Cutaneous candidiasis: treatment with miconazole nitrate


Cullin, S.I.

Cutis 19(1): 126-129

1977


In a wellcontrolled, doubleblind, randomized study, 30 patients with cutaneous candidiasis were treated with a 2% miconazole nitrate lotion or its placebo control. By the 14th day, 13 of the 15 patients [87%] treated with miconazole nitrate achieved clinical and mycologic cures. Only a single patient treated with the placebo lotion could be classified as a therapeutic cure. In a second portion of the study those patients judged to be therapeutic failures were treated with the lotion containing 2% miconazole nitrate. By combining the results of both portions of the study we find that miconazole nitrate lotion produced both a clinical and mycologic cure in all patients receiving the active lotion. The miconazole lotion formula was well tolerated by all patients and no side effects were noted. The fact that miconazole nitrate acts rapidly in relieving symptoms, is well tolerated, and is highly effective against dermatophytes, yeasts and grampositive bacteria, makes it a welcome addition to available topical therapy of skin infections.

therapeutics
for
the
clinician
New
reports
on
treatment
modalities
of
possible
interest
to
patient-caring
physicians
Cutaneous
Candidiasis:
Treatment
with
Miconazole
Nitrate
Stanley
1.
Cullen,
MD,
Gainesville,
Florida
In
a
well-controlled,
double-blind,
random-
ized
study,
30
patients
with
cutaneous
candidia-
sis
were
treated
with
a
2%
miconazole
nitrate
lotion
or
its
placebo
control.
By
the
14th
day,
13
of
the
15
patients
[87%]
treated
with
miconazole
nitrate
achieved
clinical
and
mycologic
cures.
Only
a
single
patient
treated
with
the
placebo
lotion
could
be
classified
as
a
therapeutic
cure.
In
a
second
portion
of
the
study
those
patients
judged
to
be
therapeutic
failures
were
treated
with
the
lotion
containing
2%
miconazole
nitrate.
By
combining
the
results
of
both
portions
of
the
study
we
find
that
miconazole
nitrate
lotion
produced
both
a
clinical
and
mycologic
cure
in
all
patients
receiving
the
active
lotion.
The
micon-
azole
lotion
formula
was
well
tolerated
by
all
patients
and
no
side
effects
were
noted.
The
fact
that
miconazole
nitrate
acts
rapidly
in
relieving
symptoms,
is
well
tolerated,
and
is
highly
effec-
tive
against
dermatophytes,
yeasts
and
gram-posi-
tive
bacteria,
makes
it
a
welcome
addition
to
available
topical
therapy
of
skin
infections.
Reprint
requests
to
6628
N.W.
9th
Blvd,
Gainesville,
Florida
32605.
M
iconazole
nitrate
is
a
synthetic
deriva-
tive
of
phenethyllirnidazole
with
topical
antimicrobial
activity
against
dermatophytes,
yeast,
and
gram-positive
bacteria.
1
-
4
Early
Euro-
pean
reports
of
miconazole
nitrate's
clinical
use-
fulness
grouped
dermatophyte
and
yeast
infec-
tions,
making
it
difficult
to
ascertain
miconazole
nitrate's
efficacy
in
controlling
cutaneous
candidi-
asis.
This
study
was
designed
to
establish
the
effectiveness
of
miconazole
nitrate
in
the
therapy
of
cutaneous
candidiasis.
This
paper
reports
the
results
of
this
well
controlled
study
in
patients
with
proven
Candida
albicans
infection.
Materials
and
Methods
Thirty
patients
with
cutaneous
candidal
inter-
trigo,
paronychia
or
perleche
from
the
private
practice
of
the
investigator
were
included
in
the
study.
Clinical
diagnosis
was
verified
by
the
obser-
vation
of
yeast
forms
and/or
pseudohyphae
in
scrapings
treated
with
a
20%
potassium
hydrox-
ide-dimethylsulfoxide
mixture°
and/or
in
smears
stained
by
the
Gram
technique.
Appropriate
specimens
from
all
patients
grew
colonies
identi-
fiable
as
Candida
albicans
by
developing
the
typical
dark
brown
or
black
colonies
on
Nicker-
son's
medium°
and
the
cream
colored,
smooth,
mucoid
colony
on
dermatophyte
test
medium
(DTM).
7
All
topical
and
systemic
antiinfective
therapy
was
discontinued
at
least
two
weeks
before
test
medication
was
begun
and
only
the
126
CUTIS
si
14
test
material
and
a
mild,
nonmedicated
soap
were
allowed
for
the
duration
of
the
study.
was
divided
into
two
phases.
In
T
h
e
study
phase
I,
patients
were
supplied
with
either
2%
miconazole
lotion
or
its
placebo
control.
Distribu-
tion
was
accomplished
by
a
randomized
tech-
n
ique.
Patients
were
instructed
to
apply
the
material
twice
daily
to
affected
areas.
Repeat
clinical
and
mycological
evaluations
were
accom-
plished
after
7
and
14
days
of
therapy.
Patients
judged
to
be
therapeutic
failures
after
14
days
of
treatment
were
entered
into
phase
II
of
the
study.
In
the
