Screening Candida auris through a multiplex stepwise PCR algorithm directly from clinical samples of patients suspected of otomycosis in south of Iran; Detection of five cases.

BACKGROUND: Otomycosis is an infection of the external auditory canal caused by molds and yeasts with descending frequency. Laboratory diagnosis is usually confirmed by microscopy and culture. However, they are not specific enough to reliably differentiate the causative agents, especially for rare pathogens such as Candida auris. The purpose of the current study was to the molecular screening of C. auris species from direct clinical samples of patients with suspected otomycosis in Southern of Iran. MATERIALS AND METHODS: A total of 221 ear aspirates collected from 221 patients with suspected otomycosis over a four-year period. All the ear aspirations were examined with pan-fungal primers, then those with a positive result was included in two separate reaction mixtures simultaneously to identify the most clinically relevant Aspergillus and Candida species. The validity of positive samples for C. auris was assessed by sequencing. RESULTS: Of the 189 pan-fungal positive PCRs, 78 and 39 specimens contained Aspergillus spp. and Candida spp., respectively. Furthermore, 65 specimens showed simultaneous positive bands in both Candida and Aspergillus species-specific multiplex PCR including five samples/patients with positive result for C. auris (5/189; 2.6%). Four out of five cases with C. auris species-specific PCR were reconfirmed by sequencing, while none were positive for C. auris in culture. CONCLUSION: Unfortunately, due to high treatment failure rates of antifungal classes against C. auris species, rapid and accurate identification of patients colonised with C. auris is critical to overcome the challenge of preventing transmission. This PCR assay can be successfully applied for rapid and accurate detection of C. auris directly in patient samples and is able to differentiate C. auris from closely related Candida species.

Identification of Microbial Community in Otomycosis by Metagenomic Next Generation Sequencing (mNGS): Potential Implication of Treatment with Terbinafine.

The present study was designed to identify the microbial community as well as to analyze its diversity by means of metagenomic Next Generation Sequencing (mNGS) in 17 patients with otomycosis treated with terbinafine in the Department of Otolaryngology of Shandong Provincial Hospital from June 2021 to June 2022, so as to evaluate the relationship between microbial community and terbinafine resistance. Those 17 patients were divided into two groups, i.e., Terbinafine Effective Group (TEG, n = 14 cases) and Terbinafine Resistance Group (TRG, n = 3 cases) according to the therapy effect, whose microbial community of secretion of external auditory canal was identified using mNGS. We found that the sequence of bacteria was significantly more than that of fungi and, whereas, the difference between the two groups of bacteria was not significant. There were significant differences in fungal community between the two groups. Aspergillus was the main pathogenic fungus of TEG patients while Malassezia was a dominant fungus in TRG patients. In conclusion, the results from this work indicate that Aspergillus terreusis is the main pathogenic fungus in this cohort of otomycosis patients and MNGS sequencing can offer comprehensive information about the microbial community of otomycosis. The fungus community dominated by Malassezia is more likely to be resistant to terbinafine, which provides certain guidance for clinical treatment of otomycosis with terbinafine.

Ear Infections by Non albicans Candida Species with Isolation of Rare Drug Resistant Species in a Tertiary Care Hospital of Bangladesh.

Otomycosis, a fungal infection of external ear, is challenging for both patients and otolaryngologist as it requires long term treatment and follow up. Candida spp. is second common organism causing otomycosis with Aspergillus being first. Among Candida species, C. albicans is considered as most common but in recent years there is increasing incidence of Non albicans Candida (NAC) species with greater resistance and recurrence. This descriptive type of observational study was planned to determine the species distribution and antifungal susceptibility of Candida spp. causing otomycosis. From March 2021 to February 2022, 60 patients clinically suspected of Candida associated otomycosis at Mymensingh Medical College Hospital, Bangladesh were enrolled. Specimens were taken by an otorhinolaryngologist. After culture and microscopic examination, isolated Candida species were identified by phenotypic and genotypic method and antifungal susceptibility was determined at Department of Microbiology, Mymensingh Medical College. From 60 samples 18(30.0%) were positive for Candida on microscopy and culture. Of the isolates, C. albicans were 2(11.11%) and Non albicans Candida (NAC) 16(88.89%). Five different NAC species were identified of which C. parapsilosis was predominant 5(27.77%) followed by C. tropicalis 4(22.22%) and C. famata 3(16.67%). Rare species of C. ciferrii 2(11.11)%, Kodamaea ohmeri 2(11.11%) were isolated. Candida spp. showed highest resistance to Clotrimazole 8(44.0%) followed by Itraconazole 6(33.0%), Nystatin 4(22.0%) and Fluconazole 3(17.0%). C. ciferrii and Kodamaea ohmeri showed resistance to all antifungals except Nystatin. Outcomes from this study showed a different picture of species distribution, with isolation of rare and emerging drug resistant threatening species like C. ciferri and Kodamea ohmeri which necessitates more detailed survey.

