Clinics in Dermatology (2010) 28, 202–211

Otomycosis: Diagnosis and treatment

Irina Vennewald, Dr rer nat a,⁎, Eckart Klemm, MD b
a
Institute of Laboratory Medicine, Academic Teaching Hospital Dresden-Friedrichstadt, Friedrichstrasse 41,
01067 Dresden, Germany
b
Department of Otolaryngology, Academic Teaching Hospital Dresden-Friedrichstadt, Friedrichstrasse 41,
01067 Dresden, Germany

Abstract Aspergillus and Candida spp are the most frequently isolated fungi in patients with
otomycosis. The diagnosis of otitis externa relies on the patient's history, otoscopic examination under
microscopic control, and imaging studies. Direct preparation of the specimens, particularly with optical
brighteners, mycologic culture, and histologic examination, is very important and strongly
recommended for the correct diagnosis. Patients with noninvasive fungal otitis externa should be
treated with intense débridement and cleansing, and topical antifungals. Topical antifungals, such as
clotrimazole, miconazole, bifonazole, ciclopiroxolamine, and tolnaftate, are potentially safe choices for
the treatment of otomycosis, especially in patients with a perforated eardrum. The oral triazole drugs,
itraconazole, voriconazole, and posaconazole are effective against Candida and Aspergillus, with good
penetration of bone and the central nervous system. These drugs are essential in the treatment of patients
with malignant fungal otitis externa complicated by mastoiditis and meningitis.
© 2010 Elsevier Inc. All rights reserved.

The term otomycosis is mostly used to describe fungal
infections of the external ear, including the auricle, auditory
canal, eardrum, and middle ear. Malignant invasive necro-
tizing otitis externa is an infection of the external auditory
canal that invades the skull base and the mastoid cells.
Synonyms include fungal otitis externa, fungal malignant
otitis externa, fungal necrotizing otitis externa, fungal
invasive otitis externa, and fungal otitis media.
Causative fungi
The species causing fungal infection in the ear include
molds, yeasts, and occasionally, dermatophytes. They are
about listed in Table 1. Many authors have reported about
Aspergillus and Candida isolates in patients with fungal otitis
externa.1-8 Other species such as Mucor, Fusarium, Scedos-
⁎ Corresponding author. Tel.: +49 351 480 3861; fax: +49 351 480 3236.
E-mail address: vennewald-ir@khdf.de (I. Vennewald).
porium, Hendersonula, Rhodotorula, and Cryptococcus are
very rare.1,4,9,10 Molds and yeasts are common in the auditory
canals of healthy people, but most of the isolated fungi are
Penicillium spp, and the percentage of isolated Aspergillus
and Candida spp is very low.11
The predominant molds are A niger, A fumigatus, and A
flavus, and C parapsilosis is the predominate yeast isolate.
The predominance of thermophile Aspergillus and Candida
spp is related to the inflammatory processes of the ear.
Trichophyton spp, rarely Microsporum spp, and Epider-
mophyton floccosum, occur as agents of dermatophytosis of
the external ear.12-15
Clinical manifestations, etiology,
and pathogenesis
The immunocompetence of patients is very important for
the cure and prognosis of fungal disease. Superficial
infections develop in immunocompetent patients, including

0738-081X/$ – see front matter © 2010 Elsevier Inc. All rights reserved.
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Otomycosis: Diagnosis and treatment
Table 1 Spectrum of fungi isolated from patients with
otomycosis
Aspergillus niger Scedosporium apiospermum
Aspergillus fumigatus Fusarium solani
Aspergillus flavus Hendersonula toruloidea
Aspergillus terreus Mucor spp
Aspergillus candidus Paecilomyces variotii
Aspergillus hollandicus Penicillium spp
Aspergillus alliaceus Cryptococcus neoformans
Aspergillus janus Candida parapsilosis
Aspergillus versicolor Candida albicans
Aspergillus nidulans Candida guilliermondii
Trichophyton rubrum Rhodotorula rubra
Trichophyton mentagrophytes Candida glabrata
Epidermophyton floccosum Microsporum canis
acute and chronic noninvasive (chronic colonization) fungal
otitis externa. The external auditory meatus is mostly
affected. The tympanic membrane and the middle ear
space are rarely involved.1,16-20
Patients, mostly adults, with chronic otitis media (with or
without cholesteatoma) and persistent perforation of the
tympanic membrane and otorrhea, show clinical signs of
chronic fungal colonization of the auditory canal and,
occasionally, the tympanic membrane and the cholesteatoma
space. Most of these patients have long-term relapsing
otorrhea and have been treated repeatedly with antibiotics,
without remission.
Acute fungal otitis externa will develop in patients
(mostly pediatric) after an acute bacterial otitis media with
otorrhea. Some patients have tympanic membrane perfora-
tion or a tympanostomy tube. All patients should use
ototopical antibiotics for presumed bacterial otorrhea.
Patients generally complain of ear pain, pruritus, persistent
discharge, and increasing hearing loss and show one or more
of the following signs: persistent white or colorless otorrhea
with tympanum perforation, edema, erythema of the meatal
epithelium of the auditory canal and tympanic membrane, and
whitish, cottonlike or greasy debris in the external auditory
canal, sometimes on the tympanic membrane or in the
residual space of cholesteatoma.
Primary, persistent discharge macerates the meatal
epithelium, destroys the protective barrier of the cerumen,
and may support fungal colonization of the auditory canal,
tympanic membrane, and the cholesteatoma space in patients
with otitis media. Fungal colonization can sometimes
suddenly change to a clinically relevant infection, accompa-
nied by inflammation of the meatal epithelium.
Chronic hyperplastic inflammation of the mucous mem-
brane of the middle ear and disturbance of the continuous
drainage of fluid from the middle ear cavity to the auditory
tube is the cause of tympanic membrane perforation and
relapsing otorrhea. Persistent tympanum perforation allows
fungi to enter the middle ear.1,21
Some patients with generalized skin diseases, such as
psoriasis or atopic dermatitis, are treated with topical steroids
203
for many years, and clinical signs of superficial infections
may develop, such as fungal otitis externa, mostly on the
auricle and in the auditory canal. The patients frequently
complain of itching and show seborrheic dermatitis-like skin
lesions with erythema, scaling, or red papules with a granular
surface, and fungal elements in the epidermis.
