Therapy for oropharyngeal candidiasis in the immunocompromised host: a randomized double-blind study of fluconazole vs. ketoconazole. Prophylaxis of oropharyngeal candidiasis with clotrimazole. Prophylaxis with nystatin pastilles for HIV-associated oral candidiasis. Therapy for oropharyngeal candidiasis in HIV-infected patients: a randomized, prospective multicenter study of oral fluconazole versus clotrimazole troches. The Multicenter Study Group. A randomized clinical trial of chlorhexidine in the maintenance of oral candidiasis-free period in HIV infection. Comparative study of fluconazole and clotrimazole for the treatment of vulvovaginal candidiasis. Prophylaxis of candidiasis in cancer patients. Ketoconazole and candidiasis: a controlled study. Oral nystatin prophylaxis to prevent invasive candidiasis in Neonatal Intensive Care Unit.
Optimal therapy for oropharyngeal candidiasis, a common infection in immunocompromised patients, has yet to be clearly defined. Topical therapy is usually poorly tolerated; ketoconazole is effective but absorption is highly variable. New antifungal agents have been developed to increase the therapeutic options. Fluconazole is active against yeasts, is available in both oral and intravenous formulations, and has a pharmacokinetic profile different from that of ketoconazole. This randomized double-blind study evaluates systemic antifungal therapy with fluconazole (100 mg daily) or ketoconazole (400-mg daily) for oropharyngeal candidiasis in patients with cancer. Clinical cure was observed in 15 of 19 and 14 of 18 patients treated with fluconazole and ketoconazole, respectively. Eradication of pathogenic yeasts ws documented for 10 patients in both groups. The rates of relapse were similar, but relapse occurred earlier in patients in the ketoconazole group. Overall, this study demonstrates the value of a dosage of 100 mg of fluconazole or of 400 mg of ketoconazole daily for the management of oropharyngeal candidiasis in patients with cancer. A total of 202 evaluable cancer patients were randomly assigned to receive or not receive oral clotrimazole as antifungal prophylaxis during hospitalization. Oropharyngeal candidiasis occurred in 1% of the former patients and 27% of the latter patients (P less than .00001). Candida sp were cultured from the initial throat specimens of 53 control patients and 55 patients who received prophylaxis. Oropharyngeal candidiasis subsequently developed in 2% of the former patients and 38% of the latter patients (P = less than .00001). Oral clotrimazole is an effective agent for prophylaxis of oropharyngeal candidiasis in susceptible cancer patients. To determine whether daily use of nystatin pastilles can prevent initial outbreak or recurrence of oral candidiasis in HIV-infected patients and to identify factors associated with outbreaks during 20-week follow-up, a randomized, double-blind, placebo-controlled clinical trial was conducted. Subjects were 128 HIV-infected men (aged 27-60 years) who either had had no documented episode of oral candidiasis in the previous year or had been clinically clear of oral candidiasis for at least 72 h before randomization. Study arms were two placebo pastilles, one nystatin (200,000 U) and one placebo pastille, or two nystatin pastilles daily for 20 weeks. The main outcome measure was time to oral candidiasis, as determined by potassium hydroxide (KOH) smear and fungal culture. A multivariate proportional hazards model showed that four factors were significant (p < 0.001) in predicting time to oral candidiasis: nystatin treatment (hazard ratio 0.59), history of oral candidiasis (3.58), Candida albicans carriage (2.79), and CD4 count at randomization (0.65). In this small group of subjects, nystatin appeared to be effective in delaying onset of oral candidiasis. Patients with CD4 counts < 200 who are carriers of C. albicans and have a history of oral candidiasis may be most likely to benefit from antifungal prophylaxis. A total of 334 HIV-infected patients with oral candidiasis were randomly assigned to receive 14 days of treatment with either 100 mg of oral fluconazole once daily or 10 mg clotrimazole five times daily. Both treatments were clinically effective: 98% of evaluable fluconazole-treated patients and 94% of evaluable clotrimazole-treated patients were cured or showed improvement (p = NS). Fluconazole was more effective than clotrimazole in eradicating Candida from the oral flora by the end of therapy (65% versus 48%) (p = 0.005). In addition, patients in the fluconazole-treated group were more likely to remain asymptomatic through the second week of follow-up (82.3% versus 50.0%) (p < 0.001). This difference was no longer evident by the post-therapy visit during week 4. Seven patients treated with clotrimazole and two patients treated with fluconazole discontinued therapy because of side effects. Two patients in the fluconazole group were withdrawn from therapy because of elevated serum glutamic-oxaloacetic transaminase levels, one considered possibly related to drug therapy. Fluconazole was as effective as clotrimazole in the treatment of oral candidiasis and temporarily provided a more prolonged disease-free state. Future studies are needed to define the optimal regimen for both the treatment and prevention of recurrent oral candidiasis in HIV-infected patients, addressing special attention to the issue of compliance, cost, and emergence of resistance. To determine if chlorhexidine can be used as an intervention to prolong the time to relapse of oral candidiasis.
