The use of aerosolized anti-infective medications has been proposed as a method to deliver medications directly to the infected sinus tissues as a treatment of sinusitis. This therapy involves suspending small particles of anti-infective medications in solution. A device called a nebulizer is then used to create a vapor of this solution which is inhaled through the nose. This policy discusses the use of aerosolized anti-infective therapy for the treatment of sinusitis.

Investigational/Not Medically Necessary:

The use of aerosolized anti-infective therapy for the treatment of sinusitis, including, but not limited to, the use of SinuNEB^TM and AdhesENT^TM, is considered investigational/not medically necessary.
 

The theory for administering antibiotics or anti-infectives in an aerosolized manner is to enhance the potency and effectiveness while decreasing side effects. To create an aerosolized therapy, antibiotics or anti-infectives are compounded or dissolved in a solution that is nebulized and inhaled. However, the safety and efficacy has not been demonstrated in controlled trials.

There are currently two uncontrolled studies reported in the literature evaluating the safety and efficacy of nebulized anti-infectives for the treatment of sinusitis. Both of these studies are based on retrospective patient record review. One was a pilot study including 42 patients with either an acute sinus infection or chronic sinusitis present for at least six months, who had undergone previous endoscopic sinus surgery. They were offered nebulized antibiotics or "standard" therapy. The experimental group, which included the vast majority of the study population (at 39 patients), received a culture-directed antibiotic in compounded form administered by nebulizer. Only three patients received the standard therapy option. Based on a rhinosinusitis outcome measure questionnaire and follow up nasal endoscopy, the nebulizer treated patients enjoyed a longer infection free period than the standard therapy group, 17 weeks versus 6 weeks. However, given the small number of patients in the standard treatment group, and the study as a whole, the results cannot be regarded as strong evidence of efficacy.

The second study included 41 patients with an acute sinus infection and at least a two year history of chronic sinusitis who had undergone at least one sinus surgery. A compounded antibiotic (cefuroxime, ciprofloxacin, levofloxacin or tobramycin) was given by nebulizer two to three times daily for three to six weeks. Outcomes for five selected signs and symptoms were evaluated: nasal obstruction (assessed by endoscopic exam); facial pain; cheek, forehead and eye pressure; mucopurulent rhinorrhea; and malaise on a “before and after” treatment 0-5 severity scale. The conclusion of the study was that 82.9% of patients had an “excellent” or “good” response. A “significant” or “substantial” improvement was observed in four of the five outcomes measured with malaise being the exception. However, at 3 months, 50% of the study population had a recurrent infection, either with the same infectious agent or a new organism, leading to new questions regarding long term efficacy of this therapy. Furthermore, neither of these studies included an acceptable comparison to placebo or other recognized alternative treatments, including nasal irrigation techniques (e.g., with saline or hypertonic saline), corticosteroids or decongestants.

A third study by Desrosiers and Salas-Prato was a randomized, double-blind trial of 20 patients with chronic refractory rhinosinusitis and prior endoscopic sinus surgery treated with nebulized tobramycin 80mgm in normal saline versus normal saline alone three times daily for four weeks. Outcome measures including symptoms, quality of life and endoscopic findings were reported. Both groups improved subjectively and objectively with only minor differences between them. The tobramycin group had superior pain relief at week two but not weeks four or eight. However, tobramycin appeared to increase nasal congestion and the saline alone was clearly superior in improving the symptoms of nasal obstruction at weeks two, four and eight. The authors observed that the addition of tobramycin appeared to be of “minimal benefit.”

None of the published guidelines through March 2007, on sinusitis management from professional medical organizations discuss any role for nebulized antibiotics.

There is a high degree of concern regarding the colonization or infection with drug-resistant organisms in the airway as a result of this type of therapy. The development of such conditions could put the patient at significant risk by further exacerbating their sinusitis or aiding in the development of systemic disease. This concern has not been addressed in the medical literature and proper evaluation of this risk needs to be studied.

Hwang and colleagues (2006) performed a pilot study of comparing distribution of radiolabeled saline via nasal spray compared with passive-diffusion and vortex-propelled nebulized methods in 15 patients. Ten participants had normal sinus structure and five were postoperative sinus participants. This study showed varying degrees of penetration of 30% to the frontal and sphenoid sinuses and 10% to the maxillary sinus in normal participants. In postoperative participants, there was no significant increase in sinus penetration by any of the distribution methods.

In the absence of adequate randomized, controlled studies demonstrating the effectiveness of aerosolized antibiotics when compared to established irrigation techniques, other treatment modalities or placebo treatments for acute or chronic rhinosinusitis, no definite conclusions can be drawn regarding the benefits, if any, of this form of therapy. . Although the available literature contained four studies of nebulized antibiotic treatment, only one involved a control group and this study found nebulized antibiotic treatment and placebo nebulized antibiotic treatment had essentially equal efficacy. Therefore, at this time, there is insufficient evidence to conclude nebulized antibiotic therapy is an effective and safe treatment for chronic sinusitis.

Description of Sinusitis
Sinusitis is a condition where the membrane lining the nasal sinuses becomes inflamed due to infection caused by a virus, bacteria or fungus. The nasal sinuses are air-filled spaces around the forehead, cheeks and eyes that are lined with mucous membranes. Healthy sinus tissues are open to allow the free passage of air and drainage of mucus.