Swimmers frequently present with acute bacterial otitis
externa and otomycosis. The risk of otitis externa is reported
to be five times greater in swimmers than in nonswimmers.
Heat, humidity, and water cause swelling of the stratum
corneum of the skin. The moisture from swimming or
bathing increases maceration of the skin of the auditory canal
that leads to destruction of the protective barrier of cerumen
and creates the appropriate conditions for bacterial and later
fungal growth of Aspergillus and Candida spp.
Polluted water is related to bacterial and fungal otitis
externa. To prevent acute otitis externa, it is important that
patients avoid swimming or use protective devices, including
commercial rubber or silicon earplugs. Frequent cleaning and
preventing moisture by drying the ear canal with a hair dryer
after each period of swimming are strongly recommended.
Cleaning the ear canal with cotton tip applicators should be
avoided because it traumatizes the skin and the eardrum and
compromises the mechanical barrier of the ear canal.5,22,23
Dermatophytes sometimes cause otomycosis to develop
in immunocompetent patients because the external ear canal
is covered with keratinized squamous epithelium. Effects of
dermatophytes on the skin are found on the auricle of the ear,
but rarely in the auditory canal or the tympanic membrane. It
resembles dry, scaly, and itching eczema. Patients often
report a history of many years of ringworm on different parts
of the body. The frequent etiologic species are T rubrum, T
mentagrophytes, M canis, and E floccosum. It is strongly
recommended that patients with otomycosis caused by
dermatophytes undergo a whole body examination for this
infection and be properly treated for dermatophytosis. These
patients tend to relapse due to transmission and reinfection
from another affected part of their body.12-15
In patients who are immunocompromised due to bone
marrow transplant, leukemia, cancer, immunosuppressive
drugs, AIDS, dialysis, or diabetes mellitus, fatal acute
invasive forms of fungal infection can develop in the middle
and inner ear. This can result in meningitis or mucosal fungal
invasion and destruction of the mastoid bones.
The erythematous auditory canal shows clinical signs of
fungal malignant otitis externa.24-31 Patients frequently
complain of intense ear pain, persistent discharge, increasing
hearing loss, and nausea. Progressively worsening invasive
fungal disease may be accompanied by acute facial palsy,
disequilibrium, and deafness.
Diagnosis
The diagnosis of otitis externa relies on the patient's
clinical history, the physical examination, an otoscopic
204
examination under microscopic control, imaging studies of
the head, and laboratory identification of the fungus.
Radiologic studies include computed tomography (CT),
magnetic resonance imaging (MRI), and nuclear imaging.32,33
X-ray imaging is currently not beneficial for diagnosing otitis
externa. Patients with symptoms suggestive of mastoiditis
should be examined by CT of the petrous portion of the
temporal bone. CT detects bone erosion, decreased skull base
density, abscess formation, and the involvement of the
mastoid. CT is inadequate for showing intracranial extension
and bone marrow involvement. MRI cannot detect bone
destruction but shows changes in soft tissue better than CT.
Nuclear imaging includes technetium Tc 99m scintigra-
phy and gallium scan. Technetium Tc 99m, methylene
diphosphonate scintigraphy (bone scan) is positive in almost
100% of malignant otitis externa and allows early diagnosis
of osteomyelitis. Gallium citrate Ga 67 accumulates in areas
of active inflammation and is positive for soft tissue and bone
infections. The Ga 67 scan has also been proven beneficial in
diagnosing recurrent disease. Nuclear imaging has been the
mainstay in the diagnosis and follow-up of patients with
malignant otitis externa.
Laboratory diagnosis includes direct microscopy, culture,
and histopathology. The samples from the auditory canal
contain debris and secretions that can be used for mycologic
culture. Skin biopsy specimens and surgical material from
the tympanic membrane, the residual space, and middle ear
cavity may be used for histopathology. In selected cases of
invasive fungal mastoiditis or meningitis, the detection of
fungal antigen by enzyme-linked immunosorbent assay in
serum and cerebrospinal fluid is beneficial.
Mycology
Direct examination
The samples are applied on a glass slide and treated with a
drop of 15% to 30% potassium hydroxide (KOH) containing the
optical brighteners Blankophor P Fluessig® (Bayer AG,
Leverkusen, Germany) or Calcofluor White (Sigma Aldrich
GmbH, Tandkinchen, Germany). After an incubation of 2 to 24
hours, the slide is examined by fluorescence microscopy at 330
to 390 nm. Giemsa and Gram stains may be performed. Septate
mold hyphae, occasionally with fruiting heads of Aspergillus,
pseudohyphae, or yeast cells, are common in Blankophor-
stained specimens of debris from the auditory canal. Giemsa or
Gram-stained histologic samples will detect numerous hyper-
keratotic, sometimes parakeratotic epithelial cells, some
leukocytes, and hyphae of molds or blastospores of yeasts.1,34,35
Culture
Specimens should be inoculated directly into two Sabour-
aud glucose agar tubes or plates for fungal culture. One tube/
I. Vennewald, E. Klemm
plate is incubated at 37°C and the other at room temperature
(22°C) for 14 days. The molds must be subcultured on Czapek
or malt agar. An agar medium containing cycloheximide and
chloramphenicol (Mycosel agar, BD Diagnostic Systems,
Heidelberg, Germany) should be used for dermatophytes. The
yeast isolates should be identified using different spore
production on rice agar and sugar assimilation.1 All pathogens
should be classified in accordance with the dermatophytes-
yeast-mold (DYM) system.
Alternative rapid identification of fungal pathogens from
mastoid bone samples or cerebrospinal fluid by polymerase
chain reaction in patients with invasive fungal infection is
highly recommended.
Treatment should be directed specifically against the
fungal species to prevent the development of resistance; to
detect this, in vitro susceptibility testing (agar diffusion and
agar dilution) should be performed when a systemic antifungal
treatment is used. The local concentration of topically applied
antifungal agents is neither definable nor reproducible.
