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

Randomized, double-blind trial

N= 20

To study the efficacy of nebulized topical saline-tobramycin solution in patients with chronic rhinosinusitis refractory to medical and surgical therapy

Tobramycin-saline solution (n= 10)

Saline-only solution (n= 10)

Patients with rhinosinusitis refractory to medical and surgical treatment, without immune deficiencies, who had undergone previous technically successful ESS but presented with persistent symptoms beyond the normal healing period

Patients unable to give consent, unable to follow instructions, with severe renal insufficiency, allergic to tobramycin or quinine, using loop diuretics, with pre-existing hearing loss, or with isolated frontal rhinosinusitis

Patients received 3-times daily applications of 4 mL of a 20 mg/mL tobramycin solution or a placebo solution of 0.9% sodium chloride for 4 weeks using the RinoFlow Nasal and Sinus Wash System. The placebo solution contained quinine to ensure blinding.

January 1998 to May 1998

Primary: Improvement in symptoms, quality of life, and endoscopic aspect of sinus mucosa

Secondary: Development of nasal congestion

Characteristics

Age, mean years

History of atopy

Improvement in QOL, symptoms, and endoscopic aspect

Nasal congestion

Treatment was well tolerated with no statistically significant difference in adverse events between the groups. No tobramycin-resistant organisms developed. One case of pneumonia occurred in the saline-only group.

Therapy with a 4-week course of large-particle nebulized aerosol therapy improves symptomatology and objective parameters of rhinosinusitis in patients refractory to surgical and medical therapies. Addition of tobramycin appears of minimal benefit.

The study was well-designed with a double-blind, placebo-controlled approach, ensuring robust results. However, the small sample size limits the generalizability of the findings. The study also did not explore the long-term effects of the treatment or the underlying mechanisms of action.

Efficacy of tobramycin aerosol in nasal polyposis

Multicenter interventional prospective double-blind randomized study with matched groups

N= 55

To compare bacteriological eradication between tobramycin 150 mg/3 ml versus isotonic saline, both administered by nebulization via the Easynose® device

Isotonic saline aerosol (n= 23)

Tobramycin aerosol (n= 32)

Aged 20–70 years, with health insurance cover, consenting to the study; presenting with nasal polyposis operated on for an episode of infection within the previous 3 months; with fully healed total ethmoidectomy performed at least 2 months previously; without local or systemic antibiotherapy during the previous month; with nasal polyposis not extending beyond the roof of the maxillary sinus.

Pregnancy, breast-feeding, cystic fibrosis, proven ciliary dyskinesia or known immune deficiency, kidney failure and contraindications for aminoglycosides

Patients received either tobramycin 150 mg/3 ml or isotonic saline via the Easynose® mesh nebulizer twice daily for 7 days. Long-course corticosteroid therapy was allowed if dosage had not changed for at least 1 month before inclusion. No nose-wash with physiological saline, antibiotherapy, or systemic corticotherapy was allowed during the study.

7 days of treatment

Bacteriological eradication efficacy

Isotonic saline aerosol (n= 23)

Mean age (range) in years

Gender (% male)

Time from nasal polyposis diagnosis (years)

Time from ethmoidectomy (years)

% nasal polyposis + asthma

% positive samples at D10

Staphylococcus aureus

Streptococcus pneumoniae

Streptococcus group A

Streptococcus group C

Branhamella catarrhalis

Haemophilus influenzae

Enterobacteria

Pseudomonas aeruginosa

There were 27 adverse events, none serious. The rate of adverse events did not differ between groups (P = 0.58). Adverse events mainly comprised lower respiratory issues (asthma attack, cough, bronchitis), otologic issues (otalgia, otitis), gastrointestinal issues (diarrhea, nausea) and erythematous skin lesions.

Tobramycin delivered by the Easynose® device showed significant benefit compared to saline. Local antibiotherapy for infection in patients operated on for severe nasal polyposis can reduce prescription of systemic antibiotics, contributing to the fight against emergent antibiotic resistance.

The study demonstrated significant bacteriological eradication with tobramycin aerosol, but the lack of clinical improvement may be due to the short follow-up period. The study's strengths include its randomized design and use of a novel delivery device, but limitations include the short duration and potential variability in sinonasal inflammation resolution time.

Management of chronic sinusitis in cystic fibrosis

Design

Single-center, retrospective study

N= 33

Objective

To describe the prophylactic protocol for managing chronic rhinosinusitis in cystic fibrosis patients prior to lung transplantation

Study Groups

All patients (n = 33)

Inclusion Criteria

Diagnosis of cystic fibrosis, presence of sinonasal disease (chronic rhinosinusitis), referral to the UCSD Nasal Dysfunction Clinic for complete evaluation, enrollment in the lung transplantation program, or presentation with sinonasal disease

Exclusion Criteria

Not explicitly stated

Methods

A prophylactic protocol for managing chronic sinusitis in cystic fibrosis patients involves endoscopic sinus surgery with partial middle turbinectomy, septoplasty, and large middle meatal maxillary antrostomy. Postoperatively, patients undergo pulsatile hypotonic saline irrigation to clear secretions, with daily tobramycin added to the irrigant to suppress Pseudomonas growth. Tobramycin was added once daily to the final 56–60 mL of irrigant at a dose of 20 mg (0.5 mL), diluted to one-tenth strength, and instilled into each nasal passage to inhibit the growth of Pseudomonas organisms. Posttransplant patients additionally received direct instillation of 1–2 mL of the one-tenth dilution into each maxillary sinus via the middle meatal antrostomies beginning 2–3 days after surgery.

