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21DOI: 10.24411/2181-0443/2020-10127
ЭФФЕКТИВНЫЕ МЕТОДЫ ЛЕЧЕНИЯ И ПРОФИЛАКТИКИ ОТОМИКОЗА
Рахимов Солижон Комилжонович Абдумуталипов Улугбек Шухрат угли Хайдаров Илхомжон Икромжонугли Нугманов Озодбек Журабойугли
Андижанский государственный медицинский институт
Отомикоз - заболевание, вызываемое плесневыми и дрожжеподобными грибами. Поражает среднее и внешнее ухо. Иногда после операции грибок рецидивирует. К тому же с одинаковой частотой страдают и взрослые, и дети. Риск заболевания заключается в том, что на ранних стадиях развития оно протекает практически бессимптомно. Инфекция часто обнаруживается только после возникновения серьезных осложнений. В этой статье рассказывается о лечении и профилактике отомикоза.
Ключевые слова: отомикоз, плесень, частота, бессимптомное течение.
OTOMIKOZ KASALLIGINI DAVOLASH VA OLDINI OLISHNING EFFEKTIV
METODLARI
Otomikoz - bu mog'or va xamirturushga o'xshash zamburug'lar keltirib chiqaradigan kasallik. O'rta va tashqi quloqqa ta'sir qiladi. Ba'zida zamburug'larning ko'payishi operatsiyadan keyin sodir bo'ladi. Bundan tashqari, kattalar ham, bolalar ham bir xil chastotada aziyat chekishadi. Kasallikning xavfi uning rivojlanishning dastlabki bosqichlarida deyarli asimptomatik bo'lishidadir. Infektsiya ko'pincha jiddiy asoratlar paydo bo'lgandan keyingina aniqlanadi. Ushbu maqolada otomikoz kasalligini davolash va oldini olish bo'yicha muhokama qilinadi.
Kalit so'zlar: Otomikoz, mog'or, chastota, asimptomatik.
EFFECTIVE METHODS OF TREATMENT OF OTOMYCOSIS DISEASE
Otomycosis is a disease caused by mold and yeast-like fungi. Affects the middle and outer ear. Occasionally there is a recurrence of the fungus after surgery. In addition, both adults and children suffer at the same frequency. The risk of the disease is that it is almost asymptomatic in the early stages of its development. Infection is often detected only after serious complications have occurred. This article discusses the treatment and prevention of otomycosis.
Keywords: Otomycosis, mold, frequency, asymptomatic.
Introduction: Otomycosis, an infection of the ear canal by fungi, is prevalent in hot and humid weather. Nevertheless, there is not sufficient evidence for the effectiveness of different topical
antifungal treatments. Tolnaftate, is a topical antifungal agent described to be effective in the treatment of otomycosis. Currently there are not sufficient studies
that prove its efficacy. Otomycosis is defined as superficial fungal infection of the external auditory canal (EAC). It is a common condition in China. In the outpatient clinic of the
otorhinolaryngology department, 5% to 20% of otitis externa may be seen among all patients and otomycosis has been quoted to be as high as 15% to 20% of all cases of otitis externa. Although seldom
life-threatening, otomycosis presents an annoying and stubborn condition for the patients and otolaryngologists, due to its long-term treatment, follow-up, and high recurrence rate. The mainstay of treating otomycosis is elimination of the fungal hypha and infectious material in the EAC followed by topical application of an antifungal agent. Although many antifungal agents have been reported with varying success rates, there is no consensus regarding the specific agent that may be most efficient. Nystatin is reported to be very efficient for otomycosis and is recommended as the first-line treatment in France. In our hospital, nystatin suspension has also been proposed as the first choice for many years. However, the cure rate is unsatisfactory, treatment period lasts for a long time and side effects frequently occur. A novel antifungal agent that has a strong antifungal potential, shortens treatment time, and minimizes the risk of adverse effects is needed. Otomycosis is a fungal infection in the outer ear. An otomycosis infection causes
inflammation, dry skin, and a smelly discharge in the ear canal. People most likely to be affected by otomycosis include those who live in warm, tropical climates, and those who participate in water sports. Otomycosis is often easily treated with topical antifungal medications. In this article, we look closely at otomycosis, including its causes, symptoms, treatment, and prevention.
