Nebulized antibiotics for the treatment of acute exacerbations of chronic rhinosinusitis. (Original Article).

Abstract

We studied the effectiveness of aerosol delivery of antibiotics to the sinuses via a nebulizer in 41 patients who had chronic, recurrent sinusitis that had persisted despite endoscopic sinus surgery and that had not responded to multiple courses of oral antibiotics. We compared pre-and post-treatment symptom scores in five categories: nasal obstruction, facial pain, pressure, mucopurulent rhinorrhea, and malaise. Following 3 to 6 weeks of treatment, 34 patients (82.9%) experienced either an excellent or good response to treatment. Side effects were infrequent, mild, and transient. We conclude that nebulized antibiotics should be considered for all patients with chronic sinusitis who have undergone functional endoscopic sinus surgery and who have failed to respond to oral antibiotics or who do not tolerate them.

Introduction

Chronic sinusitis is one of the most common diseases in the United States, affecting more than 30 million Americans. (1) Moreover, its incidence appears to be increasing. For example, between 1990 and 1992, patients with sinusitis reported that they had experienced approximately 73 million "restricted-activity days," a significant increase over the 50 million such days that were reported between 1986 and 1988. (1,2)

During the early 1990s, more than 13 million courses of antibiotics for sinusitis were prescribed annually in the United States, representing a 125% increase over the average number prescribed during the previous 10 years. (3) The standard management regimen has been to administer a systemic antibiotic--usually an oral drug, but occasionally an intravenous agent--for 3 to 6 weeks. Patients who do not respond to this regimen are often prescribed an additional course of therapy, which increases costs and the risk of adverse reactions. (4)

A recent institutional study conducted at the Stanford (Calif.) University Medical Center demonstrated that the local delivery of nebulized antibiotics in patients with chronic sinusitis safely led to an increase in the duration of disease-free intervals. (5) We believe that such a benefit is equally important in the community setting. Therefore, we conducted a retrospective outpatient study to systematically determine the effect that nebulized antibiotics would have on five major signs and symptoms of chronic sinusitis (6,7) in patients who had already undergone functional endoscopic sinus surgery. Our goals were to make an informed assessment of the efficacy of this treatment modality and to record the incidence of adverse effects for the purpose of compiling safety profile information. In this article, we describe our findings.

Patients and methods

We reviewed the records of 41 patients (mean age: 53.9yr) who had been treated with a nebulized antibiotic in the private-practice otolaryngology office of the lead author (P.A.S.) between July 1999 and February 2002. All patients had clinical signs of acute sinus infection and at least a 2-year history of diagnosed chronic sinus disease. All had been previously treated with at least three courses of oral antibiotics--some as many as 12 (mean: 7). All patients had undergone computed tomography (CT) at least once. All patients had had at least one sinus operation, and all had received at least one postsurgical follow-up endoscopic sinus examination. The patient population was made up of 24 women (mean age: 51.5 yr) and 17 men (mean age: 57.4 yr).

Otolaryngologists adhere to several accepted criteria for determining the presence and severity of chronic sinusitis. For this study, we selected the five signs and symptoms that we considered to be most important: nasal obstruction, facial pain, pressure in the forehead and cheeks and around the eyes, mucopurulent rhinorrhea, and malaise. The severity of these signs and symptoms was rated on a scale of 0 (best possible condition) to 5 (Worst possible condition). Scores were recorded both before and after nebulized antibiotic treatment. Each patient underwent a pre- and post-treatment evaluation that included clinical and endoscopic sinus examinations.

Each patient's response to treatment was determined by analyzing scores across the five categories with a linearly adjusted methodology based on the Rhinosinusitis Disability Index. (8-10) The treatment response was quantified by compiling the aggregate mean reduction-in-severity score. A reduction of 1.50 or more was considered excellent, 1.13 to 1.49 was good, 0.75 to 1.12 was fair, and less than 0.75 was poor.

Each patient used a nebulizer (Pan Respiratory Equipment; Monterey, Calif.) to administer topically to the sinus mucosa one antibiotic: a compounded formulation (SinusPharmacy; Carpinteria, Calif.) of either cefuroxime at 285 mg three times daily, ciprofloxacin at 90 mg twice daily, levofloxacin at 70 mg twice daily, or tobramycin at 95 mg twice daily. The choice of a particular antibiotic was based on the individual patient's history and clinical characteristics. The duration of treatment ranged from 3 to 6 weeks, depending on response.

Results

The nebulized antibiotics were self-administered at home. Each dosing required 10 to 15 minutes to complete, and patients reported no difficulty in medicating themselves.

Treatment was found to be effective (i.e., excellent or good) in 34 of the 41 patients (82.9%). An excellent response was seen in 26 patients (63.4%), a good response in eight (19.5%), fair in six (14.6%), and poor in only one (2.4%). Every patient experienced reductions in severity scores in at least two of the five symptom categories, and no patient's scores increased in any category (table 1).

