International Journal of Pediatric Otorhinolaryngology (2008) 72, 453—459
Ototopical antifungals and otomycosis: A review
Raymundo Munguia a, Sam J. Daniel a,b,*
McGill Auditory Sciences Laboratory, McGill University, Montreal, Qc., Canada H3H1P3 McGill University, Department of Otolaryngology, Montreal, Qc., Canada H3H1P3
Received 13 September 2007; received in revised form 12 December 2007; accepted 14 December 2007 Available online 14 February 2008
Otomycosis; Ototopical; Antifungals; Ototoxicity
Summary There has been an increase in the prevalence of otomycosis in recent years. This has been linked to the extensive use of antibiotic eardrops. Treatment of otomycosis is challenging, and requires a close follow-up. We present a review of the literature on otomycosis, the topical antifungals most commonly used, and discuss their ototoxic potential. Candida albicans and Aspergillus are the most commonly identiﬁed organisms. Antifungals from the Azole class seem to be the most effective, followed by Nystatin and Tolnaftate. # 2007 Elsevier Ireland Ltd. All rights reserved.
Contents 1. 2. Background . . . . . . . . . . . . . . . . . . . Methods . . . . . . . . . . . . . . . . . . . . . 2.1. Symptoms and predisposing factors 2.2. Causal agents . . . . . . . . . . . . . . 2.3. Topical treatments . . . . . . . . . . . Conclusions . . . . . . . . . . . . . . . . . . . Acknowledgements. . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 453 454 454 454 454 458 458 458
Otomycosis, also known as fungal otitis externa, has been used to describe a fungal infection of the external auditory canal and its associated complica* Corresponding author at: McGill University, Department of Otolaryngology, 2300 Rue Tupper B-240, Montreal, Qc., Canada H3H1P3. Tel.: +1 514 412 4304; fax: +1 514 412 4342. E-mail address: email@example.com (S.J. Daniel).
tions, sometimes involving the middle ear. The prevalence of otomycosis has been reported to be as low as 9% of cases of otitis externa , and as high as 30.4% in patients presenting with symptoms of otitis or inﬂammatory conditions of the ear . Prevalence is also related to the geographical area, as otomycosis is most commonly present in tropical and subtropical humid climates. The extensive and sometimes unnecessary use of antibiotic eardrops for the treatment of otitis media
0165-5876/$ — see front matter # 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijporl.2007.12.005
hearing aids with occlusive molds. Daniel tion. conﬁguration of the ear canal. We present in this article a summary of the data in the literature with regards to the topical treatment of otomycosis. Many agents with various antimycotic properties have been used. Causal agents
Many species of fungi have been identiﬁed as the cause of otomycosis in the literature reviewed. and echinocandins. leading to its death. the echinocandins are a novel class of antifungal agents. presence of cerumen acting as a support for fungal growth. the reviewed literature emphasized the importance of aural hygiene in the treatment of otomycosis.4]. Many authors believe that it is important to identify the causal agent of otomycosis in order to use the appropriate treatment. Azoles are synthetic agents that reduce the concentration of ergosterol. clotrimazole and miconazole. otorrhea. a key step in cell energy production. others believe that the most important therapeutic strategy is to select a speciﬁc treatment for otomycosis based on the efﬁcacy and characteristics of the drug regardless of the causal agent [11.3. Other factors that predispose patients to otomycosis include: pregnancy. use of systemic steroids.454 and otitis externa has been linked to the important increase in the prevalence of otomycosis. presence of open mastoid cavities. Finally. To date. pruritus. the use of few topical antifungals has persisted throughout time. Topical treatments
To date there is no FDA approved antifungal otic preparation for the treatment of otomycosis. However. and the risk of ototoxicity. The polyenes family includes amphotericin B and nystatin. Aspergillus is considered the predominant causal organism in tropical and subtropical regions . S.12]. weak immune func-
. and clinicians have struggled to identify the most effective agent to treat this condition.10].5]. the topical medication used. Secondary overgrowth of fungi is a well-known and recognized complication of the use of broad-spectrum antibiotics like quinolones . diabetes. Their mechanism of action involves interference with cell wall biosynthesis. Electronic search with ‘‘topical antimycotic OR otomycosis OR antifungal drops OR antifungal eardrops’’ identiﬁed 96 studies. It is also recommended that the antimycotic treatment chosen should be based on the susceptibility of the identiﬁed species [9. triazoles. and tinnitus [1. Munguia. better known as azoles includes: ﬂuconazole. The triazoles family. and bacterial infections. Very often. However.