Otomycosis is an infection caused by a fungus. There are several different types of fungus that can cause this infection, but most otomycosis infections are related to Aspergillus species or, less commonly, Candida. People come into contact with fungi every day in the environment, but fungi do not typically pose a problem. However, those with weakened immune systems can catch an infection more easily than others when they come into contact with a fungus. Also, people who live in hot or tropical climates are more likely to experience
otomycosis, as fungi thrive in warm, damp places. Other risk factors include: trauma to the ear from hearing aids or cotton swabs, chronic skin conditions, such as eczema, having diabetes mellitus, participating in water sports, including swimming or surfing, swimming in contaminated water, lack of cerumen, or earwax, which suppresses bacterial or fungal growth and stops the ear canal drying out. Typical symptoms of otomycosis include: hearing loss, which can be mistaken for deafness, a feeling of fullness in the ear, redness of the outer ear, itching, a more common symptom of fungal infections than bacterial ones, pain, inflammation or swelling, flaky skin, ringing in the ears, discharge from the ear, which can be white, yellow, gray, black, or green. These symptoms typically occur in one ear, but it is possible that both ears can be affected at the same time. Symptoms of otomycosis should always be evaluated by a doctor in order to get the correct diagnosis and treatment. The doctor will take a thorough medical history to determine if any risk factors are present. They will perform a physical exam with an instrument called an otoscope to look inside the ear canal and eardrum. A doctor will prescribe the correct treatment once a diagnosis of otomycosis is made. Treatment can be eardrops, topical cream, or oral medication. Firstly, a doctor usually needs to clean the ear. They may use a rinse or a suction tool to do this. Cleaning will get rid of debris or a buildup of material and allow the medication to work better. Next, the ear is cleaned and dried, as much as possible, to inhibit further growth of fungus. Note that a person should not attempt to clean their own ears with cotton swabs or other tools, as this could worsen the situation. A doctor may prescribe eardrops that contain an antifungal agent. Research has shown that 1 percent clotrimazole eardrops show high rates of cure and prevention of recurrence. Eardrops may also contain econazole, miconazole, or
amphotericin B, among other chemicals. Antifungals may also be in the form of a topical cream that is applied to the outer ear. Other topical medications might include: aluminum acetate salicylic acid, hydrogen peroxide. These agents can help to treat the fungus or soften the crust that forms to help other medications penetrate better. Oral medications, such as itraconazole or voriconazole, are usually reserved for more severe infections, or infections that are difficult to get rid of with topical agents. Some fungus species are resistant to antifungal eardrops. Oral antifungals can be a problem for people who have liver disease. Over-the-counter pain relievers, such as acetaminophen or ibuprofen, can be used to ease any minor pain. Although uncommon, complications can arise from otomycosis. Otomycosis can become a chronic condition if not adequately treated, or if it does not respond to treatment. This can also happen if a person has continued exposure to contaminated water that contains a fungus. Otomycosis can invade further than the outer ear and perforate the eardrum or travel to places that may include the inner ear or base of the skull. These types of infections typically require oral antifungal treatment and surgical management.
A complication such as this is more likely to occur in those who have a weakened immune system or diabetes mellitus. There are a few factors that can help prevent otomycosis, including: leaving a small amount of earwax in the ears for its natural anti-fungal properties, drying the ears well after swimming and bathing, using earplugs when swimming to keep water out, using a hairdryer on low speed to dry ears, being careful not to burn the skin, avoiding scratching the ears as this may damage the skin and make it easier for a fungus to invade, avoiding putting cotton swabs in the ears. In general, otomycosis is not dangerous, and it is easily treated with antifungal treatments. Otomycosis can become
chronic if someone does not respond to treatment or has a weakened immune system, diabetes mellitus, or a chronic skin condition, such as eczema. Otomycosis can usually be prevented by keeping the ears dry and avoiding contaminated water sources [1].
