Ototopical antifungals and otomycosis: A review - sepeap

International Journal of Pediatric Otorhinolaryngology (2008) 72, 453—459
www.elsevier.com/locate/ijporl
REVIEW ARTICLE
Ototopical antifungals and otomycosis: A review
Raymundo Munguia a , Sam J. Daniel a,b, *
a McGill Auditory Sciences Laboratory, McGill University, Montreal, Qc., Canada H3H1P3
b 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
KEYWORDS
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. Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 453
2. Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 454
2.1. Symptoms and predisposing factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 454
2.2. Causal agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 454
2.3. Topical treatments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 454
3. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 458
Acknowledgements. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 458
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 458
1. Background
* 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: sam.daniel@mcgill.ca (S.J. Daniel).
Otomycosis, also known as fungal otitis externa, has
been used to describe a fungal infection of the
external auditory canal and its associated complications,
sometimes involving the middle ear. The prevalence
of otomycosis has been reported to be as
low as 9% of cases of otitis externa [1], and as high as
30.4% in patients presenting with symptoms of otitis
or inflammatory conditions of the ear [2]. 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

454 R. Munguia, S.J. Daniel
and otitis externa has been linked to the important
increase in the prevalence of otomycosis. Secondary
overgrowth of fungi is a well-known and recognized
complication of the use of broad-spectrum antibiotics
like quinolones [3].
To date, there are four main classes of drugs for
the treatment of fungal infections: polyenes, triazoles,
nucleoside analogues, and echinocandins.
The polyenes family includes amphotericin B and
nystatin. The triazoles family, better known as
azoles includes: fluconazole, clotrimazole and miconazole.
The mechanism of action of the polyenes
and azole families involves an essential chemical
component called ergosterol found in the fungal cell
membrane. The drug binds to ergosterol and creates
a polar pore in the fungal membranes. This causes
ions (predominantly K + and H + ) and other molecules
to leak out of the cell, leading to its death. The
nucleoside analogues such as flucytosine work by
interfering with nucleotide synthesis; a key step in
cell energy production, metabolism, and signaling.
Finally, the echinocandins are a novel class of antifungal
agents. Their mechanism of action involves
interference with cell wall biosynthesis. Their use in
otomycosis has not been reported.
2. Methods
We performed a MEDLINE search for otomycosisrelated
articles published between January 1951
and March 2007. The resulting set of 576 articles
was then restricted to those using topical antifungals.
Electronic search with ‘‘topical antimycotic OR
otomycosis OR antifungal drops OR antifungal eardrops’’
identified 96 studies, of which 18 were
considered appropriate for review. Selected articles
had to specify the number of patients presenting
with otomycosis, the topical medication used, and
the efficacy of the treatment. Reviewing individual
cited references identified additional studies.
We present in this article a summary of the data
in the literature with regards to the topical treatment
of otomycosis, the treatment efficacy, and the
risk of ototoxicity.
2.1. Symptoms and predisposing factors
The most prominent symptoms present at the time
of diagnosis were: otalgia, otorrhea, hearing loss,
aural fullness, pruritus, and tinnitus [1,2,4]. Very
often, fungal external ear infections manifest only
in the presence of predisposing factors. Some identified
culprits include humid climate, presence of
cerumen acting as a support for fungal growth,
configuration of the ear canal, weak immune function,
diabetes, increased use of ototopical antibiotics,
and prolonged use of broad-spectrum
antibiotics such as fluoroquinolones. Other factors
that predispose patients to otomycosis include:
pregnancy, use of systemic steroids, presence of
open mastoid cavities, hearing aids with occlusive
molds, trauma, and bacterial infections. Several
recent articles have also established the potential
risk of autoinoculation of the ear canal by patients
suffering of dermatomycoses [1,5].
2.2. Causal agents
Many species of fungi have been identified as the
cause of otomycosis in the literature reviewed.
These are listed in Table 1 along with the antifungal
agent utilized for each study. Aspergillus niger and
Candida albicans are the most common causative
agents of otomycosis. Aspergillus is considered the
predominant causal organism in tropical and subtropical
regions [6]. Aspergillus niger is the most
commonly described agent in the literature [7,8].
Many authors believe that it is important to
identify the causal agent of otomycosis in order to
use the appropriate treatment. It is also recommended
that the antimycotic treatment chosen
should be based on the susceptibility of the identified
species [9,10]. However, 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 [11,12].