Despite the lack of standardized methods for testing
topically applied antifungals, some authors have published
articles about different modifications of the Clinical and
Laboratory Standards Institute (CLSI; formerly National
Committee for Clinical Laboratory Standards, NCCLS)
methods, M27-A and M38-A. Performing susceptibility
testing of antifungals requires a well-trained, experienced
laboratory staff. Good collaboration between the microbi-
ologist and the clinician is very important. All commer-
cially available tests are only suitable for susceptibility
testing of systemic antifungal drugs and are based on the
CLSI standard. The European standard developed by the
European Committee on Antimicrobial Susceptibility
Testing (EUCAST) and the German Deutsches Institut für
Normung (DIN) standard have not been widely accepted.
Standardization of susceptibility testing of topically applied
antimycotics is essential and will help clinicians decide the
relevant treatment for otomycosis.36-39
Histopathology
Surgical specimens of patients thought to have mastoiditis
or cholesteatoma should be examined histologically. Special
stains for fungi should be performed, including periodic
acid-Schiff, Grocott-Gomori's methenamine-silver, and op-
tical brighteners. Histologic studies have shown the grade
of inflammation caused by fungal growth in the ears of
affected patients.
Immunocompetent patients usually have a superficial
infection and chronic colonization of the epithelium of the
auditory canal and cholesteatoma. The histologic picture
includes the following characteristics1,16-20:
• Fungal hyphae, mostly of Aspergillus, may be
observed in the stratum corneum of the meatal
epithelium of the auditory canal, with no inflamma-
tion in the subepithelial tissue.
Otomycosis: Diagnosis and treatment
• Patients with otitis media may also demonstrate chronic
hyperplastic (polypoid) inflammation of the mucosa of
the middle ear.
• Fungal hyphae are observed in the middle ear cavity or
between horny lamellae of cholesteatoma, or both.
• No inflammatory cellular response accompanies As-
pergillus hyphae.
• Invasive growth of mycelium in the blood vessels or
bones is not observed.
Malignant otitis externa (acute invasive and chronic
invasive otomycosis) develops in immunosuppressed
patients. These forms are often associated with fungal
infections of the middle ear (mastoiditis), rarely of the inner
ear, and the skull base.
Malignant otitis externa begins as a soft-tissue infection of
the auditory canal and spreads to the skull base and mastoid.
The auditory canal has soft polypoid and granulation tissue,
frequently with necrosis of the meatal epithelium and
subepithelial tissue, with numerous fungal hyphae sur-
rounded by granulocytes. Bone erosion may be revealed
along the external auditory canal. The tympanic membrane is
thickened, frequently necrotic, and is infiltrated with
granulocytes and numerous fungal hyphae. The middle ear
mucosa and mastoid air cells contain inflammatory cells
accompanied by an invasive growth of mycelium in the blood
vessels and bones. Fungal hyphae may be observed in the
tympanic cavity, internal carotid artery, and facial nerve.24-31
Treatment
Adequate treatment of fungal infection should include the
formulation, route of administration, dose, and treatment
period according to the site and severity of the disease.
Treatment should be directed specifically against the agent of
the disease to avoid the development of resistance. The
apparent success of treatment must be confirmed by
repeatedly negative fungal cultures.
Topical therapy
Patients with superficial infections and chronic coloniza-
tion should be treated with intense débridement and
cleansing combined with topical antifungal drugs.1,40-56
Systemic treatment should not be prescribed, except perhaps
in the case of a malignant invasive (acute or chronic) otitis
externa complicated by mastoiditis or meningitis, or both.
Most patients respond to topical treatment. The advan-
tages of topical antifungals include local application, the
desired concentration of drugs on the surface of the skin will
be reached shortly after application, and a higher concentra-
tion of the antifungal at the affected site. Special attention
should be given to the choice of the vehicle and formulation,
whether solution, suspension, cream, ointment, or gel.
205
Patients with otitis externa without tympanic membrane
perforation can use different antifungal formulations,
including ointments, gels, and creams. When the tympanic
membrane is perforated, these medications should not be
used because small particles of the cream, ointment, or gel
can cause inflammation, with the development of
granulation tissue in the middle ear. Soluble topical
antifungal drugs (ear drops or gauze strips impregnated
with solution) as treatment for this group of patients are
strongly recommended.
When choosing the correct topical antifungal drugs, the
following properties should be considered:
• water soluble,
• with a low risk of ototoxicity,
• with a low allergic effect after repeated administration
of drugs,
• a broad spectrum antimycotic drug with good local
effects against yeasts and molds,
• suitable for application on pediatric patients, and
• commercially available.
Ototoxicity
Otolaryngologists are aware of the toxic potential of
ototopical medications.57-61 When a perforation in the
eardrum is present, potential ototoxicity must also be
considered. Arguably, such antifungal medication could
reach the cochlea by diffusion through the round window of
the inner ear. Clotrimazole, miconazole, bifonazole, econa-
zole, fluconazole, tolnaftate, naftifine, ciclopiroxolamine,
and nystatin are readily available antimycotic preparations
and have been reported to be effective in the topical
treatment of otomycosis.1,42-56 Despite recommendations
for their use for otomycosis, the ototoxicity of these
medications has not been well investigated. Detecting any
possible ototoxic properties will help clinicians decide the
most relevant preparation for treating otomycosis.
In addition, all commercially available antifungal otic
drops contain alcohol, solvents, acids, and antiseptics.
Unfortunately, there have not been any clinical studies on
humans for sensorineural hearing loss after the use of otic
antifungal drops. The question arises whether the available
antimycotic preparations have the potential for ototoxicity
under these conditions.
