Article Identification

Article Title: Efficacy and safety of topical ciprofloxacin/dexamethasone versus neomycin/polymyxin B/hydrocortisone for otitis externa.

Authors (top 5): Peter S Roland, Francis D Pien, Craig C Schultz, Dan C Henry, Peter J Conroy

Journal Name, Year, Volume, Issue: Current Medical Research and Opinion, 2004, Volume 20, Issue 8

Type of Study: Clinical Trial

DOI/PMID: 10.1185/030079902125004312; PMID: 15324520

Quick Reference Summary

In a randomized clinical trial, ciprofloxacin/dexamethasone (CIP/DEX) otic suspension demonstrated superior clinical cure rates (90.9% vs. 83.9%; p = 0.0375) and microbiologic eradication rates (94.7% vs. 86.0%; p = 0.0057) compared to neomycin/polymyxin B/hydrocortisone (N/P/H) in treating acute otitis externa (AOE).

Absolute risk differences were 7% for clinical cure and 8.7% for microbiologic eradication, indicating both statistical and clinical significance favoring CIP/DEX.

Core Clinical Question

In patients with acute otitis externa, does treatment with ciprofloxacin/dexamethasone otic suspension improve clinical and microbiologic outcomes compared to neomycin/polymyxin B/hydrocortisone otic suspension?

Background

Disease Overview

Acute otitis externa (AOE) is an inflammatory condition of the external ear canal, often caused by bacterial infection, leading to symptoms like ear pain, inflammation, edema, and discharge.

Prior Data on the Topic

• Topical antibiotic-steroid combinations are standard treatments for AOE, but their comparative efficacies are not well-established.
• Previous studies have shown effective microbial eradication with both CIP/DEX and N/P/H formulations.

Current Standard of Care

Treatment typically involves topical antibiotics with or without corticosteroids to reduce inflammation and eradicate infection.

Knowledge Gaps Addressed by Study

Limited head-to-head comparisons of CIP/DEX versus N/P/H formulations regarding clinical and microbiologic outcomes.

Study Rationale

To determine whether CIP/DEX offers superior clinical and microbiologic efficacy compared to the commonly used N/P/H formulation in treating AOE.

Methods Summary

Study Design

Randomized, observer-masked, parallel-group, multicenter clinical trial.

Setting and Time Period

Multicenter (specific locations not provided), conducted in 2004.

Population Characteristics

• Participants of either sex, older than 1 year.
• Diagnosed with mild, moderate, or severe AOE.
• Intact tympanic membranes.

Inclusion/Exclusion Criteria

Inclusion: Clinical diagnosis of AOE, age >1 year, intact tympanic membranes.

Exclusion: Not specified in the abstract.

Intervention Details

CIP/DEX Group: Ciprofloxacin 0.3%/dexamethasone 0.1% otic suspension, 3-4 drops twice daily for 7 days.

Control/Comparison Group Details

N/P/H Group: Neomycin 0.35%/polymyxin B 10,000 IU/mL/hydrocortisone 1.0% otic suspension, 3-4 drops three times daily for 7 days.

Primary and Secondary Outcomes

Primary: Clinical cure rates at Day 18; microbiologic eradication rates.

Secondary: Clinical response at Days 3 and 18; reduction in ear inflammation at Day 18.

Statistical Analysis Approach

Comparative analysis of cure and eradication rates using p-values to assess significance.

Sample Size Calculations

Not specified in the abstract.

Ethics and Funding Information

Not provided in the abstract.

Detailed Results

Participant Flow and Demographics

• Total Enrolled: 468 patients.
• Culture-Positive and Met Inclusion Criteria: 396 patients.

Primary Outcome Results

• Clinical Cure at Day 18: CIP/DEX 90.9% vs. N/P/H 83.9% (p = 0.0375).
• Microbiologic Eradication: CIP/DEX 94.7% vs. N/P/H 86.0% (p = 0.0057).

Effect Sizes and Confidence Intervals

Not provided in the abstract.