                A double-blinded randomized clinical trial was performed in 75 HIV/AIDS subjects with oral candidiasis. Clotrimazole troche was prescribed, and the subjects were re-examined every 2 weeks until the lesions were completely eradicated. The subjects were then randomly divided into two groups; 0.12% chlorhexidine (n = 37, aged 22-52 years, mean 34 years) and 0.9% normal saline (n = 38, aged 22-55 years, mean 38 years). They were re-examined every 2 weeks until the next episode was observed.
                The time to recurrence of oral candidiasis between the chlorhexidine and the saline group was not statistically significant (P > 0.05). The following variables were significantly associated with the time of recurrence; frequency of antifungal therapy (P = 0.011), total lymphocyte (P = 0.017), alcohol consumption (P = 0.043), and candidiasis on gingiva (P = 0.048). The subjects with lower lymphocyte showed shorter oral candidiasis-free periods (P = 0.034).
                Chlorhexidine showed a small but not statistically significant effect in maintenance of oral candidiasis-free period. This lack of significance may be due to the small sample size. Further study should be performed to better assess the size of the effect, or to confirm our findings. The introduction of the triazole antifungal agent fluconazole, which can be used via an oral route and single dose, has had a significant impact on patient compliance.
                To compare the efficacy and safety of a single oral dose of 150 mg fluconazole with that of a 100-mg clotrimazole vaginal suppository twice a day in the morning and at bedtime for 3 days in the treatment of vulvovaginal candidiasis.
                A single-blind, randomized controlled trial was conducted at Ramathibodi Hospital between June 1 and September 30, 1993.
                There were 53 women in the group treated with fluconazole and 50 in the group treated with clotrimazole. There was no significant difference between the two groups regarding clinical characteristics (age and length of follow-up period). Mycological cure rates approximately 1 week after treatment were 79.2% in the fluconazole group and 80.0% in the clotrimazole group. Approximately 4 weeks after treatment, these rates were 60.4% and 66.0%, respectively. The side effects were minimal and did not warrant any treatment. The differences in the results were not statistically significant.
                We recommend that a single oral dose of 150 mg of fluconazole be given as an alternative method of treating vulvovaginal candidiasis, but the cost is higher than for clotrimazole. Patients undergoing therapy for metastatic malignancies were randomly assigned to receive fluconazole or placebo as antifungal prophylaxis. Oropharyngeal candidiasis developed in 28% of 54 evaluable patients receiving placebo but in only 2% of 58 evaluable patients receiving fluconazole (P = .0003). Among patients receiving placebo, oropharyngeal candidiasis (thrush) occurred in 30% of those receiving antibiotic therapy and in 44% of those receiving adrenal corticosteroid therapy. Oropharyngeal candidiasis developed in 54% of the placebo patients who were colonized by Candida sp at the onset of prophylaxis. Fluconazole proved to be effective for prophylaxis of oropharyngeal candidiasis in susceptible patients and was well tolerated. A double-blind, placebo-controlled study was undertaken to determine the efficacy of ketoconazole in the treatment of candidiasis. The drug was administered orally in the dosage of 200 mg/m2 of body surface per day for two weeks to cancer patients with oral candidiasis. Randomization in a 2:1 ratio provided 36 patients treated with ketoconazole and 20 managed with a placebo. Regression of visible lesions was achieved in 26 (72%) of 36 ketoconazole-treated and four (20%) of 20 untreated patients; eradication of culturable organisms occurred in 12 (36%) of 33 ketoconazole-treated and one (7%) of 14 untreated patients; and resolution of lesions plus eradication of Candida albicans occurred in nine (25%) of 36 ketoconazole-treated and one (5%) of 20 untreated patients. Although the therapeutic efficacy of ketoconazole was demonstrated for oropharyngeal candidiasis, the magnitude of its efficacy was less than that desired. The use of oral nystatin to prevent fungal colonisation and infection in neonates in the Neonatal Intensive Care Unit (NICU) is still an open question and not yet recommended as a standard of care. To determine whether prophylactic oral nystatin results in a decreased incidence of invasive candidiasis in the newborn infants, a total of 3991 infants were divided randomly into two groups. Group A infants (n = 1995), only those neonates who were identified as yeast carriers (oral moniliasis) were treated with oral nystatin. Group B infants, all neonates who were admitted to the unit received oral nystatin, was routinely administered three times a day. Group A was divided into groups A1 and A2 (who were treated only if identified as yeast carriers). Urine and rectal cultures were taken on admission and then weekly thereafter. There were 215 (14.2%), 27 (5.6%) and 36 (1.8%) patients positive for invasive candidiasis in groups A1, A2 and B respectively. Oral nystatin prophylaxis significantly reduced the invasive candidiasis (P = 0.004) in extremely low-birth weight (ELBW) and very low-birth weight (VLBW) infants. Prophylactic administration of oral nystatine to the ELBW and VLBW infants results in a decreased risk of invasive candidiasis.
There is insufficient evidence to claim or refute a benefit for any antifungal agent in treating candidiasis. Further well designed, placebo-controlled trials assessing the effectiveness of old and new interventions for treating oral candidiasis are needed. Clinicians need to make a decision on whether to prevent or treat oral candidiasis in patients receiving treatment for cancer.