The mean aggregate score for all five symptom categories declined from 2.37 prior to treatment to 0.49 after treatment (table 2). Mean reductions in scores were seen in all five of the individual symptom categories:

Nasal obstruction. The degree of nasal obstruction of the sinus ostia was assessed by endoscopic examination. The pretreatment mean score was 2.66 and the post-treatment mean score was 0.66, which represented a substantial reduction in the degree of obstruction. Following treatment, 20 of the 41 patients (48.8%) had an obstruction score of 0 (i.e., a return to normal or near-normal) on endoscopic observation.

Facial pain. Patients subjectively rated the presence of facial pain or pain over the sinuses, as distinguished from temporomandibular pain, dental pain, or earache. The pretreatment mean score was 2.08 and the post-treatment mean score was 0.23, which represented a significant reduction in the duration and degree of pain. Of the 41 patients, 32 (78.0%) reported a score of 0 following treatment.

Pressure. Patients also subjectively rated the presence and degree of pressure in the forehead, cheeks, and periorbital area. The pretreatment mean score was 2.56 and the post-treatment mean score was 0.44, again representing a substantial reduction. A post-treatment score of 0 was reported by 24 patients (58.5%).

Mucopurulent rhinorrhea. Overall, the presence of thick purulent discharge was significant, as reflected by the pretreatment mean score of 3.02. The post-treatment mean score of 0.68 indicated a substantial reduction in the quantity and thickness of the discharge. Sixteen patients (39.0%) had a post-treatment score of 0 on clinical examination.

Malaise. The pretreatment mean score of 1.31 indicated that the presence and degree of malaise was minor. The post-treatment mean score of 0.41 represented some minor improvements in this area.

There were no significant differences in treatment responses based on sex, age, or the number of sinus operations. No patient experienced any serious adverse effect, and none was forced to discontinue treatment. Only four mild side effects were reported: two cases of dry skin around the nose or lip, one case of throat/tongue irritation, and one case of cough. The dry skin resolved during treatment upon the application of an emollient ointment. The oral irritation and the cough resolved upon the discontinuation of treatment at study's end.

Discussion

Our study indicates that the use of nebulized antibiotics for refractory, recurrent sinus infections is both effective and safe. The reduction in severity of the five signs and symptoms we measured reflects the effectiveness of this therapy, as does the high combined rate of excellent and good responses (82.9%). In fact, nebulized therapy in this group of patients was superior to oral therapy. All these patients had already undergone at least three courses of oral antibiotics, and all had a history of increasing intolerance to these agents.

Side effects were minor and transient. The safety profile indicates that nebulized antibiotic administration is well tolerated. No patient was forced to interrupt or discontinue treatment as a result of adverse effects.

We conclude that nebulized antibiotics should be considered for all patients with chronic sinusitis who have undergone functional endoscopic sinus surgery and who have failed to respond to oral antibiotics or who do not tolerate them.

Table 1

Individual pre- and post-treatment symptom scores *

                 Nasal                 Facial
Pt./Sex       obstruction               pain                Pressure
          Pre       Post        Pre     Post        Pre     Post

 1. F      5         3           3       0           3       0
 2. F      3         0           1       0           2       0
 3. F      2         1           1       0           2       0
 4. F      2         0           0       0           2       0
 5. F      3         1           3       1           3       1

 6. M      1         1           1       0           1       0
 7. M      2         1           0       0           1       0
 8. F      4         2           2       1           1       1
 9. F      3         1           2       0           2       0
10. M      2         1           0       0           2       0

11. F      0         0           1       0           1       0
12. F      2         0           1       0           2       1
13. M      1         1           1       0           2       1
14. M      1         0           1       0           1       0
15. F      1         0           2       0           2       1

16. F      4         0           2       0           3       0
17. M      3         0           3       0           3       0
18. M      5         1           0       0           3       1
19. F      2         1           3       0           3       0
20. F      0         0           0       0           2       0

21. F      3         1           2       0           2       1
22. M      1         1           0       0           2       1
23. M      1         0           3       0           3       0
24. F      1         1           2       1           2       1
25. F      4         0           2       0           2       1

26. F      2         1           2       1           2       1
27. F      3         2           3       2           3       2
28. F      5         0           5       1           5       1
29. F      4         1           3       0           3       0
30. M      3         0           2       0           4       1

31. F      3         0           3       0           3       0
32. F      3         1           4       0           4       0
33. M      3         0           3       0           3       0
34. M      0         0           3       0           3       0
35. M      2         0           N/A     N/A         4       1

36. F      2         0           3       0           3       0
37. M      3         1           2       0           2       0
38. F      5         3           4       1           4       1
39. M      5         0           3       0           3       0
40. M      5         0           2       0           2       0
41. M      5         1           5       1           5       1

              Mucopurulent
Pt./Sex        Rhinorrhea             Malaise
            Pre     Post        Pre     Post

