Efficacy of topical clotrimazole vs. topical tolnaftate in the treatment of otomycosis. A randomized controlled clinical trial

IntroductionOtomycosis, 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.ObjectivesTo compare the efficacy of clotrimazole and tolnaftate administration in the treatment of otomycosis.Material and methodsA controlled, randomized and open clinical trial included patients diagnosed with fungal external otitis who were treated with topical antifungals, randomized into two treatment groups: (1) clotrimazole cream; (2) tolnaftate solution. They were microscopically evaluated at one and two weeks of treatment to determine resolution of disease. Recurrence and complications were recorded. Demographic and clinical variables were collected and analyzed. Follow-up and final outcomes (absence of infection) were compared between groups.ResultsForty 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.ConclusionsClotrimazole cream treatment is more effective than tolnaftate for uncomplicated otomycosis. More studies are needed to corroborate our results.     

In vitro effectiveness of 13 agents in otomycosis and review of the literature

Many agents have been recommended for treating otomycosis, but no preparation has been widely accepted. To compare the effectiveness of many recommended preparations, we performed an in vitro study using 15 species of fungi and yeast cultured from patients presenting with otomycosis during the past year. By measuring zones of inhibition, we assessed the effectiveness of aqueous Merthiolate, Burow's solution (2%), VoSol HC, VoSol plain, Cortisporin suspension, clotrimazole 1%, Mycostatin, amphotericin B, ethanol 95%, miconazole, tolnaftate 1%, natamycin, and flucytosine. Most otic preparations showed little or no growth inhibition. However, Merthiolate was very effective against all organisms tested, clotrimazole was very effective against most yeast and fungi tested, and nystatin had the widest spectrum of activity among the antifungals. Tolnaftate was ineffective. Vigorous cleaning of the external auditory canal remains the mainstay in treating otymycosis, but proper laboratory identification and suitable topical therapy are also important in dealing with this capricious infection.     

Comparison of the recovery rate of otomycosis using betadine and clotrimazole topical treatment

Introduction

Otomycosis is a common diseases that can be associated with many complications including involvement of the inner ear and mortality in rare cases. Management of otomycosis can be challenging, and requires a close follow-up. Treatment options for otomycosis include local debridement, local and systemic antifungal agents and utilization of topical antiseptics.

Otomycosis in Turkey: predisposing factors,aetiology and therapy

Otomycosis usually requires long-term treatment and tends to recur. This study was performed on 87 patients with the clinical diagnosis of otomycosis and 20 controls in order to determine the pathogenic agents, predisposing factors and a cost-effective treatment. The predisposing factors included wearing head clothes (74.7 per cent), presence of dermatomycoses (34.5 per cent) and swimming (27.6 per cent). The most common pathogenic fungus was Aspergillus niger (44.8 per cent) in the otomycosis group. The only isolate was Candida albicans in the control group (2.5 per cent). We concluded that administration of four per cent boric acid solution in alcohol and frequent suction cleaning of the ear canal might be a cost-effective treatment for otomycosis since 77 per cent of the patients were treated effectively this way. Eighty per cent of the resistant cases had mixed fungal-bacterial infections, and 50 per cent of them had dermatomycoses. These resistant cases were treated by administration of tioconazole ointment.     

Drug therapy in otomycosis: An in vitro study

Otomycosis represents a small percentage of clinical external otitis. This well documented entity is often a stubborn clinical problem and, in contrast to bacterial external otitis, there is no otic preparation with specific antifungal activity. In response to this lack of otic preparations, we have surveyed in vitro a variety of available preparations to determine the general spectrum of activity against appropriate bacterial and fungal species. An agar-disc diffusion system was used testing the drugs against (1.) bacteria common in external otitis, and (2.) a variety of yeast and filamentous fungi. Aqueous Merthiolate and Cresylate demonstrated good non-specific antimicrobial activity, while nystatin and clotrimazole demonstrated specific antifungal activity. Otic preparations can now be used which have demonstrated in vitro effectiveness and give an alternate means of therapy to the now empirically selected otic preparation used for otomycosis.     

