The purpose of this study is to determine the best duration(3 versus 6 weeks) of antibiotics as part of maximal medical therapy for treating chronic sinusitis and thus preventing patients from having to have sinus surgery. The hypothesis is that in the context of maximal medical therapy 3 weeks of antibiotics is not worse than 6 weeks of antibiotics at successfully treating chronic sinusitis.

OVERVIEW This is a prospective randomized cohort study assessing duration of antibiotics (3 vs 6 weeks) as part of maximal medical therapy for chronic rhinosinusitis. Up to 100 subjects will be prospectively enrolled from patients visiting the Department of Otolaryngology-Head and Neck Surgery clinics at UNC Hospitals.

INITIAL CLINIC VISIT At the time of a clinical visit, the attending otolaryngologists will identify their patients with chronic rhinosinusitis (CRS) who are appropriate for maximal medical treatment, including antibiotics. They will introduce the study to these patients and invite them to learn more about it.

If the patient is interested in learning more about the study, the study coordinators will be contacted to provide additional information and, if the patient would like to participate in the study, provide informed consent.

If the patient is a premenopausal woman, she will be asked if she is pregnant or breastfeeding.

If she is either of these, she will be excluded from the study. All remaining women will receive a urine pregnancy test. If this urine pregnancy test is positive, the patient will be excluded from the study. Thus, for premenopausal female patients, a negative urine pregnancy test is necessary for inclusion in the study. These women will be informed that they should use an effective method of birth control during the study:

• Combined oral contraceptives
• Patch contraceptives
• Vaginal ring contraceptives
• Injectable contraceptives
• Implantable contraceptives
• Intrauterine devices or intrauterine systems
• Tubal ligation
• Barrier methods of contraception (male condom, female condom, cervical cap with spermicide, or diaphragm with spermicide)
• Vasectomy of your partner in a monogamous relationship

Women enrolled in this study will be informed that if they have a failure of birth control method during the course of the study or become pregnant during the study, they will be withdrawn from the study and further treatment will be decided according to the clinical withdrawn from the study and further treatment will be decided according to the clinical expertise of the treating otolaryngologist.

• The study coordinators will assign the patients a unique Subject ID that will be used on all patient forms with the exception of the informed consent documents and HIPAA authorization forms.
• The patient will fill out a demographics and past medical history form.
• Using a random-number generator, the patient will be randomized to receive either 3 or 6 weeks of antibiotics.
• The subject will initially be given a prescription for empiric antibiotics.The choice of empiric antibiotics will differ based on the patient's nasal polyposis status:
• If the subject has CRS with nasal polyposis (CRSwNP), s/he will be given Doxycycline 100mg BID or if allergic to doxycycline, then Augmentin 875mg BID for either 3 or 6 weeks duration. These patients will also receive a course of Prednisone (30mg x 3d, 20mg x 3d, 10mg x3d, 10mg every other day for 6 days (3 doses)) which is standard of care treatment for CRSwNP.
• If the subject has CRS without Nasal Polyposis (CRSwNP), s/he will be given Azithromycin 250mg daily, or if allergic to azithromycin, then Augmentin 875mg BID for either 3 or 6 weeks duration.
• If purulent nasal discharge is present that is appropriate for culture, the otolaryngologists will send this for culture and sensitivity analysis, which they would normally do as part of their routine clinical care. The patients will be informed that if their culture and sensitivity analysis indicates that they have an infection that can be treated with a less broad-spectrum antibiotic, then they will be prescribed culture-directed antibiotics. Otherwise, the patient can continue empiric antibiotics as previously specified.
• All study participants will also be prescribed standard of care intranasal steroids, and encouraged to perform BID saline sinus irrigation and use yogurt/over the counter probiotics to reduce GI side effects of antibiotics.

4-5 WEEKS AFTER BEGINNING TREATMENT For subjects randomized to the 3 week antibiotic group, these subjects will been seen in clinic.

During this visit (study visit #2), subjects will be asked about antibiotic compliance and side effects. Recommendation for sinus surgery will be evaluated with video-recorded nasal endoscopy and a sinus CT and made based on clinical judgement.

For subjects randomized to the 6 week antibiotic group, these subjects will be contacted by phone by the study coordinator to assess side effects and medication compliance.

7-8 WEEKS AFTER BEGINNING TREATMENT

For subjects randomized to the 6 week antibiotic group, these subjects will been seen in clinic.

During this visit (study visit #2), subjects will be asked about antibiotic compliance and side effects. Recommendation for sinus surgery will be evaluated with video-recorded nasal endoscopy and a sinus CT and made based on clinical judgement.

Inclusion Criteria:

• Diagnosis of chronic rhinosinusitis
• 18 years of age or older
• English speaking

Exclusion Criteria:

• Pregnant or breastfeeding women
• vasculitis
• cystic fibrosis
• primary ciliary dyskinesia
• allergic fungal sinusitis
• gross immunodeficiency
• current use of chemotherapy
• insulin-dependent diabetes mellitus
• recent trial of maximal medical therapy