Clinics in Dermatology (2010) 28, 202211

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 dbridement 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 necrotizing 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).
0738-081X/$ see front matter 2010 Elsevier Inc. All rights reserved.
doi:10.1016/j.clindermatol.2009.12.003

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 Epidermophyton 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

Otomycosis: Diagnosis and treatment

Table 1 Spectrum of fungi isolated from patients with
otomycosis
Aspergillus niger
Aspergillus fumigatus
Aspergillus flavus
Aspergillus terreus
Aspergillus candidus
Aspergillus hollandicus
Aspergillus alliaceus
Aspergillus janus
Aspergillus versicolor
Aspergillus nidulans
Trichophyton rubrum
Trichophyton mentagrophytes
Epidermophyton floccosum

Scedosporium apiospermum
Fusarium solani
Hendersonula toruloidea
Mucor spp
Paecilomyces variotii
Penicillium spp
Cryptococcus neoformans
Candida parapsilosis
Candida albicans
Candida guilliermondii
Rhodotorula rubra
Candida glabrata
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 perforation 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, accompanied by inflammation of the meatal epithelium.
Chronic hyperplastic inflammation of the mucous membrane 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 scintigraphy 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 Blankophorstained specimens of debris from the auditory canal. Giemsa or
Gram-stained histologic samples will detect numerous hyperkeratotic, 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 Sabouraud glucose agar tubes or plates for fungal culture. One tube/

I. Vennewald, E. Klemm
plate is incubated at 37C and the other at room temperature
(22C) 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 dermatophytesyeast-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 microbiologist and the clinician is very important. All commercially 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 fr
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 optical 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 inflammation 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 Aspergillus 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 surrounded 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 colonization should be treated with intense dbridement 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 advantages 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 concentration 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, econazole, 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
Table 2

I. Vennewald, E. Klemm
Ototoxicity of common topical antimycotic preparations tested in animal models

First author, year

Antifungal agents, solvents and aseptics

Result

Experimental animals/model

50% propylene glycol

Ototoxic

Rats/auditory brainstem
responses

Ototoxic
Ototoxic
Ototoxic
Ototoxic
Ototoxic
Ototoxic

Tom,60 2000

70% isopropyl alcohol

2% acetic acid
2% acetic acid in aluminum acetate
1% gentian violet
2% acetic acid in propylene glycol
25% m-cresyl acetate in 25% isopropanol, 5% castor oil,
propylene glycol
2% acetic acid in propylene glycol diacetate, 3% propylene glycol
2% acetic acid in deionized water
1% clotrimazole in polyethylene glycol 400
1% tolnaftate in polyethylene glycol 400
Clotrimazole 1% solution in polyethylene glycol

Jinn,61 2001

2% miconazole nitrate in benzoic acid, BHA, mineral oil,

peglicol 3 oleate, pegoxol 7 stearate, water
1% tolnaftate solution in BHT, polyethylene glycol
Nystatin 100,000 U/g cream in polysorbate 60, aluminum
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
2% acetic acid in propylene glycol

Spandow,

58

1988

Marsh,59 1989

Ototoxic
Ototoxic
Non ototoxic
Non ototoxic
Non ototoxic

Guinea pigs/auditory
brainstem responses

Guinea pigs/measurements
of hair cell loss (cochlea)

Non ototoxic
Non ototoxic
Non ototoxic

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 otomycosis 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 perforation.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 antiseptic, 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

Table 3

207

Efficacy of topical antifungal treatment of otomycosis, overview of studies in chronological order

First author,
year

Antimycotic

Administration

Bambule,42
1978
Piantoni,43
1989
Paulose,44
1989

Econazole

1% solution, 1 mL, every

other day for 10 days
1% solution, once daily,
4-15 days
Not reported
Not reported
1% solution
Not reported

Del Palacio,45
1993

Bifonazole
Clotrimazole
Gentian violet
Tolnaftate
Nystatin, neomycin,
gramicidin, triamcinolone
Acetic acid 2% in propylene
glycol with hydrocortisone
Nystatin
Acetic acid 2% in
propylene glycol
Econazole
Bifonazole
Bifonazole