Otomycosis in immunocompetent and immunocompromised patients: comparative study and literature review

A comparative clinical study was carried out that included 50 cases of otomycosis in immunocompetent patients and 50 cases of otomycosis in immunocompromised patients. Clinical presentation, predisposing factors, mycologic profile, and treatment outcomes were compared. Aspergillus spp were the most commonly isolated fungi in the immunocompetent group, and Candida albicans in the immunocompromised group. Bilateral involvement was more common in the immunocompromised group. All the patients were treated with topical clotrimazole ear drops. Four patients in the immunocompromised group did not respond to treatment with clotrimazole but were treated successfully with fluconazole ear drops. Three patients had a small tympanic membrane perforation due to otomycosis.     

Otomycosis in the north of Iran: common pathogens and resistance to antifungal agents

Otomycosis as a kind of external otitis can be caused by various species of fungi. To use the appropriate treatment, it is necessary to identify the causal agent of otomycosis. The aim of this study was to determine the pathogens that caused otomycosis and also the efficacy of different antifungal agents. 100 patients with diagnosis of otomycosis/otitis extern were entered in this study. Bacterial culture was performed by eosin methylene blue agar, blood agar; and Sabouraud dextrose agar was used to culture the fungal agents. Minimum inhibitory concentration test also was performed to determine the efficacy of Clotrimazole, Fluconazole, Ketoconazole and Nystatin on the fungal pathogens. Otomycosis was confirmed in 43 % of patients by positive culture. The most prevalent fungal pathogen was Aspergillus niger which was sensitive to Clotrimazole, Fluconazole, Ketoconazole. Candida albicans was sensitive to all drugs, in which, the most sensitivity was due to fluconazole. The most frequent fungal pathogen in our otomycosis cases is A. niger, and most of fungi that caused otomycosis are sensitive to clotrimazole.     

耳部真菌病临床分析(附187例报告)

目的探讨耳部真菌病的临床特征和防治策略。方法回顾性分析187例（257耳）耳部真菌病患者的临床资料及耳内镜表现。耳内镜检查可见外耳道深部有灰白色上皮堆积、霉样痂皮或污秽物附着、黄或黑色颗粒物贴附。耳局部清洁后将达克宁散剂（粉末）均匀喷洒于外耳道。结果全部病例随访半年，1年，1次治愈85例（99耳），复发1至2次共61例（101耳），复发3次及3次以上25例（38耳），失访16例。本组引起复发的86例（139耳）中，合并慢性中耳炎39例（48耳），外耳道狭窄（11耳），未坚持上药19例（23耳），有挖耳习惯的82例次。耳部真菌培养多为黑曲霉菌。治疗后耳内镜检查可见外耳道干燥，皮肤充血消失。结论纠正不良挖耳习惯有助于预防耳部真菌病；耳内镜的使用有助于耳部真菌病的诊断和疗效评估；积极治疗慢性中耳炎、保持患耳干燥及首次治疗坚持足够疗程用药都非常重要。     

Randomized controlled trial on the treatment of otitis externa with one per cent silver nitrate gel

Otitis externa (OE) and especially otomycosis can be very persistent and difficult to control. In the present study the efficacy of treatment of OE with a single instillation in the ear canal of one per cent silver nitrate in three per cent hypromellose gel compared to 0.1 per cent silver nitrate gel was tested in a single-blinded randomized controlled parallel group study. The outcome measure was complete resolution of the OE after one week. Forty-four patients with refractory, bacterial as well as fungal, OE entered the study, comprising 30 ears in each treatment arm. Eight patients defaulted from follow-up, five ears in each treatment arm. A single instillation of one per cent silver nitrate gel cured 23 (92 per cent) of 25 ears with OE, whereas with 0.1 per cent silver nitrate gel seven (28 per cent) of 25 ears treated were cured (Fisher-exact test, p-exact = 0.00010). In a non-controlled series of 120 ears 93.3 per cent needed only a single instillation of one per cent silver nitrate gel while another five per cent were cured after a second instillation a week later. There were no adverse reactions. OE can be treated effectively with instillation of one per cent silver nitrate gel and is particularly useful in recalcitrant otomycosis. The treatment method saves both cost and time.     

