mm mucosal thickening within 48 hours of enrollment. 

Exclusion criteria: History of chronic or recurrent sinusitis, sphenoid or nosocomially acquired 

sinusitis, suspected nonbacterial infection, obstructive anatomic lesions in nasopharynx, 

documented resistant organisms, immotile cilia syndrome, CF or odontogenic infection; immunecompromised, hypersensitivity to macrolide or beta-lactam abx; on steroids or any drug that 

interferes with efficacy and safety assessments of study medication; progressively fatal illness, 

long Q-T syndrome, severe hypokalemia, hx of drug or ETOH abuse, renal or hepatic impairment, 

and lactation or pregnancy 

Study Design: Randomized (1:1:1) Controlled Trial, double-blind, 3-arm, parallel-group design 

Treatments: Group 1: 800 mg telithromycin qd for 5 days 

Group 2: 800 mg telithromycin for 10 days 

Group 3: 500/125 mg amoxicillin/clavulanic tid for 10 days 

Outcome: (Primary) Test of Cure Outcome visit between days 17 and 24. (Secondary) Late 

post-therapy visit between days 31 and 45; cure: no infection, clinical improvement or to 

preinfection state without need for further abx; normal, improved or not worse sinus x-rays; pts 

whose signs or symptoms were unchanged or worse and who needed more abx were treatment 

failures. 

Results: 754 enrolled, 753 received at least 1 abx, 146 excluded because x-ray was not 

consistent, 

modified ITT: 607 

Clinically evaluable at end of study: 423, Group 1: 146; Group 2: 140; Group 3: 137 

184 excluded because of major protocol violation 

Clinical Failure: 

Group 1: 36/146 (24.7%); Group 2: 38/140 (27.1%); Group 3: 35/137 (25.5%) 

Microbiological Failure: 29 patients had sinus punctures. Most common organisms isolated 

were S. pneumoniae and H. influenzae. 

• Primary: Group 1: 1/7; Group 2: 1/7; Group 3: 2/10 

• Secondary: Group1: 2/7; Group 2: 2/7; Group 3: 2/7 

Adverse events: 327 patients (44%) experienced one or more treatment-emergent adverse 

events that were considered to be possibly related to a study med during the study. Diarrhea and 

nausea were the most common adverse events in each treatment group. 41 patients (5.5%) 

withdrew because of adverse events (group 1: 16 [6.6%], group 2: 14 [5.5%], group 3: 11 [4.5%]). 
C-48

7 patients (1%) experienced at least one serious adverse event – 3 in the 10-day telithromycin 

group (allergy, gastroenteritis, and pseudomembranous colitis [one patient each]) and one in the 

amox/clav group (pseudomembranous colitis) were considered drug related. No deaths occurred 

during the study. No patient had QTc interval of 500 msec. or more. 

Funding: Aventis Pharmaceutical 

Comments: Stability problem with amox/clav; 100 patients from that group were excluded, new 

population were recruited. Data from the excluded patients were not reported. 
C-49

Murray et al. 2000 ID 375 

Stated Purpose of the Study: To compare the clinical efficacy and tolerability of 

clarithromycin extended-release(ER) (1000 mg once daily) and clarithromycin immediate-release 

(IR) (500 mg twice daily) over a 14-day treatment course in patients with acute maxillary sinusitis 

Population & Setting: 284 patients from 37 investigative sites throughout the US and Canada 

between 3/1998 and 10/1998 were studied. 

Clarithromycin ER 142 mean age (range) 41.9 (13-78) males 35% 

Clarithromycin IR 141 mean age (range) 41 (15-73) males 38% 

Inclusion criteria: ≥ 12 y/o; presumptive dx of acute maxillary sinusitis supported by 

confirmatory sinus radiographs obtained within 72 hours before treatment; signs and symptoms 

for at least 7 days before and not longer than 28 days before the pretreatment visit (see paper for 

details) 

Exclusion criteria: chronic maxillary sinusitis; frontal, ethmoid or sphenoid sinusitis, systemic 

abx within 3 weeks; significant renal or hepatic impairment; pregnant or likely to become 

pregnant; see paper for others 

Study design: Phase III, randomized, controlled, double-blind, parallel-group, multicenter 

study. Randomly assigned in a 1:1 ratio at each investigative site. 

Treatments: 

Clarithromycin extended-release (ER) two 500 mg tablets once daily plus placebo for 

clarithromycin IR for 14 days 

Clarithromycin immediate-release (IR) one 500 mg tablet twice daily plus placebo for 

clarithromycin ER for 14 days 

All patients were dispensed 0.05% oxymetazoline nasal spray to be used as a decongestant 

twice daily in conjunction with clarithromycin during the 1st 3 days of study drug administration. 

Outcome: Test of cure was determined on 10 to 17 days after completion of therapy. Clinical 

cure was defined by resolution or improvement of symptoms, no worsening of x-ray appearance 

of sinuses and no further abx needed. 

Results: 284 enrolled; 283 received treatment; 38 (20 ER; 18 IR) were deemed non-assessable 

Calculated Clinical Failure Rate (100% - reported clinical cure rate): 

Clarithromycin extended release 18/122 (14.8%) 

Clarithromycin immediate release 26/123 (21.1%) 

Clinical response rates were similar in the intent-to-treat analysis per study authors. 

Adverse events: 

Adverse events were reported by 45/142 (32%) in the clarithromycin ER group and 40/141 (28%) 

in the IR group. Most commonly reported drug-related adverse events were 

 ER IR 

Abnormal taste 10% 10% 

Diarrhea 6% 8% 

Nausea 5% 9% 

No patient in this study experienced a serious adverse event. 

Premature discontinuation from treatment due to a drug-related adverse event occurred in 5/142 

(4%) of patients in the ER group and 11/141 (8%) in the IR group. 
C-50

2/142 (1%) in the ER group and 10/141 (7%) in the IR group prematurely discontinued treatment 

because of a drug-related GI or abnormal taste adverse event. 

Funding: Abbott Laboratories 

Comments: 
C-51

Namyslowski et al. 2002 ID 189 

Stated Purpose of the Study: To compare the clinical efficacy and safety of oral amox/clav 

with that of cefuroxime axetil in the treatment of chronic bacterial sinusitis and acute exacerbation 

of chronic sinusitis in adults 

Population & Setting: 231 (outpatients or inpatients) in 4 centers in Poland were enrolled. 

