EUROP. J. OBSTET. GYNEC. REPROD. BIOL., 1979,9/2,125-127 0 Elsevier/North-Holland Biomedical Press

THERAPEUTIC

NOTE

A new treatment of vaginal candidiasis: three-day treatment with econazole

C. Lecart ‘, F. Claerhout 2, R. Franck lo, P. Godts 4, C. Lilien l, L. Macours ‘, W. Schuerwegh 4, H. Longr6e 5, M. Mine 6, P. Strebelle ‘, M. Van Gijsegem ’ and S. Wesel 9 ’ Gynecology Department, University Clinic St. Luc, Louvain and Woluwe, 2 Assebroek, ’ Charleroi, ’ La Louvi&re, a Ghent and 9 Braine L ‘Alleud, Belgium and 1 o Esch/Alzette,

3 Hasselt, 4 Antwerp, Luxembourg

s Brussels,

Accepted for publication 22 November 1978 LECART, C., CLAERHOUT, I., FRANCK, R., GODTS, P., LILIEN, C., MACOURS, L., SCHUERWEGH, W., LONGRkE, H., MINE, M., STREBELLE, P., VAN GIJSEGEM, M. and WESEL, S. (1979): A new treatment of vaginal candidiasis: three-day treatment with econazole. Europ. J. Obstet. Gynec. reprod. Biol., P/2, 125 - 127. From an open comparative multicentric trial it became clear that econazole was an active and well-tolerated agent for the treatment of vulvo-vaginal mycoses. Combined treatment with pessaries and econazole cream seems to be worthwhile in order to isolate the vagina from possible Candida reservoirs or to hasten symptomatic relief. moniliasis; kolpitis; intravaginal suppositories alone, and in combination with vulva-anal topical treatment

application, as a 3-day treatment (3 vaginal suppositories of 150 mg) (Balmer, 1976; Thienpont et al., 1975). It is also presented as a vaginal cream and in various dermatological forms (cream, spray-powder, lotion and spray-solution). It seemed interesting, therefore, to investigate whether a 3-day treatment would give satisfactory results, and whether simultaneous treatment of the vulva-anal region and of the partner improved the results.

Introduction

Vaginal candidiasis is a common condition, with a high incidence of recurrence. Predisposing factors have been identified, and the importance of the milieu itself is greater than is generally appreciated (Van Breuseghem, 1977). Candida albicans is also found in the digestive tract, where it lives as a saprophyte (Morton and Rashid, 1977). During sexual intercourse, the yeast may also be transmitted to the male partner, in whom it can produce balanitis, and then be reintroduced into the vagina. It is generally believed that the therapeutic outcome of vaginal treatment can be improved by simultaneous treatment of the partner and of the vulvoanal region. We here studied econazole (Pevaryl, GynoPevaryl 150, Gyno-Pevaryl; Cilag-Chemie), an antimycotic imidazole derivative. Econazole has recently been developed, for vaginal

Material and methods

This study was designed as an open comparative multicentric trial. 260 Patients entered the trial and were randomly assigned to one of the two therapeutic designs. In one group (group I), the patients received 3 125

C. Lecart et al.: Treatment of vaginal candidiasis

126

vaginal suppositories of 150 mg econazole with the instruction to insert one suppository daily, at bedtime, on 3 consecutive days (129 patients). When the partner presented symptoms of balanitis, he was also treated with the cream for 3 days, and these patients (8 in all) were excluded from the analysis. The vulvoanal region, however, remained untreated. In the other group (group II), in addition to the 3 suppositories, the patients also received a 15 mg tube containing 1% econazole cream. They were instructed to apply some cream to the external genitalia and around the anus and, for the partner, on the glans penis (131 patients). The mean age of the patients was 31 yr in the group receiving pessaries alone (range: 17-86) and 31.5 yr in the group receiving all-round treatment (range: 13-58). Included in the first group were 24 pregnant women, 43 under hormonal contraception, 47 with normal hormonal status and 7 post-menopausal patients, two of them on estrogen therapy. In the second group, 35 patients were pregnant, 44 were taking contraceptives, 50 had a normal hormonal status, and 2 were post-menopausal patients. Vaginal candidiasis was in all cases confirmed by microscopic examination and mycological culture on Nickerson’s medium. The patients in both groups were requested to come back a week and one month after the end of treatment. The patients still positive at the first check-up received a second course of treatment, exactly the same as the first one. At each check-up, clinical symptoms (leukorrhea, pruritus and vaginal burning) were scored as marked, present or absent. A microscopic examination and a culture on Nickerson’s medium were performed to confirm mycological cure.

