Fungal otitis externa, primarily triggered by fungal infections, represents an inflammatory condition affecting the skin and subcutaneous tissues of the external ear canal. Notable causative fungi include Aspergillus, Candida, Penicillium, Mucor, among others, with Aspergillus niger (16/304; 5%) and Aspergillus fumigatus (3/304; 1%) being prevalent mold species. Common yeast strains encompass Candida paracilata (38/304; 13%), Candida albicans (10/304; 3%), and C. tropicalis (6/304; 2%)[1-4]. Symptoms often include ear tightness, swelling, severe itching, and potential anxiety [1]. In severe instances, patients may experience swelling, pain, increased discharge, hearing impairment, tinnitus, and complications like external ear canal cellulitis, stenosis, eczema, and tympanic membrane perforation[5]. Diagnosis primarily relies on clinical symptomatology, otoscopy, and laboratory assessments such as fungal cultures and microscopic examinations.
In this research, video otoendoscopy was utilized to visually assess aspects such as the cleanliness of the external ear canal, inflammation levels, condition of the tympanic membrane, and therapeutic outcomes. This assessment encompassed enhancements in ear canal cleanliness, reduction in discharge, and amelioration of inflammation. Subsequently, an endoscopic visual VAS score was employed to objectively ascertain the superiority between the two combinations. The comparative analysis focused on the efficacy of sodium bicarbonate injection ear baths paired with perisone ointment versus normal saline ear baths in conjunction with perisone ointment for treating fungal otitis externa, offering valuable insights for clinical interventions. Our clinical observations revealed that throughout the treatment of fungal otitis externa, the experimental group exhibited notably superior outcomes compared to the control group, particularly evident on the 4th and 7th days, showcasing significant symptom relief. Furthermore, the combination of sodium bicarbonate solution and perisone cream proved markedly more effective than utilizing normal saline alongside perisone cream in terms of both cleansing and enhancing the external ear canal. To investigate the underlying reasons for the notable effectiveness of this specific combination, our analysis proceeded as follows:
Impact of Alkaline Environment Created by Sodium Bicarbonate on Fungal Growth
By altering the pH of the external ear canal using 5% sodium bicarbonate injection to create an alkaline environment (pH of 8.5), the growth and metabolism of fungi are effectively impeded. Fungi thrive best within a pH range of 5.0 to 6.0, making an alkaline setting unfavorable for their proliferation. This control over alkalinity through sodium bicarbonate injection aids in managing fungal growth in the outer auditory canal and supports the treatment of otitis externa fungal infections.
The effects of this alkaline environment on fungal growth and metabolism involve various mechanisms:
- Enzyme Activity Limitation: Critical fungal enzymes such as pigment P450 enzyme and ergosterol 14α-demethylase experience restricted activity under alkaline conditions, hindering normal metabolic processes crucial for growth.
- Cell Wall Integrity: The alkaline environment disrupts the stability and integrity of the fungal cell wall, leading to disturbances in normal growth patterns.
- Ion Balance Disruption: The alkaline milieu interferes with the internal and external ion balance of the fungal cells, impacting biochemical reactions and ultimately inhibiting metabolic functions.
- Nutrient Absorption Impairment: Fungi struggle to efficiently absorb and utilize essential nutrients in alkaline conditions, constraining their growth and reproductive capabilities.
In conclusion, the alkaline environment induced by 5% sodium bicarbonate injection significantly hampers fungal growth and metabolism in the outer auditory canal. The described mechanisms encompass the restriction of enzyme activity, disruption of cell wall integrity, imbalance in ion levels, and impairment of nutrient absorption, collectively impeding the survival and reproduction of fungi in this setting.
Therapeutic Mechanism of Triamcinolone and Econazole Cream: A Comprehensive Insight into Their Combined Efficacy
Synergistic Therapeutic Approach of Triamcinolone and Econazole Cream: Harnessing the Anti-inflammatory and Antifungal Properties for Effective Symptom Relief and Fungal Infection Treatment.
