178

SAMT

DE EL 67

2 FEBRUARIE 1985

Ketoconazole in the treatment of

vaginal candidiasis
B. BLOCH,

ELSABE SMYTHE
Exclusion criteria

Summary
In a preliminary open prospective study ketoconazole
(Nizoral; Janssen) 200 mg twice daily for 5 consecutive days was found to' be extremely effective in
treating vulvovaginal candidiasis, producing cure
rates of 96% at 7 days and 92% at 28 days. The oral
route of administration has definite advantages over
the vaginal route and improves patient compliance.
No side-effects related to treatment were found in
this study.
S Afr Med J 1985; 67: 178-179.

Many new forms of therapy have become available recently for

the treatment of vaginal candidiasis, which remains a common
and troublesome problem in gynaecological practice. Until the
advent of ketoconazole (Nizoral; Janssen), all preparations
were administered by the vaginal route, which considerably
reduces patient compliance and thus effectiveness. This preliminary study was undertaken to assess the efficacy of oral
ketoconazole tablets taken daily for 5 days and to determine
the incidence and severity of side-effects of this treatment
regimen in an open prospective manner.
Previous studies H have assessed the efficacy of vaginal
imidazole preparations taking as the endpoint the absence of
yeasts in a vaginal swab within 8 or 21 days of the end of
therapy. This study assessed the clinical and bacteriological
effectiveness of oral ketoconazole at 7 and 28 days after
treatment.

Patients and methods

Twenty-five women with mycologicaily proven vulvovaginal
candidiasis were treated with ketoconazole 200 mg Cl tablet)
twice daily for 5 consecutive days; clinical and cultural response
were assessed 7 and 28 days after the end of treatment.
Patients ranged in age from 19 to 45 years (mean 32,5 years),
in weight from 49 to 92 kg (mean 67 kg) and in parity from 0
to 6 (mean 2,4).

Pregnant women, those who had received any treatment for

candidiasis during the previous 4 weeks, those who were
unreliable with regard to anendance for follow-up, those with
mixed infections and those with more than one sexual partner
were excluded from the study.

Diagnostic criteria
Candidiasis was diagnosed if convincing clinical signs and
symptoms of candidal infection were present and positive
results were obtained on microscopic examination of a wet
smear and potassium hydroxide preparation within 15 minutes
of examination, a cytological test (at first examination only),
and culture on Nickerson's medium.
Treatment with ketoconazole was instituted only if clinical
signs were present and microscopy was positive; at re-examination on days 7 and 28 the clinical findings were again evaluated
and microscopy and culture were repeated. No additional
topical or systemic antifungal therapy was allowed. Clinical
evaluation consisted of scoring for the following symptoms:
leucorrhoea, vulval pain, dyspareunia, dysuria and pruritis.
The degree of vulvitis and vaginitis was evaluated by one
observer.
. Clinical cure was r.egarded as the disappearance of signs and
symptoms with negative test results at repeat examination; all
side-effects and adverse reactions were documented on specially
designed case report forms.

Results
All 25 patients had clinical and mycological features of candidiasis on entry to the study. (\t 7 days after the end of therapy
mycological findings were positive in only 1 patient (4%); at 28
days findings were positive in 2 patients (8%). The respective
mycological cure rates at 7 and 28 days were 96% and 92%.
The frequency of coitus and date of last coitus were recorded
for all patients. From Table I it will be seen that the percentage
of patients having had previous anacks of candidiasis is higher
in the group recorded as having infrequent c~itus. This is
probably because of the pain and discomfort associated with
this infection, which would influence sexual activity. Nineteen
of the 25 patients had previously had vulvovaginal candidiasis.

Selection criteria
Sexually active women were selected, with no age exclusion.
The severity of the signs and symptoms of candidiasis was
assessed before therapy.

TABLE I. FIRST ATIACK OR PREVIOUS ATIACKS IN RELATION

TO FREQUENCY OF COITUS*

Previous
First attack
No.
0/0

Department of Obstetrics and Gynaecology, University of

Cape Town and Groote Schuur Hospital, Cape Town
B. BLOCH, M.B. CH.B., M.MED. (0. ET G.), F.R.C.O.G.
ELSABE SMYTHE, R.N., R.M., Research Sister

Regular
Infrequent
Total
*Regl)lar -

4
2

If

36
14
24

twice or more a week; infrequent -

attacks
No.
0/0
7

64

12

86

19

76

once a week or less often.

Total

11
14
25

SAMJ

Potential predisposing factors were identified in 7 of the 25

patients; these were obesity (2 patients), malignant disease (1)
and combined oral hormonal contraception (4). There was no
difference in the incidence of either first attacks or previotls
attacks in patients with and without predisposing factors
(Table 11).