According to a group of scientists [2], the results of their research were as follows: Forty eight patients were included, 28 in the clotrimazole group and 20 in the tolnaftate group. Spring was the weather most commonly associated with otomycosis, while otic manipulation was the risk factor more common in both groups. Predominant symptoms were itching and otic fullness. Aspergillus niger organism was isolated most frequently. Treatment with clotrimazole resulted in 75% resolution vs 45% resolution with treatment with tolnaftate at one week of treatment (p = 0.007). The Tolnaftate treatment group demonstrated higher recurrence rates and treatment failures, 20% and 15% respectively. Clotrimazole cream treatment is more effective than tolnaftate for uncomplicated otomycosis. More studies are needed to corroborate our results. the results of their other research were as follows: Figure 1 presents the flow diagram of the present study. Of the 48 patients studied, 28 patients were randomly selected to be included in Group 1 (Clotrimazole) and 20 in Group 2 (Tolnaftate) according to the computer randomization program. Table 1 shows the demographic characteristics and risk factors found in each group. Of the total 48 patients, 30 (62.5%) were male and 18 (37.5%) were female, with a male/female ratio of 1.6:1. Ages ranged from 12 to 77 years with an average of 41.70 ± 17.44 years. The most affected age group was 50-59, which represented 20.83% (n = 10) of all patients.
The Clotrimazole group had more male patients than the Tolnaftate group (p = 0.034). Two patients were eliminated. One patient was eliminated due to a complication at first week of
treatment and evidence of a bacterial infection. The other patient did not complete the first follow-up visit. The main occupations of the patients were housewives 18.75% (n = 9) and students 18.75% (n = 9), which was non-significant between the groups of treatment (p = 0.892). In both treatment groups, the majority of patients reported living in the city, representing 91.6% of the cases
(n = 44). Overall, spring was the season with the highest infection rate, with 43.75% (n = 21) of the cases, followed by winter, with 27.08% (n = 13). Treatment with Clotrimazole cream is more effective than treatment with Tolnaftate solution for uncomplicated otomycosis. More studies are needed to corroborate our results [3].
Flow chart of the study
Figure 1.
Evaluated to' inclusion n-57
c Excluded n=0
S DO not meet crtena (n=7)
DO not consent* n=0) c Other reasons (n«0)
Randomized (n«50)
с
r-i
Assigned to intervention group 1 Tx Ciotnmazcxe (n=28) Received assigned intervention (r*=28) Did not receive assigned intervention (rv=0)
Assigned to intervention group 2 Tx Tolnaftate (n=22) Received assigned intervention (n=22) Did not receive assigned intervention (rwO)
Lost ю follow-up (n=0) Interrupt intervention (n=0)
Lost in toBow up (n»3) Eliminated (rv=2) Interrupt «iterventlon (n=1) due to complication
Iя л £
Analyzed <n»28) Excluded from the analysis (n=0)
Analyzed (n-20) included in analysis by intent to treat (ITT) Excluded from the analysis (r>-2)
The treatment options for otomycosis are multiple, and some of its treatments do not have clear scientific support yet, as in the case of Tolnaftate. On the other hand, azoles have been reported by some studies to be very effective in the
treatment of otomycosis. In the present study, it was decided to compare Tolnaftate against Clotrimazole to
determine the efficacy of both medications in a controlled clinical trial. Regarding the epidemiology of this disease, the prevalence of otomycosis is
closely related to the geographical area; our weather has a warm, sub-humid climate and presents optimal climatological conditions for the growth of pathogenic fungi. Most studies on the etiology of otomycosis have been performed in areas of high heat and humidity in addition to dust [4, 9-17]. The prevalence by gender varies with respect to different studies; in our study, males were the most affected (62.5%), with a ratio similar to that reported by
Viswanatha; this difference was statistically significant (p = 0.034). With regard to age groups, patients in their 50s were more affected, which coincides with the results of Viswanatha [18]. The high prevalence of otomycosis in the summer has been reported by several authors; [19, 20, 21] however, in this study, the highest incidence occurred in the spring in both groups, with no statistically significance.
Table 1.
