British Journal of Venereal Diseases, 1977, 53, 126-128

Three-day clotrimazole treatment in candidalvulvovaginitisG. MASTERTON, ISABELLA R. NAPIER, JEAN N. HENDERSON, ANDJANE E. ROBERTSFrom Glasgow

SUMMARY The accepted modern practice is to treat each sexually transmitted disease with theshortest possible course of treatment consistent with success. In candidal vulvovaginitis, six daysis the minimum period that has so far been found to be successful, but we report here a furtherreduction to three days. Patients were given two clotrimazole pessaries nightly for three consecutivenights; the overall success rate was 89-4% one month after treatment. This compares favourablywith the 93 % cure rate reported with the six-day course of clotrimazole. With both the long andshort courses, patients having their first attack of genital candidosis responded better than thosewith a history of previous infection. Short courses of clotrimazole treatment are particularly valuablein dealing with uncooperative women who stop treatment at the earliest possible moment. Clinicaland laboratory diagnostic pitfalls and their possible influence upon the therapeutic outcome arealso discussed.

Introduction

Nearly half of the patients suffering from sexuallytransmitted disease seem temperamentally incapableof taking any prolonged course of treatment(Masterton et al., 1976). In some infections, singlesession treatment has resolved this problem but sofar six days is the shortest reported period fortreating candidal vulvovaginitis (Weuta, 1972;Tamura et al., 1973; Couchman, 1974; Higton,1974; Kobayashi and Amenomori, 1974; Oatesand Davidson, 1974; Tan et al., 1974). In Glasgowin a single blind trial using nystatin pessaries for thecontrol group a six-day clotrimazole pessary regimengave a cure rate of 93 % when assessed one monthafter starting treatment (Masterton et al., 1975).However during and after this trial some womenfailed to complete the six-day course so we tried theeffect of reducing the duration of treatment tothree days.

Method

Women satisfying the following criteria wereadmitted to the drug trial:

Address for reprints: Dr G. Masterton, Department of SexuallyTransmitted Diseases, 67 Black Street, Glasgow G4 OEFReceived for publication 20 September 1976

1. Those with signs and symptoms suggestingcandidal vulvovaginitis.

2. Those with pseudohyphae (not just spores seenon microscopical examination).

3. Those with Candida albicans identified onculture (to eliminate observer bias this wasdone at an independent mycological depart-ment).

Such patients were instructed to insert twoclotrimazole 100 mg pessaries high into the vaginafor three consecutive nights. They were re-examinedone and four weeks later. Subjective and objectivefindings were recorded at each visit on a four-pointscale and Gram-stained smears were examinedimmediately for pseudohyphae. High vaginal swabswere sent to the laboratory for cultural confirmation.No other anti-fungal treatment was used during thetrial and the data were subsequently analysed by anindependent statistician.

Results

Because 57 women defaulted only 103 of thoseoriginally treated could be assessed.Most improvements in the signs and symptoms

took place within the first week. Statistically theredid not appear to be any relationship between theimprovement and age, parity, or duration of

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Three-day clotrimazole treatment in candidal vulvovaginitis

infection. When the subjective and objectiveimpressions of the amount of residual vaginaldischarge were compared, the clinician appeared tograde the degree of discharge more severely than didthe patient, Table 1.

Table 1 Effect of treatment on signs and symptomsSymptoms after treatment

BeforeDegree treatment One week Four weeks

Severe 9-7 (0) (0) 0 (0 9)Moderate 85 9 (39-8) 20-4 (2-9) 11-7 (3 9)Minimal 4-8 (60 2) 74-8 (32) 61-2 (6-8)None 0 (0) 4-8 (65-1) 26-2 (88 4)

Symptoms shown in parentheses

On less controversial grounds, judging by negativecultural results at one week the overall 'cure' ratewas 99 1 %. By the end of the fourth week, 10(9 7 %) more patients had relapsed making theoverall 'cure' rate 89 4 %. However if the patientswere divided into those with a previous history ofgenital candidosis and those having their primarycandidal infection, the rates were 7517% and 95 7%respectively. In the long-term 66 of those originallytreated were followed-up for a minimum period ofsix months. During this time another nine-that is,13 *6 % of the original group-developed furthergenital candidosis, and once again those havingtheir primary infection were least affected with an88-3 % 'cure' rate compared to 53-5%.

Discussion

One-third of the patients originally treated failed tofollow instructions and could not be assessed. Manywomen regard some vaginal discharge as beingnormal; this is an attitude which may partly explainwhy they discontinued treatment as soon as thecompelling symptoms of itching and burning haddisappeared, generally about the third or fourth dayafter treatment had started. Thus uncooperativeattitudes are not solely confined to the fecklesspatients; some apparently dependable womenbehave in the same manner. Hence the mostsuccessful treatment is likely to be the one which iseffective in the shortest period of time.