second
phase
of
the
study,
patients
were
treated
an
additional
14
days
with
a
lotion
from
coded
containers,
and
evaluated
weekly.
Patients
experiencing
clinical
and
mycologic
clearing
in
phase
I
were
not
entered
into
phase
II,
but
were
reexamined
at
days
21
and
28
to
detect
any
evidence
of
relapse.
All
the
medication
on
the
phase
II
part
of
the
study
was
2%
miconazole
nitrate,
a
fact
unknown
to
the
investigator
until
the
code
was
revealed
at
the
end
of
the
study.
This
portion
of
the
study
was
designed
by
the
sponsor
to
insure
that
all
patients
would
receive
adequate
therapy
for
their
disease,
while
also
providing
additional
information
on
efficacy
and
required
duration
of
therapy.
No
medication
was
to
be
applied
to
the
clinically
affected
areas
for
at
least
12
hours
prior
to
evaluation
on
days
7,
14,
21
&
28.
In
those
patients
not
entered
into
he
phase
II
portion
of
the
study,
no
treatment
f
any
kind
was
applied
between
the
end
of
)tease
I
part
of
the
study
and
the
28th
day
follow-
up
visit.
esults
In
phase
I,
15
patients
received
active
medica-
tion
and
15
received
the
placebo.
By
day
fourteen,
13
of
the
15
patients
[87%]
treated
with
micona-
zole
nitrate
achieved
clinical
and
mycologic
cures.
The
two
patients
who
did
not
have
a
complete
therapeutic
cure
in
the
first
two
weeks,
responded
in
phase
II
to
the
second
course
of
active
therapy
(Table
I
and
II).
No
relapses
were
noted
at
the
28th
day
examination
in
the
13
patients
from
phase
I
with
therapeutic
cures.
Symptomatic
relief
from
miconazole
therapy
was
no
ted
within
the
first
48
hours
in
12
of
15
patients
in
phase
1
of
the
study.
n
the
placebo
group,
the
clinical
signs
per-
led
and
mycologic
tests
remained
positive
in
patients.
Only
a
single
patient
could
be
classi-
TABLE
I:
Patients
Classified
According
to
KOH,
Culture,
and
Clinical
Evaluation
at
the
End
of
Phase
I
Miconazole
KOH
Result
Neg
Pos
Culture
Result
Neg
Pos
Neg
Pos
Clinical
Evaluation:
Good-Excellent
13*
0
0
0
Fair-No
Change
0
0
1
1
Placebo
KOH
Result
Neg
Pos
Culture
Result
Neg
Pos
Neg
Pos
Clinical
Evaluation:
Good-Excellent
1*
0
0
1
Fair-No
Change
0 0
0
13
*Therapeutic
Cures
TABLE
II:
Patients
Classified
According
to
KOH,
Culture,
and
Clinical
Evaluation
at
the
End
of
Phase
II
Miconazole
KOH
Result
Neg
Pos
Culture
Result
Neg
Pos
Neg
Pos
Clinical
Evaluation:
Good-Excellent
16*
0
0
0
Fair-No
Change
0
0
0
0
*Therapeutic
Cures
fled
as
a
therapeutic
cure
at
day
14
in
the
placebo
group
of
patients.
This
patient
had
interdigital
candidiasis
of
the
hand.
Phase
II
medication
produced
a
therapeutic
cure
in
the
remaining
14
patients
(Table
I
and
II).
Combining
the
results
of
patients
treated
in
phase
I
and
phase
II,
we
find
that
miconazole
produced
a
therapeutic
cure
in
all
29
patients
receiving
the
active
lotion.
In
27
patients,
a
cure
was
obtained
within
14
days
of
active
therapy
while
two
patients
required
additional
therapy.
The
miconazole
lotion
formula
was
well
toler-
ated
by
all
of
the
patients
and
no
side
effects
were
noted.
Commentary
The
need
for
a
safe
and
effective
topical
anti-
yeast
preparation
has
been
intensified
by
an
increased
incidence
of
cutaneous
and
mucocuta-
neous
candidiasis.
Miconazole
has
been
success-
127
ume
19,
January
1977
Cullen
fully
used
in
the
topical
treatment
of
cutaneous
and
vaginal
candidiasis
1
-
8-19
with
greater
than
90%
of
the
patients
showing
clinical
and
mycologic
clearing.
Peeters
et
al"
suggested
a
regeneratory
effect
on
Doderlein's
bacilli,
as
well
as
a
normaliza-
tion
of
the
vaginal
pH.
By
limiting
this
study
to
patients
with
proven
Candida
albicans
infection,
and
studying
these
patient's
in
a
well-controlled,
double-blind
manner,
the
therapeutic
effect
of
this
broad
spectrum,
topical
antimicrobial
agent
in
cutaneous
candidiasis
could
be
established.
The
cause
of
the
increased
incidence
of
candidia-
sis
is
attributed
to
the
widespread
use
of
oral
contraceptives,
systemic
antibiotics,
immu
no-
suppressants,
as
well
as
to
the
almost
universal
use
of
the
less
absorbent,
heat-retaining
synthetic
fibers
in
clothing
manufacture.
Although
most
workers
agree
that
there
is
an
increased
number
of
patients
with
candidiasis,
especially
vaginal
candidiasis,
some
doubt
the
relative
importance
of
the
often
repeated
precipitating
factors.
In
a
recent
study
2
'
evaluating
long-term
tetracycline
therapy
for
acne
vulgaris,
the
incidence
of
vaginal
candidiasis
was
only
1.3%.
In
the
examination
of
an
unselected
group
of
453
women
with
the
major
symptom
of
a
vaginal