A small number of antifungals (active ingredients) and
other major ingredients (solvents) that have been tested for
ototoxicity in experimental animals, primarily rodents, are
listed in Table 2.58-61 Potential ototoxic drugs were instilled
directly into the round window of the middle ear of
experimental animals. These studies demonstrated the
cochlear toxicity of many of these agents. Acetic acid,
cresyl acetate, and gentian violet caused severe damage to
inner ear function. Evidently, propylene glycol (50%) and
isopropyl alcohol (70%) quickly penetrated the membrane
to the inner ear and damaged the inner ear. The critical
206 I. Vennewald, E. Klemm

Table 2 Ototoxicity of common topical antimycotic preparations tested in animal models

First author, year Antifungal agents, solvents and aseptics Result Experimental animals/model
58
Spandow, 1988 50% propylene glycol Ototoxic Rats/auditory brainstem
responses
70% isopropyl alcohol Ototoxic
2% acetic acid Ototoxic
2% acetic acid in aluminum acetate Ototoxic
1% gentian violet Ototoxic
2% acetic acid in propylene glycol Ototoxic
Marsh,59 1989 25% m-cresyl acetate in 25% isopropanol, 5% castor oil, Ototoxic Guinea pigs/auditory
propylene glycol brainstem responses
2% acetic acid in propylene glycol diacetate, 3% propylene glycol Ototoxic
2% acetic acid in deionized water Ototoxic
1% clotrimazole in polyethylene glycol 400 Non ototoxic
1% tolnaftate in polyethylene glycol 400 Non ototoxic
Tom,60 2000 Clotrimazole 1% solution in polyethylene glycol Non ototoxic Guinea pigs/measurements
of hair cell loss (cochlea)
2% miconazole nitrate in benzoic acid, BHA, mineral oil, Non ototoxic
peglicol 3 oleate, pegoxol 7 stearate, water
1% tolnaftate solution in BHT, polyethylene glycol Non ototoxic
Nystatin 100,000 U/g cream in polysorbate 60, aluminum Non ototoxic
hydroxide compressed gel, titanium oxide, glyceryl monostearate,
polyethylene glycol monostearate 400, simethicone, sorbic acid,
propylene glycol, ethylenediamine, polyoxyethylene fatty alcohol
ether, sorbitol solution, methyl paraben, propyl paraben, HCl,
white petrolatum, water
Jinn,61 2001 2% acetic acid in propylene glycol Ototoxic Chinchilla/hair cell
loss (cochlea)
BHA, Butylated hydroxyanisole; BHT, butylated hydroxytoluene; HCl, hydrochloric acid.

concentration of alcohol is 20%.58 Gentian violet caused
signs of vestibular damage.
Ototoxic effects of five topical antimycotic agents were
examined in guinea pigs by measuring hair cell loss of the
inner ear.59,60 Five readily available topical antimycotic
preparations were instilled into the middle ears of test
animals during a 7-day period. This study suggested that
clotrimazole, miconazole, and tolnaftate are potentially safer
antimycotic choices than nystatin for the treatment of
otomycosis in patients with a perforated eardrum. The
differences make comparisons of ototoxicity between
experimental animals and humans difficult, but the need
for testing for ototoxicity in humans remains.
Table 3 summarizes the therapies used to treat oto-
mycosis caused by yeasts and molds.1,42-56 The authors
described patients with fungal otitis externa with prominent
symptoms such as otalgia, otorrhea, hearing loss, and aural
fullness, and some patients had a tympanic membrane perfo-
ration.1,45,48-50,52-54 The use of ototopical antibacterial agents
has been debated in the literature for many years, but only a
few publications exist about antifungal topical treatments.
An important consideration is that not all of these studies
reported mycologic or clinical details nor were complete cure
rates always documented, information that is very important
for evaluating results; therefore, efficacy (%) among the
studies was not possible to assess. More comparative studies
using different treatment schedules are needed to show
whether topical antifungal treatment offers advantages in the
management of otomycosis.
These studies reported success in the topical treatment of
fungal otitis externa against molds and yeasts using
clotrimazole, miconazole, bifonazole, ciclopiroxolamine,
and tolnaftate. These antifungals have more favorable
properties, including a broad spectrum of activity against
pathogens, higher cure rates, low ototoxicity, greater
compliance, and commercial availability as a solution.
Antimycotics, antiseptic, and solution of dyes
Seven main groups of topical drugs are currently available
for treating fungal infection: five antimycotics, one antisep-
tic, and one solution of dyes.
Polyenes
The polyenes include amphotericin B, nystatin, and
natamycin.44,48,52,53,62,63 The polyenes are fungicidal and
have a spectrum of activity against yeasts, biphasic fungi,
dermatophytes, and molds. Nystatin can be administered
topically as a cream, ointment, suspension, or powder;
amphotericin B, as a suspension; and natamycin, which is
commercially available as an ophthalmologic preparation, as
an ointment or solution.
Otomycosis: Diagnosis and treatment 207

Table 3 Efficacy of topical antifungal treatment of otomycosis, overview of studies in chronological order
First author, Antimycotic Administration Patients, Patients, age Efficacy, Study design
year No. clinical cure
Bambule,42 Econazole 1% solution, 1 mL, every 30 19-67 years 100% Retrospective
1978 other day for 10 days
Piantoni,43 Bifonazole 1% solution, once daily, 23 1 mon-71 years 100% Prospective
1989 4-15 days
Paulose,44 Clotrimazole Not reported 171 ⁎ 19-80 years ⁎⁎ 89% Prospective ⁎⁎
1989 Gentian violet Not reported
Tolnaftate 1% solution 81%
Nystatin, neomycin, Not reported 81%
gramicidin, triamcinolone 79%
Acetic acid 2% in propylene Not reported 71%
glycol with hydrocortisone
Nystatin Not reported 68%
Acetic acid 2% in Not reported 67%
propylene glycol
Econazole Not reported 61%
Del Palacio,45 Bifonazole 1% solution, 35 Not reported 72.5% Prospective,
1993 once daily, 7 days randomized
Bifonazole 1% cream, once daily,
7 days
Tisner,46 1995 Sodium ethyl 0.1% solution 152 11-78 years 93.4% Prospective
mercuriosalicylate
(merthiolate)
Chander,47 Mercurochrome Solution, 4 drops twice 40 All age groups, 100% Prospective ⁎⁎
1996 daily, 14 days most 21-30 years ⁎⁎
Clotrimazole Solution, 4 drops twice 23 100%
daily, 14 days
Miconazole Solution, 4 drops twice 17 100%
daily, 14 days
Kurnatowski,48 Fluconazole 0.2% solution, thrice daily 96 ⁎ Not reported 89% Prospective ⁎⁎
2001 and 50 mg oral once daily
for 21 days