2.3. Topical treatments
To date there is no FDA approved antifungal otic
preparation for the treatment of otomycosis. Many
agents with various antimycotic properties have
been used, and clinicians have struggled to identify
the most effective agent to treat this condition.
Antifungal agents typically reach some popularity
for a short period of time, until non-desirable side
effects are identified or until a new medication
appears on the market. However, the use of few
topical antifungals has persisted throughout time,
including Nystatin and the azoles family. In addition
to topical therapy, the reviewed literature emphasized
the importance of aural hygiene in the treatment
of otomycosis, as intuitively ototopical
medications work best following cleaning of secretions
and debris [1,13].
Table 2 summarizes the studies using topical
antifungal agents, the dosage utilized, and the
efficacy of treatment.
Azoles are synthetic agents that reduce the concentration
of ergosterol, an essential sterol in the

Ototopical antifungals and otomycosis 455
Table 1 Otomycosis: description of the most common causal agents and treatment
Causal agent Treatment Author
Aspergillus (species not specified) Clotrimazole Ologe and Nwabuisi [17]
Bassiouny et al. [10]
Ketoconazole Nong et al. [19]
Ho et al. [1]
Itraconazole Nong et al. [19]
Clotrimazole Schrader (2003)
Aspergillus flavus Itraconazole, terbinafide Karaarslan et al. [24]
Aspergillus fumigatus Miconazole Dyckhoff et al. [21]
Amphotericin B Kintzel et al. [26]
Acetic acid Jackman et al. [3]
Clotrimazole Jackman et al. [3]
Martin et al. [13]
Tolnaftate Martin et al. [13]
Aspergillus niger Borneol Chang and Li [7]
Tolnaftate Damato [30]
Ciclopiroxolamine, boric acid del Palacio et al. [37]
Itraconazole Hoshino and Matsumoto [8]
Mercurochrome Mgbor and Gugnani [4]
Mishra et al. [32]
Boric acid Ozcan et al. [5]
Clotrimazole Pradhan et al. [15]
5-Fluorocytosine Than et al. [38]
Itraconazole, terbinafide Karaarslan et al. [24]
Fluconazole Kurnatowski and Filipiak [2]
Amphotericin B Ette et al. [27]
Thimerosal Tisner et al. [31]
Aspergillus terreus Lanoconazole Egami et al. [14]
Candida albicans Ketoconazole Cohen and Thompson [20]
Ho et al. [1]
Thimerosal Tisner et al. [31]
Amphotericin B Ette et al. [27]
O’Day (2004)
Clotrimazole Jhadav (2003)
Schrader (2003)
Bassiouny et al. [10]
Ologe and Nwabuisi [17]
Jackman et al. [3]
Martin et al. [13]
Itraconazole Nong et al. [19]
Fluconazole Kurnatowski and Filipiak [2]
Tolnaftate Martin et al. [13]
Acetic acid Jackman et al. [3]
Candida parapsilosis Clotrimazole, tolnaftate Martin et al. [13]
Fluconazole Kurnatowski et al. [2]
Scedosporium apiospermum Clotrimazole Bhally et al. [16]
Scopulariopsis brevicaulis Nystatin Besbes et al. [25]
normal cytoplasmic membrane. They are a class of
five-membered nitrogen heterocyclic ring compounds
containing at least one other noncarbon
atom, nitrogen, sulfur or oxygen [14]. Clotrimazole
is the most widely used topical azole [15,16]. It
appears to be one of the most effective agents
for the management of otomycosis, with a reported
rate of effectiveness that varies from 95% to 100% in
most studies [6,10] with the exception of one study
reporting a lower efficacy rate of 50% [3]. Clotrimazole
has an antibacterial effect, and this is an
added advantage when treating mixed bacterial—

Table 2 Otomycosis: topical treatment efficacy represented in percentage
Author Study design Antifungal Posology Number of
patients
Jadhav et al. [6] Prospective Clotrimazole 1% solution 4 drops tid 1 month 79 100
Piantoni et al. [23] Prospective Bifonazole 1% solution, once a day 4—15 days 23 100
Nong et al. [19] Randomized prospective Miconazole Once a day 2 weeks 110 97.6
Ketoconazole Once a day 2 weeks 97.5
Clotrimazole Once a day 2 weeks 90
Thymol alcohol Three times per day for 2 weeks 80
Ologe and Nwabuisi [17] Prospective Clotrimazole 1% cream once a day 2 weeks 141 96