discharge,
Lohmeyer
et
at
8
were
able
to
demonstrate
Candida
albicans
infec-
tion
by
culture
in
15%
of
the
cases.
In
a
study
designed
to
determine
the
prevalence
of
yeast
infections
as
well
as
the
effectiveness
of
micona-
zole
therapy,
Vanheule
et
a1
22
reported
an
amaz-
ingly
high
incidence
of
vulvar
or
scrotal
infection,
predominantly
due
to
Candida
albicans,
of
20.7%
of
121
premature
infants
and
of
13.2%
of
38
children
under
the
age
of
six.
The
development
of
such
undesirable
side
effects
as
permanent
atrophic
striae
in
the
groin
and
allergic
sensitization
by
one
or
more
of
the
multiple
ingredients
of
Mycolog°
cream
has
rendered
this
widely
used
combination
product
less
useful
than
it
had
been
in
the
past.
Micona-
zole
nitrate,
1-[2,4-dichloro-B-(2,4-dichloroben-
zyloxy)phenethyl]
imidazole
mononitrate,
was
first
synthesized
in
1969,
23
and
has
been
available
in
Europe
since
1971.
The
broad
spectrum
antimi-
crobial
action
of
this
compound
against
a
wide
variety
of
pathogenic
organisms
has
been
con-
firmed
in
clinical
studies.
24-27
When
applied
locally
in
guinea
pigs
with
cutaneous
candidiasis,
miconazole
has
been
found
to
exert
a
better
effect
than
amphotericin,
nystatin
and
primaricin.
2
Similar
results
have
been
demonstrated
in
hu-
mans.
11
Miconazole
appears
to
act
primarily
on
the
yeast
cell
membranes
inducing
selective
permeability
changes.
28
Early
European
studies
suggested
that
miconazole
had
antiyeast
value,
but
many
of
these
studies
28-33
combined
dermato-
phyte
and
yeast
infections
under
the
term
"fungal
origin",
making
it
difficult
to
determine
the
degree
of
effectiveness
against
pure
yeast
infections.
Early
studies
9,31
tended
to
have
large
numbers
of
patients
in
which
the
causative
organism
was
not
isolated,
therefore
leaving
doubt
as
to
the
correct
diagnosis.
Miconazole
appears
to
be
quite
safe
as
there
were
no
systemic
or
topical
adverse
reactions
either
in
this
study
or
in
any
of
those
reported
in
the
literature.
Miconazole
has
been
reported
34
'
35
to
be
effective
and
non-toxic
when,
used
systemically
by
oral
or
intravenous
adminis-
tration
for
systemic
candidiasis.
Multiple
studies
24
.
23,3
°
report
very
rapid
relief
of
symptoms
with
miconazole
therapy.
In
fact
one
investigator
30
suggested
that
it
has
a
true
antipruritic
effect.
Patients
were
accordingly
questioned
concerning
the
rapidity
with
which
they
experienced
symptomatic
relief.
Twelve
of
the
15
patients
who
received
miconazole
in
the
first
part
of
this
study
experienced
relief
of
their
symptoms
within
the
first
48
hours
of
therapy.
Product
Information—Miconazole
nitrate:
(John-
son
&
Johnson
Dermatologic
Division).
References
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AA:
Further
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179,
1972.
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antimycotic
for
the
local
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of
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treatment
of
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in
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W
et
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43,
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the
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Rundschau
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191,
1974.
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F
et
al:
Observations
on
candidal
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I
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688,
1972.
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SI,
Cohan
RH:
Minocycline
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in
acne
vulgaris.
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17:
1208,
1976.
22.
Vanheule
R
et
al:
Prevalence
and
treatment
with
micona-
zole
of
fungal
skin
infections
in
children
and
premature
infants.
Castellanis
2:
91,
1974.
23.
Godefroi
EF
et
al:
The
preparation
and
antimycotic
properties
of
derivatives
of
L-phenethylimidazole.
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Chem
12:
784,
1969.
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Mandy
Si,
Garrott
TC:
Miconazole
treatment
for
severe
dermatophytosis.
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230:
72,
1974.
25.
Fulton
JE
Jr:
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for
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19,
January
1977
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