耳真菌病的真菌学与治疗方法研究

目的：了解耳真菌病的致病菌种及其药物敏感性,进而探讨有效的治疗方法。方法：①从３２５例本病患者中随机选出的１１０例进行真菌增减及菌种鉴定。②用Ｅｔｅｓｔ技术,以酮康唑（ＫＥ）、伊曲康唑（ＩＴ）、氟康唑（ＦＣ）、氟胞嘧啶（ＦＬ）及二性霉素Ｂ（ＡＰ）５种药物试条进行药敏测试。③将３２５例患者随机分４组,分别用复方达克宁霜、酮康唑霜、克霉唑软膏及麝香草酚酒精作局部治疗;对局部治疗无效的３０例,用ＩＴ作间     

Mycotic infection of the ear (otomycosis): a prospective study

Otomycosis (fungal infection of the ear) is not uncommon clinical problem encountered in our ENT practice. It makes up to 6 per cent of all patients with symptoms of ear disease seen in the Outpatient Clinic. Of the 193 patients with a clinical diagnosis of otomycosis, 171 cases produced positive fungal isolates. In this study Aspergillus species (niger and fumigatus) have been the most common fungal pathogens. Various aetiopathological factors have been examined in detail, and the available literature reviewed. The results of the treatment by nine antifungal agents currently available in Bahrain have been analysed.     

Otomycosis in Khozistan

Otomycosis is a common ear problem in the Khozistan Province of the Southern Iran. A study of 52 patients of otomycosis showed earache and itching are the commenest presenting symptoms of this predominantly unilateral disease. Otoscopy usually shows a greyish while mass in the external auditory canal with canal wall hyperaemia and varying degrees of canal wall oedema. The mass may occasionally be black or brownish-white or yellow in colour. The possible predisposing factors in otomycosis are discussed in this paper. The fungi isolated were Candida (50% of the patients), Aspergillus (19.23%), Pencillium (7.69%) and Mucor (1.92%) Fungi could be seen but not identified in 9.61% of the patients and in 11.53% the slide examination and the culture were negative. Irrespective of the type of fungal infection 1% tolnaftate and 1% clotrimazole solutions were found to be highly effective against otomycosis whereas 2% acetic acid alone or acetic acid in alcohol were almost ineffective.     

Prevalence of otomycosis in outpatient department of otolaryngology in Tribhuvan University Teaching Hospital,Kathmandu, Nepal

Otomycosis is a not-uncommon clinical problem encountered in our otolaryngology practice. We report 100 diagnoses (107 ears) of otomycosis, of which, on microbiological examination, 87 specimens (81.3%) showed positive fungal cultures. Of these, a single isolate was found in 85 cases (79.4%), mixed isolates were found in 2 cases, and 20 cases (18.7%) had no growth. The most common fungal pathogen found was Aspergillus, followed by Candida albicans. The causative factors for otomycosis were examined. The results of treatment with clotrimazole were analyzed.     

Treatment of fungal infections of upper respiratory tract and ear

Fungi, in comparison with other pathogenic factors, have high pathogenicity. The number of fungal species which are able to infect people is over 500. The upper respiratory tract and ear have permanent contact with external environment which makes their ontocenoses open to continuous exchange of microorganisms of which they consist. In etiology of inflammatory processes 21 species which belonging to 3 genera (Zygomycota, Ascomycota, Basidiomycota) of fungi play important role. Administration of antifungal drugs can be: prophylactic, empiric preemptive and therapeutic. Physicians may prescribe antibiotics (mainly pollens: amphotericin B, natamycin and nystatin) and chemiotherapeutics (mainly azoles and fluorpirymidins, pigments, chlorhexidine and chlorquinaldol). In ENT practice topical and systemic drugs can be administrated. Topical lozenges include amphotericin B, clotrimazole, chlorhexidine or chlorquinaldol and oral gels: nystatin and miconazole. Some of drugs are in the form of suspension/solution, which can be used for inhalation, into the sinus, for swabbing or for lavage: amphotericin B, natamycin, nystatin, clotrimazol, flucytosine, miconazole, fluconazole, vorykonazole, caspofungin. It should be underlined that only a few of dugs can be absorbed from the digestive tract: flucytosine, fluconazole, itraconazole, ketoconazole, miconazole, vorykonazole.     