 Intent to treat population 

Amox/Clav 115 mean age 37 males 57% 

Cefuroxime 116 mean age 41 males 47% 

Inclusion criteria: ≥ 18 y/o; hospitalized and non-hospitalized; chronic sinusitis > 3 months; 

abnormal x-ray; acute exacerbation of chronic sinusitis confirmed by x-ray, symptoms ≤ 4 weeks 

with a history of at least 2 acute sinusitis requiring abx the previous 12 months; antral sinus 

puncture within 48 hours prior to starting therapy and evidence of the presence of an infection for 

which oral antibiotic therapy with either amox/clav or cefuroxime was appropriate (no further 

explanation given, see paper for details regarding inclusion criteria) 

Exclusion criteria: history of hypersensitivity reaction to beta-lactam abx or received abx 

within 2 weeks prior to enrollment; confirmed or suspected allergic sinusitis; see paper for rest 

Study design: prospective, randomized, parallel, open, multicenter 

Treatments: 

Amox/Clav 875/125 mg oral twice a day for 14 days 

Cefuroxime axetil 500 mg oral twice a day for 14 days 

Outcome: 

Primary: clinical response at the end of therapy (study day 15-18) 

Results: 231 in intention-to-treat population; 206 evaluable

Intent to treat population 

Reported failure rate: amox/clav 3/115 (2.6%) cefuroxime 8/116 (6.9%) 

Reported Indeterminate rate: amox/clav 6/115 (5.2%) cefuroxime 8/116 (6.9%) 

Calculated failure rate (100% - reported clinical cure rate): 

 amox/clav 9/115 (7.8%) cefuroxime 16/116 (13.8%) 

Clinically evaluable population 

Reported failure rate: amox/clav 3/104 (2.9%) cefuroxime 8/102 (7.8%) 

Reported Indeterminate rate: amox/clav 2/104 (1.9%) cefuroxime 4/102 (3.9%) 

Calculated failure rate (100% - reported clinical cure rate): 

 amox/clav 5/104 (4.8%) cefuroxime 12/102 (11.8%) 

Microbiological failure in evaluable population: 

Amox/clav 22/65 (33.8%) 

Cefuroxime 20/62 (32.3%) 

Adverse events: 

 Amox/Clav (n=115) Cefuroxime (n=116) 

Patients with at least 1 adverse event 8 (7%) 11 (9.5%) 

Patients with serious adverse event* 1 (0.9%) 3 (2.6%) 

Patients with drug related adverse event 5 (4.3%) 5 (4.3%) 
C-52

Diarrhea 2.6%) 3 (2.6%) 

Urticaria 0 2 (1.7%) 

Facial edema 0 1 (0.9%) 

Discontinuation of med 2° to adverse event 4 (3.5%) 9 (7.8%) 

*amox/clav group: 1 experienced an eye disorder the day after starting treatment 

 cefuroxime group: 1 urticaria related to study drug; 1 underwent maxillary sinus surgery 7 days 

 after starting treatment; 1 experienced a cardiovascular disorder and was 

 hospitalized 

Funding: 

Comments: 

 
C-53

Rakkar et al. 2001 ID 97064 

Stated Purpose of the Study: To compare the efficacy and safety of a 10-day oral treatment 

of moxifloxacin with amoxicillin/clavulanate for the outpatient management of uncomplicated 

acute sinusitis of suspected bacterial origin 

Population & Setting: 475 patients in 85 primary care practice sites in US, study years not 

specified 

Moxifloxacin = 234 (Intent To Treat) Mean age (range)= 43 (19-78) males= 31% 

Amox/Clav = 237 Mean age (range)= 42 (18-87) males= 35% 

Inclusion criteria: ≥ 18 y/o; outpatient men and non-pregnant women, clinical dx of acute 

suspected bacterial sinusitis ≥ 7 days but < 30 days duration (nasal congestion, post-nasal 

drainage, frequent coughing or throat clearing, frontal headache, malar tenderness/pain and 

purulent nasal discharge) 

Exclusion criteria: symptoms > 4 weeks (chronic sinusitis) or frequent recurrent acute sinusitis 

(> 2 episodes within the past 12 months despite appropriate therapy; history of sinus surgery and 

others (see paper) 

Study design: Prospective, multicenter, non-blinded, two-arm comparative study. Patients 

were randomly assigned to one of two treatment groups using a block design random code. A pill 

count was used to assess patient compliance at completion of the study. 

Treatments: 

Moxifloxacin 400 mg once a day for 10 days 

Amox/Clav 875 mg twice a day for 10 days 

Outcome: 

Primary: Clinical response at the test-of-cure visit (14-21 days post treatment) was the primary 

efficacy variable. 

Secondary: Clinical response at day 26-46 post treatment 

Results on Intent to Treat (ITT) population: 

475 patients randomized into 2 groups moxifloxacin (238) and amox/clav (237). 4 patients in the 

moxifloxacin group never received the study medication and were excluded from the ITT 

population in the study. 85% (199/234) of moxifloxacin and 82% (194/237) of amox/clav reported 

clinical resolution. 

Clinical Failure (ITT): Primary: moxifloxacin 35/234 (15%) and amox/clav 43/237 (18.1%) 

Secondary (denominator assumed): moxifloxacin 6/234 (2.6%) and amox/clav 4/237 (1.7%) 

134 patients were excluded from per protocol (efficacy) analysis (see table 1 in paper). 

The per protocol (efficacy) population included 170 moxifloxacin and 171 amox/clav treated 

patients. 86% of moxifloxain and 84% for amox/clav reported clinical resolution. 

Clinical Failure (patients who actually received study medications): Primary: Moxifloxacin 24/170 

(14%) and Amox/clav 27/171 (16%) 

Secondary (denominator assumed): moxifloxacin 6/170 (3.5%) and amox/clav 6/171 (3.5%) 

Adverse events: 471 patients were evaluated for safety, treatment emergent adverse events 

were reported for 136 (58%) moxifloxacin and 124 (52%) amox/clav treated patients. Premature 

discontinuation due to any adverse event was required in 5% (12) and 3% (8) of patients, 

respectively. Drug-related adverse events were reported in 30% of moxifloxacin and 25% of 

amox/clav treated patients and were primarily GI-related: nausea (11% moxifloxacin, 5% 
C-54

amox/clav) and diarrhea (3% moxifloxacin, 10% amox/clav). An elevation in hepatic enzymes 

(100% above baseline for ALT/AST) was noted 0-6 days post-treatment in a small number of 

patients. Specifically, enzyme elevations were observed in 1.7% of moxifloxacin-treated patients 

(n=4) compared with 4.6% of amox/clav treated patients (n=11). 

Funding: Bayer 

Comments: Use of oral or nasal decongestants or antihistamines was permitted during the 

study period, including phenylephrine nose drops as needed. Systemic or topical corticosteroids 

were not allowed unless the patient had been on long-term therapy before study entry. 
C-55

Roos et al. 2002 ID 240 

Stated Purpose of the Study: To compare the efficacy and tolerability of a 5 and 10 day 

course of oral treatment with telithromycin 800 mg once daily in patients with community acquired 

acute maxillary sinusitis 

Population & Setting: 343 from 37 centers in 9 countries (Austria, Croatia, Czech Republic, 

Denmark, Finland, France, Germany, Greece and Sweden) enrolled. The study was conducted 

between 4/1998 and 4/1999. 