Baseline demographic characteristics and risk factors in Clotrimazole and
Tolnaftate groups
Demographic characteristics Group 1 Clotrimazole (n = 28) Group 2 Tolnaftate [л = 20) value
Gender (male) 21 (75%) 9 (4596) 0.034
Age in years (average; 42.75 40.25 0.665
Diabetic 2 (7.1496) 0 0.222
Use of earphones 7 (25%) 7 (3596) 0.452
Use of hearing aid 1 (3.596) 1(596) 0.807
Eai manipulation T\ith objects 23 (S2.1496) 14(7096) 0.324
Swimming 1 (3.596) 0 0.393
Place of residence "with unpaved streets 16 (57.1496) 14(7096) 0.324
Otomycosis is mainly reported as unilateral in immunocompetent patients, [22] however, Prasad [8] mentioned that 5% of cases are bilateral, which is similar to our findings of 6%. The most frequent signs and symptoms reported in the literature
are pruritus, otalgia, otorrhea, otic fullnes s, hearing loss and tinnitus, [2, 6, 8, 2024] all of which were present in our patients without statistically significant differences between groups.
Generally, otomycosis diagnosis is based on clinical findings, however, in this study it was also confirmed by mycological laboratory findings. In the direct examination, 100% of the samples from Group 1 and 90% of the samples from Group 2 demonstrated fungal structures. Culture findings vary widely. For example, Hueso-Gutiérrez25 reported only 22.6% positive cultures, while other studies have achieved yields close to 79%, and in this study the yield was high, confirming the diagnosis in 96% of cases.
Several studies report that the most frequently isolated fungi (genus) are Aspergillus and Candida, the most common species being A. niger and C. albicans. [2, 8-26] Araiza [27] reported A. flavus as the most common pathogen in Mexico City. In our study, the most frequent genus was Aspergillus, 89.2% in Group 1 and 95% in Group 2. In both groups, the most common species was A. niger, corresponding to that reported by other studies in hot and humid regions. Treating otomycosis is difficult due to high recurrence rates. Failure to respond to the initial treatment has been reported up to 13% by Ho and recurrences vary from 5% to 15% [28, 29].
The treatment recommendations are to control predisposing factors, local debridement and the use of antifungal agents, which was done with our patients from the first day of assessment. During the first week of treatment, subjective characteristics were evaluated, with pruritus being the most frequent symptom in both groups, similar to that reported in the literature. Regarding antifungals,
the imidazole group showed an 80% resolution rate in the initial application with scant probability of recurrence according to the Malik study [12]. On the other hand, Jackman named Clotrimazole as the most popular and effective treatment,[30] and others have reported effectiveness rates of 50-100% [3, 14, 16, 29]. These findings coincide with the results of this study, where 82.14% of the cases treated with Clotrimazole completely resolved after one week of treatment. In our study, only 7.14% of Clotrimazole patients presented recurrence, and the infection was resolved with one more week of treatment without requiring treatment change. Furthermore, the application of Clotrimazole was easier and less expensive for the patient because it was carried out in the doctor's office and the patient had a check-up every week. Regarding Tolnaftate, it has been
recommended for refractory cases; however, our results showed that only 45% of cases resolved after one week of treatment, 20% presented recurrence, 10% required a change in treatment to Clotrimazole, which resolved the infection, and 5% of the cases presented complications. However, recurrences, change in treatment or complications were not statistically significant, probably due to the small sample of this study. Furthermore, there was a significant difference between the two treatment groups in the resolution of otomycosis after the first and second weeks of treatment. The Tolnaftate treatment also required greater patient adherence because it was applied at home every 12 h for 7 days. The cream is probably more efficacious than the drops because it covers all the extension of the EAC skin and stays in contact with this surface for a longer time. Limitations of these studies mainly were the lack of treatment blinding, since both patients and doctors were aware which treatment was assigned. The difficulty in blinding resided on different treatment presentations, since in one group medication cream was applied in the doctor's office and the other topical drops at home. Furthermore, the latter treatment required more compliance from the patient, which was assessed in subsequent patient visits. Since our sample is small, more randomized controlled trials are needed to corroborate our results. On the other hand, the highlights of this research include the comparison of two treatment options for otomycosis scarcely described in previous literature, as well as a careful design of a randomized controlled trial. According to the results of this research, weekly application of Clotrimazole is recommended in patients with uncomplicated otomycosis [29,30]. The diagnosis of otomycosis requires vigilance from clinicians especially for patients without typical fungal appearances. Fungal smear or culture is the gold
standard in the diagnosis of suspected otomycosis. Topical application of TAEC coupled with mechanical debridement under endotoscope is an effective, convenient, and well-tolerated treatment for otomycosis.