Efficacy and safety of eberconazole 1% otic solution compared to clotrimazole 1% solution in patients with otomycosis

Purpose

To demonstrate non-inferiority of eberconazole 1% otic solution to clotrimazole 1% solution, and to compare their safety profiles in the treatment of otomycosis.

Presumption diagnosis: otomycosis. A 451 patients study

Otomycosis is a common disease. We try to analyze the causative factors for otomycosis in our environment. Our study includes 451 patients with a presumed diagnosis of otomycosis. The patients were included by ear, nose and throat specialist and general doctors; the diagnosis was confirmed in 24.43% and 16.16% respectively. The most common fungal pathogen found was Aspergillus spp. and Candida sp. The high frecuency of Aspergillus Niger may be because of the diferent ways of gathering samples. The abundance of Candida parapsilosis in the samples that came from general doctors may be because the inadequate treatment with topic antibiotics contributes fungal proliferation. We conclude that the causative factors for otomycosis could be avoided or treated. Treatment with antifungal agents is not enought to ensure complete cure, an furthermore the treatment should be aimed to restore the physiology of the external auditory cannal.     

Topical antibiotic, antifungal, and antiseptic solutions decrease ciliary activity in nasal respiratory cells

This study was designed to investigate whether topical solutions, as they are used in the treatment of selected cases of rhinosinusitis, influence nasal mucociliary clearance. The objective of this study was to evaluate the effects of the following topical solutions on the ciliary beat frequency (CBF) of nasal respiratory cells: ofloxacin as an antibiotic; Betadine and hydrogen peroxide (H2O2) as antiseptic; and amphotericin B, itraconazole, and clotrimazole as antifungal solutions. Differences are described between effects of each of these substances and we clarify whether ciliotoxic effects are dose dependent and if they can be reduced or eliminated by diluting the concentration of the applied solution. In a prospective study, nasal respiratory cells were harvested from healthy individuals and CBF was measured while cells were perfused with cell culture medium and the respective topical solution, using a Dvorak/Stotler exposure chamber. Controls were perfused with cell culture medium only. Video interference contrast microscopy was used to monitor CBF. A decrease of CBF occurred after application of all topical solutions used in this study. Except for clotrimazole, all solutions showed significantly stronger effects at high concentrations compared with diluted solutions. Our results indicate that topical application of antifungal, antibiotic, and antiseptic solutions may cause a marked impairment of mucociliary clearance. The strong dose dependence of these ciliotoxic effects indicates the need for a careful selection of the adequate concentration when using topical treatment in the nose.     

Comparison of the efficacy and safety of moxifloxacin and trovafloxacin for the treatment of acute,bacterial maxillary sinusitis in adults

