Sinusitis or rhinosinusitis is a common problem seen by every family physician and internist and even psychiatrist.  It is typically treated with antibiotics, which help for most acute bacterial infections.  However,  chronic sinusitis is a common problem and is often minimally responsive to antibiotics.  In fact, some studies have even found that acute sinusitis improves almost as fast on placebos as on antibiotics.  Other research suggests that fungal infections play a major role in chronic sinusitis.  This was a long neglected topic until just the last few years.  The topic became more popular when a Mayo Clinic team reported that 96% of the 202 patients they saw with chronic sinusitis had fungal infections and 75% got better with amphotericin B, an intranasal solution against fungi.

Despite the report and a couple similar reports, it appears that endoscopic surgery still dominates the treatment of chronic sinusitis.  It is somewhat confusing to me.  Another confusing issue to me is that I haven't seen any mention to the possibility that the high rates of fungal sinusitis might be caused by repeated antibiotic treatments, themselves.  I like the intranasal amphotericin B.  However, I couldn't even find such a solution for sale anywhere in the U.S.  I did find it for a very reasonable price from a British internet source (http://www.mastersmarketing.com ).  I have started using it with my patients.

Cultures for nasal fungi are totally worthless since almost all of us have some fungi in our noses.  There are a huge variety of fungi found in the human nose, many of which can cause problems.  It seems like the most sensible approach might be to try the treatment in any case of chronic sinusitis before spending the big money on ENT appointments, CT scans, endoscopy, and endoscopic surgery.   I also wonder about the possible benefits of probiotics, i.e. yogurt with live cultures of lactobacillus. According to one report, a protective layer of lactobacillus does not exist only on the GI tract mucosa, it is important on all exterior body surfaces including those of the eye, the nose, the mouth, the respiratory tract, the vagina, not to forget the skin (Nutr Hosp. 2001 Nov-Dec;16(6):239-56).  While eating live culture yogurt has been found to decrease pathogenic bacteria in the nose by 19% in the one published study, another study used lactobacillus intranasally in an experiment with recombinant genetics.  I have also started a small research study using simple store bought live culture yogurt diluted 2:1 and used to irrigate nasally for subacute or chronic sinusitis.  Several studies have found that such a direct approach is quite effective intravaginally where yogurt lactobacilli have been used successfully against both pathogenic bacteria and yeast.

Antibiotics Didn't Help Acute Rhinosinusitis But Caused Side-Effects: In a Swiss DB PC study of 252 patients with purulent nasal discharge and at least 48 hours of maxillary and frontal sinus pain, those treated with amoxicillin(875mg)-clavulanate(125mg) twice a day for six days did not improve any faster than those given placebo although those with a positive rhinoscopy exam did improve 0.6 days faster, a minimal impact. Diarrhea was four times more common with the antibiotic. Effect of amoxicillin-clavulanate in clinically diagnosed acute rhinosinusitis: a placebo-controlled, double-blind, randomized trial in general practice. Bucher HC, Tschudi P, Young J, Periat P, Welge-Luussen A, Zust H, Schindler C; BASINUS (Basel Sinusitis Study) Invetigators. Arch Intern Med. 2003 Aug 11-25;163(15):1793-8

Antibiotics Minor Benefit for Sinusitis: In a 2-week DB PC study of 135 adult patients with a complaint of sinusitis and with pus in the nasal cavity, facial pressure, or nasal discharge lasting longer than 7 days, the half given the standard antibiotic amoxicillin for 10 days showed slightly faster improvement (8 vs. 12 days) but improvement was not significantly different at the end of two weeks, e.i. 30% more in the amoxicillin group felt complete improvement, or 48% vs. 37%. Are antibiotics beneficial for patients with sinusitis complaints? A randomized double-blind clinical trial. Merenstein D, Whittaker C, et al. Johns Hopkins. J Fam Pract. 2005 Feb;54(2):144-51