5-day telithromycin 167 median age (range) 34 (18-65) male 49.7% 

10-day telithromycin 168 median age (range) 39 (18-66) male 48.2% 

Inclusion criteria: 18-65 y/o with a dx of acute maxillary sinusitis; x-ray showing total sinus 

opacity or air-fluid level and at least 1 clinical criterion (see paper for details) 

Exclusion criteria: chronic sinusitis (> 1 month); recurrent sinusitis (> 3 episodes that required 

abx in the previous 12 months); concomitant sphenoidal sinusitis; patients were suspected nonbacterial infections or microbiologically documented infection with pathogens known to be 

resistant to telithromycin before treatment were also excluded; known long QT syndrome; 

pregnancy; lactation; other abx 7 days prior to study entry 

Study design: randomized, double-blind study; patients were pre-screened by sinus puncture; 

susceptibility testing was performed using disk diffusion methods at each individual center; disk 

zone inhibition and MIC testing were also carried out by a central laboratory; 

Method of randomization not stated; 

Blinding was maintained by matching placebos. 

Treatments: 

Telithromycin 800 mg once daily for 5 days, matching placebo once daily on study day 6-10 

Telithromycin 800 mg once daily for 10 days 

Outcome: 

Primary – Primary efficacy variable was the rate of clinical cure at the post-therapy/test of cure 

visit (days 17-21) in the clinical per-protocol population. Clinical cure was defined as the 

improvement or return to preinfection state, or improvement with persistence of residual 

symptoms but with no need for subsequent abx, with a sinus x-ray or CT scan that was either 

normal or improved. 

Secondary – Secondary efficacy variables were clinical outcome at the late post-therapy visit 

(days 31-36) along with bacteriologic outcome at the post-therapy/test of cure and late posttherapy visits. 

Results: 343 enrolled, 341 randomized; 336 received at least 1 dose of medication; of the 336, 

one was excluded because x-ray was not consistent with acute maxillary sinusitis; 335 in the 

modified intent-to-treat population; 79 excluded for major protocol violations, leaving 256 in the 

clinical per-protocol population 

 Telithromycin 5-day 10-day 

Post-therapy, TOC days 17-21 

Calculated Clinical Failure Per-protocol 11/123 (8.9%) 12/133 (9%) 

Calculated Failure mod ITT 29/167 (17.4%) 21/168 (12.5%) 

Late post-therapy, days 31-36 

Calculated Clinical Failure Per-protocol 12/108 (11.1%) 12/120 (10.8%) 
C-56

Calculated Failure mod ITT 32/167 (19.2%) 23/168 (13.7%) 

Microbiological Failure 

 Telithromycin 5-day 10-day 

Post-therapy, TOC days 17-21 

Calculated Bacteriological Failure Per-protocol 5/70 (7.1%) 7/69(10.1%) 

Calculated Failure mod ITT 17/97 (17.5%) 11/104 (10.6%) 

Late post-therapy, days 31-36 

Calculated Bacteriological Failure Per-protocol 6/60 (10%) 8/61 (13.1%) 

Calculated Failure modITT 20/97 (20.6%) 13/104 (12.5%) 

Adverse events: 

166 in 5-day group and 167 in 10-day group were included in the safety analysis. 

50/166 (30.1%) in 5-day group and 64/167 (38.3%) in 10-day group experienced at least 1 

treatment-emergent adverse event. 

6/166 (3.6%) in 5-day group and 1/167(0.6%) in 10-day group discontinued the study because of 

adverse events. The events in the 5-day group were diarrhea, nausea, vomiting, cholelithiasis, 

facial edema, infection, and increased alkaline phosphatase levels (1 each). GI pain was the 

reason for discontinuation of the one patient in the 10-day group. 

1 patient in the 5-day group had increased aspartate transaminase that was considered to be 

clinically noteworthy abnormal laboratory value (CNALV, defined as >3 upper limit of normal) 

1 patient in the 10-day group had increased ALT that was considered to be CNALV. 

The patients recovered without sequelae. 

Adverse event ≥ 2% in either Rx group 5-day (166) 10-day (167) 

Diarrhea 16 (9.6%) 22 (13.2%) 

Nausea 8 (4.8%) 4 (2.4%) 

GI pain 3 (1.8%) 8 (4.8%) 

Vaginal Moniliasis 5 (3%) 3 (1.8%) 

Increased ALT 4 (2.4%) 1 (0.6%) 

Vertigo 1 (0.6%) 4 (2.4%) 

Funding: 

Comments: Patients with pathogens known to be resistant to telithromycin before treatment 

were excluded; authors Leroy, Rangaraju and Boutalkb associated with Aventis Pharma 
C-57

Seggev et al. 1998 ID 563 

Stated Purpose of the Study: To compare the safety and efficacy of amox/clav given orally 

every 12 hours with that given every 8 hours in patients with acute bacterial maxillary sinusitis 

Population & Setting: 170 patients from 11 centers in US and Canada participated. 

12-hour group 61 (pts completed study) mean age (range)= 39.3 (23 – 75) male= 50.8% 

8-hour group 73 (pts completed study) mean age (range)= 40.3 (18 - 81) male= 39.7% 

Inclusion criteria: ≥ 18 y/o; acute bacterial maxillary sinusitis < 4 weeks duration (see paper 

for clinical criteria) and abnormal x-ray (opacification, air fluid level, or ≥ 5 mm swelling of the 

mucosa) or abnormal CT scan; baseline serum creatinine < 2.3 mg/dL 

Exclusion criteria: hx of hypersensitivity to PCN, cephalosporins, or other beta-lactams; 

pregnancy or lactation; chronic sinusitis as defined by 2 or more episodes within the previous 12 

months or continuing symptoms for longer than 4 weeks; intraorbital or intracranial complications 

that interfered with the interpretation of a radiograph or CT scan of the affected sinuses; see 

paper for others 

Study design: multi-center, randomized, double-blind, double-dummy (each patient received 1 

of the 2 active treatments with a placebo of the alternative treatment, parallel; method of 

randomization not stated 

Treatments: 

Amox/Clav 875/125 mg every 12 hours plus an oral placebo every 8 hours for 14 days 

Amox/Clav 500/125 mg every 8 hours plus an oral placebo every 12 hours for 14 days 

Nasal steroids and decongestants, oral antihistamines and decongestants were allowed at the 

investigator’s discretion. 

Outcome: 

Primary: Clinical response was assessed 2 to 3 days after completion of treatment. Clinical 

success was defined as either cure or improvement. 

Secondary: Clinical response was assessed 2 – 4 weeks after the end of treatment. 