Pigmentum Castellani, 2.5% suspension, thrice per Not reported 90.6%
natamycin, and 24 hours and 50 mg oral
fluconazole oral once daily for 21 days
Del Palacio,49 Ciclopiroxolamine 1% cream, once daily 17 18-76 years 60% Prospective,
2002 for 1 week randomized ⁎⁎
Ciclopiroxolamine 1% solution, once daily 17 18-76 years 65%
for 1 week
Boric acid 5% in ethanol, once daily 30 45-90 years 80%
for 1 week
Vennewald,1 Clotrimazole 1% solution, once daily 58 Retrospective ⁎⁎
2003 for 2-4 weeks
Amphotericin B 0.5% suspension, once 1 16-90 years 100%
daily for 4 weeks
Kunelskaya,50 Naftifine Solution, once-twice 108 12-76 years 85.2% Prospective
2004 daily for 2 weeks
Kryukov,51 Terbinafine 250 mg daily for 27 19-63 years 74% Prospective
2005 2-4 weeks
Jackmann,52 Acetic acid/propylene Not reported 15 17 mon-29 40% Retrospective ⁎⁎
2005 glycol years ⁎⁎
Clotrimazole Not reported 8 50%
Nystatin Not reported 2 50%
Aluminium acetate otic Not reported 1 0%
Martin,53 2005 Clotrimazole Not reported 27 16 days-18 100% in Retrospective ⁎⁎
years ⁎⁎ all groups
(continued on next page)
208 I. Vennewald, E. Klemm

Table 3 (continued)
First author, Antimycotic Administration Patients, Patients, age Efficacy, Study design
year No. clinical cure
Tolnaftate Not reported 27
Fluconazole, oral Not reported 25
Acetic acid Not reported 14
Fluconazole, topical Not reported 6
Oral fluconazole and Not reported 10
acetic acid
Vioform powder Not reported 5
Amphotericin B, oral Not reported 2
Nystatin Not reported 1
Treatment unspecified Not reported 50
Ho,54 2006 Cresylate otic Thrice daily 44 6-91 years 86% Retrospective
Ketoconazole ointment 1 to 3 cm3 once a week 44 95%
Aluminium acetate otic Not reported 7 86%
Kiakojuri,55 Miconazole 2% cream, one application 55 16-76 years 96,6% Prospective
2007
Miconazole and acetic acid 2% cream and 3% drops 58 15-98 years 100%
in 97 % ethanol,
one application
Kunelskaja,56 Naftifine 1st-3rd day: 1% solution 30 19-60 years 100% Prospective
2008 twice daily
4th-7th day: 1% cream
twice daily
2nd-4th week: once daily
5th-6th week: every
second day
⁎ Total number of patients
⁎⁎ In all groups of study.

The ototoxicity of amphotericin B and natamycin has not
been tested. Amphotericin B and nystatin are not commer-
cially available as otic preparations; nevertheless, they can be
prepared as a solution or a suspension for treating
otomycosis. A few authors have provided instructions for
preparing amphotericin B and nystatin solutions without
solvents or preservatives.64
Imidazoles
The imidazoles include bifonazole, clotrimazole, econa-
zole, ketoconazole, and miconazole.1,42-45,47,48,52-55,62,63 The
imidazoles are fungistatic and marked by a broad spectrum of
activity against dermatophytes, yeasts, molds, and gram-
positive bacteria. The ototoxicity of bifonazole, econazole,
ketoconazole, and fluconazole has not been tested. Miconazole
and clotrimazole were not ototoxic in animal models.
The commercially available formulations for topical
treatment include cream, gel, ointment, and solution.
Instructions for the preparation of clotrimazole, ketoconazole,
and miconazole and fluconazole solution without solvents or
preservatives have been reported by a few authors.41,64
Allylamines
Naftifine and terbinafine, agents from the allylamines
group, are effective because of their potent antifungal
activity.50,51,56 Allylamines are fungicides and antimycotic
drugs with very high activity against dermatophytes and low
efficacy against yeasts and molds. Ototoxicity of allylamines
was not evaluated. Commercial formulations for topical
treatment are available for naftifine as a cream, gel, and
solution, and for terbinafine as a cream.
Pyridone
Other available topical medications for the treatment of
otomycosis reported include ciclopiroxolamine, belonging to
the pyridone group.49,65 The effect of ciclopiroxolamine is
fungistatic-fungicide, which has shown in vitro good activity
against dermatophytes, yeasts, molds, and gram-negative
and gram-positive bacteria. Another interesting feature is that
the compound possesses anti-inflammatory activity similar
to hydrocortisone. The ototoxicity of ciclopiroxolamine was
not tested. Topical formulations are cream, solution, and gel.
Thiocarbamates
Tolnaftate belongs to the group of thiocarbamates. It is an
active fungicidal drug against dermatophytes, yeasts, and most
molds, excluding A niger.44,53 Tolnaftate was not ototoxic in
animal models. Topical formulations are cream and solution.
Mercury compounds
Mercurochrome, an odorless organic mercurial com-
pound, is commonly used as an antibacterial topical agent as
Otomycosis: Diagnosis and treatment
a 1% to 2% solution.46,47 Its antifungal properties after
topical application have not been widely studied. Cost
factors make it accessible for developing countries. The drug
has shown good clinical and mycologic cure and may be
recommended to treat fungal otitis in patients. The
ototoxicity of mercurochrome was not tested. Mercuro-
chrome is no longer approved by the Food and Drug
Administration (FDA) because it contains mercury. Topical
formulation is as a solution.
Solutions of dyes
Triphenylmethane dyes with antiseptic, anti-inflammatory,
antibacterial, and antifungal activity include brilliant green
(1%), malachite green (1%), fuchsin (1%), and gentian violet
(crystal violet) solution.44,48,54 These are still being used
in some countries and are FDA approved. The use of
combined dyes to treat otomycosis is not accepted by many
patients due to the need to paint the auditory canal with these
compounds. It is important to point out that some triphenyl-
methane dyes (gentian violet and cresyl acetate) were
ototoxic in animal models.
Topical formulations are available in a 0.5% to 1% solution.
Systemic therapy
The treatment of immunocompromised patients consists
of the application of combined systemic and topical
antifungal drugs after surgical débridement of the infected
tissue. Topical medication is generally enough to treat
patients with otomycosis. Nevertheless, the use of systemic
drugs can improve the outcome of topical medication of the
auditory canal, especially in patients with an underlying
disease. Basically, the treatment of patients with fungal
mastoiditis or cerebral mycosis, or both, consists of the
application of systemic drugs. The addition of topical
medication after surgical débridement is beneficial.