Otomycosis is a common infectious otologic disease that affects mainly the external auditory canal (EAC), but in some cases, it can also affect the tympanic membrane or the middle ear. Although usually not life-threatening, persistent aggravating symptoms, such as suppurative discharge, tinnitus, otalgia, and itching, significantly reduce patients' quality of life. Once the mycotic infection causes tympanic membrane perforation, the sound conduction system in the middle ear is impaired, and subsequently, hearing loss occurs [31-33]. Moreover, otologic surgery will probably fail if mycotic infection is not resolved [34]. Despite the fact that there is still no widely accepted standard treatment and a large discrepancy in procedures used exists among clinic otorhinolaryngologic physicians, topical imidazole
administration combined with the removal of fungal debris in the ear is now widely used and has been proven as one of the most effective methods [35-38]. Although it is effective in a majority of patients, it is still considered a challenging problem in 5%-17% of refractory cases [39-41]. According to another group of scientists [42], in 2 years, 991 patients were diagnosed with otomycosis, of which 55 (5.5%) patients failed to gain successful recovery through the standard method and were included. The average age of the patients was 39.31±15.62 years. Twentynine (52.6%) patients were male. The symptom spectrum of patients included "sensation of ear fullness," "hearing loss," "otalgia," "tinnitus," and "itching." The most common symptom was sensation of ear fullness (98.2%), followed by hearing loss (67.3%), otalgia (32.7%), and tinnitus (16.4%). Itching was observed in only two patients (3.6%). In the physical
examination, at the first visit, pus in the EAC was noted in 17 patients (30.9%). Evident mycotic hyphae were observed in 53 patients (96.4%). Cerumen impaction was observed in 15 (27.3%) patients. Some patients presented with only one abovementioned symptom or sign, but other patients experienced a combination of these symptoms. All samples were confirmed to be mold-positive by both culture and fluorescent staining. Four types of molds were involved. No case of single yeast infection was observed. The most common strain was Aspergillus terreus (50.9%), followed by Aspergillus flavus (29.1%), A. niger (10.9%), and Aspergillus fumigatus (9.1%). Seasonality is an important factor in infectious diseases. The information on the dates that patients were prescribed 1% topical voriconazole and microbe was combined. Refractory otomycosis is frequently encountered in the clinic, which is a challenging problem for clinicians. There are at least two disadvantages of the conventional treatment method. First, manual cleaning of the EAC could not always thoroughly remove infection-related objects because of the curvature and narrowness of the EAC. Second, regardless of the formulation (ointment or solution), imidazoles, as firstgeneration azole antifungal drugs, have limitations in clinical application because of suboptimal spectrum of activity and development of resistance [19]. In our hospital, although the standard treatment procedure had been strictly applied, the ratio of refractory cases still accounted for 5.5%, which was lower than the ratio reported in most other reports [9-11]. As we mentioned in the Introduction section, pharmacologically, voriconazole should be the right choice. However, different from fungal keratitis, voriconazole is rarely used in otomycosis for unknown reasons, specifically for topical medications. Systemic use of voriconazole (oral administration) was frequently reported in invasive or refractory cases. Although proven effective, the
administration duration of voriconazole was significantly long (12-52weeks) to become a regular treatment in all patients
[20.21]. As a triazole antifungal drug, systemic use of voriconazole for >3months is not only an economic burden but might also lead to the development of adverse effects such as hepatotoxicity, visual disturbances, and phototoxicity
[20.22]. It was unfortunate that there are still no existing topical voriconazole drops, although it has been proven safe and effective in fungal keratitis. In our study, single application of topical voriconazole was sufficiently effective to resolve refractory otomycosis within 2 weeks. It was a remarkable result not only because topical voriconazole drops were effective but also because of two potential advantages we discovered in the study: (1) In cases in which mold hyphae could not be totally eradicated, it could be resolved by the application of topical voriconazole drops without further clearing. It was rational to hypothesize that it might be unnecessary to remove fungus-related objects before the application of topical voriconazole drops. (2) The treatment period was short (2 weeks). Considering these two advantages, the application of topical voriconazole drops might become an optimal treatment in the future. It should be taken into account that we did not include patients with tympanic membrane perforation because there was still no evidence that 1% topical voriconazole was safe to use in the middle or inner ear. In fact, the challenge of treatment for invasive otomycosis was greater than that in noninvasive ones. We believe that if the safety of using 1% topical voriconazole in the middle and inner ear was demonstrated, it might also be a more favorable method than systemic use of voriconazole. Therefore, 1% topical voriconazole drop administration was a potential ideal treatment for refractory otomycosis. It might also replace the classical methods and become a standard treatment for all
types of otomycosis. Further studies are required to better evaluate this treatment.