THE MICROBIOLOGICAL STRUCTURE OF OTOMYCOSIS: SENSITIVITY PROFILE OF AGENTS TO ANTIFUNGAL DRUGS.

OBJECTIVE: Aim: To study the species composition of microorganisms isolated from patients with otomycosis, and to control the sensitivity of isolated microorganisms to the most commonly used antifungal drugs. PATIENTS AND METHODS: Materials and methods: The main group of study was 132 patients with a preliminary diagnosis of Otomycosis was carried out in the period 2020-2022.To study the sensitivity of isolated microorganisms to antifungal drugs, the Himedia paper disk method (India) was used. RESULTS: Results: Analysis of studies showed that among 132 patients, fungal infection was found in 101 patients (76%), the cultural method - in 31 patients (23.5%); of them women - 56 (42.4%), men - 60 (45.5%) aged 16 to 76; children - 16 (12.1%) aged 6 to 12 years. However, among all patients (n = 132) with otomycosis, fungal lesions of the outer ear prevail, which were detected in 85 (64.4%) patients, that is, fungal otitis was detected in 47 (35.6%). CONCLUSION: Conclusions: The general structure of the species spectrum of etiologically significant pathogens of otomycosis: Candida spp. (78.0%) of the total spectrum of isolates. The sensitivity of isolated micromycetes to antifungal drugs varied in different fungal species and in different antifungal drugs.

Otomycosis: The foremost aetiological agent causing otitis externa and the antifungal susceptibility pattern in North-Western Iran.

BACKGROUND: Otomycosis is considered a recurring fungal ear infection. The external auditory canal provides an appropriate and optimal situation for fungal growth. OBJECTIVES: The study aimed to identify the causative agents of otomycosis and determine corresponding antifungal drug susceptibility patterns in north-western Iran. METHODS: From October 2020 until November 2021, 200 patients attended an otolaryngology referral centre with otitis externa, and their ear discharge and debris were examined and cultured. The identification of the fungal agents was implemented by polymerase chain reaction-restriction fragment length polymorphism and sequencing. In vitro antifungal susceptibility testing of the isolates was conducted in accordance with the CLSI broth microdilution protocols. RESULTS: The prevalence of otomycosis was measured 50.5% (n = 101/200). The majority of patients were in their forties (n = 35, 34.6%) and female (n = 57, 56.4%), and the most prevalent symptom was otalgia (56.4%). The most underlying factor was remarked manipulation employing a cotton swab (65.3%). Regarding fungus, Aspergillus section Nigri (58.57%) was the foremost isolate, followed by Aspergillus section Flavi (19.23%) and Candida parapsilosis (14.96%). The predominance of Aspergillus isolates had minimal in vitro sensitivity to tioconazole and nystatin. Candida species represented higher geometric mean minimum inhibitory concentrations (MIC) against nystatin. The MIC of three Aspergillus species isolates shown above the epidemiologic cut-off values (ECV) against itraconazole. CONCLUSIONS: Otomycosis incidence surpassed in comparison with the previous study as the most common cause of otitis externa. The MIC distribution of Aspergillus species isolates against triazole antifungals is close to the defined ECVs and likely outrun it over time.

The effects of peracetic acid solution on the treatment of otomycosis in an animal model: a new antifungal drug?

