Clinical Policy Bulletin: Aerosolized or Irrigated Anti-infectives for Sinusitis
Aetna considers nasally aerosolized or irrigated anti-infectives experimental and investigational for the treatment of sinusitis and other indications because there is inadequate published clinical evidence of the effectiveness of this approach.
The SinuNEB (SinusPharmacy) is a device that nebulizes antibiotics, anti-fungals, and medications for the treatment of sinusitis. According to the manufacturer of the SinuNEB, administration of anti-infectives via nebulization directly to the lining of the sinuses results in a more rapid response, greater effectiveness, reduced re-infection, and fewer side effects than oral or intravenous anti-infective administration. The brand name for the unique formulations used by SinusPharmacy in their treatment of sinusitis is AdhesENT. These special formulations supposedly can increase the medication's adherence in the sinus cavities, and improve the effectiveness of the aerosolized treatment by allowing delivery to the disease site.
However, there are insufficient published clinical studies to support these claims. SinusPharmacy (Scheinberg et al, 2002) reported on the results of an uncontrolled study of nebulized antibiotics 41 patients with sinusitis, reported an “excellent” or “good” outcome in 34 patients (82 %) after 3 to 6 weeks of treatment. Vaughan and Carvahlo (2002) reported on a retrospective chart review of patients with chronic sinusitis who were treated with nebulized antibiotics. The investigators reported clearing of the initial bacteria that the nebulized antibiotic was directed against in 28 patients, clearing of infection and a new infection with a different organism in 10 patients, clearing and re-infection with the same organism in 6 patients, and persistent infection in 6 patients. Because these were not prospective, randomized studies, no firm conclusions about the effectiveness of nebulized antibiotics in sinusitis can be drawn from these studies.
Published randomized clinical studies of nebulized antibiotics found that nebulized antibiotics have no significant effect. A randomized clinical study from Desrosiers et al (2001) involving 20 patients with chronic, refractory sinusitis found no clinically significant difference in effectiveness between nebulized tobramycin-saline solution and nebulized saline. These results lead the authors to conclude that "addition of tobramycin [to saline nebulizer] appears to be of minimal benefit."
A pilot study by Videler et al (2008) found nebulized topical antibiotic therapy was no more effective in relieving sinusitis symptoms than saline-based placebo in patients with recalcitrant chronic rhinosinusitis. The investigators reported on a randomized, placebo-controlled, double-blind, cross-over pilot study that was conducted in 14 patients with recalcitrant chronic rhinosinusitis. Nasal irrigation with bacitracin/colimycin or placebo using the RhinoFlow nebulizer twice daily was administered in combination with oral levofloxacin. Severity of a diversity of symptoms was measured using the visual analog score (VAS), a Disease-Specific Symptom Score and the SF-36 questionnaire. Nasal endoscopic findings were also assessed. The investigators reported that, for most VAS items and Disease-Specific Symptom Scores, a reduction in severity of symptoms was noted in both the bacitracin/colimycin and the placebo group. No significant difference was found between the 2 arms (bacitracin/colimycin versus placebo). Most SF-36 items improved, compared with the situation before treatment in both groups. However, no significant difference was found between the verum and placebo arm. Endoscopic findings did not reveal significant differences when comparing the 2 treatments. The investigators concluded that the outcome of this study suggests a beneficial effect of nebulizing the nose with saline. The investigators noted that this study again shows that adding antibiotics to local saline is not effective. "Although the placebo-controlled studies looking at the effect of local antibiotics are all small they all point to the same direction: no effect. Definite conclusions however need a large randomized, multicenter study."
Anti-infectives have also been administered by nasal irrigation in sinusitis. There is a lack of reliable clinical evidence of the effectiveness of nasally irrigated anti-infectives in sinusitis.
No published guidelines on sinusitis management from leading professional medical organizations discuss any role for nebulized or nasally irrigated antibiotics. Thus, aerosolized or nasally irrigated anti-infectives are considered experimental and investigational for the treatment of sinusitis.
Hageman et al (2006) stated that although the theory behind aerosolized administration of antibiotics seems to be sound, there are limited available data to support the routine use of this modality. Due to the gaps still existing in the knowledge base regarding the routine use of aerosolized antibiotics, caution should be exercised when attempting to administer antimicrobials via this route in situations falling outside clearly established indications such as the treatment of patients with cystic fibrosis or Pneumocystis pneumonia.
Laube (2007) noted that compared to research into aerosolized delivery of drugs to treat lung disease, research into nasal delivery of aerosolized drugs to treat sinusitis has been significantly neglected. This is despite the fact that more people suffer from sinusitis than asthma in the United States, and its consequences result in considerable discomfort, lost work days, and money spent on health care. A number of studies have shown that a high proportion of aerosolized medications delivered by metered dose inhalers and aqueous spray devices deposits in the anterior 1/3 of the nasal cavity. However, the important targets for treating sinusitis lie beyond this region. These include the middle meatus, the superior and posterior regions of the nasal cavity and the sinuses themselves. The author examined the particle-related and device-related factors that are known to improve intra-nasal delivery of aerosolized medications to these targets and their effectiveness in patients with disease. Based on this review, it is recommended that companies that are interested in improving aerosol delivery to treat sinusitis utilize both in vivo imaging modalities and in vitro models of the nasal cavity and sinuses to assess intra-nasal aerosol delivery and device performance during the development stage. Once device design has been optimized, it is recommended that device manufacturers and pharmaceutical companies move beyond the current reliance on anecdotal reporting and uncontrolled trials to clinical studies that are randomized and placebo-controlled and that quantify changes both in symptoms and in functional parameters to determine drug effectiveness with their device.