TABLE I

Results

Out of the 252 patients included in the study, 235 attended both check-ups. The 17 remaining patients missed one of the two follow-u;, examinations, and were excluded from the study. Group I treated with 3 suppositories alonk 112 patients attended both check-ups. One week after treatment, 79 (70.5%) were mycologically cured. One month after treatment, a relapse occurred in 5 patients, which gave a cure rate of 66% one month after one course of treatment with 3 suppositories. The 33 patients still positive at the first followup examination received a second course of treatment (3 suppositories). 19 of them were cured one month later, which means an overall cure rate, after one or two courses of treatment, of 83% (93 patients out of 112). Group II treated with 3 suppositories + cream 123 attended both check-ups. At the first checkup, 102 (83%) were mycologically cured; 97 of them still had a negative culture for Candida one month after the end of the treatment (79%). Eleven patients were found negative after a second course of treatment. The overall cure rate is thus 87% (108 patients out of 123). These results are shown in Table I. Clinicalfindings Table II shows the evolution

of the symptomatol-

Mycological cure rate

Type of treatment (no. of patients)

Controls

Cured Group I: Suppositories alone (112)

1 wk 1 mth

Group II: Suppositories + cream (123)

1 wk 1 mth

2nd Treatment

Total

Not cured

Cured

Not cured

Cured

33 (27%) 38 (32%)

19 (57%)

14 (43%)

93 (83%)

19 (16%)

21(17%) 26 (21%)

11(52%)

10 (48%)

108 (87%)

15 (13%)

1st Treatment

19 (70.5%) 74 (66%) 102 (83%) 97 (79%)

Not cured

C. Lecart et al.: Treatment of vaginal candidiasis

TABLE II

127

Clinical results Prior to treatment ++

1 mth after treatment ___-

1 wk after treatment

+

-

++

+

_

i-t

+

_

69 70 50

16 13 28

4 4 3

20 22 25

88 86 84

2 1 1

8 12 17

102 99 94

72 58 62

9 10 10

3 2 3

24 22 31

96 99 89

2 1 2

7 11 18

114 111 103

Suppositories alone (n = 112)

Burning Pruritus Leukorrhea

21 29 34

Suppositories + cream (n = 123)

Burning Pruritus Leukorrhea

42 55 51

ogy under treatment with 3 econazole 150 mg vaginal suppositories with or without associated treatment with cream. Discussion The good results obtained with both therapeutic regimens show that a 3-day treatment with 3 suppositories of econazole is efficacious as such in the treatment of vaginal candidiasis. The 24 patients who remained positive after a second course of treatment were equally distributed in the 3 groups (pregnancy, contraception, normal hormonal status). It might be interesting to investigate more closely those cases of candidiasis resistant to the therapy. If we consider the results obtained after one course of treatment, we find a significant difference at both check-ups in favor of a combined therapy, involving not only vaginal treatment but also treatment of the vulvo-anal region and of the partner (P< 0.05, Chi-square test, two-by-two contingency table). Vaginal candidiasis usually remains confined to the vulvo-anal region and does not spread into systemic infection, and so favors local treatment. One must, however, try to isolate the vagina from possible reinfection sources, such as the ano-vulvar route, and the partner, and thus prevent immediate relapse until the vaginal milieu has been normalized. The product is very well tolerated. Intolerance to suppositories or cream was mentioned in 3 and 6 cases, respectively. This intolerance manifested itself by a burning sensation on introducing the suppositories and/or applying the cream.

The treatment of the male partner seems to have been both accepted and well tolerated. The symptoms subsided rapidly in both groups. The patients reported, however, that the vaginal suppositories alone did not bring such quick relief. The need for an external treatment is thus emphasized when the patient complains of severe vulvar pruritus. A last comment should be made on the acceptability of the treatment. The 3-suppository treatment represents a new and important step towards better patient cooperation. Longer treatments are often abandoned after a few days, when the vulvo-vaginal symptoms have subsided. The mycological efficacy of this 3-suppository treatment 8 days after end of the treatment assures the clinician that mycological cure will be obtained within the ‘compliance’ period of the patient.

References

Balmer, J.A. (1976): Three-day therapy of vulvovaginal candidiasis with econazole: a multicentric study comprising 996 cases. Amer. J. Obstet. Gynec., 126, 435-441. Morton. R.S. and Rashid, S. (1977): Candidal vaginitis. Natural history, predisposing factors and prevention. Proc. roy. Sot. Med., 70, 3-6. Thienpont, D., Van Cutsem, T., Van Nueten, J.M., Niemegeers, C.J.E. and Marsboom, R. (1975): Biological and toxicological properties of econazole, a broad spectrum antimycotic. Arzneimittel-Forsch., 25, 224-230. Van Breuseghem, (1977): Vues actuelles sur l’eprddmiologie des mycoses. 262.

Bull. Mem. Acad. R. Med. Belg., 132, 253-

Reprint requests to: Prof. C. Lecart, Department

of Gynecology, University Hospital St. Luc, 10 Avenue Hippocrate, Woluwe B - 1200, Belgium.