Results: 

Reported end of therapy Clinical Failure Rate (100% - reported clinical success rate in evaluable 

population): 

 12-hour group = 4/61 (6.6%) 8-hour group = 9/73 (12.3%) 

Calculated Intent to treat failure rate (100% - reported ITT clinical success rate): 

 12-hour group = 15/87 (17.2%) 8-hour group = 12/83 (14.5%) 

Reported 2-4 wk follow up Failure Rate (100% - reported persistent cure plus recurrence rate in 

evaluable population): 

 12-hour group = 4/61 (6.6%) 8-hour group = 10/73 (13.7%) 

Adverse events: 2 patients in the 12-hour group and 2 patients in the 8-hour group reported 

adverse events (12-hour group, 1 with diarrhea and 1 with coughing; 8-hour group, 1 with 

coughing and 1 with rash) that led to withdrawal from the study. 

 Amox/clav 12-hour 8-hour 

 n=87 n=83 

possible drug related adverse 9 (10.3%) 17 (20.5%) 
C-58

genital moniliasis 2 (2.3%) 6 (7.2%) 

nausea 1 (1.1%) 3 (3.6%) 

diarrhea 2 (2.3%) 1 (1.2%) 

abdominal pain 1 (1.1%) 2 (2.4%) 

dyspepsia 1 (1.1%) 2 (2.4%) 

fungal infection 2 (2.3%) 0 

dizziness 0 2 (2.4%) 

see table 4 in paper for others. 

Funding: SmithKline Beecham 

Comments: 16/87 (18.4%) in the 12-hour group and 22/83 (26.5%) in the 8-hour group received 

concurrent nasal steroids. 
C-59

Sher 2002 ID 209 

REJECTED STUDIES: Adverse events extraction only

Stated Purpose of the Study: Evaluate the efficacy and safety of gatifloxacin 400 mg once 

daily in adults with acute uncomplicated bacterial sinusitis, community-acquired pneumonia and 

acute bacterial exacerbations of chronic bronchitis. *Note: only the diagnosis of acute 

uncomplicated rhinosinusitis is included in this study 

Population and Setting: 11,564 adult patients enrolled by 2,795 investigators in the US over 

an unknown time period. 

Diagnoses included in the study:

Acute uncomplicated bacterial rhinosinusitis 

Treatment: Gatifloxacin 400 mg QD x 10 days 

Study Design: open-label, multicenter, noncomparative study. 

Adverse Events Included in Analyses: All patients who received at least one dose of 

gatifloxacin (N=11,476) were evaluated for safety from the first day of study drug therapy to 7-14 

days after the last dose of gatifloxacin by office visit or telephone. Adverse events were 

monitored until resolution or stabilization. The definition of serious adverse events included 

cancer, death or persistent or significant disability; were life-threatening; required prolonged 

hospitalization; resulted in drug dependence, abuse or overdose; jeopardized the patient; or 

required intervention to prevent a serious outcome. 

Adverse Events: 1605/11,476 subjects (14.0%) experience drug-related adverse events. 

Most common adverse events deemed drug-related: 

Symptom % (N=11,476)

Nausea 4.4% 

Dizziness 1.8% 

Diarrhea 1.4% 

Headache 1.0% 

41/11,476 (0.4%) experienced adverse events related to the cardiovascular system. No patients 

displayed abnormal electrocardiograms. 14 serious adverse events occurred in 11,476 patients 

(0.1%) and included: allergic reaction, facial/tongue edema, bacterial infection, migraine, 

diarrhea, hepatitis, hyperglycemia, hypoglycemia, confusion, asthma, increased cough and 

convulsion. 

Funding: Bristol-Myers Squibb Co. 

Comments: Use of intranasal corticosteroids, oral or topical decongestants and antihistamines 

was permitted. 
C-60

Sher et al. 2002 ID 257 

Stated Purpose of the Study: To compare the clinical efficacy of 5-day course of gatifloxacin, 

10-day course of gatifloxacin and 10-day course of amoxicillin/clavulanate in patients with acute, 

uncomplicated maxillary sinusitis 

Population & Setting: 445 patients from 30 study centers were enrolled. Study years not 

specified. 

5-day Gatifloxacin 149 mean age (range) 41.13 (18-74) males 36% 

10-day Gatifloxacin 141 mean age (range) 42.38 (18-72) males 35% 

Amox/Clav 155 mean age (range) 41.88 (18-89) males 36% 

Inclusion criteria: >18 y/o; clinical dx of acute uncomplicated maxillary sinusitis for at least 7 

days and radiographic findings, opacification, air/fluid level, or mucosal thickening of ≥ 5 mm in 1 

or both maxillary sinuses (see paper for details) 

Exclusion criteria: sinusitis > 28 days, complicated sinusitis, anatomic abnormalities, >1 dose 

of systemic antibiotic within 7 days of enrollment and others (see paper). 

Study design: Multicenter, investigator-blinded, randomized. Patients were randomized to 

treatment by means of a centralized telephone system. A permuted block design was used to 

minimize imbalance in treatment arms at each site and in the study overall. Patients in each 

treatment group received blister cards containing the appropriate combination of active drug and 

matching placebo tablets to provide 10 days of twice-daily therapy. 

Treatments: 

Gatifloxacin 400 mg once daily for 5 days 

Gatifloxacin 400 mg once daily for 10 days 

Amox/Clav 875 mg twice daily for 10 days 

Outcome: Primary: clinical response was determined by the investigator at each site and was 

classified as cure, failure, or unable to determine. Clinical cure was defined as improvement in or 

resolution of all acute signs and symptoms. Test of cure visit took place 7 to 14 days after the 

completion of study treatment. 

Results: 405/445 patients were classified as clinically evaluable. 40 unevaluable patients were 

distributed evenly between groups (see paper for details)

Calculated Clinical Failure Rate (100% - reported clinical cure rate): 

5-day Gatifloxacin 35/137 (25.6%) 

10-day Gatifloxacin 26/127 (20.5%) 

Amox/Clav 40/141 (28.4%) 

Adverse events: 

 5-day Gatifloxacin 10-day Gatifloxacin Amox/Clav 

vaginitis 9% of women 9% of women 14% of women 

diarrhea 9% of subjects 7% of subjects 14% of subjects 

nausea 9% 14% 4% (p=0.007) 

Ten patients discontinued therapy due to ≥ 1 drug-related adverse event (2, 5 and 3 patients in 5-

day gatifloxacin, 10-day gatifloxacin and amox/clav, respectively). 

One patient in the amox/clav group discontinued therapy due to elevated liver enzymes. 
C-61

Three patients in the 10-day gatifloxacin group had abnormal baseline laboratory values (2 

elevated aspartate aminotransferase level; 1 elevated bilirubin level) that had worsened 7 to 23 

days after the completion of therapy. 