OBJECTIVE: This study aimed to investigate the therapeutic effects of 1 per cent and 0.01 per cent peracetic acid as an antifungal agent in animal otomycosis. METHOD: After creating a superficial scratch in the external auditory canal of guinea pigs, a suspension of Aspergillus niger, Aspergillus fumigatus and candida were inoculated into the ears of the animals. After otomycosis, the effect of 1 per cent or 0.01 per cent peracetic acid on otomycosis was evaluated by otomicroscopy and culture at 10 days post-treatment and compared with 2 per cent acetic acid as the control. RESULTS: A 10-day treatment with 1 per cent peracetic acid and 2 per cent acetic acid (control) showed normal otomicroscopy and negative cultures compared with 0.01 per cent peracetic acid. Drug sedimentation or other side effects in the external auditory canal or tympanic membrane were not observed during treatment with peracetic acid. CONCLUSION: The findings of this study confirm that the treatment of otomycosis with 1 per cent peracetic acid in an animal model is beneficial and may be a novel therapeutic treatment for otomycosis.

In Vitro Combination of Terbinafine with Ketoconazole Against Aspergillus Species with Terbinafine High MIC Values Isolated From Otomycosis.

Otomycosis is a common mycotic infection of the external auditory canal, and Aspergillus species are one of the most frequent causative agents worldwide. The limited antifungal arsenal, the high toxicity and side effects of antifungal agents, and the growing resistance to the currently available antifungals underscore the need for new therapeutic strategies. The present study aimed to evaluate the combined in vitro efficacy of terbinafine and ketoconazole against Aspergillus species with terbinafine high MIC values isolated from patients with otomycosis.84 Aspergillus species with high MIC values to terbinafine (≥ 4 µg/ml), consisting of A. flavus, A. tubingensis, A. niger, and A. terreus, were included in this study. The checkerboard microdilution method evaluated the in vitro interactions using the CLSI reference technique. Synergistic effects were observed for 66.67% (56/84) of all isolates (FICI ranging from 0.19 to 0.5). However, the interactions of terbinafine and ketoconazole exhibited indifference in 33.33% (28/84) of the isolates, and no antagonism was observed for any combination. The interaction of terbinafine and ketoconazole showed synergistic activity against Aspergillus species with high MIC values, suggesting that this is an alternative and promising approach for treating otomycosis.

Fungal necrotizing external otitis: diagnosis, management and outcomes of 15 cases.

Fungal necrotizing external otitis (NEO) is a rare disease. It is an aggressive and potentially fatal infection. The most commonly reported pathogen is Candida. We aim through this study to share our experience in the management of fungal necrotizing external otitis and discuss its diagnosis tools, anti-fungal treatment choice, and outcomes. We included fifteen patients with diagnosis criteria of fungal NEO; clinical features of NEO with positive culture swabs and/or positive serologic test to a fungal pathogen. The mean age was of 70 years with a prevalence of males. The main symptoms were otalgia (n=15) and otorrhea (n=7). Facial palsy was observed in four cases. Fungal pathogens were Candida(n=10) and Aspergillus (n=5). Complications were observed in eight cases: extension to the temporo-mandibular (n=4), abscess in the retropharyngeal space (n=2), abscess in the parapharyngeal space (n=1) and thrombophlebitis of the internal jugular vein (n=1). Six patients were treated with fluconazole, eight with voriconazole, and one patient with itraconazole. After a mean duration of 52 days of antifungal therapy, fourteen patients have been cured with normalization of the ear symptoms, biological, and imaging features. One patient died of septic shock. No recurrence of the disease was observed after a follow-up of 12 months in all cases.

Otomycosis caused by the cryptic and emerging species Aspergillus sydowii: two case reports.

Two cases of otomycosis have been reported in patients undergoing tympanomastoidectomy. The first one had chronic otitis media, hypertrophic concha and nasal septum deviation, tympanic perforation and otorrhea. The second had otalgia, pruritus, chronic otitis media and cholesteatoma. Direct examination showed mycelial septate filaments with a branch at an angle close to 45°, later identified as Aspergillus sydowii by sequencing the BenA and CaM genes. Susceptibility testing showed low MIC of amphotericin B, itraconazole, ketoconazole and ciclopirox olamine. In both cases, ketoconazole was instituted for 10 days. Otomycosis is a challenge as it is primarily recurrent in patients undergoing surgery. The clinical implication, the identification of the emerging pathogen and the determination of MIC were necessary for the knowledge of the epidemiological profile and establishment of the treatment.