According to another group of scientists [43], All patients were cured within 3 weeks of starting treatment. Four of the patients in group A and 22 of the patients in group B complained of the drops stung but any patient did not refuse the treatment. None returned with recurrence within 6 months. Table I shows the number of patients who had been cured in each group at their weekly visit. Table II shows the severity of otitis externa in our patients at presentation. Usually discharge, tinnitus and pain were improved respectively at the begining of treatment in both groups. Sensation of fulness and itching were improved later. We observed decreasing the mycelial mat and swelling first and, debris and erythema later in every other day control of patients. The patients with low scores were treated usually in one week, and the patients with high scores were treated in two or three weeks. We established that pre and posttherapic audiometries were normal in all patients. Successful treatment of otomycosis depends on the physician's diligence in properly cleaning the affected ear canal. We believe that this is best done under magnification (With the operating microscope). Otten, removing the fungal mat results in a bleeding red epithelium that is exquisitely tender. The patient must understand that severc:i visits for vigorous aqd thorough cleaning may be necessary at two or three day intervals, in addition to topical therapy and strict precautions to prevent water from entering the ear [44]. Than et al in Burma showed that topical 5-FC applied once a week to the external ear canal had a 100% cure rate. Nystatin ointment was second best. Than suggest that boric acid powder is a good alternative in parts of the world where other agents are not available or too costly. Erkan et al found that topical application of acetic acid 12 %) + hydrocortisone combinations twice a day
for three weeks were very effective. Marsh and Tom assessed the ototoxicity of acetic acid in guinea pigs evoked brainstem responses (BSR) were obtamed prior to and 1,2,4, and 6 hours after instillation of the compounds into the middle ear. A 47 dB or greater loss was found after using VoSol which contain propylene glycol. We did not establish any hearing loss in our patients after treatment because there was no Propylene glycol in Drop A together with acetic acid. On the other hand all the
tympanic membranes were intact in our patients [45,46].
Conclusion: In summary, in this article, we discussed the treatment of otomycosis. In the article, we also touched on the results of research by several scientists. Hopefully, more in-depth research on the treatment of otomycosis will be conducted and this article will serve as an impetus for this in-depth research.
References:
1. Medically reviewed by Daniel Murrell, M.D. — Written by Shannon Johnson on May 24, 2018. What to know about otomycosis.
2. Jimenez-Garcia, L., Celis-Aguilar, E., Díaz-Pavón, G., Muñoz Estrada, V., Castro-Urquizo, Á., Hernández-Castillo, N., & Amaro-Flores, E. (2019). Efficacy of topical clotrimazole vs. topical tolnaftate in the treatment of otomycosis. A randomized controlled clinical trial. Brazilian Journal of Otorhinolaryngology. doi:10.1016/j.bjorl.2018.12.007.
3. Vega-Nava CT, Borrego-Montoya CR, Vásquez-Del Mercado E, Vega-Sánchez DC, Arenas R. Otitis externa de origen fúngico. Estudio de 36 pacientes en un hospital general. An Orl Mex. 2015;60:175---8.
4. Linstrom C, Lucente F. Diseases of the external ear. In: Bailey J, Johnson T, Newlands D, editors. Head & neck surgeryotolaryngology. Philadelphia, PA: Lippincott Williams & Wilkins; 2014. p. 1987---2002.