Funding: 

Comments: Authors Li & Pierce associated with Bristol-Myers Squibb 
C-62

Siegert et al. 2000 ID 415 

Stated Purpose of the Study: To compare the efficacy and safety of moxifloxacin with that of 

cefuroxime axetil for the treatment of acute bacterial sinusitis in adults. 

Population & Setting: 

498 patients in 60 centers in 7 countries: Finland, France, Germany, Greece, Israel, Spain and 

Sweden 

Moxifloxacin group (n=242) mean age= 40.4 y/o 109 males (45%) 

Cefuroxime group (n=251) mean age= 40.3 y/o 111 males (44.2%) 

Inclusion Criteria: ≥ 18 y/o outpatients; acute bacterial sinusitis; sinusitis diagnosed either 

bacteriologically or clinically on the basis of sinus x-ray together with 2 or more symptoms: 

purulent nasal d/c or nasal congestion, post-nasal drainage, frequent coughing or throat clearing, 

malar tenderness or pain, frontal headache 

Exclusion Criteria: hx of hypersensitivity to study or related drug, chronic sinusitis, received 

systemic abx within 48 hours of enrollment; pregnancy, lactation and others (see original paper) 

Study Design: Prospective, randomized, multicenter, double-blind phase III clinical trial; 

method of randomization not stated 

Treatment: Moxifloxacin 400 mg in AM, placebo in PM for 7 days; placebo twice a day on study 

days 8-10 

 Cefuroxime Axetil 250 mg twice a day for 10 days 

Outcome (Primary): End of treatment examination on study day 14 (4 days after the end of Rx); 

Clinical response was the primary efficacy evaluation. 

Secondary: follow up evaluation 27-31 days after the end of treatment 

Results: 498 enrolled; 493 randomized; 436 evaluable 

On study day 14: 

In ITT population, reported Failure: 11/242 in Moxifloxacin; 22/251 in Cefuroxime 

 reported Indeterminate: 9/242 in Moxifloxacin; 7/251 in Cefuroxime 

 reported Missing: 6/242 in Moxifloxacin; 3/251 in Cefuroxime 

Calculated Clinical Failure Rate in ITT population (100% - (number of clinical resolution/total 

ITT population) x100%): 26/242 (10.7%) in Moxifloxain; 32/251 (12.7%) in Cefuroxime 

In evaluable population, reported Failure rate: 7/211 (3.3%) in Moxifloxacin; 21/225 (9.3%) in 

Cefuroxime 

At follow up 27-31 days after the end of treatment: 

Calculated Cinical Failure Rate in follow up population (100% - (number of clinical success/total 

follow up population) x100%): 19/204 (9.3%) in Moxifloxacin; 22/204 (10.8%) in Cefuroxime 

Reported Microbiological failure rate at end of treatment (day 10): 6/109 (5.5%) in 

Moxifloxacin group; 19/115 (16.5%) in the Cefuroxime group. 
C-63

Adverse events: 

 Moxifloxacin (n=242) Cefuroxime (n=252) 

Any adverse event 105 (43.4%) 88(35.1%) 

Drug-related adverse event 74 (30.6%) 56 (22.3%) 

Serious adverse event* 3 (1.2%) 8 (3.2%) 

Discontinuation 2° to adverse event 14 (5.8%) 11 (4.4%) 

Diarrhea 23 (9.5%) 15 (6%) 

Abdominal pain 10 (4.1%) 7 (2.8%) 

Nausea 9 (3.7%) 5 (2%) 

Vomiting 8 (3.3%) 4 (1.6%) 

Vertigo 7 (2.9%) 2 (0.8%) 

*details not provided in paper 

Funding:

Comments: authors Hampel and Sommerauer associated with Bayer 
C-64

Siegert et al. 2003 ID 143 

Stated Purpose of the Study: To compare the efficacy and safety of 7-day courses of 

faropenem daloxate (300 mg twice daily) and cefuroxime axetil (250 mg twice daily) in adult 

patients with acute bacterial sinusitis. 

Population & Setting: 

10/200-6/2001 

561 patients in 43 centers: France, Germany, Greece, Israel, Lithuania, Spain and Sweden 

Faropenem group (n=228) mean age= 41.4 y/o 90 males (39.5%) 

Cefuroxime group (n=224) mean age= 42.5 y/o 103 males (46%) 

Inclusion Criteria: ≥ 18 y/o; acute sinusitis based on at least purulent ant/post nasal d/c or 

nasal congestion, and at least 2 minor symptoms like frequent throat clearing, facial/malar 

tenderness or pressure, halitosis, ear discomfort or fever AND x-ray with air-fluid level, 

opacification or ≥ 6 mm mucosal thickening of at least one sinus 

Exclusion Criteria: hx of hypersensitivity to study or related drug, chronic or recurrent sinusitis, 

received systemic abx > 24 hours within 7 days of enrollment; and others (see original paper) 

Study Design: Prospective, multicenter, double-blind comparative study; randomly assigned 

1:1 to one of two treatment groups using a block design computer-generated random code 

Treatment: Faropenem daloxate 300 mg bid for 7 days 

 Cefuroxime Axetil 250 mg bid for 7 days 

Outcome (Primary): Post-therapy (7 to 16 days after the end of Rx); 

Clinical cure: disappearance of signs and symptoms or significant improvement and no further 

therapy required 

Clinical Failure: no change, insufficient improvement or reappearance of Si/Sx’s 

Bacteriological Response: Cultures were collected pre and post Rx, eradication: causative 

organism was not present at the post Rx. If no sample was obtained in patient who improved, 

eradication was presumed 

Results: 561 enrolled; 558 randomized; 

Drop Outs: 51 in Faropenem group and 55 in Cefuroxime group were excluded (reasons include 

violation of time schedule for eval and concomitant intake of steroids) 

228 in Faropenem and 224 in Cefuroxime were analyzed for clinical efficacy; 

Clinical failure: 25/228 in Faropenem; 26/224 in Cefuroxime 

Microbiological failure: Out of 136 patients with pathogenic organisms, most common 

organisms isolated at baseline were S. pneumoniae (64), H. influenzae (41), S. aureus (20) and 

M. catarrhalis (12). 

Failure: 6/71 (8.5%) in the Faropenem group; 6/65 (9.2%) in the Cefuroxime group. 

Adverse events: Faropenem, 46/274 (16.8%); cefuroxime, 49/273 (17.9%); most were in 

digestive and skin and appendages systems. 

Drug related event: faropenem 26/274 (9.5%); cefuroxime 28/273 10.3%); 3 patients in 

cefuroxime group had abnormal liver function tests, 0 in faropenem group; 1 patient in faropenem 

group experienced a drug-related adverse event of severe intensity, i.e., the coagulation test 

increased. Treatment was discontinued as a result of an adverse event in 7 patients (2.6%) of the 

faropenem group and 2 patients (0.7%) who received cefuroxime. 