By blending the anti-inflammatory capabilities of triamcinolone with the potent antifungal properties of econazole, this cream offers a comprehensive solution for alleviating inflammation and combatting fungal infections. The distinct mechanisms of action are outlined below:
1. Triamcinolone:
Triamcinolone, classified as a glucocorticoid, exhibits profound anti-inflammatory and anti-allergic effects. Specifically in cases of fungal infections, it aids in mitigating skin inflammation and curbing immune system hyperactivity. This results in alleviation of common inflammatory symptoms like itching, redness, and swelling.
2. Econazole:
As a member of the Miconazole family, econazole represents a broad-spectrum antifungal agent. It disrupts ergosterol 14α-demethylase activity present in fungal cell membranes, by impeding enzymes within the pigment P450 system. By obstructing the synthesis of essential components required for fungal cell membrane integrity, econazole induces dysfunction within the cell membrane, eventually leading to either fungal cell death or growth inhibition. The selection of econazole is attributed to its heightened sensitivity towards Aspergillus compared to other antifungal agents like tioconazole, nystatin, amphotericin B, and carpofungin. Research indicates significant resistance rates of Aspergillus to amphotericin B and carpofungin at 50% and 72% [6], respectively, while in vitro sensitivities of Aspergillus to tioconazole and nystatin remain notably low[3].
In summary, the combined application of triamcinolone and econazole cream not only assuages inflammatory symptoms but also eradicates fungal pathogens through synergistic actions, thereby achieving comprehensive treatment efficacy against fungal infections. Clinical practice necessitates flexible adjustments in dosage and treatment duration based on individual patient conditions to ensure optimal therapeutic outcomes. For severe cases, extending the use of sodium bicarbonate injection ear baths and peri-sonal ointments may be recommended to thoroughly eliminate fungal presence. All patients should undergo a minimum 3-month follow-up, with visits scheduled at the 2nd and 3rd month intervals to monitor recurrences. In instances of recurrence, repeating the aforementioned regimen for an additional 7 days is advised.
Antifungal mechanism of combination therapy
This research assessed the effectiveness of combining sodium bicarbonate injection with perisone cream in treating fungal otitis externa. Findings indicated that the combined treatment demonstrated notable benefits compared to the control group, showing improvements in endoscopic score, fungal eradication, and overall response rate. Particularly in terms of enhancing the endoscopic score, the combined therapy exhibited superior performance and a reduced recurrence rate. The substantial enhancement in fungal clearance achieved through the combination of sodium bicarbonate and perisone cream is likely attributed to the inhibition of fungal hyphal growth and spore germination.
The cellular mechanism underlying the antifungal effects of this combination therapy involves disrupting fungal cell integrity, mitochondrial function, and key signaling pathways. By interfering with cellular processes such as the cell cycle, mitochondrial autophagy, and cell wall maintenance, the combined treatment disrupts structural elements within cells and mitochondria, impacting tricarboxylic acid cycling, mitochondrial membrane potential, and ATP production. Furthermore, there is a reduction in ergosterol content in various cellular membranes, further contributing to the inhibition of fungal growth [7].
Moreover, the combination of sodium bicarbonate and a bacterial antagonist displayed a considerable inhibitory effect on mycelial growth and spore germination of M. fructigina, resulting in a fungal inhibition rate ranging from 60.97% to 100%. In contrast, using sodium bicarbonate or the bacterial antagonist alone led to lower inhibition rates varying from 9.27% to 64.83%[8].
Transcriptomic analysis revealed that the combination therapy influenced 309 up-regulated and 233 down-regulated key fungal genes. Upregulated genes primarily participated in amino acid metabolism, steroid biosynthesis, and cell wall-related functions, while downregulated genes impacted various cellular metabolic processes[9].
Overall, the combined regimen exploits the strengths of both medications, enhancing therapeutic outcomes, shortening treatment duration, and lowering recurrence rates. This approach holds significant promise for enhancing patients' quality of life by offering improved efficacy in managing fungal infections.