Aspergillus are fungi that can cause ear disease. In severe infections, these fungi can be present for long periods inside the ear, and commonly belong to the species Aspergillus section Nigri and Aspergillus flavus. In this work, we present two cases of ear infections by a different species, Aspergillus sydowii. Patients had obstructed nasal cavities, crooked internal separation of the nose and complaints of secretion in the ear. The efficient diagnosis allowed a treatment that resulted in the death of the fungus and the cure of the patient.

Definite therapy of mixed infection alleviates refractory dilemma of adult chronic suppurative otitis media.

The characteristics, risk factors, microbial distributions and effective treatment regimens for Chronic suppurative otitis media (CSOM) patients intractable to empirical therapy were analyzed. Adult CSOM patients of China Medical University Hospital from 2018 to 2020 were included. Subjects of refractory and non-refractory groups were investigated for characteristics of age, sex, nation, comorbidities, otomycosis, and associated complications. Risk factors, microbiology distributions, and treatment regimens were analyzed. Twenty-six refractory patients (55.0 ± 17.7 years) and 66 non-refractory patients (54.1 ± 13.7 years) were studied. A significantly higher rate of otomycosis and CSOM complications was observed in refractory group than in non-refractory one (73.1% vs. 36.4%; p = 0.002; 57.7% vs. 10.6%, p < 0.001, respectively). Multivariate analysis revealed atopic diathesis (p = 0.048), otomycosis (p = 0.003) and CSOM complications (p < 0.001) were risk factors of refractory CSOM. Coagulase-negative staphylococci (CoNS) and methicillin-resistant Staphylococcus aureus (MRSA) were the prevailing pathogens. Patients of refractory group tented to have higher rates of mixed infection (42.9%% vs. 23.7%) and significantly more included fungal pathogen (19.0% vs. 2.6%; p = 0.049) than those of non-refractory cohort. Topical treatment of fungus significantly improved outcome of refractory CSOM. Atopic diathesis, otomycosis, and CSOM-associated complications were risk factors of refractory CSOM. Systemic and local treatment to possible drug-resistant pathogens, likely CoNS and fungus, possible improves recalcitrant CSOM. Correspondingly, early identification of CSOM complications, routine culture and susceptibility testing and treatment of resistant bacteria and fungus are key elements to the successful management of adult CSOM.

Treatment of otomycosis with clotrimazole: results accordingly with the fungus isolated.

BACKGROUND: Otomycosis is usually caused by Candida spp or Aspergillus spp. While Candida is usually multissensitive to available antifungals, Aspergillus is not. Topical antifungals for otomycosis that are available in Portugal are scarce, and systemic treatments have too many interactions and contraindications. OBJECTIVES: Determine otomycosis epidemiology, microbiology and treatment results. METHODS: Observational study that included patients followed in Professor Doutor Fernando Fonseca Hospital, between 2011 and 2020. Otomycosis diagnosis was obtained through ear drainage culture, and every case was treated with 1% clotrimazole ear drops plus ear cleaning once per week. RESULTS: Aspergillus was found in ear drainage culture in 43.9% of patients and Candida in the remaining. There was a significant statistical difference between patients with otomycosis caused by Aspergillus versus Candida in treatment duration from 25.0 days (16.5-43.0) versus 14.0 days (7.0-18.5) (p < .001), respectively. CONCLUSIONS: Otomycosis was more frequently caused by Candida, and this type of otomycosis is treated faster with clotrimazole 10 mg/dL plus ear cleaning, when compared with otomycosis by Aspergillus. SIGNIFICANCE: If otomycosis causative agent is identified or suspected, a prediction of the time needed till the resolution of otomycosis can be made, when clotrimazole ear drops are used.

A Chronic Autochthonous Fifth Clade Case of Candida auris Otomycosis in Iran.