Funding: Bayer 
C-65

Simon 1999 ID 475 

Stated Purpose of the Study: To compare the effectiveness of 10, 15, and 20 days of 

ceftibuten therapy versus 14 days of erythromycin-sulfisoxazole therapy in treating acute sinusitis 

in childhood 

Population & Setting: 200 patients from a single private practice in US were enrolled in the 

study. Enrollment period from 4/1996 to 7/1997. 

Erythromycin-sulfisoxazole 50 age range = 8 mos to 11 years males 58% 

Ceftibuten 10 days 50 age range = 9 mos to 12 years males 52% 

Ceftibuten 15 days 50 age range = 6 mos to 17 years males 44% 

Ceftibuten 20 days 50 age range = 6 mos to 16 years males 44% 

Inclusion criteria: persistent purulent nasal drainage for at least 10 days plus day and 

nighttime cough 

Exclusion criteria: none stated 

Study design: randomized, single-blinded (patient’s family), parallel study; method of 

randomization not stated 

Treatments: 

Erythromycin-sulfisoxazole (erythromycin component: 40 mg/kg/day) divided into 4 doses for 14 

days 

Ceftibuten 9mg/kg/day (maximum dose 400 mg/day) for 10 days 

Ceftibuten 9mg/kg/day (maximum dose 400 mg/day) for 15 days 

Ceftibuten 9mg/kg/day (maximum dose 400 mg/day) for 20 days 

Outcome: 

Primary: Effectiveness of the therapy was confirmed by the phone interview during the treatment 

course and confirmed by evaluation for clinical response 1 week after the treatment was 

completed. Success was determined by resolution of purulent nasal drainage and cough. 

Failure constituted persistence of the manifestations or more intense symptoms during the 

treatment. Secondary: Children were followed up for recurrence 40-50days after treatment 

imitation. 

Results: Reported failure rate, denominators not stated 

Primary: 

Erythromycin-sulfisoxazole 4% 

Ceftibuten 10 days 8% 

Ceftibuten 15 days 8% 

Ceftibuten 20 days 0% 

Secondary:

Erythromycin-sulfisoxazole 10% 

Ceftibuten 10 days 12% 

Ceftibuten 15 days 8% 

Ceftibuten 20 days 8% 

Adverse events: no information 

Funding:

Comments: sinus films not obtained; no placebo comparison 
C-66

Stefansson et al. 1998 ID 97076 

Stated Purpose of the Study: Phase IV study to compare the efficacy and safety of 

cefuroxime axetil and clairthromycin administered twice daily in the treatment of acute sinusitis. 

Population & Setting: 370 patients with clinical dx of sinusitis from 22 centers in Czech 

Republic, Finland, Iceland, Israel, Jordan, Poland, South Africa & Sweden 

185 in cefuroxime group mean age = 36.5 yrs males= 46% 

185 in clarithromycin group mean age = 37.2 yrs males= 39% 

Inclusion criteria: ≥ 18 y/o; clinical dx of sinusitis; initial onset of symptoms within 30 days of 

study entry; opacification and/or air fluid level in the maxillary sinus; 2 of the following symptoms: 

rhinorrhea, nasal congestion, facial pain 

Exclusion criteria: received systemic abx within previous 7 days; a dx of chronic sinusitis (>30 

days’ duration) or received abx for recurrent sinusitis during the previous 30 days; received nasal 

steroid preparations or nasal washout; undergone or required sinus surgery; known hypersensitivity to cephalosporins or macrolides; reduced renal function or marked hepatic impairment; 

immune deficiency or participated in a clinical trial within 1 month prior to enrollment 

Study design: randomized, double-blind, parallel-group, multicenter study; no further details 

provided 

Treatments: Cefuroxime Axetil oral 250 mg twice a day for 10 days 

 Clarithromycin oral 250 mg twice a day for 10 days 

 Placebo twice daily (?) 

Outcome: Primary – Cure defined by improved or resolved clinical signs and symptoms 

assessed 1-3 days after completion of treatment and absent at follow up 28-35 days posttreatment, confirmed by x-ray. Improvement defined by improvement but incomplete resolution of 

clinical signs and symptoms, confirmed by x-ray at follow up. 

Secondary – follow-up 28-35 days post-treatment 

Results: 370 patients were recruited; 185 randomized into each group; 357/370 (96%) had x-ray 

showing air fluid level and/or opacification. 22 from cefuroxime and 17 from clarithromycin group 

were discontinued. Principal reasons were failure to return (11 cefuroxime, 8 clairthromycin), lack 

of efficacy (7 in each group) and adverse events (2 clairthromycin). 24 excluded from clinicallyevaluable population as a result of protocol violations 

Calculated Clinical failure rate in ITT (100%-reported rate of cured or improved): 

9% in cefuroxime group 

7% in clarithromycin group 

At follow up 28-35 days post treatment, relapse, failure or unevaluable: 

32/185 in cefuroxime group 

42/185 in clarithromycin group 

Adverse events: 17/185 in cefuroxime and 18/185 in clarithromycin reported drug-related 

adverse event. These were mainly GI (13 cefuroxime and 8 clarithromycin). 3 clarithromycin had 

infection or inflammation of the reproductive tract. Serious adverse events recorded in 

clarithromycin group: maxillary antral abscess, convulsions and collapse during local anesthesia. 

Funding:
C-67

Comments: x-ray results obtained after randomization (even though it is one of the inclusion 

criteria); overlapping definitions of “Cure” and “Improvement”; unclear why placebo is mentioned 

in the methods section; 39 patients were discontinued from the study but 354 patients had results 

reported (39+354=393>370 sample size)??? 

Authors Sedani & Staley associated with GlaxoWellcome Research & Development, UK. 
C-68

Sterkers 1997 ID 633 

Stated Purpose of the Study: To compare the efficacy and tolerability of 8 days of ceftibuten 

400 mg once a day, ceftibuten 200 mg twice a day, and amox/clav 500/125 mg three times a day 

in the treatment of acute sinusitis in adults 

Population & Setting: 

458 patients enrolled from 58 centers in France, study years not specified. 