Today, the number of available systemic antifungal
agents for otomycosis is abundant. The early antimycotics,
such as amphotericin B66-69 and ketoconazole,17,20 have
been supplanted in recent years, first by fluconazole48,53 and
itraconazole, 70-73 and now by posaconazole 74,75 and
voriconazole.76-83
The following requirements for systemic antifungals are
important:
• a broad-spectrum against yeasts and molds,
• very good diffusion into synovial fluid and bone
tissue,
• a high ability to penetrate the blood-brain barrier and
reach a high antifungal drug concentration in the
cerebrospinal fluid and the central nervous system,
• well-tolerated compared with the earlier antifungal
drugs, amphotericin B and ketoconazole,
• comparable in treatment efficacy with other antifungal
drugs, and
• both intravenous and oral administration.
209
The molecular weight of antimycotic substances is
essential for the function and efficacy of antifungal drugs.
For example, drugs with molecular weight greater than 500
Dalton cannot penetrate the cornea. The diffusion of drugs is
limited by a high frictional force.64
The triazoles show many favorable properties for the
treatment of mastoiditis and otogenic cerebral mycosis
(aspergillosis and zygomycosis). All triazoles have a low
molecular weight, but the three compounds most frequently
used are itraconazole, voriconazole, and posaconazole.
These are broad-spectrum antifungal drugs with good
efficacy against Candida and Aspergillus; in addition,
posaconazole has good efficacy against Zygomycetes.
Voriconazole has very good penetration of bone tissue and
reaches a high concentration in synovial fluid.81,82 This
property makes voriconazole essential for the treatment of
patients with fungal mastoiditis or otogenic meningitis.83
The Infectious Diseases Working Party (AGIHO) of the
German Society of Hematology and Oncology and the
Infectious Diseases Society of America have recently
presented recommendations (guidelines) for treating inva-
sive fungal infections.84-86
Conclusions
The prognosis of otomycosis is good in immunocom-
petent patients. Topical antifungals such as clotrimazole,
miconazole, bifonazole, ciclopiroxolamine, and tolnaftate
have more favorable properties, including a broad
spectrum of activity against pathogens, low ototoxicity,
and the availability of commercial solutions. There are
potentially safer choices for the treatment of otomycosis,
particularly in patients with perforated eardrum. Invasive
forms of otomycosis can develop in immunosuppressed
patients, with lethal consequences if not treated properly.
Itraconazole, voriconazole, and posaconazole, are among
the triazoles that have good efficacy against Candida and
Aspergillus. Voriconazole, and posaconazole show good
penetration of bone tissue and the central nervous
system, properties that make triazoles essential for the
treatment of patients with fungal mastoiditis and otogenic
cerebral mycosis.
References
1. Vennewald I, Schönlebe J, Klemm E. Mycological and histological
investigations in humans with middle ear infections. Mycoses 2003;46:
12-8.
2. Gutierrez PH, Alvarez SJ, Sanudo EG, et al. Presumed diagnosis: a
study of 451 patients. Acta Otorrinoloringol Esp 2005;56:181-6.
3. Fasunla J, Ibekwe T, Onakoya P. Otomycosis in western Nigeria.
Mycoses 2008;51:67-70.
4. Enweani IB, Iqumbor H. Prevalence of otomycosis in malnourished
children in Edo State, Nigeria. Mycopathologia 1997-1998;140:85-7.
210
5. Loh KS, Tan KK, Kumarasinghe B, Leong HK, Yeoh KH. Otitis
externa—the clinical pattern in a tertiary institution in Singapore. Ann
Acad Med Singapore 1998;27:215-8.
6. Dorko E, Jenca A, Orencák M, Virágová S, Pilipcinec E. Otomycoses
of candidal origin in eastern Slovakia. Folia Microbiol (Praha) 2004;49:
601-4.
7. Amigot SL, Gomez CR, Luque AG, Ebner G. Microbiogical study of
external otitis in Rosario City, Argentina. Mycoses 2003;46:312-5.
8. Bineshian F, Irajian G, Koochak-Alavi SK, et al. A study on the
frequency of fungal agents in otitis externa in Semnan. Iran J Pathol
2006;1:141-4.
9. Choo MJ, Yang SK, Jin HR, Lee OJ. Localized cryptococcal infection
combined with cholesteatoma of the ear. Otolaryngol Head Neck Surg
2002;126:453-4.
10. Bhally HS, Shields C, Lin SY, Merz WG. Otitis caused by Scedos-
porium apiospermum in an immunocompetent child. Int J Pediatr
Otorhinolaryngol 2004;68:975-8.
11. Schönborn C, Holzegel K. Zur Pilzflora des gesunden äuβeren
Gehörganges. Dermatol Wochenschr 1967;153:760-70.
12. Watanabe S. Dermatophytosis of the external auditory meatus. J Med
Vet Mycol 1986;24:485-6.
13. Derebery MJ, Berliner K. Foot and ear disease—the dermatophytid
reaction in otology. Am Laryngol Rhinol Otol Soc Annu Meet Pap
1995;106:181-6.
14. Buzina W, Lang-Loidolt D, Ginter-Hanselmayer G. Trichophyton
rubrum in the external auditory meatus. Mycoses 2004;47:85-6.
15. Ozcan M, Ozcan KM, Karaaslan A, et al. Concomitant otomycosis and
dermatomycoses: a clinical and microbiological study. Eur Arch
Otorhinoloringol 2003;260:24-7.
16. Ohki M, Ito K, Ishimoto SI. Fungal mastoiditis in an immunocompetent
adult. Eur Arch Otorhinolaryngol 2001;258:106-8.
17. Tiwari S, Singh SM, Jain S. Chronic bilateral suppurative otitis media
caused by Aspergillus terreus. Mycoses 1995;38:297-300.
18. Cunningham M, Yu VL, Turner J, Curtin H. Necrotizing otitis externa
due to Aspergillus in an immunocompetent patient. Arch Otolaryngol
Head Neck Surg 1988;114:554-6.
19. Hoshino T, Matsumoto M. Otomycosis: subdermal growth in calcified
mass. Eur Arch Otorhinolaryngol 2006;263:875-8.
20. Dhindsa MK, Maidu J, Singh SM, et al. Chronic suppurative otitis
media caused by Paecilomyces variotii. J Med Vet Mycol 1995;33:
59-61.
