The effects of caspofungin and voriconazole in an experimental fungal infection of the ear due to Aspergillus

Abstract

The purpose of the study was to evaluate the effectiveness of caspofungin and voriconazole in the treatment of experimental Aspergillus otitis media in an experimental rabbit model. A total of 30 New Zealand white rabbits were divided into four treatment groups and one control group. The rabbits were immunosuppressed by cyclophosphamide and triamcinolone acetonide. The right ear of each rabbit was infected by an injection of the inoculum of 0.1 ml (8.6 x 103 CFU/0.1 ml) of Aspergillus fumigatus into the middle ear cavity. At 72 h after the inoculation, amphotericin B 1 mg/kg per day (n = 6), itraconazole 10 mg/kg per day (n = 6), voriconazole 10 mg/kg per day (n = 6) and caspofungin 5 mg/kg per day (n = 6) were injected to each treatment group. No antifungal drug was administered to the control group (n = 6). Clinical and histopathological examination scores and microbiological analysis of middle ear mucosa were compared.There was statistically significant difference in the clinical scores, histopathological scores, and mean CFU/g between the treatment and control groups (P < 0.05). There was no statistically significant difference among the treatment groups in the clinical and histopathological scores, whereas there was statistically significant difference in the mean CFU/g (P < 0.05). The mean CFU/g of amphotericin B and caspofungin groups were similar and both were lower than the itraconazole and voriconazole groups. Also, the mean CFU/g of voriconazole group was lower than the itraconazole group (P < 0.05). Caspofungin and voriconazole were demonstrated at least as effective as amphotericin B and itraconazole. We suggest that caspofungin and voriconazole may be considered for the treatment of fungal infection of the ear.

Are Systemic Voriconazole and Caspofungin Ototoxic? An Experimental Study with Rats

“…In an in vitro study conducted by Erbek et al [20] it was reported that both agents showed the same activity rate (97.8%) as amphotericin B against the fungi tested. When assessed with clinical, microbiological, and histopathological techniques, caspofungin and voriconazole were shown to be as effective as amphotericin B and itraconazole, which were considered the standard regimens towards the treatment of fungal infections of the ear [6]. Voriconazole is currently considered as the first line therapeutic option for invasive aspergillosis, based on its high intrinsic anti- Aspergillus activity [7].…”

“…It has been recommended as the primary therapy for acute invasive aspergillosis in international guidelines [2]. Additionally, voriconazole has shown significant activity in patients with central nervous system and bone aspergillosis [6, 7]. Long term treatment with this antifungal agent is well tolerated and it is available for intravenous and oral use [7].…”

“…Then, the rats were randomly divided into 4 groups (groups I-IV), each group consisting of 8 rats. In group I voriconazole 10 mg/kg/day (Vfend, Pfizer, Istanbul, Turkey), and in group II caspofungin 5 mg/kg/day (Candidas, Merck Sharp & Dohme, Istanbul, Turkey) were injected intraperitoneally (ip) for 7 days [6]. Group III served as the positive control and received gentamicin (120 mg/kg/day) ip for 7 days.…”

“…Fatal acute invasive fungal infections can develop in immunocompromised patients with bone marrow transplantation, leukemia, cancer, AIDS, diabetes mellitus, or in patients that require immunosuppressive drugs or who undergo kidney dialysis; in these cases, a systemic antifungal therapy may be required [4]. Fungal sinusitis and invasive fungal external otitis are well-known fungal infections of the head and neck region [5, 6]. …”