When sinuses are inflamed, they become red, puffy and block the normally open passageways. This condition prevents proper ventilation and drainage of mucus allowing harmful pathogens to collect and infect the sinus tissues.

According to the National Library of Medicine, over 30 million people contract sinusitis each year. Sinusitis can be acute, lasting anywhere from two to eight weeks. In chronic sinusitis, the symptoms persist much longer and frequently resist treatment or have a tendency to recur after apparently responding to treatment. Under normal circumstances, sinusitis is initially treated with saline nose drops, humidification and warm compresses applied to the nose/face. If the infection persists, a doctor may prescribe a bacterial oral anti-infective medication. Additionally, nasal steroids may be prescribed to reduce inflammation. For more serious or chronic conditions surgical intervention may be appropriate. Most fungal sinus infections require surgical intervention.

Description of Treatment Technology
Surgery for sinusitis is intended to clean and drain the sinuses, especially in patients with recurrent episodes of inflammation despite medical treatment. Surgery may also involve repair of a deviated septum or removal of nasal polyps that may be a contributing factor to recurrent infections.

The use of aerosolized anti-infective medications has been proposed as a treatment of sinusitis. This therapy involves suspending small particles of anti-infective medications in solution. A device called a nebulizer is then used to create a vapor of this solution that is inhaled through the nose. It is theorized that this method can be used to directly deliver medications to the infected tissues to fight infections. However, this theory has not been adequately studied. The risks of this therapy are currently unknown.

Potential Risks
There is some risk of the colonization or infection in the airways with drug-resistant organisms with this aerosolized anti-infective therapy for sinusitis. This risk has not been adequately evaluated in studies at this time.

Aerosolized: referring to any substance in the form of ultramicroscopic solid or liquid particles dispersed or suspended in air or gas

Anti-infective: a substance that may be used in fighting infections; this may include antiviral medications as well as antifungals, and antibacterials

Sinusitis: a condition characterized by inflammation of the membrane lining the nasal sinuses

The following codes for treatments and procedures applicable to this policy are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

Services are Investigational/Not Medically Necessary:

When the code describes a procedure indicated in the Policy section as investigational/not medically necessary.

HCPCS

ICD-9 Diagnosis Code

When services are also Investigational/Not Medically Necessary:

HCPCS

ICD-9 Diagnosis Code

Peer Reviewed Publications:

1. Benninger MS, Ferguson BJ, Hadley JA, et al. Adult chronic rhinosinusitis: definitions, diagnosis, epidemiology, and pathophysiology. Otolaryngol Head Surgery. 2003; 129(3 Suppl):S1-S32. 
2. Desrosiers MY, Salas-Prato M. Treatment of chronic rhinosinusitis refractory to other treatments with topical antibiotic therapy delivered by means of a large-particle nebulizer: results of a controlled trial. Otolaryngology Head Neck Surg. 2001; 125(3):265-269. 
3. Hwang PH, Woo RJ, Fong KJ. Intranasal deposition of nebulized saline: a radionuclide distribution study. Am J Rhinol. 2006; 20(3):255-261.
4. Scheinberg PA, Otsuji A. Nebulized antibiotics for the treatment of acute exacerbations of chronic rhinosinusitis. Ear Nose Throat J. 2002; 81(9):648-652. 
5. Vaughan WC, Carvalho G. Use of nebulized antibiotics for acute infections in chronic sinusitis. Otolaryngol Head Neck Surg. 2002; 127(6):558-568.

Government Agency, Medical Society, and Other Authoritative Publications:

1. American Academy of Allergy Asthma & Immunology. Sinusitis. Available at: http://www.aaaai.org/patients/publicedmat/tips/sinusitis.stm. Accessed on March 7, 2007.
2. American Academy of Otolaryngology−Head and Neck Surgery. Fact Sheet: Fungal Sinusitis. Available at: http://www.entnet.org/healthinfo/sinus/fungal_sinusitis.cfm. Accessed on February 6, 2007.
3. Hayes Inc. Hayes Alert Technology Assessment Brief. Nebulized Antibiotic Therapy for Chronic Sinusitis. Lansdale, PA: Hayes, Inc.; August 2003.

1. National Institute of Allergy and Infectious Diseases (NIAID). Sinusitis. Updated on January 30, 2006. Available at: http://www.niaid.nih.gov/factsheets/sinusitis.htm. Accessed on March 7, 2007.
2. National Library of Medicine. Medical Encyclopedia: Sinusitis. Available at: http://www.nlm.nih.gov/medlineplus/ency/article/000647.htm. Accessed on March 7, 2007.

AdhesENT^TM
SinuNEB^TM

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

Federal and State law, as well as contract language, including definitions and specific contract provisions/exclusions, take precedence over Medical Policy and must be considered first in determining eligibility for coverage. The member's contract benefits in effect on the date that services are rendered must be used. Medical Policy, which addresses medical efficacy, should be considered before utilizing medical opinion in adjudication. Medical technology is constantly evolving, and we reserve the right to review and update Medical Policy periodically.

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