Candida auris, a multidrug-resistant nosocomial pathogen, has emerged globally with high morbidity and mortality among immunocompromised individuals and COVID19 hospitalized patients. Five major clades of C. auris have been previously described. The fifth clade is exclusively found in Iran where C. auris isolates are genetically distinct from other clades by > 200,000 single-nucleotide polymorphisms. The origin of C. auris remains unclear, and limited clinical data are available at present regarding clade V infection or colonization. Herein, another case of otomycosis in Iran caused by an isolate of C. auris belonging to the fifth clade is reported. Genotyping revealed that the obtained C. auris isolate from Isfahan clustered with earlier clade V isolates from Babol, cities around 600 km separated, which indicates that C. auris clade V is established in Iran. C. auris is thought to exist more commonly in Iran, given that limited diagnostic capacity in the country has probably curbed the identification of more C. auris cases. Therefore, surveillance of the environment, patients and healthcare facilities in different geographical regions in Iran is urgently required.

First molecular report of causative agent of otomycosis due to Aspergillus luchuensis.

Otomycosis is a fungal infection of the external auditory canal caused mainly by the genus Aspergillus. Aspergillus luchuensis, an industrially important fungus, is a member of Aspergillus section Nigri. In this report, we present a case of otomycosis due to Aspergillus luchuensis in a 43-year-old female patient. We performed a partial PCR-sequencing of ß-tubulin and calmodulin genes to identify the isolate to the species level. Further, we determined the in vitro susceptibility of the isolate to nystatin, clotrimazole and itraconazole according to the Clinical & Laboratory Standards Institute (CLSI) M38-A2 protocol. Accordingly, the minimum inhibitory concentrations of clotrimazole, nystatin and itraconazole were 0.25µg/mL, 0.5µg/mL and 1µg/mL, respectively. This is the first report of clinically relevant isolation of Aspergillus luchuensis identified by a molecular technique as a causative agent of otomycosis.

The Role of Candida Albicans in Routine Clinically Suspected Otomycosis.

BACKGROUND: Candida albicans and non-albicans Candida species are considered as commensal yeasts of many cavities including the external auditory canal (EAC) in healthy individuals. These fungal microorganisms can also act as opportunist pathogens and cause otomycosis. In this study, the patients of clinically suspected otomycosis were specifically investigated mycologically to elucidate the role of Candida albicans and non-albicans Candida species. MATERIAL AND METHODS: A prospective observational study was conducted from July 2016 and June 2017 at the Laboratory of Parasitology and Mycology of the Sourô SANOU University Hospital in Bobo-Dioulasso, Burkina Faso. Identification of Candida isolates was using conventional phenotypic methods. Antifungal susceptibility tests were carried out by disk diffusion method in accordance with CLSI standard document M44-A for yeasts. RESULTS: Out of 160 patients with clinically diagnosed otomycosis, 77(48.1%) were investigated positive for Candida species. Candida albicans (61%) was the most isolated species and non-albicans Candida species accounted for 39% of the isolates, with mainly Candida spp (22.1%), Candida krusei (10.4%), Candida dubliniensis (5.2%) and Candida glabrata (1.3%). Nystatin showed the highest efficacy (95.9%), followed by ketoconazole (90.4%), clotrimazole (83.6%), miconazole (72.6%) and amphotericin B (63.0%). CONCLUSION: Otomycosis due to Candida species should be especially considered, since they have a wide number of potential virulence factors that cause fungal infections. Also, antifungal susceptibility testing should be performed in order to select the appropriate antifungal therapy.

CONTEXTE: Candida albicans et les espèces de Candida non albicans sont considérées comme des levures commensales de nombreuses cavités, y compris le conduit auditif externe (CAE) chez les individus sains. Ces micro-organismes fongiques peuvent également agir comme des agents pathogènes opportunistes et provoquer une otomycose. Dans cette étude, les patients cliniquement suspectés d'otomycose ont été spécifiquement étudiés mycologiquement pour élucider le rôle des espèces de Candida albicans et non albicans Candida. MATÉRIEL ET METHODS: Une étude observationnelle prospective a été menée de juillet 2016 à juin 2017 au Laboratoire de Parasitologie et Mycologie du CHU Sourô SANOU à BoboDioulasso, Burkina Faso. L'identification des isolats de Candida utilisait des méthodes phénotypiques conventionnelles. Des tests de sensibilité aux antifongiques ont été réalisés par la méthode de diffusion sur disque selon le document standard CLSI M44-A pour les levures. RÉSULTATS: Sur 160 patients atteints d'otomycose cliniquement diagnostiquée, 77 (48,1 %) ont été testés positifs pour les espèces de Candida. Candida albicans (61 %) était l'espèce la plus isolée et les espèces non albicans Candida représentaient 39 % des isolats, avec principalement Candida spp (22,1 %), Candida krusei (10,4 %), Candida dubliniensis (5,2 %) et Candida glabrata (1,3%). La nystatine a montré l'efficacité la plus élevée (95,9 %), suivie du kétoconazole (90,4 %), du clotrimazole (83,6 %), du miconazole (72,6 %) et de l'amphotéricine B (63,0 %). CONCLUSION: L'otomycose due aux espèces de Candida doit être particulièrement considérée, car elles ont un grand nombre de facteurs de virulence potentiels qui provoquent des infections fongiques. En outre, des tests de sensibilité aux antifongiques doivent être effectués afin de sélectionner le traitement antifongique approprié. Mots-clés: Candida albicans; Otomycoses; routine; sensibilité antifongique; Burkina Faso.