R. and prolonged use of broad-spectrum antibiotics such as ﬂuoroquinolones. The mechanism of action of the polyenes and azole families involves an essential chemical component called ergosterol found in the fungal cell membrane. These are listed in Table 1 along with the antifungal agent utilized for each study. Reviewing individual cited references identiﬁed additional studies. there are four main classes of drugs for the treatment of fungal infections: polyenes. Some identiﬁed culprits include humid climate. This causes ions (predominantly K+ and H+) and other molecules to leak out of the cell.
2. as intuitively ototopical medications work best following cleaning of secretions and debris [1.
2. hearing loss. metabolism. of which 18 were considered appropriate for review.
2. Selected articles had to specify the number of patients presenting with otomycosis.2. until non-desirable side effects are identiﬁed or until a new medication appears on the market. including Nystatin and the azoles family. fungal external ear infections manifest only in the presence of predisposing factors. Aspergillus niger is the most commonly described agent in the literature [7. Table 2 summarizes the studies using topical antifungal agents. and the efﬁcacy of treatment. The resulting set of 576 articles was then restricted to those using topical antifungals. the dosage utilized. the treatment efﬁcacy.8]. trauma. increased use of ototopical antibiotics. and the efﬁcacy of the treatment. Antifungal agents typically reach some popularity for a short period of time.1. an essential sterol in the
2. and signaling.2.13]. The nucleoside analogues such as ﬂucytosine work by interfering with nucleotide synthesis. nucleoside analogues.J. The drug binds to ergosterol and creates a polar pore in the fungal membranes. In addition to topical therapy. Several recent articles have also established the potential risk of autoinoculation of the ear canal by patients suffering of dermatomycoses [1. Methods
We performed a MEDLINE search for otomycosisrelated articles published between January 1951 and March 2007. Symptoms and predisposing factors
The most prominent symptoms present at the time of diagnosis were: otalgia. aural fullness. Aspergillus niger and Candida albicans are the most common causative agents of otomycosis. Their use in otomycosis has not been reported.
 Ologe and Nwabuisi  Jackman et al.10] with the exception of one study reporting a lower efﬁcacy rate of 50% . 
Itraconazole Fluconazole Tolnaftate Acetic acid Candida parapsilosis Scedosporium apiospermum Scopulariopsis brevicaulis Clotrimazole. with a reported rate of effectiveness that varies from 95% to 100% in most studies [6.  Dyckhoff et al.  Bhally et al.  Ette et al. It appears to be one of the most effective agents
for the management of otomycosis.  Nong et al.  Tisner et al.16].  Kurnatowski and Filipiak  Ette et al. sulfur or oxygen .  Jackman et al.  Martin et al. Clotrimazole has an antibacterial effect.  Ozcan et al. terbinaﬁde Miconazole Amphotericin B Acetic acid Clotrimazole Tolnaftate Aspergillus niger Borneol Tolnaftate Ciclopiroxolamine.  Martin et al.  Kintzel et al.  Egami et al.  Nong et al.Ototopical antifungals and otomycosis
Table 1 Otomycosis: description of the most common causal agents and treatment Causal agent Aspergillus (species not speciﬁed) Treatment Clotrimazole Ketoconazole Itraconazole Clotrimazole Aspergillus ﬂavus Aspergillus fumigatus Itraconazole.  Kurnatowski et al.  Karaarslan et al.  Schrader (2003) Karaarslan et al.  Besbes et al.  Than et al.  Nong et al.  Martin et al.  Hoshino and Matsumoto  Mgbor and Gugnani  Mishra et al. terbinaﬁde Fluconazole Amphotericin B Thimerosal Aspergillus terreus Candida albicans Lanoconazole Ketoconazole Thimerosal Amphotericin B Clotrimazole Author Ologe and Nwabuisi  Bassiouny et al. nitrogen. Clotrimazole is the most widely used topical azole [15.  Tisner et al.  Ho et al.  Pradhan et al. 