Kley [18] Prospective Clotrimazole 0.25 mg/ml once a day 8—12 days 39 94.8
Tisner et al. [31] Prospective Thimerosal Not reported 152 93.4
Than et al. [38] Prospective 5-Fluorocytosine 10% ointment 7—10 days 189 90
Ho et al. [1] Retrospective Cresylate otic Three times per day 1—3 weeks 51 86
Ketoconazole otic 1—3 cc one application 1 week 48 95
Aluminium acetate otic 0.5% solution 1—3 weeks 18 86
Kurnatowski et al. [2] Prospective Fluconazole 0.2% solution/three times per day 21 days 96 89.4
Mgbor and Gugnani [4] Randomized prospective Locacorten-vioform 1% solution every other day 7—10 days 23 66.6
Mercurochrome 1% solution every other day 7—10 days 23 95.8
Clotrimazole 1% solution every other day 7—10 days 24 75
del Palacio et al. [37] Randomized prospective Cyclopirox olamine 11% cream 1 week 20 80
Cyclopirox olamine 1% solution 1 week 20 95
Boric acid 1 week 40 72.5
Ozcan et al. [5] Prospective Boric acid 4% solution in alcohol 87 77
Cohen and Thompson [20] Prospective Ketoconazole Not reported 9 100
Jackman et al. [3] Retrospective Acetic acid otic Not reported 15 40
Clotrimazole 8 50
Nystatin 2 50
Aluminium acetate otic 1 0
Bhally et al. [16] Case report Clotrimazole 0.25 mg/ml 1 100
Mishra et al. [32] Case report Mercurochrome 1% solution 1 100
Dyckhoff et al. [21] Review Miconazole 0.25% solution — —
Bassiouny et al. [10] In vitro Clotrimazole otic 01—4 mg/ml — 100
Econazole 1% solution — 100
Miconazole 0.1—4 mg/ml — 90
Cyclopirox olamine otic Not reported — 57
Egami et al. [14] In vitro Lanoconazole 0.1 mg/ml — 100
Efficacy
(%)
456 R. Munguia, S.J. Daniel

Ototopical antifungals and otomycosis 457
fungal infections. It is considered free of ototoxic
effects [17,18]. There are no reports of clinical
evidence of clotrimazole ototoxicity. Clotrimazole
is available as a powder, a lotion, and a solution.
Ketoconazole and fluconazole are azole antifungal
agents that have a broad spectrum of activity.
This family of chemical components is effective in
treating the most common etiological agents of
otomycosis. Ketoconazole has shown an efficacy
of 95—100% in vitro against Aspergillus species
and Candida albicans; it is available as a 2% cream.
[1,19,20]. Topical fluconazole has been reported
effective in 90% of cases in several series. Fluconazole
suspension is available with either 350 mg or
1400 mg of fluconazole. After reconstitution with
24 ml of distilled water or purified water (USP), each
Table 3 Otomycosis treatment and risk of ototoxicity
Antifungal Tested for ototoxicity Author
5-fluorocytosine Not tested Than et al. [38]
Acetic acid otic Ototoxic Jackman et al. [3]
Jinn et al. [36]
Aluminium acetate otic Non ototoxic Ho et al. [1]
Jackman et al. [3]
Amphotericin B Not tested Nong et al. [19]
Bifonazole Not tested Piantoni et al. [23]
Boric Acid Ototoxic del Palacio et al. [37]
Ozcan et al. [5]
Clotrimazole Non ototoxic Bhally et al. [16]
Jackman et al. [3]
Tom [29]
Mgbor and Gugnani [4]
Ologe and Nwabuisi [17]
Bassiouny et al. [10]
Jadhav et al. [6]
Cresylate otic Ototoxic Ho et al. [1]
Cyclopirox olamine 1% otic Not tested Bassiouny et al. [10]
del Palacio et al. [37]
Cyclopirox olamine 11% otic Not tested del Palacio et al. [37]
Econazole Not tested Bassiouny et al. [10]
Fluconazole Non ototoxic Kurnatowski et al. [2]
Nong et al. [19]
Itraconazole Not tested Nong et al. [19]
Ketoconazole Non ototoxic Cohen and Thompson [20]
Nong et al. [19]
Ho et al. [1]
Lanoconazole Not tested Egami et al. [14]
Locacorten-vioform Ototoxic Mgbor and Gugnani [4]
Mercurochrome 1% Non ototoxic (FDA banned) Mgbor and Gugnani [4]
Mishra et al. [32]
Miconazole Non ototoxic Bassiouny et al. [10]
Dyckhoff et al. [21]
Nystatin Not tested Jackman et al. [3]
Gentian Violet Ototoxic Tom [29]
Spandow [35]
Thimerosal Not tested Tisner et al. [31]
The bolded text refers to drugs that have been classified in the literature as non-ototoxic (safe). The italic text refers to drug that
have been classified as ototoxic (non-safe).