Ceftibuten 400 mg once a day 152 mean age 38.4 males 32% 

Ceftibuten 200 mg twice a day 157 mean age 41.8 males 41% 

Amox/clav 500/125 mg thrice a day 149 mean age 43.1 males 44% 

Inclusion criteria: sinusitis with purulent nasal discharge, confirmed by rhinoscopy; presence 

of fluid or opacification of the maxillary sinus on a plain radiograph 

Exclusion criteria: age < 15 y/o; chronic sinusitis; abx treatment within 8 days of enrollment; 

allergy to beta lactam or lidocaine; renal insufficiency and others (see paper) 

Study design: Multi-center, comparative, randomized, open-label, parallel-group design; 

method of randomization not stated 

Treatments: 

Ceftibuten 400 mg once a day for 8 days 

Ceftibuten 200 mg twice a day for 8 days 

Amox/clav 500/125 mg thrice a day for 8 days 

Outcome: 

Primary – clinical and radiological outcome 2 days after the end of treatment 

Secondary – follow up on study day 40 

Results: 

Reported Clinical failure rate on day 10: Ceftibuten 400 mg once a day 23/134 (17.2%) 

 Ceftibuten 200 mg twice a day 18/138 (13%) 

 Amox/clav 500/125 thrice a day 14/128 (10.9%) 

Reported Clinical failure rate on day 40: Ceftibuten 400 mg once a day 25/134 (18.7%) 

 Ceftibuten 200 mg twice a day 24/138 (17.4%) 

 Amox/clav 500/125 thrice a day 16/128 (12.5%) 

Bacteriological Failure according to pathogen (Date of assessment not specified) 

 Ceftibuten 400 once a day 200 twice a day Amox/Clav thrice a day 

H. Flu 2/19 (10.5%) 4/33 (12.1%) 2/26 (7.7%) 

S. Pneumoniae 6/23 (26.1%) 2/23 (8.7%) 4/25 (16%) 

M. Catarrhalis 2/7 (28.6%) 1/5 (20%) 1/10 (10%) 

Adverse events: 

 Ceftibuten 400 once a day 200 twice a day Amox/Clav thrice a day 

At least 1 adverse event 20/150 (13.3%) 16/154 (10.4%) 16/146(11%) 

Drug related adverse event 13/150 (8.7%) 6/154 (3.9%) 7/146 (4.8%) 

GI adverse event 17/150 (11.3%) 11/154 (7.1%)) 15/146 (10.3%) 
C-69

# withdrawn 2° adverse 3/150 (2%) 4/154 (2.6%) 5/146 (3.4%) 

Funding: 

Comments: 

 
C-70

Steurer & Schenk 2000 ID 417 

Stated Purpose of the Study: To compare the efficacy and safety of cefdinir and amox/clav 

in patients with acute maxillary sinusitis. 

Population & Setting: 569 (Intent-to-treat) patients in 16 medical centers in Europe 

participated 

Cefdinir 600 mg once a day = 182 Median age= 30 Males= 58.8% 

Cefdinir 300 mg twice a day = 198 Median age= 32 Males= 58.1% 

Amox/Clav 500/125 thrice a day=189 Median age= 29 Males= 60.3% 

Inclusion criteria: ≥13 y/o; males and non-lactating females unlikely to be pregnant during Rx; 

all patients had maxillary sinus aspirations 

Exclusion criteria: subacute or chronic maxillary sinusitis (> 3 weeks); frontal and ethmoid 

sinusitis, diseases that precluded evaluation of response to study medication (i.e., chronic dental 

disease, foreign bodies, local traumas) and others (see paper) 

Study design: Investigator-blinded, randomized, comparative, multicenter phase III study with 

3 parallel treatment groups. For each study center an independent randomized schedule was 

prepared that was consistent with the planned ratio of 1:1:1 for the 3 treatment groups. Patients 

were given consecutive patient numbers after screening. Medication was dispensed by a third 

person; the patients were instructed not to reveal the type of medication to the investigator. 

Treatments: 

Cefdinir 600 mg once a day for 10 days 

Cefdinir 300 mg twice a day for 10 days 

Amoxicillin 500 mg/Clavulanate 125 mg three time a day for 10 days 

Outcome: 

Primary: Clinical cure based on professional opinion and microbiological response at test of cure 

visit on days 7-15 post therapy 

Secondary: Long-term follow up on days 21-25 post therapy 

Results: 

Clinical failure (evaluable patients): Cefdinir 600 mg once a day 5/93 (5.4%) 

 Cefdinir 300 mg twice a day 10/96 (10.4%) 

 Amox/Clav thrice a day 4/106 (3.8%) 

Microbiological failure (evaluable patients): 

 Cefdinir 600 mg once a day 2/123 (1.6%) 

 Cefdinir 300 mg twice a day 13/131 (9.9%) 

 Amox/Clav thrice a day 10/138 (7.2%) 

Long term follow up microbiological failure (evaluable patients):

 Cefdinir 600 mg twice a day 3/109 (2.8%) 

 Cefdinir 300 mg twice a day 11/103 (10.7%) 

 Amox/Clav thrice a day 6/116 (5.2%) 

Adverse events: 

Cefdinir once a day 75/181 (41%); Cefdinir twice a day 88/197 (45%); Amox/Clav 94/189 (50%) 

experienced at least one adverse event (see table 7 in paper). The most frequent adverse event 

is GI related. Diarrhea was the most common reason for discontinuation of treatment. 

3 patients of the cefdinir OD group and 12 patients of the cefdinir BD and amox/clav groups 

discontinued treatment because of an adverse event. 
C-71

Funding: Parke-Davis 

Comments: This data reported previously in Gwaltney 1997 ID 648 article? 
C-72

Sydnor 1998 ID 590 

REJECTED STUDIES: Adverse Events extraction only 

Stated Purpose of the Study: Evaluate the efficacy and safety of levofloxacin in treating adult 

outpatients with acute bacterial sinusitis 

Population and Setting: 329 patients at 24 centers in unknown countries over an unknown 

time period. 

Diagnoses included in the study:

Acute, bacterial maxillary sinusitis 

Treatment: Levofloxacin 500 mg QD x 10-21 days 

Study Design: multicenter, noncomparative prospective study. Tablets were film coated 

possibly for masking purposes. 

Adverse Events Included in Analyses: Safety evaluations were performed from the first 

dose of the study drug until the first post-therapy visit (2-5 days after completion of therapy or 

upon early withdrawal for subjects discontinuing the study). Evaluation included assessment of 

adverse events, results of laboratory tests, physical examination findings and vital sign 

measurements. 

Funding: R W Johnson Pharmaceutical Research Institute 

Comments: Use of intranasal or systemic corticosteroids was permitted and use of 

decongestants was encouraged. 

Adverse Events: 29/329 (9%) subjects reported at least one adverse event considered to 

definitely or probably related to levofloxacin. Most adverse events were mild to moderate in 

severity. 

Most common adverse events: 

Symptom % (N=329)

Diarrhea 2.7% 

Flatulence 1.5% 

Nausea 1.2% 

8 subjects (2.4%) reported serious adverse events were reported, two of which were considered 

related to levofloxacin administration (genital moniliasis and rash). 6 subjects (1.8%) 

discontinued the study due to adverse events (including rash, pruritus, edema, diarrhea, nausea 

and abdominal pain) all of which were considered related to levofloxacin administration. One 

subject had a myocardial infarction while on levofloxacin, although the episode was not 

considered related to study drug. There were no significant changes in lab tests, vital signs or 

physical exam findings. 
C-73

Varonen et al. 2003 ID 97080 

Stated Purpose of Study: Compare the effects of antibiotics to that of placebo in clinically 

diagnosed acute maxillary sinusitis (AMS) in adults and to study whether sinus ultrasound would 

help to detect patients who would benefit from antibiotic therapy. 

