Dexamethasone phosphate in antibiotic ear drops for the treatment of acute bacterial otitis externa

ABSTRACT

Objectives: To compare the efficacy and safety of polymyxin sulfate 7500 IU/neomycin sulfate 3500 IU/dexamethasone phosphate 0.1% (PN + Dx) otic solution with polymyxin sulfate 7500 IU/neomycin sulfate 3500 IU (PN − Dx) in patients with acute bacterial otitis externa (AOE), in order to determine the possible benefit of the addition of dexamethasone.

Research design and methods: Active controlled, double-blind, randomized, parallel group, multi-center clinical trial in ear, nose, and throat (ENT) specialist practices with a planned interim analysis for sample size adaptation. In total, 338 patients aged 18–76 who had a previous episode of otitis externa within the last year were randomized to receive 10 ± 2 days of treatment with two drops, three times daily, of either PN + Dx or PN − Dx.

Main outcome measures: Change in the clinical symptom score (consisting of the subscores redness, swelling, pain, and secretion) and of the visual analogue scale (VAS) rating for pain from Visit 1 (Day 1) to Visit 2 (Day 4 ± 1), patient's assessment of efficacy at Visit 3 (Day 10 ± 2), and the frequency and type of adverse events.

Results: There was a significantly greater reduction of swelling from Visit 1 to Visit 2 with PN + Dx, and more patients rated the efficacy of PN + Dx as ‘very good’ or ‘good’ at Visit 3 (p = 0.03). There was also a significantly greater decrease in the clinical symptom score from Visit 1 to Visit 2 in the PN + Dx group in patients who had at least a moderately severe symptom score with more than seven points at Visit 1 (p = 0.01) and in patients suffering from their current episode of otitis externa for more than 2 days (p = 0.02). In total, 14 adverse events were reported during the study period with no related adverse drug reactions for PN + Dx.

Conclusions: The addition of dexamethasone phosphate to polymyxin B/neomycin significantly reduces swelling in patients with AOE and leads to significantly higher patient's ratings of treatment efficacy. It especially leads to an overall reduction of symptoms in cases of moderately or more severe otitis externa and cases lasting for more than 2 days.

Key words: :

• Dexamethasone
• Neomycin
• Otitis externa
• Polymyxin B
• Topical anti-infective agents

Acknowledgments

Declaration of interest: This study was funded by an unrestricted research grant from Alcon Pharma Germany GmbH. The sponsor has asserted no influence on the performance of this clinical trial. The authors have written this manuscript independently and under no influence by the sponsor.

R.M. has served as a scientific advisor to Alcon Pharma, the manufacturer of the marketed product described in this publication. The remaining authors state that they have no financial interest in the products mentioned within this article.

The authors gratefully acknowledge Dr. Thomas McDonald's continuous scientific support of this endeavor. We also thank Dr. Irmtrud Pelzer for her valuable contributions in designing and conducting this study, and Mrs. Gena Kittel for proofreading the manuscript.

The following ENT specialists recruited patients for this study: Dr. med. Christine Barth (Wiesbaden), Dr. med. Frank Burkart (Radolfzell), Dr. med. Rüdiger Gering (Willich), Dr. med. Peter Hinterkausen (Köln), Dr. med. Georg Krückels (Aachen), Dr. med. Norbert Pasch (Aachen), Dr. med. Babette Panzer (Buxtehude), Dr. med. Anke Prasch-Beginen (Viersen), Ralf Sählbrandt (Duisburg), Dr. med. Axel Schadel (Darmstadt), Dr. med. Gerhard Schindlbeck (Viernheim), Dr. med. Jürgen Schlee (Eschweiler), Dr. med. Wilhelm Schütz (Jülich), Taufik Shahab (Köln), Dr. med. Martin Sondermann (Aachen), Dr. med. Joachim Spaeth (Düren), Dr. med. Nicole Christina Stuhrmann (Frankfurt), Dr. med. Alfred Nachtsheim (Aachen), Dr. med. Jürgen Palm (Röthenbach), Dr. med. Heike Scholz (Lüdenscheid), Dr. med. Tatjana von Stackelberg (Düsseldorf).