Antibiotics Helped Sinusitis Slightly But Half Had No Ultrasound Evidence: In a Finnish DB PC study of 150 patients with the clinical symptoms of acute sinusitis, half were treated with an antibiotic twice a day for seven days (doxycycline 100 mg, or amoxicillin 750 mg or penicillin VK 1500 mg). At 14 days, 80% of the antibiotic group and 66% of the placebo group had recovered, a non-significant difference favoring the antibiotic (p=0.07). All patients were given ultrasounds and only half had objective evidence of sinusitis. Treatment of acute rhinosinusitis diagnosed by clinical criteria or ultrasound in primary care. A placebo-controlled randomised trial. Varonen H, Kunnamo I, Savolainen S, Makela M, Revonta M, Ruotsalainen J, Malmberg H. Scand J Prim Health Care. 2003 Jun;21(2):121-6 Ed: Normally, ultrasounds are too expensive for simple cases of sinusitis.

Antifungal Spray Helps Acute Rhinosinusitis: In a small 20-patient German DB PC study of a fusafungine spray twice a day vs. placebo, those on the antifungal spray showed evidence of decreased symptoms within 24 hours and a significant advantage (p=0.03) over the placebo. Topical treatment of rhinosinusitis with fusafungine nasal spray. A double-blind, placebo-controlled, parallel-group study in 20 patients. Mosges R, Spaeth J, Berger K, Dubois F. Arzneimittelforschung. 2002;52(12):877-83

Antifungal Spray Doesn't Help: In a 78-patient DB PC study of an amphotericin B spray (0.2 mL at 3 mg/mL) 4 times a day for 8 week, only 2 of 28 patients responded. Symptoms were actually worse after amphotericin B. Topical antifungal treatment of chronic rhinosinusitis with nasal polyps: A randomized, double-blind clinical trial. Weschta M, Rimek D, Formanek M, Polzehl D, Podbielski A, Riechelmann H. University of Ulm. J Allergy Clin Immunol. 2004 Jun;113(6):1122-8. Ed: This dosage seems quite low.

Adding Steroid Nasal Spray to Antibiotic Slight Benefit: In a huge drug company-funded study of 967 acute sinusitis patient in a DB PC study with all given the very expensive amoxicillin-clavulanate (Augmentin) antibiotic, half of the patients were also given a new steroid mometasone furoate nasal spray (Nasonex). Symptoms decreased in the Nasonex group by 50% vs. 44% for placebo.  Although this difference is very small, thanks to the massive size of the study, it was statistically significant. Normal, Illinois. Effective dose range of mometasone furoate nasal spray in the treatment of acute rhinosinusitis. Nayak AS, Settipane GA, Pedinoff A, Charous BL, Meltzer EO, Busse WW, Zinreich SJ, Lorber RR, Rikken G, Danzig MR; Nasonex Sinusitis Group.

Budesonide Steroid Spray Helps Sinusitis: In a DB PC study of 167 patients whose rhinosinusitis did not improve despite two weeks of antibiotic treatment, budesonide in an aqueous nasal spray (BANS) 128 micrograms b.i.d. for 20 weeks found morning combined symptom scores (CSS) in patients receiving BANS decreased by a mean of -1.85, versus -1.02 in the placebo group (p = 0.005); corresponding values for evening CSS were -1.78 and -1.02. BANS produced significant reductions in nasal congestion and discharge scores, and improved patients' sense of smell (morning only), versus placebo. Peak nasal inspiratory flow (PNIF) increased significantly during BANS treatment. In allergic patients, BANS significantly (p < 0.001) reduced both morning -1.40 and evening -1.37 CSS from baseline versus placebo, but changes in non-allergic patients were not significant. PNIF was significantly (p < 0.01) increased in both allergic and non-allergic patients from baseline versus placebo. Efficacy and tolerability of budesonide aqueous nasal spray in chronic rhinosinusitis patients. Lund VJ, Black JH, Szabo LZ, Schrewelius C, Akerlund A. London, United Kingdom.  Rhinology. 2004 Jun;42(2):57-62