Chang and Li  Damato  del Palacio et al.  Jackman et al. They are a class of ﬁve-membered nitrogen heterocyclic ring compounds containing at least one other noncarbon atom.  Cohen and Thompson  Ho et al.  Kurnatowski and Filipiak  Martin et al. boric acid Itraconazole Mercurochrome Boric acid Clotrimazole 5-Fluorocytosine Itraconazole.  O’Day (2004) Jhadav (2003) Schrader (2003) Bassiouny et al.  Martin et al. and this is an added advantage when treating mixed bacterial—
.  Jackman et al. tolnaftate Fluconazole Clotrimazole Nystatin
normal cytoplasmic membrane.
 Ho et al.1 mg/ml
Table 2 Otomycosis: topical treatment efﬁcacy represented in percentage Author Jadhav et al. 
Ozcan et al. 
Case report Case report Review In vitro
0.25 mg/ml 1% solution 0.  Nong et al.8 93.2% solution/three times per day Â 21 days 1% solution every other day Â 7—10 days 1% solution every other day Â 7—10 days 1% solution every other day Â 7—10 days 11% cream Â 1 week 1% solution Â 1 week 1 week 4% solution in alcohol Not reported Not reported Number of patients 79 23 110 Efﬁcacy (%) 100 100 97. 
Prospective Prospective Retrospective
Bhally et al.5% solution Â 1—3 weeks 0.1—4 mg/ml Not reported 0.5 77 100 40 50 50 0 100 100 — 100 100 90 57 100
Ologe and Nwabuisi  Kley  Tisner et al.6 97. Daniel
Egami et al. 
Prospective Prospective Prospective Prospective Retrospective
141 39 152 189 51 48 18 96 23 23 24 20 20 40 87 9 15 8 2 1 1 1 — — — — — —
Kurnatowski et al.  Mishra et al.6 95.4 66.  Mgbor and Gugnani 
Prospective Randomized prospective
del Palacio et al.4 90 86 95 86 89.  Dyckhoff et al.  Than et al.25 mg/ml once a day Â 8—12 days Not reported 10% ointment Â 7—10 days Three times per day Â 1—3 weeks 1—3 cc one application Â 1 week 0.8 75 80 95 72. Munguia. once a day Â 4—15 days Once a day Â 2 weeks Once a day Â 2 weeks Once a day Â 2 weeks Three times per day for 2 weeks 1% cream once a day Â 2 weeks 0.25% solution 01—4 mg/ml 1% solution 0.  Bassiouny et al.  Study design Prospective Prospective Randomized prospective Antifungal Clotrimazole Bifonazole Miconazole Ketoconazole Clotrimazole Thymol alcohol Clotrimazole Clotrimazole Thimerosal 5-Fluorocytosine Cresylate otic Ketoconazole otic Aluminium acetate otic Fluconazole Locacorten-vioform Mercurochrome Clotrimazole Cyclopirox olamine Cyclopirox olamine Boric acid Boric acid Ketoconazole Acetic acid otic Clotrimazole Nystatin Aluminium acetate otic Clotrimazole Mercurochrome Miconazole Clotrimazole otic Econazole Miconazole Cyclopirox olamine otic Lanoconazole Posology 1% solution 4 drops tid Â 1 month 1% solution.  Piantoni et al.5 90 80 96 94. 
.J.  Cohen and Thompson  Jackman et al.
Clotrimazole is available as a powder. Fluconazole suspension is available with either 350 mg or 1400 mg of ﬂuconazole.  Kurnatowski et al.  Nong et al.19.  del Palacio et al. After reconstitution with 24 ml of distilled water or puriﬁed water (USP). Ketoconazole and ﬂuconazole are azole antifungal agents that have a broad spectrum of activity.  Jadhav et al.  Dyckhoff et al.  Ozcan et al.  Jackman et al.  del Palacio et al.  Nong et al.  Egami et al. It is considered free of ototoxic effects [17.  Ho et al.  Jackman et al. 