TABLE 11. FIRST ATTACK OR PREVIOUS ATTACKS IN RELATION

TO PREDISPOSING FACTORS

First attack
No.
%
No predisposing
factors
Predisposing
factors
Total

Previous
attacks
No.
%

22

14

29
24

6""

Total

78

18

71

19

76

7
25

A number of clinical signs and symptoms were evaluated

(Table Ill). Leucorrhoea was present in all patients, and the
evolution of this symptom was observed to differ from the
mycological fmdings. However, leucorrhoea is a nonspecific
symptom which can be present in the absence of pathogenic
bacterial infection, which may explain its persistence.
Eighteen patients (72%) presented with troublesome pruritus,
14 (56%) with dysuria, 12 (48%) with vaginitis and 11 (44%)
with vulvitis and dyspareunia. Only 3 patients (12%) presented
with vulval pain. All these symptoms and signs responded to
therapy, indicating excellent clinical response.

VOLUME 67

2 FEBRUARY 1985

179

No side-effects were documented during treatment or in the

fellow-up period.

Discussion
In this pilot open prospective study ketoconazole was found to
be highly effective and well tolerated in the treatment of
vaginal candidiasis. Its efficacy is superior or equal to that of
many vaginal preparations such as econazole nitrate, for which
cure rates of 84,9% and 92,4% have been documented at two
dosage schedules, ISO mg/d for 3 days and 50 mg/d for 14
days.5
The ideal form of treatment for this condition would appear
to be an equally effective single-dose oral treatment, which
will in all probability become available in the future. Patient
compliance is likely to improve with the use of this oral
preparation, which will eliminate the need for vaginal preparations.

REFERENCES
I. Winner HI, Hutley R. Candida Albicans. Boston: Little, Brown, 1964: 5-7.
2. Kozinn PJ, Taschdjian CL. Candida albicans: saphrophyre or pathogen?
]AMA 1966; 198: 190-192.
3. Bardiaux M, Bonhomme J, Ceimail P et al. Nouvelle apport dans le
ttaitemenr des mycoses vulvo-vaginalis: l'econazole. Sem Hop Ther 1976; 52:

493-499.

4. Odds Fe. Cure and relapse with antifungal therapy. PTo<: R Sac Med 1977;
70: suppl4, 24-32.
5. Bloch B, Krerzel A. Econazole nitrate in the treatment of candidal vaginitis.
S AfT Med] 1980; 58: 314-316.

TABLE Ill. CLINICAL RESULTS OF KETOCONAZOLE THERAPY IN 25 PATIENTS

Before treatment
No.
%
Leucorrhoea
Pruritus
Dysuria
Vaginitis
Vulvitis
Dyspareunia
Vulval pain

25
18

100

14

56

12
11
11

44
44

12

72

1 wk after end
of treatment
No.
%
16
1

64
4

1 moo after end

of treatment
%
No.

10

40

48

4
4

News and Comment/Nuus en Kommentaar

Behandeling van anale fissuur
Hierdie minder emstige chirurgiese toestand is al beskryf as
iets wat net met iemand anders gebeur, maar enigiemand wat
al 'n anale fissuur ondervind het, weet onomwonde dat die pyn
en ongerief buite alle verhouding tot die grootte van die letsel
is. Die algemeenste behandeling vir hierdie toestand is eenvoudige anale dilatasie, maar bedenkinge oor die doeltreffendheid hiervan in vergelyking met laterale subkutane sfinkterotomie het gelei tot 'n proef waarin die twee behandelings
toegepas is (Jensen er al., Br Med J 1984; 289: 528). Agt-envyftig pasiente is by die toets betrek en ewekansig toegewys

aan een van die twee behandelingsgroepe. Die helfte van die
pasiente het eenvoudige anale dilatasie ondergaan, en die
ander helfte laterale subkutane sfinkterotomie. Alle prosedures
is onder plaaslike verdowing uitgevoer.
Geen ernstige komplikasies het in een van die groepe voorgekom nie en geen verskil LO.V. onmiddellike pynverligting,
genesing of afwesigheid van werk is waargeneem nie. Agt
herhalings is egter in die dilatasiegroep aangeteken, maar slegs
een in die sfinkterotomiegroep, en funksionele resultate was in
19. groep aansienlik beter. Daar is dus bevind dat laterale
subkutane sfinkterotomie die behandeling van keuse is vir
idiopatiese chroniese anale fissuur wat teen konserwatiewe
behandeling weerstandig is.