Cineole Helped Sinusitis: Cineole is a type of oil found in some type of eucalytus oil, rosemary oil, bay leaves, and cinnamon. It is sold on the internet. A German 7-day DB PC study of 152 patients with non-purulent rhinosinusitis was done with half receiving 100 mg twice a day of cineole. In the cineole group, there was greater improvement in symptoms: headache on bending, frontal headache, sensitivity of pressure points of trigeminal nerve, impairment of general condition, nasal obstruction, and rhinological secretion. Mild side effects, possibly associated with medication, were observed in two patients as heartburn and exanthema after treatment with cineole. Authors recommend cineole trial is such patients before antibiotics. Therapy for Acute Nonpurulent Rhinosinusitis With Cineole: Results of a Double-Blind, Randomized, Placebo-Controlled Trial. Kehrl W, Sonnemann U, Dethlefsen U. Marienkrankenhaus and Universitatsklinik Eppendorf. Laryngoscope. 2004 Apr;114(4):738-742. 

Ciprofloxacin as Good as Clarithromycin (Biaxin): In a 14-day DB study of 457 adults with acute sinusitis, ciprofloxacin 500 mg twice daily for 10 days did as well as clarithromycin 500 mg twice daily for 14 days: clinical resolution 84% vs. 91%. At the 1-month follow-up, 10% of CLARI-treated patients relapsed vs. 4% CIP-treated patients. Double-blind comparative trial of ciprofloxacin versus clarithromycin in the treatment of acute bacterial sinusitis. Sinusitis Infection Study Group. Clifford K, et al. Ann Otol Rhinol Laryngol 1999 Apr;108(4):360-7. Generic clarithromycin costs $140 vs. $55 for the ciprofloxacin at Walgreens (my wholesale cost for ciprofloxacin is $4.00).

Fungus Caused 96% of Chronic Sinusitis and Amphotericin B Lavage Helped 75%:  Mayo Clinic fungal cultures of nasal secretions were positive in 202 (96%) of 210 consecutive chronic rhinosinusitis (CRS) patients. Allergic mucin was found in 97 of 101 surgical cases. Allergic fungal sinusitis was diagnosed in 94 of 101 consecutive surgical cases with CRS. Immunoglobulin E-mediated hypersensitivity to fungal allergens was not evident in the majority of AFS patients. Proposed a change in terminology from AFS to eosinophilic fungal rhinosinusitis. Mayo Clin Proc. 1999 Sep;74(9):877-84; An open trial of amphotericin B in 51 randomly selected patients with chronic rhinosinusitis applied intranasally as 20 mL of a 100 microg/mL solution twice daily. Improvement of symptoms was observed in 75%. Endoscopically, 35% became disease free, and 39% more had improvement of at least one stage (P <.001). No effect was seen in 25%. CT scans before and after demonstrated a reduction in inflammatory mucosa thickening that had occluded the paranasal sinuses (P <.0001 in maxillary sinus). Mayo. Intranasal antifungal treatment in 51 patients with chronic rhinosinusitis. Ponikau JU, Sherris DA, Kita H, Kern EB. J Allergy Clin Immunol. 2002 Dec;110(6):862-6

  Amphotericin B Nasal Lavage Helped: Patients performed nasal lavage with 20 ml of a one per one thousand amphotericin B suspension in each nostril, twice a day, for four weeks. All patients continued their saline nasal lavage and their conventional topical corticosteroid spray. In the 74 patients, before anti-fungal treatment, the distribution of nasal polyposis was: 13 patients in stage I (17.5 per cent), 48 patients in stage II (65 per cent) and 13 patients in stage III (17.5 per cent). After anti-fungal nasal lavages, the total disappearance of nasal polyposis was observed in 39%. Eight patients were stage I, 21 stage II, and none stage III. In patients who have had previous endoscopic polypectomy and functional endoscopic sinus surgery, total disappearance of nasal polyposis was seen in 47%. Hyper-reactivity to fungal organisms could be one of the mechanisms underlying the development of nasal polyposis. J Laryngol Otol. 2002 Apr;116(4):261-3