Efficacy of Clotrimazole 1% Solution Compared to Econazole Nitrate 1% + Triamcinolone Acetonide 0.1% Cream in Patient with Otomycosis.

Fungal infection of the ear canal is called Otomycosis. It is more common in hot and humid condition. There are many modalities of treatment or therapeutic agent for treatment of otomycosis. Econazole Nitrate 1% + Triamcinolone Acetonide 0.1% cream is a topical antifungal agent described to be effective in the treatment of otomycosis. This study was performed to compare the efficacy of topical application clotrimazole 1% solution and Econazole Nitrate 1% + Triamcinolone Acetonide 0.1% cream in the treatment of otomycosis. A controlled, randomized and open clinical trial was carried out in ENT department of Mymensingh Medical College Hospital, Mymensingh, Bangladesh from January 2020 to July 2020. Patients diagnosed with fungal otitis externa who were treated with topical antifungals were included in this study. They were randomized into two treatment groups: i) Clotrimazole 1% solution, 2) Econazole Nitrate 1% + Triamcinolone Acetonide 0.1% cream. Patients were microscopically evaluated at 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 two groups. One hundred & two (102) patients were included, 51 in the clotrimazole 1% solution group and 51 in the Econazole Nitrate 1% + Triamcinolone Acetonide 0.1% cream group. Predominant symptoms are pain, pruritus, aural fullness and hearing loss. Aspergillus organism was isolated most frequently (63.73%). Treatment with clotrimazole 1% solution groups resulted in 88.23% resolution vs. 80.39% resolution with Econazole Nitrate 1% + Triamcinolone Acetonide 0.1% cream at 2 weeks of treatment. Econazole Nitrate 1% + Triamcinolone Acetonide 0.1% cream group demonstrated higher treatment failure 11.76 and 19.60 respectively. Clotrimazole 1% solution is more effective than Econazole Nitrate 1% + Triamcinolone Acetonide 0.1% cream for uncomplicated otomycosis. More study is needed to corroborate our results.

Topical azole treatments for otomycosis.