5. Rosenfeld RM, Brown L, Cannon CR, Dolor RJ, Ganiats TG, Hannley M, et al. Clinical practice guideline: acute otitis externa. Otolaryngol Head Neck Surg. 2006;134:S4---23.
6. Barati B, Okhovvat S, Goljanian A, Omrani M. Otomycosis in central Iran: a clinical and mycological study. Iran Red Crescent Med J. 2011;13:873---6.
7. Grunstein E, Santos F, Selesnick S. Trastornos de oído externo. In: Lawlani A, editor. Current Diagnóstico y tratamiento en Otorrinolaringología y cirugía de cabeza y cuello. New York, NY: McGraw Hill; 2009. p. 624---40.
8. Prasad SC, Kotigadde S, Shekhar M, Thada ND, Prabhu P, D'Souza T. Primary otomycosis in the Indian subcontinent: predisposing factors, microbiology, and classification. Int J Microbiol. 2014;2014:1---9.
9. Pontes ZB, Silva AD, Lima E, Guerra M, Oliviera N, Carvalho M, et al. Otomycosis: a retrospective study. Braz J Otorhinolaryngol. 2009;75:367---70.
10. Moghadam AY, Asadi MA, Dehghani R, Mahmoudabadi AZ, Rayegan F, Hooshyar H, et al. Evaluating the effect of a mixture of alcohol and acetic acid for otomycosis therapy. Jundishapur J Microbiol. 2010;3:66---70.
11. Stern Jc, Lucente FE. Otomycosis. Ear Nose Throat J. 1988;67:804---10.
12. Malik AA, Malik SN, Aslam MA, Rasheed D. Comparative efficacy of topical clotrimazole and 3% salicylic acid in otomycosis. Rawal Med J. 2012;13:46---9.
13. Ruz S, Breinbauer H, Corssen C. Otitis externa micótica y perforación timpánica: reporte de dos casos. Rev Otorrinolaringol Cir Cabeza Cuello. 2010;70:245---52.
14. Munguía R, Daniel SJ. Ototopical antifungals and otomycosis: a review. Int J Pediatr Otorhinolaryngol. 2008;72:453---9.
15. Fasunla J, Ibekwe T, Onakoya P. Otomycosis in western Nigeria. Mycoses. 2008;51:67---70.
16. Khan F, Muhammad R, Khan MR, Rehman F, Iqbal J, Khan M, et al. Efficacy of topical clotrimazole in treatment of otomycosis. J Ayub Med Coll Abbottabad. 2013;25:78---80.
17. Instituto Nacional de Estadística e Informática INEGI [INEGI website].
18. Wiswanta B, Naseerudddin Kh. Fungal infections of the ear in Immunocompromised host: a review. Mediterr J Hematol Infect Dis. 2011;3:e2011003.
19. Paulose KO, Al-Khalifa S, Shenoy P. Mycotic infection of the ear (otomycosis): a prospective study. J Laryngol Otol. 1989;103:3---5.
20. Ozcan MK, Ozcan M, Karaarslan A, Karaarslan F. Otomycosis in Turkey: predisposing factors, aetiology and therapy. J Laryngol Otol. 2003;117:39---42.
21. Ghiacei S. Survey of otomycosis in north-western area of Iran. Med J Mashhad Uni Med Sci. 2001;43:85---7.
22. Nowrozi H, Arabi FD, Mehraban HG, Tavakoli A, Ghooshchi G. Mycological and clinical study of otomycosis in Tehran, Iran. Bull Environ Pharmacol Life Sci. 2014;3:29---31.
23. Kurnatowski P, Filipiak A. Otomycosis: prevalence, clinical symptoms, therapeutic procedure. Mycoses. 2001;44:472---9.
24. Mgbor N, Gugnani HC. Otomycosis in Nigeria: treatment with mercurochrome. Mycoses. 2001;44:395---7.
25. Hueso-Gutiérrez P, Jiménez-Alvarez S, Gil-Carcedo E, GilCarcedo L, Ramos-Sánchez C, Vallejo-Valdezate L. Presumed diagnosis: otomycosis. A study of 451 patients. Acta Otorrinolaryngol Esp. 2005;56:181---6.