 1. F        3       1           3       0
 2. F        3       0           2       0
 3. F        2       0           1       0
 4. F        3       0           0       0
 5. F        3       0           3       1

 6. M        2       1           1       0
 7. M        3       1           1       1
 8. F        4       1           N/A     N/A
 9. F        3       1           1       0
10. M        2       0           0       0

11. F        2       0           1       0
12. F        2       0           2       1
13. M        2       0           N/A     N/A
14. M        2       1           1       1
15. F        2       0           N/A     N/A

16. F        4       1           0       0
17. M        3       1           0       0
18. M        2       1           2       1
19. F        3       0           2       2
20. F        3       1           0       0

21. F        2       0           N/A     N/A
22. M        2       0           1       1
23. M        3       0           N/A     N/A
24. F        2       1           2       1
25. F        3       1           2       1

26. F        2       1           0       0
27. F        3       2           N/A     N/A
28. F        5       3           3       0
29. F        4       1           2       0
30. M        5       1           0       0

31. F        3       0           N/A     N/A
32. F        4       1           2       0
33. M        3       0           0       0
34. M        3       0           0       0
35. M        5       1           N/A     N/A

36. F        3       1           1       0
37. M        2       1           0       0
38. F        4       1           1       1
39. M        5       1           3       1
40. M        3       1           N/A     N/A
41. M        5       1           5       1

* Range: 0 = best possible condition; 5 = worst possible condition.
Table 2

Mean pre- and post-treatment symptom scores *

                          No. of    Mean     Standard
Signs and symptoms       patients   score    deviation  CI + (p = 0.05)

Nasal obstruction
  Pretreatment              41     2.658537  1.510128      0.462203
  Post-treatment            41     0.658537  0.794033      0.243039

Facial pain
  Pretreatment              40     2.075     1.327954      0.411512
  Posttreatment             40     0.225     0.479717      0.148658

Pressure
  Pretreatment              41     2.560976  1.001219      0.306401
  Post-treatment            41     0.439024  0.549945      0.168321

Mucopurulent rhinorrhea
  Pretreatment              41     3.02439   0.987112      0.302146
  Post-treatment            41     0.682927  0.649578      0.198808

Malaise
  Pretreatment              32     1.3125    1.229673      0.425818
  Post-treatment            32     0.40625   0.559918      0.193992
Aggregate totals    Sum of
for all five signs  all raw    Mean    Standard
and symptoms        scores    score    deviation  CI + (p = 0.05)

  Pretreatment        463    2.374359  1.211217      0.169999
  Post-treatment       95    0.487179  0.606638      0.08514

* Range: 0 = best possible condition; 5 = worst possible condition.

+ Confidence interval.

References

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(2.) Benson V. Marono MA. Current estimates from the National Health Interview Survey, 1993. National Center for Health Statistics. Vital Health Stat 1993;10:182.

(3.) Green M, Wald ER. Emerging resistance to antibiotics: Impact on respiratory infections in the outpatient setting. Ann Allergy Asthma Immunol 1996;77:167-73.

(4.) Kaliner MA. Recurrent sinusitis: Examining medical treatment options. Am J Rhinol 1997;11:123-32.

(5.) Vaughan W, Carvalho G. Use of nebulized antibiotics for acute infections in chronic sinusitis [abstract]. Otolaryngol Head Neck Surg 2001;125:159-61.

(6.) Leopold D, Ferguson BJ, Piccirillo JF. Outcomes assessment. Otolaryngol Head Neck Surg 1997;117(Suppl 3);S58-68.

(7.) Piccirillo JF, Edwards D, Haiduk A, et al. Psychometric and clinimetric validity of the 31-item rhinosinusitis outcome measure (RSOM-31). Am J Rhinol 1995;9:297-306.

(8.) Benninger MS, Senior BA. The development of the Rhinosinusitis Disability Index. Arch Otolaryngol Head Neck Surg 1997;123:1175-9.

(9.) Senior BA, Glaze C, Benninger MS. Use of the Rhinosinusitis Disability Index (RSDI) in rhinologic disease. Am J Rhinol 2001;15:15-20.

(10.) Birch DS, Saleh HA, Wodehouse T, et al. Assessing the quality of life for patients with chronic rhinosinusitis using the "Rhinosinusitis Disability Index." Rhinology 2001;39:191-6.

From a private otolaryngology practice, Santa Barbara, Calif. (Dr. Scheinberg), and the clinical research group, SinusPharma, Inc., Carpinteria, Calif. (Dr. Otsuji).

Reprint requests: Philip A. Scheinberg, MD, 536 E. Arrellaga St., Suite 104, Santa Barbara, CA 93103. Phone:[phone]; fax: [phone].

This community-based research project was conducted at the otolaryngology office of Philip A. Scheinberg, MD, in Santa Barbara, Calif. Dr. Scheinberg is a member of the Scientific Advisory Board of SinusPharma, Inc.