BACKGROUND: Otomycosis is a fungal infection of the outer ear, which may be treated with topical antifungal medications. There are many types, with compounds belonging to the azole group ('azoles') being among the most widely used. OBJECTIVES: To evaluate the benefits and harms of topical azole treatments for otomycosis. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The search date was 11 November 2020. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in adults and children with otomycosis comparing any topical azole antifungal with: placebo, no treatment, another type of topical azole or the same type of azole but applied in different forms. A minimum follow-up of two weeks was required. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were: 1) clinical resolution as measured by the proportion of participants with complete resolution at between two and four weeks after treatment (however defined by the authors of the studies) and 2) significant adverse events. Secondary outcomes were 3) mycological resolution and 4) other less serious adverse effects. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We included four studies with 559 participants from Spain, Mexico and India. Three studies included children and adults; one included only adults. The duration of symptoms was not always explicitly stated. Mycological resolution results were only reported in one study. The studies assessed two comparisons: one type of topical azole versus another and the same azole but administered in different forms (cream versus solution). A. Topical azoles versus placebo None of the studies assessed this comparison. B. Topical azoles versus no treatment None of the studies assessed this comparison. C. One type of topical azole versus another type of topical azole i) Clotrimazole versus other types of azoles (eberconazole, fluconazole, miconazole) Three studies examined clotrimazole versus other types of azoles. The evidence is very uncertain about the difference between clotrimazole and other types of azole in achieving complete clinical resolution at four weeks (risk ratio (RR) 0.80, 95% confidence interval (CI) 0.59 to 1.07; 3 studies; 439 participants; very low-certainty evidence). The anticipated absolute effects are 668 per 1000 for clotrimazole versus 835 per 1000 for other azoles. One study planned a safety analysis and reported no significant adverse events in either group. The evidence is therefore very uncertain about any differences between clotrimazole and other types of azole (no events in either group; 1 study; 174 participants; very low-certainty evidence). Clotrimazole may result in little or no difference in mycological resolution at two weeks follow-up (RR 1.01, 95% CI 0.96 to 1.06; 1 study; 174 participants; low-certainty evidence) or in other (less serious) adverse events at two weeks follow-up (36 per 1000, compared to 45 per 1000, RR 0.79, 95% CI 0.18 to 3.41; 1 study; 174 participants; very low-certainty evidence). ii) Bifonazole cream versus bifonazole solution One study compared bifonazole 1% cream with solution. Bifonazole cream may have little or no effect on clinical resolution at two weeks follow-up when compared to solution, but the evidence is very uncertain (RR 1.07, 95% CI 0.73 to 1.57; 1 study; 40 ears; very low-certainty evidence). Bifonazole cream may achieve less mycological resolution compared to solution at two weeks after the end of therapy, but the evidence for this is also very uncertain (RR 0.53, 95% CI 0.29 to 0.96; 1 study; 40 ears; very low-certainty evidence). Five out of 35 patients sustained severe itching and burning from the bifonazole solution but none with the bifonazole cream (very low-certainty evidence). AUTHORS' CONCLUSIONS: We found no studies that evaluated topical azoles compared to placebo or no treatment. The evidence is very uncertain about the effect of clotrimazole on clinical resolution of otomycosis, on significant adverse events or other (non-serious) adverse events when compared with other topical azoles (eberconazole, fluconazole, miconazole). There may be little or no difference between clotrimazole and other azoles in terms of mycological resolution. It may be difficult to generalise these results because the range of ethnic backgrounds of the participants in the studies is limited.

Efficacy of topical isoconazole nitrate in the treatment of otomycosis.

PURPOSE: Various agents with various antifungal properties are widely used for otomycosis eradication. However, there is still no consensus on the most effective agent. Therefore, the present study aims to investigate the efficacy of topical 1% isoconazole nitrate cream in the treatment of otomycosis. METHODS: This prospective study included 43 patients who were applied to our outpatient clinic with complaints of ear pain, itching, aural fullness, and hypoacusis, and were diagnosed with unilateral otomycosis. After aspiration and cleaning, the external ear canal was filled with 1% isoconazole nitrate cream using an iv cannula and insulin syringe. Control examinations were performed on the 5th, 10th, 15th, and 20th days. In the follow-up examinations, patients were asked about how many days after the cream administration the pain and itching completely relief and the answers were recorded. RESULTS: In the first control examination of 23 (92%) of 25 patients with pain, it was observed that the pain and otoendoscopic examination findings completely recovered. In the second control, it was found that both pain and otoendoscopic examination findings completely recovered in the remaining 2 patients (25 patients, 100%). 35 patients complained of itching and it was observed that itching and otoendoscopic examination findings completely recovered in 26 patients (75%) in the first control, 5 more patients (31 patients, 88.6%) in the second control, and 2 more patients (33 patients, 94.3%) in the third control examination. CONCLUSION: Isoconazole nitrate cream appears to be an effective and easily applicable agent for the treatment of otomycosis.

Otomycosis in Africa: Epidemiology, diagnosis and treatment.

