Abstract
Objective: This study was conducted
to compare the use of two different antifungal agents from the azoles family; Miconazole
cream applied topically on the skin of the external canal and tympanic membrane
and Clotrimazole otic drops.
Methods: Ninety patients aged (12-72)
years who presented with otomycosis at Prince Hashim
Hospital in Zarka between
October 2007 to June 2009 were enrolled in this study. Patients were divided
into two groups, group A (48 patients): patients were treated by toileting and
application of Miconazole cream, group B (42 patients): patients were treated
by toileting and using Clotrimazole 1% (otozol) otic drops. Patients followed
after one and two weeks. One way ANOVA
test was used to calculate the significant differences at P<0.05 between the
means of the study treatment groups
Results: Patients in group A (Miconazole)
showed a better response to treatment in comparison to patients in group B (Clotrimazole
drops).
Conclusion: Although the two
treatment regimens showed no statistically significant difference due to the
small number of cases, Micanazole cream after toileting is a better choice due
to its lower cost and better compliance
Key
words: Clotrimazole
(otozol), Miconazole, Ootomycosis, Toileting.
JRMS
September 2011; 18(3): 34-37
Introduction
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.(1) It is one of the
common conditions encountered in a general otolaryngology clinic setting and
its prevalence has been quoted to be as
high as 9% among patients who present with signs and symptoms of otitis externa.(2)
There is an alarming increase in its incidence
due to the wide spread use of broad-spectrum antibiotics, steroids and other
chemotherapeutic agents. It has been postulated that indiscriminate use of
topical ear drops has increased the incidence of fungal infections of the
external auditory canal.(3)
The
fungi that produce otomycosis are generally saprophytic fungi species that
abound in nature and that form a part of the commensal flora of healthy
external auditory canal. These fungi are commonly Aspergillus and Candida.
Aspergillus niger
is usually the predominant agent although A.flavus, A.fumigatus, A. terreus
(filamentous fungi), Candida albicans and C. parapsilosis (yeast-like
fungi) are also common.(4)
Fungal
infections occur more frequently in tropical or subtropical climates or during
periods of intense heat and humidity. It is common in patients who have
undergone open cavity mastoidectomy and those who wear hearing aids.(5)
Jones (1965) reported that patients who had recurrent attacks of otitis externa
had primary fungal infections with a super-added bacterial pathogen, the latter
cleared up with treatment but the fungal infection was not eradicated, causing relapses.(6)
The
clinical symptoms most frequently observed in these patients were burning
sensation in the ear, pruritis, sensation of fullness in the ear, otalgia,
otorrhoea, loss of hearing, tinnitus and severe headaches.(7)
There are four main classes of drugs for the
treatment of fungal infections: polyenes, triazoles, nucleoside analogues, and
echinocandins. The polyenes family includes Amphoterecin B and Nystatin. The Triazoles
family, better known as azoles includes: Fluconazole, Clotrimazole and Miconazole.
The mechanism of action of polyenes and azole families involves an essential
chemical component called ergosterol found in the fungal cell membrane. The
drug binds to ergosterol leading to its death.(1)
Different
studies in the literature compared the efficacy of clotrimazole and Miconazole
otic solutions in the treatment of otomycosis, some indicating equal efficacy
while other studies were in favor of Clotrimazole, but none of the studies
compared the efficacy of Clotrimazole otic drops with miconazole cream (3, 6,
8, and 9).
This
study was conducted to compare the use of two deferent antifungal agents from
the azoles family; Miconazole cream applied topically on the skin of the
external canal and tympanic membrane and Clotrimazole otic drops.
Methods
This
comparative study was conducted at Prince
Hashim Hospital
in Zarka from October 2007 to June 2009, patients of ages (12-72) years who
presented with otomycosis were enrolled in the study.
Exclusion
criteria include:
-
Otitis externa with external auditory meatus
stenosis.
-
Chronic discharging ear.
-
Previous ear surgery.
The
criteria of clinical
diagnosis were history and characteristic
findings on otoscopic examination. The classical appearance looked like a
grayish white plug resembling wet blotting paper, yellowish spores, a whitish,
furry structure, or blackish spores covering the canal and sometimes the
tympanic membrane also.
All
the affected ears were thoroughly cleaned with suction under magnified otoscopy.
After complete removal of debris and the fungal mass, cultures are not
routinely obtained because there is generally a rapid response to the treatment.
All the patients were instructed to avoid water entering their ears and they
offered to choose between two topical treatment regimens; Group A 48 patients (53.3%)
were treated by the Micanazole cream which was applied in the clinic directly
onto the involved external auditory canal after toileting. Application is facilitated with a small syringe
(3 cc) and an 18 gauge IV catheter. The micanazole cream is held in place by
its innate viscosity and the shape of the external auditory canal. The ear
canal is inspected 1 week later and residual cream is removed and a second
application is used for persistent disease, all cases were followed up after 2 weeks.
Group B 42 patients were treated by topical application of Clotrimazole 1% (Otozol)
otic drops, 2-3 drops three times a day in the affected ear. All of them were
followed up after, one and two weeks.
Patient’s
response to treatment was divided as follows:
Good response: when the external
auditory canal and tympanic membrane were dry with no remnant of secretions.
Moderate
response:
when there was minimal secretions (not dry).
No response: still full of
secretions.
One way
ANOVA test was used to calculate the significant differences at P<0.05
between the means of the study treatment groups
Results
Ninety-eight
patients were initially enrolled in the study, aged from 12-72 years (mean age
42.3). Fifty three patients in group A
and 45 patients in group B. There was no statistical difference in age or
gender between the two groups.