Cresylate otic Cyclopirox olamine 1% otic Cyclopirox olamine 11% otic Econazole Fluconazole Itraconazole Ketoconazole
Ototoxic Not tested Not tested Not tested Non ototoxic Not tested Non ototoxic
Lanoconazole Locacorten-vioform Mercurochrome 1% Miconazole Nystatin Gentian Violet Thimerosal
Not tested Ototoxic Non ototoxic (FDA banned) Non ototoxic Not tested Ototoxic Not tested
The bolded text refers to drugs that have been classiﬁed in the literature as non-ototoxic (safe).Ototopical antifungals and otomycosis fungal infections. There are no reports of clinical evidence of clotrimazole ototoxicity.  Ho et al. Ketoconazole has shown an efﬁcacy of 95—100% in vitro against Aspergillus species and Candida albicans.  Tom  Mgbor and Gugnani  Ologe and Nwabuisi  Bassiouny et al.  Bassiouny et al.  Jackman et al.  Tom  Spandow  Tisner et al. and a solution. This family of chemical components is effective in treating the most common etiological agents of
Table 3 Otomycosis treatment and risk of ototoxicity Antifungal 5-ﬂuorocytosine Acetic acid otic Aluminium acetate otic Amphotericin B Bifonazole Boric Acid Clotrimazole Tested for ototoxicity Not tested Ototoxic Non ototoxic Not tested Not tested Ototoxic Non ototoxic Author Than et al. 
457 otomycosis.  Bassiouny et al.  Cohen and Thompson  Nong et al.  Ho et al.18]. [1. The italic text refers to drug that have been classiﬁed as ototoxic (non-safe).  Mgbor and Gugnani  Mgbor and Gugnani  Mishra et al.  Piantoni et al.20].  del Palacio et al.  Nong et al. a lotion. Topical ﬂuconazole has been reported effective in 90% of cases in several series.  Jackman et al. each
Bhally et al. it is available as a 2% cream.  Bassiouny et al.  Jinn et al.
Other available topical medications for the treatment of otomycosis reported in the literature
R. Tisner in 1995 reported an efﬁcacy of 93. Ho. Less data exists regarding the safety of the use of ototopical medications in the presence of a tympanic membrane perforation. and ringwormit. N. a well-known topical antiseptic. A major advantage of nystatin is the fact that it is not absorbed across intact skin. Cyclopirox acts by chelating polyvalent cations (Fe3+ or Al3+) resulting in inhibition of the metal-dependent enzymes that are responsible for the degradation of peroxides within the fungal cell.J.J.g. Conclusions
Many species of fungi have been identiﬁed as a cause of otomycosis with Aspergillus niger and Candida albicans being the most common culprits.
 T.38]. April. R. Reported efﬁcacy rates vary from 50% to 80% [3. ﬂuconazole. however. despite its side effects. 1%) solution in water. J. Nystatin is not available as an otic preparation.27]. Table 3 lists the ototoxicity potential for some of the antifungals. including tinea pedis (athlete’s foot). Coker. including Candida species. Nong in 1999 reported that Aspergillus and Candida albicans were sensitive to the use amphotericin B as demonstrated in antifungal susceptibility tests [19. Daniel include cyclopirox olamine. It has been recommended in refractory cases of otomycosis. Nystatin can be administered as a cream. there have been attempts to use Mercurochrome. Otomycosis in Nigeria: treatment with mercurochrome. Gentian Violet is typically prepared as a weak (e. and was shown to be non-ototoxic [28. Bifonazole is an antifungal agent that was commonly used in the 1980s. Otolaryngol Head Neck Surg 135 (2006) 787—791.  P. Many molds and yeasts are sensitive to nystatin. Boric acid can be used to treat yeast and fungal infections such as vaginal yeast infections caused by Candida albicans. Boric acid is a mild acid often used as an antiseptic. tinea cruris (jock itch). mercurochrome is no longer approved by the FDA due to the fact that it contains mercury.5. boric acid. Overall antifungals from the azoles class such as clotrimazole. antibacterial. or a powder. Studies report an efﬁcacy rate of up to 80%. Tolnaftate is available as a 1% solution that can be easily instilled into the ear .4].T. M. J. Bifonazole and derivatives inhibited the growth of most fungi with an efﬁcacy of up to 100% [22. It is also used to prevent athlete’s foot. however it can be prepared as a solution or a suspension for the treatment of otomycosis. Topical antibiotic induced otomycosis.4% with the use of thimerosal (merthiolate) for the treatment of otomycosis . and is FDA approved.29].26. and antifungal activity. clinical symptoms. and 5-ﬂuorocytocine . followed by nystatin and tolnaftate. for life-threatening fungal infections.8% and 100% [32.