This review sets out to highlighted knowledge gaps regarding the epidemiological, diagnostic (clinical and laboratory) and therapeutic aspects of otomycosis in Africa. A computerized literature search for otomycosis related articles were performed using MEDLINE. The search encompassed articles published in early January 1980 to May 2019 yielded 220 articles. Electronic search on PubMed was performed with the specific keywords. This review shows the higher prevalence rates of otomycosis in Africa. These prevalences varies from one country to the other and also from one population to another within the same country. The main symptoms are otalgia, otorrhea, hearing loss, aural fullness, pruritus, and tinnitus. Otomycosis is due to several predisposing factors, however, use of topical antibiotic/steroid eardrops, trauma to the external ear canal or instrumentation of the ear, being exposed to hot humid atmospheres, and close contact with water are the common risk factors. Aspergillus species are the most commonly identified organisms compared with Candida species. Worldwide, A. niger and C. albicans are the most commonly described agents of otomycosis in Africa. The Laboratory diagnosis of otomycosis is usually confirmed by mycologic tests relied on a set of evidences. Further conventional methods such as Chromagar Candida System, latex agglutination test, Biochemical tests (Api 20C AuxTM and auxanogram), phenotypical tests (Germ-tube and chlamydosporulation), and rRNA gene sequencing (PCR) are performed to improve diagnosis and the management of the disease. Adequate treatment of otomycosis includes microscopic suction clearance of fungal mass, discontinuation of topical antibiotics and treatment with antifungal eardrops for three weeks.

Various topical antifungal agents in otomycosis, which is the best?

OBJECTIVE: To assess the effectiveness of some topical non-specific antifungal agents compared to topical specific antifungal drugs in otomycosis therapy. METHODS: The single-blind comparative prospective study was conducted from January 1, 2018, to January 1, 2019, at the outpatient department of Al Yarmouk Teaching Hospital, Baghdad, Iraq, and comprised patients presenting with signs and symptoms of otomycosis. The clinical diagnosis was made using otomicroscopy and was confirmed by ear swab results. They were classified into 3 equal groups, with group A receiving 1% clotrimazole ear drops, group B 3% salicylic acid drops, and group C 10% povidone iodine drops. Treatment in all the groups lasted three weeks. Data was analysed using SPSS 20. RESULTS: Of the 120 patients, 40(33.3%) were in each of the three groups. Overall, there were 62(51.6%) males and 58(48.4%) females with a mean age of 30.79±7.82 years. The left ear was affected in 70(58.33%) patients, and the right ear in 50(41.66%). The most commonly detected symptom was itching in 102(85%) patients. The type of fungus detected was aspergillus niger in 67(55.84%) patients and candida albicans in 53(44.16%). The overall response to treatment was in 90(74.99%) patients; group A 39(97.5%), group B 29(72.5%), and group C 21(52.5%) (p=0.0001). CONCLUSIONS: Local antifungal agents clotrimazole, 3% salicylic acid and 10% povidone iodine were effective in the treatment of otomycosis with varying degrees of success, with clotrimazole being the most effective.

Administration of 1% topical voriconazole drops was effective and safe in the treatment of refractory otomycosis without tympanic membrane perforation.

BACKGROUND: Refractory otomycosis is a common condition that is difficult to treat. OBJECTIVES: This study aimed to evaluate the effectiveness of 1% topical voriconazole drops in the treatment of otomycosis. METHODS: This retrospective analysis was conducted from November 2017 to November 2019. Patients who had refractory otomycosis without tympanic membrane perforation confirmed by microbial culture and fluorescent staining were included in the study. All patients were treated with 1% topical voriconazole drops hourly at daytime for 2 weeks. Evaluation of effectiveness was conducted 1 month after the completion of topical voriconazole treatment. Before and after topical voriconazole treatment, hearing tests were performed in all patients. RESULTS: Fifty-five patients were included in this study. The reasons for refractoriness were resistant recurrence to imidazole drugs (50 cases, 90.9%) and difficulty in cleaning the external auditory canal (5 cases, 9.1%). The most common strain was Aspergillus terreus (50.9%), followed by Aspergillus flavus (29.1%), Aspergillus niger (10.9%), and Aspergillus fumigatus (9.1%). After 2 weeks of treatment with 1% topical voriconazole drops, otomycosis in all patients was resolved. There was no significant change in bone conduction before and after topical voriconazole treatment (paired t-test, P = 0.5023; linear correlation analysis, R2 = 0.98; equation, y = 1.003x-0.284). Adverse effects, such as blurred vision and phototoxicity, were not observed in any patient. CONCLUSIONS: Administration of 1% topical voriconazole drops was effective and safe in the treatment of refractory otomycosis without tympanic membrane perforation within 2 weeks.