458 R. Munguia, S.J. Daniel
ml of reconstituted suspension contains 10 mg or
40 mg of fluconazole [2,13]. Miconazole cream 2%
has also demonstrated an efficacy rate of 90%
[10,21]. Bifonazole is an antifungal agent that was
commonly used in the 1980s. The antifungal potency
of bifonazole 1% solution has been reported to be
similar to that of clotrimazole and miconazole;
however, it varies from species to species. Bifonazole
and derivatives inhibited the growth of most
fungi with an efficacy of up to 100% [22,23].
Nystatin is a polyene macrolide antibiotic that
inhibits sterol synthesis in the cytoplasmic membrane
[24]. Many molds and yeasts are sensitive to
nystatin, including Candida species. A major advantage
of nystatin is the fact that it is not absorbed
across intact skin. Nystatin is not available as an otic
preparation; however it can be prepared as a solution
or a suspension for the treatment of otomycosis.
Nystatin can be administered as a cream, an
ointment, or a powder. Reported efficacy rates vary
from 50% to 80% [3,25].
Amphotericin B is a member of the polyenes
family. It has been replaced by safer agents in most
cases but is still used, despite its side effects, for
life-threatening fungal infections. Nong in 1999
reported that Aspergillus and Candida albicans were
sensitive to the use amphotericin B as demonstrated
in antifungal susceptibility tests [19,26,27].
Tolnaftate acts by distorting hyphae and inhibiting
the mycelial growth of susceptible fungi that
cause skin infections, including tinea pedis (athlete’s
foot), tinea cruris (jock itch), and ringwormit.
It has been recommended in refractory cases of
otomycosis, and was shown to be non-ototoxic
[28,29]. Tolnaftate is available as a 1% solution that
can be easily instilled into the ear [30].
In recent years, there have been attempts to use
Mercurochrome, a well-known topical antiseptic, to
treat otomycosis. Along with merthiolate (thimerosal),
mercurochrome is no longer approved by the
FDA due to the fact that it contains mercury. Tisner
in 1995 reported an efficacy of 93.4% with the use of
thimerosal (merthiolate) for the treatment of otomycosis
[31]. Mercurochrome has been used specifically
for cases reported in humid environments
with a reported efficacy rate between 95.8% and
100% [32,4].
Gentian Violet is typically prepared as a weak
(e.g. 1%) solution in water. It has been used since the
1940s to treat otomycosis as it is an aniline dye with
antiseptic, anti-inflammatory, antibacterial, and
antifungal activity. It is still in use in some countries,
and is FDA approved. Studies report an efficacy rate
of up to 80%. [20,33—35].
Other available topical medications for the treatment
of otomycosis reported in the literature
include cyclopirox olamine, boric acid, and 5-fluorocytocine
[36]. Cyclopirox acts by chelating polyvalent
cations (Fe 3+ or Al 3+ ) resulting in inhibition of
the metal-dependent enzymes that are responsible
for the degradation of peroxides within the fungal
cell. Boric acid is a mild acid often used as an
antiseptic, and insecticide. Boric acid can be used
to treat yeast and fungal infections such as vaginal
yeast infections caused by Candida albicans. Itis
also used to prevent athlete’s foot.
5-Fluorocytocine (also known as flucytosine) acts
penetrating fungal cells and is converted to fluorouracil,
which competes with uracil interfering with
fungal RNA and protein synthesis [37,5,38]. Table 3
lists the ototoxicity potential for some of the antifungals.