Tisner,46 1995 Sodium ethyl

mercuriosalicylate
(merthiolate)
Chander,47
Mercurochrome
1996
Clotrimazole
Miconazole
Kurnatowski,48 Fluconazole
2001

Del Palacio,49
2002

Pigmentum Castellani,
natamycin, and
fluconazole oral
Ciclopiroxolamine
Ciclopiroxolamine
Boric acid

Vennewald,1
2003

Clotrimazole
Amphotericin B

Kunelskaya,50
2004
Kryukov,51
2005
Jackmann,52
2005

Martin,53

Naftifine
Terbinafine

Acetic acid/propylene
glycol
Clotrimazole
Nystatin
Aluminium acetate otic
2005 Clotrimazole

Patients, Patients, age

No.

Efficacy,
Study design
clinical cure

30

19-67 years

100%

Retrospective

23

1 mon-71 years

100%

Prospective

171

19-80 years

89%

Not reported

81%
81%
79%
71%

Not reported
Not reported

68%
67%

Not reported
1% solution,
once daily, 7 days
1% cream, once daily,
7 days
0.1% solution

35

Not reported

61%
72.5%

152

11-78 years

93.4%

Solution, 4 drops twice

40
daily, 14 days
Solution, 4 drops twice
23
daily, 14 days
Solution, 4 drops twice
17
daily, 14 days
0.2% solution, thrice daily 96
and 50 mg oral once daily
for 21 days
2.5% suspension, thrice per
24 hours and 50 mg oral
once daily for 21 days
1% cream, once daily
17
for 1 week
1% solution, once daily
17
for 1 week
5% in ethanol, once daily 30
for 1 week
1% solution, once daily
58
for 2-4 weeks
0.5% suspension, once
1
daily for 4 weeks
Solution, once-twice
108
daily for 2 weeks
250 mg daily for
27
2-4 weeks
Not reported
15
Not reported
Not reported
Not reported
Not reported

8
2
1
27

Prospective

Prospective,
randomized

Prospective
Prospective

100%
All age groups,
most 21-30 years
100%
100%
Not reported

89%

Not reported

90.6%

18-76 years

60%

18-76 years

65%

45-90 years

80%

Prospective

Prospective,
randomized

Retrospective
16-90 years

100%

12-76 years

85.2%

Prospective

19-63 years

74%

Prospective

17 mon-29
years

40%

Retrospective

16 days-18
years

50%
50%
0%
100% in
all groups

Retrospective

(continued on next page)

208

I. Vennewald, E. Klemm

Table 3 (continued)
First author,
year

Ho,54 2006

Kiakojuri,55
2007

Antimycotic

Administration

Tolnaftate
Fluconazole, oral
Acetic acid
Fluconazole, topical
Oral fluconazole and
acetic acid
Vioform powder
Amphotericin B, oral
Nystatin
Treatment unspecified
Cresylate otic
Ketoconazole ointment
Aluminium acetate otic
Miconazole

Not reported
Not reported
Not reported
Not reported
Not reported

27
25
14
6
10

Not reported
Not reported
Not reported
Not reported
Thrice daily
1 to 3 cm3 once a week
Not reported
2% cream, one application

5
2
1
50
44
44
7
55

2% cream and 3% drops

in 97 % ethanol,
one application
1st-3rd day: 1% solution
twice daily
4th-7th day: 1% cream
twice daily
2nd-4th week: once daily
5th-6th week: every
second day

Miconazole and acetic acid

Kunelskaja,56
2008

Naftifine

Patients, Patients, age

No.

6-91 years

Efficacy,
Study design
clinical cure

16-76 years

86%
95%
86%
96,6%

58

15-98 years

100%

30

19-60 years

100%

Retrospective

Prospective

Prospective

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 commercially 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, econazole, 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 grampositive 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 compound, 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. Mercurochrome 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 triphenylmethane dyes (gentian violet and cresyl acetate) were
ototoxic in animal models.
Topical formulations are available in a 0.5% to 1% solution.

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 invasive fungal infections.84-86

Systemic therapy
The treatment of immunocompromised patients consists
of the application of combined systemic and topical
antifungal drugs after surgical dbridement 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 dbridement 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.

Conclusions
The prognosis of otomycosis is good in immunocompetent 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.

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