Although ciprofloxacin plus fluocinolone acetonide is safe and effective for the treatment of acute otitis externa (AOE), this dual therapy is not superior to either ciprofloxacin or fluocinolone acetonide alone. These findings were published in JAMA Network Open.
Between 2017 and 2018, researchers conducted a phase 3, randomized, double-blind, active-controlled trial at 36 sites in the United States. Included patients (N=493) were those aged 6 months and older with AOE for less than 21 days. Patients were randomly assigned in a 2:2:1 fashion to receive either dual therapy with ciprofloxacin (otic solution, 0.3%) plus fluocinolone acetonide (otic solution, 0.025%; n=197), or monotherapy with either ciprofloxacin (n=196) or fluocinolone acetonide (n=100). All patients received treatment twice daily for a total of 7 days, with evaluations at baseline (visit 1), days 3 to 4 (visit 2), days 8 to 10 (visit 3), and days 15 to 17 (visit 4). The primary outcome was the rate of therapeutic cure at the end of treatment, a combination of both clinical and microbiologic cure. Clinical cure was defined as the resolution of edema, otalgia, and otorrhhea symptoms, and microbiologic cure was defined as bacteriologic eradication.
Among patients in the dual therapy, ciprofloxacin monotherapy, and fluocinolone monotherapy cohorts, the mean age was 37.8, 38.4, and 38.7 years; 28.4%, 29.1%, and 29.0% were younger than 18 years; 49.2%, 51.5%, and 56.0% were girls or women; 82.2%, 82.1%, and 82.0% were White; 18.8%, 16.8%, and 16.0% had Pseudomonas aeruginosa infections; and 13.2%, 12.2%, and 8.0% had Staphylococcus aureus infections, respectively.
At visit 4, the therapeutic cure rates were 87.4%, 75.8%, and 80.0% among patients in the dual therapy, ciprofloxacin, and fluocinolone cohorts, respectively. Owing to these findings, dual therapy was found to be significantly superior to ciprofloxacin alone (mean difference [MD], 11.6%; 95% CI, 0.7-22.4; P =.04) but not to fluocinolone alone (MD, 7.4%; 95% CI, -6.0 to 20.7; P =.25).
The median time to otalgia clearance was 5.0 days among patients who received dual therapy compared with 5.9 days (95% CI, 4.3-7.3; P =.002) and 7.7 days (95% CI, 6.7-9.0; P <.001) for those who received monotherapy with either ciprofloxacin (P =.002) or fluocinolone (P <.001), respectively. Similar results were noted among patients infected with P aeruginosa or S aureus, with the median time to otalgia clearance significantly decreased among those who received dual therapy (5.9 days) compared with those who received either ciprofloxacin (6.9 days; P <.001) or fluocinolone alone (7.6 days; P =.01).
Treatment-related adverse events were reported by 3.1% of patients who received dual therapy, 2.6% of those who received ciprofloxacin alone, and none of those who received fluocinolone alone. The most common events among patients who received dual therapy vs those who received ciprofloxacin alone were application site pain (2.0% vs 0%), cerumen impaction (0.5% vs 0%), otomycosis (0.5% vs 0.5%), and pruritus (0% vs 1.0%). Patients who received ciprofloxacin alone also reported dizziness (1.0%), headache (1.0%), nausea (0.5%), and lethargy (0.5%).
This study was limited by the lower than expected number of included patients with positive bacterial cultures at baseline.
Although ciprofloxacin plus fluocinolone acetonide was not superior to ciprofloxacin alone or fluocinolone acetonide alone, these findings “suggest the benefits of combining the antibiotic ciprofloxacin and the corticosteroid fluocinolone acetonide to better manage patients with AOE, with regard to both the bacterial infection and the typical disease signs and symptoms,” the researchers concluded.
Disclosure: Multiple authors declared affiliations with industry. Please see the original reference for a full list of disclosures.
Chu L, Acosta AM, Aazami H, et al. Efficacy and safety of ciprofloxacin plus fluocinolone acetonide among patients with acute otitis externa: a randomized clinical trial. JAMA Netw Open. 2022;5(7):e2221699. doi:10.1001/jamanetworkopen.2022.21699