Secondary Outcome Results

• Clinical Response at Day 3: CIP/DEX significantly better (p = 0.0279).
• Clinical Response at Day 18: CIP/DEX significantly better (p = 0.0321).
• Reduction in Ear Inflammation at Day 18: CIP/DEX significantly better (p = 0.0268).

Subgroup Analyses

Clinical responses improved significantly in both pediatric and adult populations.

Adverse Events/Safety Data

• Both CIP/DEX and N/P/H were well tolerated.
• Specific adverse events were not detailed in the abstract.

Results Tables

Outcome	Intervention Group (CIP/DEX)	Control Group (N/P/H)	Difference	P-value
Clinical Cure at Day 18	90.9%	83.9%	+7.0%	0.0375
Microbiologic Eradication	94.7%	86.0%	+8.7%	0.0057
Clinical Response at Day 3	Significantly better			0.0279
Clinical Response at Day 18	Significantly better			0.0321
Ear Inflammation Reduction	Significantly better			0.0268

Note: Confidence intervals are not provided in the abstract.

Authors' Conclusions

• Primary Conclusions: A 7-day treatment regimen with CIP/DEX otic suspension administered twice daily is both clinically and microbiologically superior to N/P/H otic suspension administered three times daily in managing mild to severe acute otitis externa.
• Authors' Interpretation of Results: CIP/DEX offers better outcomes in terms of cure rates and microbial eradication without compromising safety compared to N/P/H.
• Clinical Implications Stated by Authors: CIP/DEX may be considered a more effective first-line treatment option for AOE, potentially improving patient outcomes.
• Future Research Recommendations: Not specified in the abstract.

Critical Analysis

A. Strengths

• Methodological Strengths:
  • Randomized, observer-masked design reduces selection and observer biases.
  • Multicenter approach enhances the generalizability of the findings.
  • Adequate sample size (N=468) increases the power to detect significant differences.
• Internal Validity Considerations: Clear inclusion criteria and standardized treatment protocols support robust internal validity.
• External Validity Considerations: Inclusion of both pediatric and adult patients broadens the applicability across age groups.

B. Limitations

• Study Design Limitations: Observer masking may be compromised if drop administration frequency is noticeable.
• Potential Biases: Lack of detailed information on funding sources and conflicts of interest may affect bias assessment.
• Generalizability Issues: Results are applicable only to patients with intact tympanic membranes, excluding those with perforations.
• Statistical Limitations: Confidence intervals and effect sizes are not reported, limiting the understanding of the precision of results.
• Missing Data Handling: The abstract does not address how missing data or patient dropouts were managed.

C. Literature Context

(Note: Limited information available as only the abstract is provided.)

• This Trial's Contribution: Provides a direct comparison between CIP/DEX and N/P/H formulations, demonstrating the superior efficacy of CIP/DEX in treating AOE.
• Comparison with Existing Evidence: Aligns with previous studies supporting the use of antibiotic-steroid combinations for AOE but extends knowledge by offering a head-to-head comparison.

Clinical Application

• How Findings Change Current Practice: CIP/DEX otic suspension may be preferred over N/P/H due to higher clinical cure and microbiologic eradication rates with a similar safety profile.
• Specific Patient Populations or Scenarios: Applicable to patients older than 1 year with mild to severe AOE and intact tympanic membranes, including both pediatric and adult populations.
• Implementation Considerations: CIP/DEX requires fewer daily administrations (twice daily) compared to N/P/H (three times daily), potentially improving patient adherence.
• Integration with Existing Evidence: Reinforces the efficacy of antibiotic-steroid combinations in AOE management, supporting the selection of CIP/DEX based on superior outcomes.

How To Use This Info In Practice

Practitioners should consider prescribing ciprofloxacin/dexamethasone otic suspension as a first-line treatment for acute otitis externa due to its demonstrated superior efficacy and comparable safety to neomycin/polymyxin B/hydrocortisone formulations.