Surgery Advocates Predominate: The author reports that endoscopic sinus surgery is and should remain the mainstay of treatment for fungal sinusitis in immunocompetent patients. Surg Infect (Larchmt). 2003 Summer;4(2):199-204

Fungal: 31% of Chronic Cases Found Fungal: A University of Adelaide prospective study of 349 patients receiving endoscopic surgery for chronic sinusitis found 31% of cases to be fungal. Nasal polyposis and thick fungal-like sinus mucin were common in these patients. Am J Rhinol. 2003 May-Jun;17(3):127-32

Fungal: Types of Fungus Extremely Diverse: In a study of sinusitis patients and healthy controls tested over 28 months, 619 strains of fungi were cultivated from 233 subjects. Eighty-one species were identified, with a maximum of nine different species per person. The most prevalent isolates belonged to the genera Penicillium, Aspergillus, Cladosporium, Alternaria and Aureobasidium. Med Mycol. 2003 Apr;41(2):149-61. Fungal cultures were positive in 87% of chronic sinusitis patients and 91% of healthy controls. Clusters of eosinophils and fungal elements are present simultaneously within the mucus of chronic rhinosinusitis patients and appear to be a marker of the disease. Laryngorhinootologie. 2003 May;82(5):330-40. Fungal elements were found in 28 of 37 patients (75.5%) and eosinophilic mucin in 35 of 37 patients (94.6%). Neither fungi nor eosinophils were present in 2 of 37 patients (5.4%). Laryngoscope. 2003 Feb;113(2):264-9

Guaifenesin Helped HIV Patients with Rhinosinusitis: In a 23-patient DB PC study of chronic rhinosinusitis in HIV positive patients, guaifenesin, a mucolytic, at 2400 mg per day did help decrease nasal congestion and thin the post-nasal drainage. The role of guaifenesin in the treatment of sinonasal disease in patients infected with the human immunodeficiency virus (HIV). Wawrose SF, Tami TA, Amoils CP. Laryngoscope. 1992 Nov;102(11):1225-8. Ed: Numerous European studies have shown that mucolytics have a small, positive effect in decreasing the frequently of recurrent episodes of acute bronchitis in chronic bronchitis patients.

Sinusitis: French Report 13% Chronic Sinusitis Fungal:  In 600 patients suffering from maxillary sinusitis 81 cases were fungal (13,4%). Aspergillus fumigatus and Candida albicans were the most frequently isolated fungi. Three clinical forms could be distinguished: (1) a muco-purulent form (35 cases); (2) a budding and/or caseous form (22 cases), and (3) a pseudotumoral form (24 cases). 42 patients treated with a 1% econazol (base) solution were healed. Dermatologica. 1979;159(Suppl 1):180-6

Sinusitis: Antibiotic Nebulizer Works Better: 42 patients studied - all adults who suffered recurrent sinus infections after surgery - 76 percent reported "significant improvement" in symptoms, confirmed through physical exams and sinus endoscopies. Significantly, the patients who benefited from the treatment remained free of infection for an average of 17 weeks, compared with six weeks previously. Like Clark, they reported few side effects and improved quality of life. Stanford, Otolaryngology, Head and Neck Surgery 12/02

Sinusitis: Allergic Fungal Sinusitis Surgery: 10% of chronic sinusitis said to be AFS. Although the specific treatment of AFS generally is controversial, most otorhinolaryngologists would agree that surgical intervention is one universal mainstay of therapy. According to the authors, minimally invasive but complete surgical exenteration of disease, with polypectomy and marsupialization of the involved sinuses, is a mandatory component of treatment. Allergy Asthma Proc. 2003 Sep-Oct;24(5):307-11. The use of itraconazole, short-burst low-dose oral corticosteroids, topical corticosteroids, and endoscopic surgery is a safe and clinically effective regimen in the management of AFS. Clinical experience suggests medical management of recurrent AFS with itraconazole, an anti-fungal agent, may avoid revision surgery. Am J Rhinol. 2003 Jan-Feb;17(1):1-8