Eight
patients were excluded from the study, 3 presented with severe otitis externa,
2 had past history of discharging ear and 3 patients had previous ear surgery.
Table
I. Presenting complaint at the time of diagnosis
|
Complaint
|
Number
|
%
|
|
Otalgia
|
50
|
55
|
|
Aural
fullness
|
35
|
38.8
|
|
Itching
|
31
|
34.4
|
|
Otorrhea
|
26
|
28.8
|
|
Hearing
loss
|
20
|
22.2
|
Table
II.
Treatment response after one week
|
Treatment
response
|
Group A
Toileting+miconazole (48)
|
Group B
Toileting+otozol E/D (42)
|
P value
|
|
No
|
%
|
No
|
%
|
|
Good
|
35
|
72.9
|
23
|
54.7
|
0.140
|
|
Moderate
|
8
|
16.6
|
12
|
28.5
|
|
|
No
|
5
|
10.4
|
7
|
16.6
|
|
Table
III.
Treatment response after 2 weeks
|
Treatment
response
|
Group A
Toileting+miconazole (48)
|
Group A
Toileting+miconazole (48)
|
P value
|
|
|
No
|
%
|
No
|
%
|
|
|
Good
|
40
|
83.3
|
30
|
1.4
|
|
|
Moderate
|
6
|
12.5
|
9
|
21.4
|
0.075
|
|
No
|
2
|
4.1
|
3
|
7.1
|
|
Total
number of patients found to be eligible in our study was ninety, 48 patients in
group A (toileting and Miconazole cream). Forty two patients in group B (toileting and
Clotrimazole otic drops).
The
most common presenting complaint at time of diagnosis was otalgia, followed by
aural fullness, itching, and otorrhoea and hearing loss. (Table I)
After
one week, 35 patients from group A showed good response, 8 patients moderate
response and 5 patients still with no response, while 23 patients from group B
found to have good response, 12 with moderate response and 7 with no response. The
results were statistically not significant with a significance value 0.14,
which is less than the significance level of 0.05. (Table II)
After
two weeks, 40 patients in group A found to have good response, 6 had moderate
response and only 2 patients had no response. In group B, 30 patients showed
good response, 9 had moderate response and 3 patients with no response. The
results were statistically not significant with a significance value 0.075.
(Table III)
Discussion
Otomycosis
is an entity frequently encountered by otolaryngologist and can usually be
diagnosed by clinical examination.(8) Treatment
recommendations have included local debridement, discontinuation of topical antibiotics, and local/systemic
antifungal agents.(2)
In Jordan, particularly at the Royal Medical Services, we usually treat
otomycosis by mechanical cleansing of the canal followed by local application
of antifungal cream or prescribing
antifungal otic drops to the patient and follow them every week till recovery. In our study,
we compared two modalities of otomycosis treatment, cleaning of visible fungal
elements in the external auditory canal by suction (toileting) and application
of Miconazole cream directly onto the involved external auditory canal skin at
the clinic by ENT doctor and toileting followed by use of otozol ear drops by
the patients.
In
our study application of miconazole cream after toileting the external auditory
canal gave the best result as 40 patients out of 48 (83%) showed complete
recovery after two weeks. Although using clotrimazole ear drops after toileting
gave good response but this modality is still less effective than application
of miconazole cream after both one week and two weeks, statistically the
results were not significant in both groups. Although multiple in vitro studies
have examined the efficacy of various antifungal agents, there is no consensus
on the most effective agent.(9) Some studies showed that
clotrimazole was one of most effective agents for management of otomycosis,
with reported rate of effectiveness that varies from 95% to 100 %.(10)
Miconazole cream 2% has also demonstrated an efficacy rate of 90 %.(11)
Azoles
are synthetic agents that reduce the concentration of ergosterol, an essential
sterol in the normal cytoplasmic membrane. They are a class of five-membered
nitrogen heterocyclic ring compounds containing at least one other noncarbon
atom, nitrogen, sulfer or oxygen.(12) Clotrimazole is the
most widely used topical azole.(13) It is available as
powder, a lotion, and a solution. It is considered free of ototoxic effects.(14)
Miconazole is an imidazole that has been successfully used for over 30 years
for the treatment of superficial and cutaneous disease. This agent is
distinguished from other azoles by possessing two mechanisms of action. The
first mechanism is shared with other azoles and involves the inhibition of
ergosterol synthesis. Another mechanism involves inhibition of peroxidases,
which results in the accumulation of peroxide within the cell resulting in cell
death.(15)
Predisposing
factors such as a failure in the ear‘s defense mechanisms (changes in the
coating epithelium, changes in ph, quantitative and qualitative changes in ear
wax), bacterial infection, hearing aid or hearing prosthesis, self inflicted trauma
(use of Q-tips to clean the ears, swimming, broad spectrum antibiotic agents,
steroids and cytostatic medications, neoplasia and immune disorders, all of
which can render the host susceptible to the development of otomycosis.(16)
The
analysis of complaints reported by patients investigated in this study showed
that the most common symptoms were otalgia followed by aural fullness and
itching, while in a study done by Kurnatowski and Filipiak showed that the most
common symptom is pruritus then sensation of fullness and ear discharge.(17)
Limitations
of the Study
Further
future study with a larger number of patients and longer period of follow up is
needed
Conclusion
Although
the two treatment regimens showed no statistically significant difference due
to the small number of cases, Micanazole cream after toileting is a better
choice due to its lower cost and better compliance.
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