Duration

Treatment: 1989 to 1994

Outcome Measures

Baseline Characteristics

All subjects (n = 33)

Age, years

Female

Indication for surgery

Nasal polyposis

Chronic sinusitis

Paranasal sinus abnormalities

5

14

18

FEV₁

Abbreviations: FEV₁ = forced expiratory volume in 1 s; FVC= forced vital capacity; BP = blood pressure; EBL = estimated blood loss; Sao₂, = saturation with oxygen, arterial blood

Results

Endpoint

All subjects (n = 33)

Adverse Events

One orbital hematoma was successfully managed, no operative or perioperative deaths reported.

Study Author Conclusions

Sinonasal disease is universal in patients with cystic fibrosis. Endoscopic sinus surgery provides access to the nose and paranasal sinuses, so that daily pulsatile hypotonic saline irrigations can effectively clean thick, tenacious, infected secretions. Aerosolized topical tobramycin inhibits the growth of Pseudomonas organisms. With the regimen described in this article, the nose and paranasal sinuses can remain clean and healthy. It is hypothesized that a clean nose contributes to healthier lungs. The UCSD protocol, which was developed to reduce the incidence of Pseudomonas pneumonia following pulmonary transplantation, is now used in all patients with cystic fibrosis who have significant sinonasal disease. 

InpharmD Researcher Critique

Limitations include the small, single-center, retrospective design, lack of a control group, reliance on subjective outcomes, absence of standardized long-term follow-up, and potential confounding from coexisting allergic or inflammatory upper airway conditions. 

Sinonasal inhalation of tobramycin vibrating aerosol in cystic fibrosis patients with upper airway Pseudomonas aeruginosa colonization: results of a randomized, double-blind, placebo-controlled pilot study

Randomized, double-blind, placebo-controlled pilot study

N=9

To evaluate the effects of sinonasal inhalation of tobramycin on P. aeruginosa quantification in nasal lavage; and on patient quality of life, measured with the Sino-Nasal Outcome Test (SNOT-20), and otologic and renal safety and tolerability

Tobramycin (n=6)

Placebo (n=3)

Diagnosed with CF, confirmed by two positive sweat tests and/or genetic analysis; chronic P. aeruginosa colonization of the LAW, with pathogen detected in NL within 28 days prior to inclusion; age ≥7 years; ability to utilize the PARI Sinus™ for nasal inhalation; ability to perform NLs

Sinonasal surgery within 3 months; nasal bleeding; ear drum perforation; severe damage to the eighth cranial nerve; advanced renal insufficiency; critical general condition; FEV1 <30%; pulse oximetry <93% without O2-substitution; exacerbation at randomization with need for new systemic antibiotics; treatment with systemic antibiotics for P. aeruginosa infection 14 days before randomization or during the study; history of adverse reactions to tobramycin or placebo; pregnancy or breastfeeding; participation in another therapeutic clinical study within 30 days prior to baseline

Patients were randomized to inhalation of tobramycin (80 mg/2 mL) or placebo (2 mL isotonic saline) once daily (4 minutes/nostril) with the PARI Sinus™ nebulizer over 28 days. Nasal lavage was obtained before starting and 2 days after the end of each treatment period by rinsing each nostril with 10 mL of isotonic saline

28 days

Change in numbers of P. aeruginosa colonies in NL

Age (years)

1

2

4

5

6

7

8

9

28 days of facultative open-label treatment with tobramycin

Tob/†

Tob/tob

Tob/tob

Tob/tob

Tob/†

Tob/†

Iso sal/tob

Iso sal/tob

Iso sal/tob

Notes:

*P. aeruginosa detection in NL below quantifiable levels (taken as 10x colony counts);

† patients not taking the second open-label treatment with tobramycin.

Abbreviations: tob, tobramycin; iso sal, isotonic saline

Sinonasal inhalation was well tolerated, with serum tobramycin <0.5 mg/L and stable creatinine.

No serious adverse events were observed.

One patient showed bilateral hearing impairment due to noise trauma unrelated to the study.

Sinonasal inhalation of vibrating antibiotic aerosols appears promising for reducing pathogen colonization of paranasal sinuses and for control of symptoms in patients with CF.

The study was limited by its small sample size and the unequal distribution of patients in the treatment groups. The pilot nature of the study means that larger trials are needed to confirm these findings. The study showed promising results in terms of sinonasal symptom improvement and pathogen reduction, but statistical significance was not reached for pathogen reduction due to the small sample size.