21. Borkowski G, Gurr A, Stark T, et al. Funktionelle und morphologische
Störungen des mukoziliären Systems bei der sekretorischen Otitis
media. Laryngorhinootologie 2000;79:135-8.
22. Agius AM, Pickles JM, Burch KL. A prospective study of otitis externa.
Clin Otolaryngol Allied Sci 1992;17:150-4.
23. Wang MC, Liu CY, Shiao AS, Wang T. Ear problems in swimmers.
J Chin Med Assoc 2005;68:347-52.
24. Haruna S, Haruna Y, Schachern PA, et al. Histopathology update:
otomycosis. Am J Otolaryngol 1994;15:74-8.
25. Chen D, Lalwani AK, House JW. Choo D. Aspergillus mastoiditis in
acquired immunodeficiency syndrome. Am J Otol 1999;20:561-7.
26. Strauss M, Fine E. Aspergillus otomastoiditis in acquired immunode-
ficiency syndrome. Am J Otol 1991;12:49-53.
27. Muñoz A, Martínez-Chamorro E. Necrotizing external otitis caused by
Aspergillus fumigatus: computed tomography and high resolution
magnetic resonance imaging in an AIDS patient. J Laryngol Otol 1998;
112:98-102.
28. Bellini C, Antonini P, Ermanni S, et al. Malignant otitis externa due to
Aspergillus niger. Scand J Infect Dis 2003;35:284-8.
29. Phillips P, Bryce G, Shepherd J, Mintz D. Invasive external otitis
caused by Aspergillus. Rev Infect Dis 1990;12:277-81.
30. Gordon G, Giddings NA. Invasive otitis externa due to Aspergillus
species: case report and review. Clin Infect Dis 1994;19:866-70.
31. Menachof MR, Jackler RK. Otogenic skull base osteomyelitis caused
by invasive fungal infection. Otolaryngol Head Neck Surg 1990;102:
285-9.
I. Vennewald, E. Klemm
32. Carfrae MJ, Kesser BW. Malignant otitis externa. Otolaryngol Clin
North Am 2008;41:537-49.
33. Sreepada GS, Kwartler JA. Skull base osteomyelitis secondary to
malignant otitis externa. Curr Opin Otolaryngol Head Neck Surg 2003;
11:316-23.
34. Monod M, Baudraz F, Ramelet AA, et al. Direct mycological
examination in dermatology: a comparison of different methods.
Dermatologica 1989;179:183-6.
35. Rüchel R, Schaffrinski M, Seshan KR, Cole GT. Vital staining of fungal
elements in deep-seated mycotic lesions during experimental murine
mycoses using the parenterally applied optical brightener Blankophor.
Med Mycol 2000;38:231-7.
36. Seibold M, Tintelnot K. Susceptibility testing of fungi—current status
and open questions. In: Jucker E, editor. Antifungal agents: advances
and problems. Birkhäuser: Basel; 2003. p. 193-241.
37. Karaarslan A, Arikan S, Ozcan M. In vitro-activity of terbinafine and
itraconazole against Aspergillus species isolated from otomycosis.
Mycoses 2004;47:284-7.
38. Kaya AD, Kiraz N. In vitro susceptibilities of Aspergillus spp. causing
otomycosis to amphotericin B, voriconazole and itraconazole. Mycoses
2007;50:447-50.
39. Polak A, Jäckel A, Noack A, Kappe R. Agar sublimation test for the in
vitro determination of the antifungal activity of morpholine derivatives.
Mycoses 2004;47:184-92.
40. Munguia R, Daniel SJ. Ototopical antifungals and otomycosis: a
review. Int J Pediatr Otorhinoloryngol 2008;72:453-9.
41. Dyckhoff G, Hoppe-Tichy T, Kappe R, Dietz A. Antimykotische
Therapie bei Otomykose mit Trommelfelldefekt. HNO 2000;48:18-21.
42. Bambule J, Grigoriu D. Otomycoses and their treatment. Mykosen
Suppl 1978;1:82-6.
43. Piantoni S, Narne S, Bottin R, Solazzo A, Bianchi W. Bifonazolo
lozione 1% nella terapia delle otomicosi. Clin Ter 1989;130:23-7.
44. Paulose K, Khalifa F, Shenoy F, et al. Mycotic infection of the ear
(otomycosis). A prospective study. J Laryngol Otol 1989;103:30-5.
45. Del Palacio A, López-Suso MJ, Moore MK, et al. Long term follow-up
of otomycosis and its treatment with bifonazole. J Med Vet Mycol
1993;31:435-47.
46. Tisner J, Millán J, Rivas P, et al. [Otomycosis and topical application of
thimerosal: study on 152 cases]. Acta Otorrinolaringol Esp 1995;46:85-9.
47. Chander J, Maini S, Subrahmanyan S, et al. Otomycosis—a clinico-
mycological study and efficacy of mercurochrome in its treatment.
Mycopathologia 1991;135:9-12.
48. Kurnatowski P, Filipiak A. Otomycosis: prevalence, clinical symptoms,
therapeutic procedure. Mycoses 2001;44:472-9.
49. Del Palacio A, Cuétara MS, López-Suso MJ, et al. Randomized
prospective comparative study: short-term treatment with ciclopirox-
olamine (cream and solution) versus boric acid in the treatment of
otomycosis. Mycoses 2002;45:317-28.
50. Kunelskaia VY. [Fungale otitis: new treatment options]. Vestn
Otorinolaringol 2004:46-8.
51. Kriukov AI, Shadrin GB, Balandin AV, et al. [Lamisil in the treatment
of patients with oto- and pharyngomycoses]. Vestn Otorinolaringol
2005:47-9.
52. Jackman A, Ward R, April M, Bent J. Topical antibiotic induced
otomycosis. Int J Pediatr Otorhinolaryngol 2005;69:857-60.
53. Martin TJ, Kerschner JE, Flanary VA. Fungal causes of otitis externa
and tympanostomy tube otorrhea. Int J Pediatr Otorhinolaryngol 2005;
69:1503-8.
54. Ho T, Vrabec JT, Yoo D, Coker NJ. Otomycosis: clinical features and
treatment implications. Otolaryngol Head Neck Surg 2006;135:787-91.