3. Conclusions
Many species of fungi have been identified as a cause
of otomycosis with Aspergillus niger and Candida
albicans being the most common culprits.
Overall antifungals from the azoles class such as
clotrimazole, fluconazole, ketoconazole and miconazole
are more effective, followed by nystatin and
tolnaftate.
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. Less data exists
regarding the safety of the use of ototopical medications
in the presence of a tympanic membrane
perforation.
Acknowledgements
The authors wish to thank Ms Françoise Brosseau-
Lapré for her assistance, and for editing the manuscript.
References
[1] T. Ho, J.T. Vrabec, D. Yoo, N.J. Coker, Otomycosis: clinical
features and treatment implications, Otolaryngol Head Neck
Surg 135 (2006) 787—791.
[2] P. Kurnatowski, A. Filipiak, Otomycosis: prevalence, clinical
symptoms, therapeutic procedure, Mycoses 44 (2001) 472—
479.
[3] A. Jackman, R. Ward, M. April, J. Bent, Topical antibiotic
induced otomycosis, Int J Pediatr Otorhinolaryngol 69 (2005)
857—860.
[4] N. Mgbor, H.C. Gugnani, Otomycosis in Nigeria: treatment
with mercurochrome, Mycoses 44 (2001) 395—397.

Ototopical antifungals and otomycosis 459
[5] K.M. Ozcan, M. Ozcan, A. Karaarslan, F. Karaarslan, Otomycosis
in Turkey: predisposing factors, aetiology and therapy,
J Laryngol Otol 117 (2003) 39—42.
[6] V.J. Jadhav, M. Pal, G.S. Mishra, Etiological significance of
Candida albicans in otitis externa, Mycopathologia 156
(2003) 313—315.
[7] S.P. Chang, Y.C. Li, Observation of cell ultrastructuse in
suppurative otitis media treated with bosneol and application,
Zhongguo Zhong Yao Za Zhi 25 (2000) 306—308.
[8] T. Hoshino, M. Matsumoto, Otomycosis: subdermal growth in
calcified mass, Eur Arch Otorhinolaryngol 263 (2006) 875—
878.
[9] R.R. Arthur, R.H. Drew, J.R. Perfect, Novel modes of antifungal
drug administration, Expert Opin Investig Drugs 13
(2004) 903—932.
[10] A. Bassiouny, T. Kamel, M.K. Moawad, D.S. Hindawy, Broad
spectrum antifungal agents in otomycosis, J Laryngol Otol
100 (1986) 867—873.
[11] J. Araiza, P. Canseco, A. Bonifaz, Otomycosis: clinical and
mycological study of 97 cases, Rev Laryngol Otol Rhinol
(Bord) 127 (2006) 251—254.
[12] C.C. Blyth, P. Palasanthiran, T.A. O’Brien, Antifungal therapy
in children with invasive fungal infections: a systematic
review, Pediatrics 119 (2007) 772—784.
[13] T.J. Martin, J.E. Kerschner, V.A. Flanary, Fungal causes of
otitis externa and tympanostomy tube otorrhea, Int J
Pediatr Otorhinolaryngol 69 (2005) 1503—1508.
[14] T. Egami, M. Noguchi, S. Ueda, Mycosis in the ear, nose and
throat, Nihon Ishinkin Gakkai Zasshi 44 (2003) 277—283.
[15] B. Pradhan, N.R. Tuladhar, R.M. Amatya, Prevalence of
otomycosis in outpatient department of otolaryngology in
Tribhuvan University Teaching Hospital, Kathmandu, Nepal,
Ann Otol Rhinol Laryngol 112 (2003) 384—387.
[16] H.S. Bhally, C. Shields, S.Y. Lin, W.G. Merz, Otitis caused by
Scedosporium apiospermum in an immunocompetent child,
Int J Pediatr Otorhinolaryngol 68 (2004) 975—978.
[17] F.E. Ologe, C. Nwabuisi, Treatment outcome of otomycosis in
Ilorin, Nigeria, West Afr J Med 21 (2002) 34—36.
[18] E. Kley, A contribution to the treatment of otomycoses
(author’s transl), Laryngol Rhinol Otol 55 (1976) 765—767.