CPT Codes / HCPCS Codes / ICD-9 Codes
Other CPT codes related to the CPB::
HCPCS codes not covered for indications listed in the CPB::
Ultrasonic/electronic aerosol generator with small volume nebulizer
Nebulizer, ultrasonic, large volume
Nebulizer, durable, glass or autoclavable plastic, bottle type, for use with regulator or flowmeter
Nebulizer, with compressor and heater
Other HCPCS codes related to the CPB::
Filter, disposable, used with aerosol compressor
Filter, non-disposable, used with aerosol compressor or ultrasonic generator
Aerosol mask, used with DME nebulizer
Aerosol compressor, adjustable pressure, light duty for intermittent use
ICD-9 codes not covered for indications listed in the CPB::
461.0 - 461.9
473.0 - 473.9
The above policy is based on the following references:
American Academy of Pediatrics. Subcommittee on Management of Sinusitis and Committee on Quality Improvement. Clinical Practice Guideline: Management of sinusitis. Pediatrics. 2001;108(3):798-808.
Snow V, Mottur-Pilson C, Hickner JM; American Academy of Family Physicians; American College of Physicians-American Society of Internal Medicine; Centers for Disease Control; Infectious Diseases Society of America. Principles of appropriate antibiotic use for acute sinusitis in adults. Ann Intern Med. 2001;134(6):495-497.
Spector SL, Bernstein IL, Li JT, et al. Parameters for the diagnosis and management of sinusitis. Ann Allergy Asthma Immunol. 1998;102(6 Pt 2):S107-S144.
University of Michigan Health System. Acute rhinosinusitis in adults. Ann Arbor, MI: University of Michigan Health System; December 1999.
Institute for Clinical Systems Improvement. Acute sinusitis in adults. ICSI health care guidelines; no. GRD02. Bloomington, MN: Institute for Clinical Systems Improvement (ICSI); December 1999.
Institute for Clinical Systems Improvement. Rhinitis. Bloomington, MN: Institute for Clinical Systems Improvement (ICSI); June 2000.
Agency for Healthcare Research and Quality (AHRQ). Diagnosis and treatment of acute bacterial rhinosinusitis. Evidence Report/Technology Assessment Number 9. AHCPR Publication No. 99-E016. Rockville, MD: AHRQ, 1999.
Brooks I, Gooch WM 3rd, Jenkins SG, et al. Medical management of acute bacterial sinusitis. Recommendations of a clinical advisory committee on pediatric and adult sinusitis. Ann Otol Rhinol Laryngol Suppl. 2000;182:2-20.
Ressel G. Principles of appropriate antibiotic use: Part III. Acute rhinosinusitis. Centers for Disease Control and Prevention. Am Fam Physician. 2001;64(4):685-686.
Sinus and Allergy Health Partnership. Antimicrobial treatment guidelines for acute bacterial rhinosinusitis. Otolaryngol Head Neck Surg. 2000;123(1 Pt 2):5-31.
SinusPharmacy. SinuNEB. Carpinteria, CA: SinusPharmacy Inc.; 2001. Available at: http://www.sinuneb.com. Accessed January 15, 2002.
Scheinberg PA, Otsuhi A. Nebulized antibiotics for the treatment of acute exacerbations of chronic rhinosinusitis. Ear Nose Throat J. 2002;81(9):648-652.
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. Otolaryngol Head Neck Surg. 2001;125(3):265-269.
Vaughan WC. Nebulization of antibiotics in management of sinusitis. Curr Infect Dis Rep. 2004;6(3):187-190.
Wahl KJ, Otsuji A. New medical management techniques for acute exacerbations of chronic rhinosinusitis. Curr Opin Otolaryngol Head Neck Surg. 2003;11(1):27-32.
Vaughan WC, Carvalho G. Use of nebulized antibiotics for acute infections in chronic sinusitis. Otolaryngol Head Neck Surg. 2002;127(6):558-568.
Klepser ME. Role of nebulized antibiotics for the treatment of respiratory infections. Curr Opin Infect Dis. 2004;17(2):109-112.
American Academy of Pediatrics. Subcommittee on Management of Sinusitis and Committee on Quality Improvement. Clinical practice guideline: Management of sinusitis. Pediatrics. 2001;108(3):798-808.
Slavin RG, Spector SL, Bernstein IL, et al. The diagnosis and management of sinusitis: A practice parameter update. J Allergy Clin Immunol. 2005;116(6 Suppl):S13-S47.
Hagerman JK, Hancock KE, Klepser ME. Aerosolised antibiotics: A critical appraisal of their use. Expert Opin Drug Deliv. 2006;3(1):71-86.
Laube BL. Devices for aerosol delivery to treat sinusitis. J Aerosol Med. 2007;20 Suppl 1:S5-S17; discussion S17-S18.
Dubin MG, Liu C, Lin SY, Senior BA. American Rhinologic Society member survey on 'maximal medical therapy' for chronic rhinosinusitis. Am J Rhinol. 2007;21(4):483-488.
Videler WJ, van Drunen CM, Reitsma JB, Fokkens WJ. Nebulized bacitracin/colimycin: A treatment option in recalcitrant chronic rhinosinusitis with Staphylococcus aureus? A double-blind, randomized, placebo-controlled, cross-over pilot study. Rhinology. 2008;46(2):92-98.
Moeller W, Schuschnig U, Meyer G, et al. Ventilation and aerosolized drug delivery to the paranasal sinuses using pulsating airflow - a preliminary study. Rhinology. 2009;47(4):405-412.
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