Acute Otitis Externa-Antimicrobial Resistance in the US and Canada: Phase III Study Outcomes

The goal of this investigation was to characterize the microbiological profile and antimicrobial susceptibility patterns of pathogens isolated from AOE patients of 2 vehicle-controlled Phase III clinical trials and evaluate pathogen eradication rates achieved with finafloxacin otic suspension. In vitro MIC comparisons to other fluoroquinolones (ciprofloxacin, ofloxacin) are reported as supplementary susceptibility data and do not reflect direct randomized clinical comparisons.

A total of 2683 bacteria isolated from 1234 AOE patients enrolled in 2 Phase III clinical studies in the United States, Puerto Rico, and Canada were analyzed. Specimens were collected from the external ear of subjects with AOE. Species-level identification for each bacterial isolate recovered was obtained by combining phenotypic and genotypic data. End point minimum inhibitory concentration (MIC) testing was performed using Clinical and Laboratory Standards Institute recommended methods.

72.7% of the pre-therapy bacteria were Gram-positive and 27.3% Gram-negative. Most frequent bacterial isolates were Staphylococcus spp. (46.7%) followed by Pseudomonas spp. (19.5%). Methicillin resistance was detected in 17.0% of S. aureus (MRSA) and 33.2% of S. epidermidis (MRSE) isolates. Ciprofloxacin resistance was identified in 12.5% of S. aureus and 14.0% of S. epidermidis isolates. Finafloxacin eradicated 86.4% of the MRSA isolates and 80.6% of the MRSE isolates. Finafloxacin eradicated ciprofloxacin-resistant Staphylococcus spp. in 74.4% and ciprofloxacin-resistant Pseudomonas spp. in 87.5% of treated patients.

Finafloxacin demonstrated high eradication rates in AOE patients with methicillin-resistant S. epidermidis and S. aureus, as well as in patients with ciprofloxacin-resistant Staphylococcus spp.- and Pseudomonas spp., irrespective of the pathogen's resistance profile. These in vitro findings, together with observed eradication rates in the vehicle-controlled trials, suggest that finafloxacin may offer advantages in the treatment of resistant organisms, particularly under acidic pH conditions. However, direct clinical trial comparisons have not been conducted.

Clinical trial registry name: ClinicalTrials.gov. URL: https://clinicaltrials.gov/. Identifier: NCT01535599 and NCT01535560.