The authors wish to thank Ms Franc ¸oise BrosseauLapre ´ for her assistance. A. S. Mycoses 44 (2001) 472— 479. [20. It is still in use in some countries. Munguia.  A. Miconazole cream 2% has also demonstrated an efﬁcacy rate of 90% [10. Otomycosis: prevalence.458 ml of reconstituted suspension contains 10 mg or 40 mg of ﬂuconazole [2. Jackman. Vrabec.13]. it varies from species to species. and insecticide. D. Amphotericin B is a member of the polyenes family. H. Mycoses 44 (2001) 395—397. to treat otomycosis.25]. anti-inﬂammatory. which competes with uracil interfering with fungal RNA and protein synthesis [37. ketoconazole and miconazole are more effective. Mgbor.  N. Filipiak.23]. an ointment. Mercurochrome has been used speciﬁcally for cases reported in humid environments with a reported efﬁcacy rate between 95. Ward. Bent. therapeutic procedure. It has been used since the 1940s to treat otomycosis as it is an aniline dye with antiseptic. Otomycosis: clinical features and treatment implications. Nystatin is a polyene macrolide antibiotic that inhibits sterol synthesis in the cytoplasmic membrane .
3. Yoo.21]. and for editing the manuscript. Tolnaftate acts by distorting hyphae and inhibiting the mycelial growth of susceptible fungi that cause skin infections. Along with merthiolate (thimerosal). 5-Fluorocytocine (also known as ﬂucytosine) acts penetrating fungal cells and is converted to ﬂuorouracil. In recent years. The antifungal potency of bifonazole 1% solution has been reported to be similar to that of clotrimazole and miconazole. Gugnani.C. Our review of the literature did not reveal any case reports of antifungals ototopical medication causing ototoxicity when used to treat otomycosis with an intact tympanic membrane.33—35]. It has been replaced by safer agents in most cases but is still used. Kurnatowski. Int J Pediatr Otorhinolaryngol 69 (2005) 857—860.
West Afr J Med 21 (2002) 34—36.L.J.  A.W. M. P. Lin Chuang Er Bi Yan Hou Ke Za Zhi 13 (1999) 438—440. Etiological signiﬁcance of Candida albicans in otitis externa.Ototopical antifungals and otomycosis
 K.A. Nong. Ayadi. Nong. D.  T.W. et al.K. Amatya. Mehta. A case of adult type sialidosis with partial betagalactosidase deﬁciency without myoclonus. M. Sellami. Adiego.A. Hindawy. Ozcan.  S. Sharma. S.com
. K. Rivas. Int J Pediatr Otorhinolaryngol 68 (2004) 975—978. Saunders.S.  K. Makni. Ologe.D.E. Spandow. A. Naing. G. Laryngoscope 111 (2001) 2105—2108. M. I. Prevalence of otomycosis in outpatient department of otolaryngology in Tribhuvan University Teaching Hospital. Huang. J Laryngol Otol 117 (2003) 39—42. Garau.sciencedirect. P. Ueda. J. P. Arthur.  S. F. R. J. Li.O. P. Kathmandu. S.. Nwabuisi. Rev Laryngol Otol Rhinol (Bord) 127 (2006) 251—254.E. Bassiouny. O’Brien. Tom. C. Karaarslan. F. M.J.R. Ette.R. Boguifo. Adjoua. P. Min. P. Mycopathologia 156 (2003) 313—315. G.M.  T.  R. Nihon Ishinkin Gakkai Zasshi 44 (2003) 277—283. M. Mycotic infection of the ear (otomycosis): a prospective study. Rev Laryngol Otol Rhinol (Bord) 110 (1989) 173—177. Ayers.  F.  G. nose and throat. Drug therapy in otomycosis: an in vitro study. aetiology and therapy. M. J Laryngol Otol 103 (1989) 30—35. W. Karaarslan. Bianchi.  E. Dyckhoff. C. Eur Arch Otorhinolaryngol 263 (2006) 875— 878. J.H. Mishra. Palasanthiran. Nepal.J.  J. Ototoxicity of common topical antimycotic preparations.K. Araiza. Cohen. Paulose. John.M. del Palacio. E. Perfect. S.S. Mycosis in the ear. In vitro activity of terbinaﬁne and itraconazole against Aspergillus species isolated from otomycosis. Ozcan.25% in sterile water. Martin.  