Antifungal Therapy of Aspergillus Invasive Otitis Externa: Efficacy of Voriconazole and Review

Abstract

Invasive otitis externa (IOE) due to Aspergillus is a rare, potentially life-threatening, invasive fungal infection affecting immunocompromised patients. The invasive process may lead to skull base osteomyelitis with progressive cranial nerve palsies and can result in irreversible hearing and neurological impairment. We report two cases of Aspergillus IOE treated with voriconazole alone and a literature review of antifungal therapy of Aspergillus IOE. Twenty-five patients, including the two described in the present report, were analyzed. Eighteen patients were treated with amphotericin B, and nine of them received itraconazole as an additional agent. Three patients received initial therapy with itraconazole, and one patient was treated with both voriconazole and caspofungin therapy. The two patients in the present report received voriconazole therapy alone with good clinical and biological tolerance despite prolonged treatment. The last patient did not receive antifungal therapy, as the diagnosis was made postmortem. Eighteen patients underwent an initial extensive surgical debridement. The majority of the patients had a favorable outcome, 17 patients experienced a complete recovery, and 6 showed a partial improvement. Both of the patients reported on here had favorable outcomes, and no aggressive surgical debridement was required. Although voriconazole has been shown to be effective for the treatment of invasive aspergillosis, its precise role in the management of Aspergillus IOE had not been documented. These observations demonstrate that voriconazole could be an effective and well-tolerated therapeutic option for the management of Aspergillus IOE.Invasive otitis externa (IOE) is a particular entity among ear infections (6). Its main feature is its spreading from the external auditory canal to adjacent anatomical structures including soft tissues, cartilage, and bone. The invasive process can lead to skull base osteomyelitis, progressive cranial nerve palsies, and even death if IOE is not recognized and treated early. Invasive external otitis typically occurs in elderly diabetic patients, and Pseudomonas aeruginosa is the most common causative microbial pathogen (11,35).Fungal pathogens, mostly Aspergillus spp., are a rare cause of IOE (5). As for other localizations of invasive aspergillosis, Aspergillus IOE occurs in immunocompromised patients, usually with profound and long-lasting neutropenia or under longterm steroid therapy (21), as well as in patients with uncontrolled diabetes mellitus (14).The treatment of Aspergillus sp. IOE classically includes extensive surgical debridement and intensive long-term antifungal therapy including amphotericin B and/or itraconazole. Despite this management, this pathology is associated with substantial morbidity and mortality, mostly due to late diagnosis and patient comorbidities (2, 37). Treatment failure could also be a result of suboptimal therapeutic management as a consequence of antifungal agent toxicity. In particular, the side effects of amphotericin B, especia...

Fungal malignant external otitis

“…7 Fungi are rarely involved in MEO, and have been identified particularly in immune-compromised nondiabetic patients, such as patients with AIDS or acute leukemia. 2,8 Aspergillus fumigates is the most common cause of fungal MEO. 8,9 The traditional and well-accepted treatment for MEO is prolonged anti-pseudomonal therapy for at least 6 weeks as well as local treatment with lavage and eardrops.…”

“…2,8 Aspergillus fumigates is the most common cause of fungal MEO. 8,9 The traditional and well-accepted treatment for MEO is prolonged anti-pseudomonal therapy for at least 6 weeks as well as local treatment with lavage and eardrops. When cure is not achieved after 6 weeks, the antibiotic treatment is continued and other treatment modalities are considered, such as surgery for debridement 10e13 and hyperbaric oxygen chamber.…”

Treatment of refractory Aspergillus otomycosis with voriconazole: case series and review

“…Three patients responded well to voriconazole and did not need surgery. 7,9 In the present study, three out of five cases of Aspergillus invasive otitis externa had a good response to voriconazole. One of the two cases with relapsed symptoms after voriconazole discontinuation needed surgical debridement.…”

“…In addition, the median total dose of amphotericin B administered was 2 g (range 0.8-2.5 g) for Aspergillus invasive otitis externa, and patients required prolonged hospitalisation. 7 Voriconazole is a broad-spectrum azole which exhibits high anti-Aspergillus activity. It is currently considered the first-line therapeutic option for invasive aspergillosis.…”

Chronic Invasive Aspergillus Sinusitis and Otitis with Meningeal Extension Successfully Treated with Voriconazole

“…Diabetes mellitus is not recognized as an IA risk factor per se, although innate immunity and adaptive immunity are altered (1,5,7,8). However, uncontrolled diabetes is a risk factor for fungal invasive otitis (9)(10)(11)(12) and was the main underlying disease in three reported cases of CNS IA (13)(14)(15).…”