26. Mishra GS, Mehta N, Pal M. Chronic bilateral otomycosis caused by aspergillus niger. Mycoses. 2004;47:82---4.
27. Araiza J, Canseco P, Bonifaz A. Otomycosis: clinical and mycological study of 97 cases. Rev Laryngol Otol Rhinol. 2006;127:251---4.
28. Kaur R, Mittal N, Kakkar M, Aggarwal AK, Mathur MD. Otomycosis: a clinicomycologic study. Ear Nose Throat J. 2000;79:606---9. 29. Jadhav VJ, Pai M, Mishra G. Etiological significance of Candida albicans in otitis externa. Mycopathologica. 2003;156:313---5.
29. Jackman A. Case report topical antibiotic induced otomycosis. Int J Pediatr Otorhinolaryngol. 2005;69:957---60.
30. Li Y, He L. Diagnosis and treatment of otomycosis in southern China. Mycoses. 2019;62(11):1064-1068.
31. Gharaghani M, Seifi Z, Zarei MA. Otomycosis in Iran: a review. Mycopathologia. 2015;179(5-6):415-424.
32. Koltsidopoulos P, Skoulakis C. Otomycosis with tympanic membrane perforation: a review of the literature [published online May 29, 2019]. Ear Nose Throat J. doi:10.1177/0145561319851499.
33. Punia RS, Singhal SK, Kundu R, Das A, Chander J. Fungal suppurative otitis media (histopathology) among patients in North India. Head Neck Pathol. 2019;13(2):149-153.
34. Arndal E, Glad H, Hom0e P. Large discrepancies in otomycosis treatment in private ear, nose, and throat clinics in Denmark. Dan Med J. 2016;63(5):A5231.
35. Romsaithong S, Tomanakan K, Tangsawad W, Thanaviratananich S. Effectiveness of 3 per cent boric acid in 70 per cent alcohol versus 1 per cent clotrimazole solution in otomycosis patients: a randomised, controlled trial. J Laryngol Otol. 2016;130(9):811-815.
36. Mofatteh MR, Naseripour YZ, Yousefi M, Namaei MH. Comparison of the recovery rate of otomycosis using betadine and clotrimazole topical treatment. Braz J Otorhinolaryngol. 2018;84(4):404-409.
37. Philip A, Thomas R, Job A, Sundaresan VR, Anandan S, Albert RR. Effectiveness of 7.5 percent povidone iodine in comparison to 1 percent clotrimazole with lignocaine in the treatment of otomycosis. ISRN Otolaryngol. 2013;2013:239730.
38. Anwar K, Gohar MS. Otomycosis; clinical features, predisposing factors and treatment implications. Pak J Med Sci. 2014;30(3):564-567.
39. Kiakojori K, Bagherpour JN, Khafri S, Mahdavi OS. Assessment of response to treatment in patients with otomycosis. Iran J Otorhinolaryngol. 2018;30(96):41-47.
40. Dundar R, lynen 1. Single dose topical application of clotrimazole for the treatment of otomycosis: is this enough? J Audiol Otol. 2019;23(1):15-19.
41. Zhang, S., Jin, M., Hu, S., Zhang, Y., & Zhou, G. (2020). Administration of 1% topical voriconazole drops was effective and safe in the treatment of refractory otomycosis without tympanic membrane perforation. Annals of Otology, Rhinology & Laryngology, 000348942094678. doi:10.1177/0003489420946783.
42. Treatment of otomycosis with acetic acid and boric acid otomikozun asetik as it ve borik asitle teda vis i. Mustafa erkan, tahsln asian, omit soyuer.
43. Stern JC, Lucente F : Otomycosis. Ear Nose Throat J 67:809-810,1988.
44. Stern JC, Shah MK, Lucente FE: In vitro effectiveness of 13 agents in otomycosis and review of the literature. Laryngoscope 98: 1173-1177, 1988.
45. Than KM, Kyaw SN, Myo M: Otomycosis in Burma, and its treatement. Am J Trop Med Hyg 29:620-623,1980.