S. Jung.Y.  P. A.E. Jinn. Ann Pharmacother 28 (1994) 333—335.M.  O. Hno 48 (2000) 18—21.  T. V. Mycoses in otorhinolaryngology. Am J Otolaryngol 9 (1988) 327—335. Al Khalifa. Otomycosis: clinical and mycological study of 97 cases. Ette. Am J Trop Med Hyg 29 (1980) 620—623. Otolaryngol Head Neck Surg 100 (1989) 134—136. S. Treatment outcome of otomycosis in Ilorin. Cuetara. Expert Opin Investig Drugs 13 (2004) 903—932. A contribution to the treatment of otomycoses (author’s transl). Jadhav. C. Li. Novel modes of antifungal drug administration. Noguchi. Yao.J. Tuladhar. A. Ozcan. M. Otomycosis in Burma.O. Int J Pediatr Otorhinolaryngol 69 (2005) 1503—1508. Castellote.C. Valles. Church. Clin Ter 130 (1989) 23—27.L.  V. Bamba. Fungal causes of otitis externa and tympanostomy tube otorrhea. Otomycosis due to Scopulariopsis brevicaulis. Narne. Rev Laryngol Otol Rhinol (Bord) 123 (2002) 77—78.W. Trausch. The round window as access route for agents injurious to the inner ear. Otomycosis and topical application of thimerosal: study of 152 cases. A. Kappe.  J. P. Lopez-Suso. Minerva Med 64 (1973) 24—26.E.  R. Chang.M. Chronic bilateral otomycosis caused by Aspergillus niger. Arikan. T. T. M. Thompson. D. K.T.E.  G. Morimatsu.S. Shields. Laryngoscope 88 (1978) 1755— 1760. H. K.R. Okamoto. Canseco.W. Marsh. H. Bonifaz. Lin. Apropos of 167 cases. Laryngol Rhinol Otol 55 (1976) 765—767.  L.  B. Drew.  T.C. Amor. Yamaguchi. Cheikh-Rouhou. Mycoses 45 (2002) 317—328. Fakhry. Copfer.  K. Than. Russell. Flanary.R.  A. M. C. L. Laryngoscope 110 (2000) 509—516. J Laryngol Otol 100 (1986) 867—873. Pradhan. Bottin.  A.A. T.  T. Kamel. Ototoxicity of antimycotics. M. N. 1% bifonazole lotion in the therapy of otomycosis.S. S. A. Therapy with tolnaftate in otomycosis due to Aspergillus niger. R.R. Hoppe-Tichy.
 H. Dietz. A. Shenoy. M. Blyth. Acta Otorrinolaringol Esp 46 (1995) 85—89. Ann Otol Rhinol Laryngol 112 (2003) 384—387. W. Mycoses 47 (2004) 284— 287. Matsumoto. A. E. Otomycosis in Turkey: predisposing factors. Ann Otol Rhinol Laryngol 99 (1990) 427—431.S. Merz. Damato. Karaarslan. Determination of ototoxicity of common otic drops using isolated cochlear outer hair cells. M. R. Anniko.S. and its treatment. Kim. Shooji. Tisner. Solazzo. R. Otitis caused by Scedosporium apiospermum in an immunocompetent child. M.  H.  M. Hirai. The observation of mycology and clinical efﬁcacy in 325 cases with otomycosis.P. Zhongguo Zhong Yao Za Zhi 25 (2000) 306—308. Besbes.H. Kerschner. P. Pal. Observation of cell ultrastructuse in suppurative otitis media treated with bosneol and application. Nigeria. J. T. Mishra.
Available online at www. Cheng. Y. M. L. Millan. Antimycotic therapy in otomycosis with tympanic membrane perforation.  A. M. Piantoni. Tom. R.R. Randomized prospective comparative study: shortterm treatment with ciclopiroxolamine (cream and solution) versus boric acid in the treatment of otomycosis.H.  P. Antifungal therapy in children with invasive fungal infections: a systematic review. Broad spectrum antifungal agents in otomycosis. Otic administration of amphotericin B 0. F. Kley. Hoshino. N. A. K. D. E.  C.G. Kintzel. J. Otitic candidiasis in children: an evaluation of the problem and effectiveness of ketoconazole in 10 patients. Rinsho Shinkeigaku 23 (1983) 1—8. Moller. Lawrence. Otomycosis: subdermal growth in calciﬁed mass. Moawad. Mycoses 47 (2004) 82—84. Pal.  H. S. W. Kharrat. Pediatrics 119 (2007) 772—784. Ozcan. K.T. J. Egami. Bhally.