Because of these differences between the objectiveand subjective impressions we based our judgementupon the cultural findings. We noted a disagreementbetween the microscopical and cultural findings atthe first examination after treatment. In one-third ofthe patients scanty fungal elements were visible onmicroscopical examination but these could not be

cultured and clinically the patients continued toimprove. It may be that those fungi which took upthe Gram stain had been severely damaged but hadnot then completely disintegrated. Whatever thetrue explanation cultural examination appearsessential.For practical reasons anti-fungal treatment

sometimes anticipated the cultural confirmation.Thus some women who were believed on clinical ormicroscopical grounds to be suffering from genitalcandidosis were treated with clotrimazole. Whenthis opinion was not confirmed by culture the womenwere not included in the trial but it was noted thatonly 109 (70 3%) of the 155 patients so diagnosedhad benefited from three-day clotrimazole treatmentat the first examination. Obviously culturally-provedcases only should be included in trials of anti-fungalpreparations otherwise inaccurate conclusions areprobable.We did not exclude from the trial patients with a

previous history of genital candidosis but weassessed their results separately. At four weeks thefailure rate was 24 3 % in patients with a previoushistory of genital candidosis, but it was much less(4-3 %O) in those women having their primaryinfection. Thus the overall results of any clinicaltrial are likely to be influenced by the proportionalrepresentation of these two types of patients in thegroup under treatment. For example, three years ago(Masterton et al., 1975) we carried out a single blindtrial of six-day clotrimazole pessary treatment usingidentical trial parameters. One-fifth of these patientshad a previous history of genital candidosis and theoverall failure rate was 7 %. In the current three-daytrial one-third of the women had had genitalcandidosis previously and this time our overallfailure rate was 10 6% (Table 2).Table 2 Comparison of two clotrimazole regimens in thetreatment of confirmed genital candidosis

Patients assessed at four weeks

Length of Previous No. Culture Overallcourse candidosis positive % culture(days) positive %3 No 70 3 (4*3) 10 6

Yes 33 8 (24 3)6 No 45 1 (2-2) 7 0

Yes 12 3 (25)

These results are satisfactory but only in the shortterm. In some of the patients who were followed-upfor a minimum period of six months genital candi-dosis reappeared. Although we have no idea of theprecise aetiology of these recurrences, relapses, orreinfections the result was that the 'cure' rate inthose having their primary infection decreased to

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G. Masterton, Isabella R. Napier, Jean N. Henderson, and Jane E. Roberts

88 3% and in those women who had had previouscandidosis the 'cure' rate was 53 5 %. Obviouslymore attention must be given to the local, systemic,and personal factors which may affect the continua-tion of candidal infection.We concluded that the three- and the six-day

clotrimazole pessary regimens gave satisfactoryresults and can be recommended for uncooperativepatients who readily reject the discipline of regularmedication. Such short-term treatment is particularlyeffective if the patient is suffering from genitalcandidosis for the first time, but abbreviated regimensare not recommended for patients who have ahistory of candidosis. Such patients should receivea longer course of treatment, for instance 12 days ofclotrimazole, and a thorough search should be madefor probable precipitating factors.We thank our nursing and medical colleaguesfor their co-operation and Dr T. F. Elias-Jones,Director City Laboratory, for the laboratoryinvestigations. Above all we thank Dr C. S. Good,Senior Medical Advisor, Bayer Ltd for his valuableassistance in preparing this paper.

References

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Higton, B. K. (1974). A trial of clotrimazole and nystatin in vaginalcandidiasis. Postgraduate Medical Journal, 50, Supplement 1,95-97.

Kobayashi, T., and Amenomori, Y. (1974). Results of a clinicalinvestigation of clotrimazole (Canesten), a new antimycoticsubstance, in the therapy of vaginal fungal infections. Journal ofInternational Medical Research, 2, 366-369.

Masterton, G., Henderson, J., Napier, I. R., and Moffett, M. (1975).Six day clotrimazole therapy in vaginal candidiasis. Current MedicalResearch and Opinion, 3, 83-88.

Masterton, G., Moffett, M., Henderson, J., and Napier, I. R. (1976).Six day clotrimazole (Canesten) therapy in vaginal candidiasis.Munchener medizinische Wochenschrift, 118, Supplement 1, 56-59.

Oates, J. K., and Davidson, F. (1974). Treatment ofvaginal candidiasiswith clotrimazole. Postgraduate Medical Journal, 50, Supplement1, 99-102.

Tamura, S., Kuramoto, H., Yamada, T., Majima, H., and Miyamoto,H. (1973). The therapy of candida vaginitis and candida vulvo-vaginitis with a new antimycotic substance, clotrimazole. CurrentMedical Research and Opinion, 1, 540-546.

Tan, C. G., Milne, L. J. R., Good, C. S., and Loudon, J. D. 0. (1974).A comparative trial of six day therapy with clotrimazole andnystatin in pregnant patients with vaginal candidiasis. PostgraduateMedical Journal, 50, Supplement 1, 102-105.

Weuta, H. (1972). Clotrimazole vaginal tablets, cream and solution-clinical investigation in an open study. Drugs made in Germany,15, 121-132.

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