55. Kiakojuri K, Roushan M, Sepidgar S. Suction clearance and 2% topical
miconazole versus the same combination with acidic drops in the
treatment of otomycosis. Southeast Asian J Trop Med Public Health
2007;38:749-52.
56. Kunelskaia VY, Shadrin GB. [The efficiency and safety of stepwise
exoderil therapy for otitis external mycotica]. Vestn Otorinolaringol
2008:59-62.
Otomycosis: Diagnosis and treatment
57. Brummett RE, Harris RF, Lindgren JA. Detection of ototoxicity from
drugs applied topically to the middle ear space. Laryngoscope 1976;86:
1177-87.
58. Spandow O, Anniko M, Moller A. The round window as access route
for agents injurious to the inner ear. Am J Otolaryngol 1988;9:327-35.
59. Marsh RR, Tom LWC. Ototoxicity of antimycotics. Otolaryngol Head
Neck Surg 1989;100:134-6.
60. Tom LWC. Ototoxicity of common topical antimycotic preparations.
Laryngoscope 2000;110:509-15.
61. Jinn TH, Kim PD, Russell PT, et al. Determination of ototoxicity of
common otic drops using isolated cochlear outer hair cells. Laryngo-
scope 2001;111:2105-8.
62. Lawrence TL, Ayers LW, Sauders WH. Drug therapy in otomycosis: an
in vitro study. Laryngoscope 1978;88:1755-60.
63. Stern JC, Shah MK, Lucente FE. In vitro effectiveness of 13 agents in
otomycosis and review of the literature. Laryngoscope 1988;98:
1173-7.
64. Behrens-Baumann W. Antifungal agents. In: Behrens-Baumann W,
editor. Mycosis of the eye and its adnexa. Basel: Karger; 1999.
p. 27-51.
65. Jue SG, Dauson GW, Brogden RN. Ciclopirox olamine 1% cream. A
preliminary review of its antimicrobial activity and therapeutic use.
Drugs 1985;29:330-41.
66. Harley WB, Dummer JS, Anderson TL, Goodman S. Malignant
external otitis due to Aspergillus flavus with fulminant dissemination to
the lungs. Clin Infect Dis 1995;20:1052-4.
67. Hall PJ, Farrior JB. Aspergillus mastoiditis. Otolaryngol Head Neck
Surg 1993;108:167-70.
68. Tuzcu A, Bahceci M, Celen MK, et al. Necrotizing (malignant) otitis
externa: an unusual localization of mucormycosis. Indian J Med
Microbiol 2006;24:289-91.
69. Goyal A, Tyagi I, Syal R, Marak RS, Singh J. Apophysomyces elegans
causing acute otogenic cervicofacial zygomycosis involving salivary
glands. Med Mycol 2007;45:457-61.
70. Yates PD, Upile T, Axon PR, et al. Aspergillus mastoiditis in a patient
with acquired immunodeficiency syndrome. J Laryngol Otol 1997;111:
560-1.
71. Kuruvilla G, Job A, Mathew J, Ayyappan AP, Jacob M. Septate fungal
invasion in masked mastoiditis: a diagnostic dilemma. J Laryngol Otol
2006;120:250-2.
72. Slack C, Watson DW, Abzug MJ, et al. Fungal mastoiditis in
immunocompromised children. Arch Otolaryngol Head Neck Surg
1999;125:73-5.
211
73. Finer G, Greenberg D, Leibovitz E, et al. Conservative treatment of
malignant (invasive) external otitis caused by Aspergillus flavus with
oral itraconazole solution in a neutropenic patient. Scand J Infect Dis
2001;34:227-9.
74. Kok J, Gilroy N, Halliday C, et al. Early use of posaconazole in the
successful treatment of rhino-orbital mucormycosis caused by Rhizopus
oryzae. J Infect 2007;55:e33-e36.
75. Ferguson TD, Schniederjan SD, Dionne-Odom J, et al. Posaconazole
treatment for Apophysomyces elegans rhino-orbital zygomycosis
following trauma for a male with well-controlled diabetes. J Clin
Microbiol 2007;45:1648-51.
76. Parize P, Chandesris MO, Lanternier F, et al. Antifungal therapy of
Aspergillus invasive otitis externa: efficacy of voriconazole and review.
Antimicrob Agents Chemother 2009;53:1048-53.
77. Ling SS, Sader C. Fungal malignant otitis externa treated with
hyperbaric oxygen. Int J Infect Dis 2008;12:550-2.
78. Amonoo-Kuofi K, Tostevin P, Knight JR. Aspergillus mastoiditis in a
patient with systemic lupus erythematosus: a case report. Skull Base
2005;15:109-12.
79. Stratov I, Korman TM, Johnson PD. Management of Aspergillus
osteomyelitis: report of failure of liposomal amphotericin B and
response to voriconazole on an immunocompetent host and literature
review. Eur J Clin Microbiol Infect Dis 2003;22:277-83.
80. Baumgarthner BJ, Rakita RM, Backous DD. Scedosporium apiosper-
mum otomycosis. Am J Otolaryngol 2007;28:254-6.
81. Mouas H, Lutsar I, Dupont B, et al. Voriconazole for invasive bone
aspergillosis: a worldwide experience of 20 cases. Clin Infect Dis 2005;
40:1141-7.
82. Denes E, Boumediene A, Durox H, et al. Voriconazole concentrations
in synovial fluid and bone tissues. J Antimicrob Chemother 2007;59:
818-9.
83. Schwartz S, Ruhnke M, Ribaud P, et al. Improved outcome in central
nervous system aspergillosis, using voriconazole treatment. Blood
2005;106:2641-5.
84. Böhme A, Ruhnke M, Buchheidt D, et al. Treatment of invasive fungal
infections in cancer patients—recommendations of the Infectious
Diseases Working Party (AGIHO) of the German Society of
Hematology and Oncology (DGHO). Ann Hematol 2009;88:97-110.
85. Pappas PG, Rex JH, Sobel JD, et al. Guidelines for treatment of
candidiasis. Clin Infect Dis 2004;38:161-89.
86. Walsh TJ, Anaissie EJ, Denning DW, et al. Treatment of aspergillosis:
clinical practice guidelines of the Infectious Diseases Society of
America. Clin Infect Dis 2008;46:327-60.