Population & Setting: 150 patients from 9 primary care centers in Finland were randomized. 

Study took place from 11/1998 to 10/1999. 148 analyzed (2/150 had missing data). 

Antibiotic group (n=88) Mean age= 40.6 yrs Males= 24 (27%) 

Placebo group (n=60) Mean age= 38.1 yrs Males= 20 (33%) 

Inclusion Criteria: >18 y.o.; clinical diagnosis of acute maxillary sinusitis (minimum 3 

symptoms and one sign; symptoms: nasal obstruction, discharge, headache, postnasal drip, 

cough, sinus pain, unilateral facial pain, maxillary toothache, hyposmia, anosmia, malaise and 

fever; signs: purulent secretion in nasal cavity, discharge in pharynx and tenderness in sinus 

tapping). 

Exclusion Criteria: AMS symptoms > 30 days, abx the previous month, allergy to study meds, 

pregnancy or breast feeding, exacerbation of chronic sinusitis, previous paranasal sinus or sinus 

surgery, clinical suspicion of dental or frontal sinusitis or pan-sinusitis or suspicion of a severe 

complication. 

Study Design: a double-blind, randomized (treatments were previously randomized in blocks of 

20 consecutive patients at the Military Pharmacy in Helsinki and distributed in identical sealed 

bottles; the study medications were coded with six-number individual codes and physicians, 

patients and the main researcher remained blind until the recruitment ended), placebo-controlled 

multicenter trial. 

Treatments: 4 treatment groups, all for 7 days: amoxicillin 750 mg x2, penicillin V 1500 IU x2, 

doxycline 100 mg x2 or placebo x2. Placebo group was doubled: 2/5 received placebo. 

Outcome: (Primary) Recovery at the 2- week (after initial consultation) follow up by telephone 

survey of patients own reported symptoms. (Secondary) subjective symptom scores on days 3 

and 10 in patient diaries, frequency of side effects, duration of sinusitis, use of additional meds 

and the frequency of chronic or recurrent sinusitis and number of physician consultations during 

the 1-year follow up. 

Results: 

Clinical Failure: 18/88 in antibiotic group; 19/59 in placebo (chi square 3.33, df=1, p=0.068) 

Drop outs: Out of 60 in the placebo group, one was excluded for pregnancy, one was not 

reached by phone. 

Other outcome: On day 3, the difference in symptom scores was 2.1 (p=0.048). Patients 

receiving abx recovered faster than those receiving placebo. By day 10, the difference had 

disappeared. 

Adverse events:

Out of 82 in abx group (stomach pain 18 (22%), diarrhea 6 (7%), fatigue 5 (6%), rash 2 (2%), 

headache 3 (6%), vaginal discharge 3 (4%)) 

Out of 48 in placebo group (stomach pain 6 (12%), diarrhea 3 (6%), fatigue 3 (6%), headache 3 

(4%). 

Funding: Government and industry 

Comments: subgroup data for each antibiotic was not reported 
C-74

Weis et al. 1998 ID 545 

Stated Purpose of the study: To compare the efficacy and safety of 10-day oral regimens of 

ciprofloxacin and cefuroxime axetil in the treatment of clinical acute rhinosinusitis in adult in 

primary care settings 

Population & Setting: 1414 patients were enrolled by 127 physicians in US between 2/17/98 

and 5/29/98 

Ciprofloxacin 712 mean age 43.5 males 31.5% 

Cefuroxime 702 mean age 43.5 males 34.3% 

Inclusion criteria: ≥ 18 y/o; < 4 weeks duration of acute rhinosinusitis; at least 2 major or 1 

major and 2 minor factors (Major: facial congestion/fullness, nasal 

drainage/purulence/discoloration, hyposmia/anosmia, facial pain/pressure, fever, nasal 

obstruction/blockage; Minor: headache, halitosis, fatigue, dental pain, cough, ear 

pain/pressure/fullness) 

Exclusion criteria: hypersensitivity to carboxyquinolones or beta-lactam agents or anaphylaxis 

to PCN or its derivatives; hx of chronic sinusitis; pregnancy or lactation; baseline serum creatinine 

> 3 mg/dL; see paper for rest 

Study design: open-label, prospective, randomized, nationwide, multicenter, outpatient 

comparative trial; randomly assigned to one of two treatment groups through the use of a blockdesign random code computer-generated at Bayer Corporation 

Treatments: 

Ciprofloxacin 500 mg tablet twice a day for 10 days 

Cefuroxime 250 mg tablet twice a day for 10 days 

Outcome: Primary efficacy: clinical response 4-16 days post therapy 

Results: 1414 randomized; 1223 were efficacy valid; 1219 clinically evaluable 

Clinical Failure rate (100% - reported clinical resolution rate): 

 Ciprofloxacin 54/613 (8.8%) 

 Cefuroxime 60/606 (9.9%) 

Adverse events: 

 Ciprofloxacin (n=711) Cefuroxime (n=700) 

Drug-related adverse event: 80 (11.3) 81 (11.6) 

 Nausea 18 (2.5%) 12 (1.7%) 

 Diarrhea 7 (1.0%) 14 (2.0%) 

 Headache 4 (0.6%) 7 (1.0%) 

 Vaginitis 4 (0.6%) 7 (1.0%) 

Discontinuation 2° to adverse events 27/712 (3.8%) 26/702 (3.7%) 

Funding: Bayer 

Comments: 
C-75
D-1

APPENDIX D. Peer Reviewers 

We gratefully acknowledge the following individuals who reviewed the initial draft of this report 

and provided us with constructive feedback. Acknowledgments are made with the explicit 

statement that this does not constitute endorsement of the report. 

David Atkins, MD, MPH 

Center for Outcomes and Evidence 

Agency for Healthcare Research and Quality 

Rockville, Maryland 

Mark Sawyer, MD 

University of California, San Diego School of 

Medicine 

La Jolla, California 

Reviewer, Pediatric Infectious Disease 

 Society

Michael Brady, MD 

College of Medicine and Public Health 

Ohio State University 

Columbus, Ohio 

Chair, Clinical Affairs Committee 

Pediatric Infectious Disease Society 

Jonathan L. Temte, MD, PhD 

Department of Family Medicine 

University of Wisconsin 

Madison, Wisconsin 

Reviewer, American Academy of Family 

 Physicians 

Richard Haydon, MD 

Chandler Medical Center 

University of Kentucky 

Lexington, Kentucky 

Chair, Allergy and Immunology Committee 

American Academy of Otolaryngology- 

 Head and Neck Surgery 

Executive committee, 

Section on Otolaryngology 

American Academy of Pediatrics