In this multicentre, multinational, comparative, double-blind clinical trial, out-patients with both symptoms and radiographic evidence of acute sinusitis were randomly assigned to receive either a seven-day, once daily (o.d.) oral regimen of moxifloxacin (400 mg) or a 10-day o.d. oral regimen of trovafloxacin (200 mg). Among 452 patients considered valid for clinical efficacy, moxifloxacin treatment was found to be statistically equivalent to trovafloxacin (96.9 per cent vs 92.1 per cent -95 per cent CI = 0.6 per cent; 8.9 per cent) at the seven to 10 days post-therapy assessment. At follow-up, the success rate in the moxifloxacin group was 94.9 per cent and that for the trovafloxacin group was 97.6 per cent (95 per cent CI = -4.9 per cent; 1.3 per cent). The predominant causative organisms were Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus followed by Enterobacteriaceae and Moraxella catarrhalis. The bacteriological success rate at the post-therapy evaluation was similar in both treatment groups: 94.4 per cent and 90.1 per cent in the moxifloxacin and trovafloxacin groups respectively (95 per cent CI = -3.0 per cent; 11.9 per cent). Only three of the 103 baseline isolated pathogens still persisted in the moxifloxacin group, whereas there were 10 of the 121 isolates that failed to respond in the trovafloxacin treatment group. At least one drug-related event was reported by 16.9 per cent of the moxifloxacin-treated patients and by 22.3 per cent of those who received trovafloxacin. CNS events such as dizziness and vertigo were reported more than five times more often in patients receiving trovafloxacin than in the moxifloxacin group. Trovafloxacin recipients were also more than twice as likely to discontinue treatment due to adverse events than moxifloxacin-treated patients. Overall, moxifloxacin was at least as effective clinically and bacteriologically as trovafloxacin and better tolerated.     

Otomycosis: clinical and mycological study of 97 cases

OBJECTIVE: To report otomycosis in a retrospective study and correlate clinical, epidemiological and therapeutic factors. MATERIAL AND METHOD: This study comprises 97 cases of clinically and mycologically proven otomycosis or fungal otitis externa gathered during a 12-year period. RESULTS: Most cases were unilateral (90.7%) and the main predisposing factors associated with the disease were trauma (secondary to the constant scratching) and the use of topical antibiotics. Major causal agents were several species of Aspergillus (63.9%), of which Aspergillus flavus was commonest (26%), followed by Candida albicans (26.8%) and Aspergillus niger (21%). CONCLUSION: The treatment of choice is mainly local toilet of the external auditory canal and the use of systemic antifungal agents to prevent re-infection and the spread of disease.     

Ototoxicity of common topical antimycotic preparations

OBJECTIVE: To determine the ototoxic effects of five commonly used topical antimycotic agents-clotrimazole, miconazole, nystatin, tolnaftate, and gentian violet-in the guinea pig. DESIGN: A controlled animal study in which the ototoxicity of commonly used topical antifungal agents was investigated by measurement of hair cell loss. METHODS: Several readily available topical antimycotic preparations were instilled into the middle ears of female Hartley guinea pigs over a 1-week period. Two weeks after the last instillation, the animals were euthanized. An active control group was treated with neomycin to confirm the adequacy of the treatment in delivering a known ototoxin; an untreated control group defined the normal distribution of hair cells. The temporal bones were removed, and the cochleas were fixed and dissected. The basilar membranes were examined under the scanning electron microscope. A map of hair cell survival was made for each row in segments of each turn. RESULTS: The untreated control animals had no discernible hair cell loss in the two lower turns. In the apical turn and sometimes the third turn, loss of hair cells was a common finding, this is a known effect of aging in this species. The animals treated with neomycin had damage consistently in the basal turn, sometimes extending into the second turn, as well as the expected hair cell loss in the apical turn. Clotrimazole, miconazole, or tolnaftate did not cause any hair cell loss in the first two turns. Hair cell loss in the third and fourth turns was similar to that of the untreated control group. Likewise, nystatin exhibited no evidence of ototoxicity. Of note, however, the preparation used in this study left a persistent residue in the round window niche. Of the first four animals treated with gentian violet, three developed pronounced behavioral signs of vestibular damage, and three demonstrated extensive middle ear inflammation and extensive new bone growth. Hair cell counts were not attempted because the extreme bone growth interfered with successful perfusion and dissection. CONCLUSIONS: Extrapolating from guinea pigs to humans requires caution. However, it is likely that guinea pigs are, if anything, more susceptible to topical ototoxins than are humans. The specific antimycotics clotrimazole, miconazole, and tolnaftate appear to be safe. Gentian violet has the potential for severe damage. The persistent residue left by the nystatin preparation is cause for concern and is a reminder that both the active ingredient and vehicle must be considered in evaluation of safety.