[19] H. Nong, J. Li, G. Huang, D. Nong, P. Cheng, C. Yao, The
observation of mycology and clinical efficacy in 325 cases
with otomycosis, Lin Chuang Er Bi Yan Hou Ke Za Zhi 13
(1999) 438—440.
[20] S.R. Cohen, J.W. Thompson, Otitic candidiasis in children:
an evaluation of the problem and effectiveness of ketoconazole
in 10 patients, Ann Otol Rhinol Laryngol 99 (1990)
427—431.
[21] G. Dyckhoff, T. Hoppe-Tichy, R. Kappe, A. Dietz, Antimycotic
therapy in otomycosis with tympanic membrane perforation,
Hno 48 (2000) 18—21.
[22] H. Yamaguchi, K. Okamoto, M. Shooji, M. Morimatsu, S.
Hirai, A case of adult type sialidosis with partial betagalactosidase
deficiency without myoclonus, Rinsho Shinkeigaku
23 (1983) 1—8.
[23] S. Piantoni, S. Narne, R. Bottin, A. Solazzo, W. Bianchi, 1%
bifonazole lotion in the therapy of otomycosis, Clin Ter 130
(1989) 23—27.
[24] A. Karaarslan, S. Arikan, M. Ozcan, K.M. Ozcan, In vitro
activity of terbinafine and itraconazole against Aspergillus
species isolated from otomycosis, Mycoses 47 (2004) 284—
287.
[25] M. Besbes, F. Makni, F. Cheikh-Rouhou, H. Sellami, K. Kharrat,
A. Ayadi, Otomycosis due to Scopulariopsis brevicaulis,
Rev Laryngol Otol Rhinol (Bord) 123 (2002) 77—78.
[26] P.E. Kintzel, D.E. Trausch, A.L. Copfer, Otic administration of
amphotericin B 0.25% in sterile water, Ann Pharmacother 28
(1994) 333—335.
[27] A. Ette, M. Bamba, P. Adjoua, J. Boguifo, E.E. Ette, K. Fakhry,
et al., Mycoses in otorhinolaryngology. Apropos of 167 cases,
Rev Laryngol Otol Rhinol (Bord) 110 (1989) 173—177.
[28] R.R. Marsh, L.W. Tom, Ototoxicity of antimycotics, Otolaryngol
Head Neck Surg 100 (1989) 134—136.
[29] L.W. Tom, Ototoxicity of common topical antimycotic preparations,
Laryngoscope 110 (2000) 509—516.
[30] P.J. Damato, Therapy with tolnaftate in otomycosis due to
Aspergillus niger, Minerva Med 64 (1973) 24—26.
[31] J. Tisner, J. Millan, P. Rivas, I. Adiego, A. Castellote, H. Valles,
Otomycosis and topical application of thimerosal: study of 152
cases, Acta Otorrinolaringol Esp 46 (1995) 85—89.
[32] G.S. Mishra, N. Mehta, M. Pal, Chronic bilateral otomycosis
caused by Aspergillus niger, Mycoses 47 (2004) 82—84.
[33] K.O. Paulose, S. Al Khalifa, P. Shenoy, R.K. Sharma, Mycotic
infection of the ear (otomycosis): a prospective study, J
Laryngol Otol 103 (1989) 30—35.
[34] T.L. Lawrence, L.W. Ayers, W.H. Saunders, Drug therapy in
otomycosis: an in vitro study, Laryngoscope 88 (1978) 1755—
1760.
[35] O. Spandow, M. Anniko, A.R. Moller, The round window as
access route for agents injurious to the inner ear, Am J
Otolaryngol 9 (1988) 327—335.
[36] T.H. Jinn, P.D. Kim, P.T. Russell, C.A. Church, E.O. John, T.T.
Jung, Determination of ototoxicity of common otic drops
using isolated cochlear outer hair cells, Laryngoscope 111
(2001) 2105—2108.
[37] A. del Palacio, M.S. Cuetara, M.J. Lopez-Suso, E. Amor, M.
Garau, Randomized prospective comparative study: shortterm
treatment with ciclopiroxolamine (cream and solution)
versus boric acid in the treatment of otomycosis, Mycoses 45
(2002) 317—328.
[38] K.M. Than, K.S. Naing, M. Min, Otomycosis in Burma, and its
treatment, Am J Trop Med Hyg 29 (1980) 620—623.
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