Safety and efficacy of single-dose fluconazole compared with a 7-day regimen of itraconazole in the treatment of AIDS-related oropharyngeal candidiasis. Therapy for oropharyngeal candidiasis in HIV-infected patients: a randomized, prospective multicenter study of oral fluconazole versus clotrimazole troches. The Multicenter Study Group. Single-dose versus 7 days of fluconazole treatment for oral candidiasis in human immunodeficiency virus-infected patients: a prospective, randomized pilot study. A dose comparison study of a new triazole antifungal (D0870) in HIV-positive patients with oral candidiasis. Randomized, double-blind, multicenter study of caspofungin versus amphotericin B for treatment of oropharyngeal and esophageal candidiases. Itraconazole prophylaxis for fungal infections in patients with advanced human immunodeficiency virus infection: randomized, placebo-controlled, double-blind study. National Institute of Allergy and Infectious Diseases Mycoses Study Group. Itraconazole oral solution versus clotrimazole troches for the treatment of oropharyngeal candidiasis in immunocompromised patients. Clinical trial: clotrimazole troche vs. itraconazole oral solution in the treatment of oral candidosis in AIDS patients. A multicenter randomized trial evaluating posaconazole versus fluconazole for the treatment of oropharyngeal candidiasis in subjects with HIV/AIDS. Treatment of oral thrush in HIV/AIDS patients with lemon juice and lemon grass (Cymbopogon citratus) and gentian violet. Comparative efficacy of topical therapy with a slow-release mucoadhesive buccal tablet containing miconazole nitrate versus systemic therapy with ketoconazole in HIV-positive patients with oropharyngeal candidiasis. Weekly fluconazole for the prevention of mucosal candidiasis in women with HIV infection. A randomized, double-blind, placebo-controlled trial. Terry Beirn Community Programs for Clinical Research on AIDS. Prophylaxis with nystatin pastilles for HIV-associated oral candidiasis. Randomized trial of itraconazole oral solution for oropharyngeal candidiasis in HIV/AIDS patients. Efficacy of alcohol-based and alcohol-free melaleuca oral solution for the treatment of fluconazole-refractory oropharyngeal candidiasis in patients with AIDS. Efficacy, tolerability and development of resistance in HIV-positive patients treated with fluconazole for secondary prevention of oropharyngeal candidiasis: a randomized, double-blind, placebo-controlled trial. A double-blind comparison of itraconazole oral solution and fluconazole capsules for the treatment of oropharyngeal candidiasis in patients with AIDS. A comparison between fluconazole tablets and clotrimazole troches for the treatment of thrush in HIV infection. Fluconazole prophylaxis of recurrent oral candidiasis in HIV-positive patients. Itraconazole versus ketaconazole in the treatment of oral and oesophageal candidosis in patients infected with HIV. Thrush can be prevented in patients with acquired immunodeficiency syndrome and the acquired immunodeficiency syndrome-related complex. Randomized, double-blind, placebo-controlled study of 100-mg oral fluconazole daily. Comparison of fluconazole and ketoconazole for oropharyngeal candidiasis in AIDS. A randomized clinical trial of chlorhexidine in the maintenance of oral candidiasis-free period in HIV infection. Fluconazole versus ketoconazole in the treatment of oropharyngeal candidiasis in HIV-infected children. Multicentre Study Group. Comparison of itraconazole and ketoconazole in HIV-positive patients with oropharyngeal or esophageal candidiasis. Human Immunodeficiency Virus Itraconazole Ketoconazole Project Group. A randomized trial of continuous or intermittent therapy with fluconazole for oropharyngeal candidiasis in HIV-infected patients: clinical outcomes and development of fluconazole resistance. Fluconazole once a week as secondary prophylaxis against oropharyngeal candidiasis in HIV-infected patients. A double-blind placebo-controlled study. A randomized study of the use of fluconazole in continuous versus episodic therapy in patients with advanced HIV infection and a history of oropharyngeal candidiasis: AIDS Clinical Trials Group Study 323/Mycoses Study Group Study 40. Oropharyngeal candidiasis in patients with AIDS: randomized comparison of fluconazole versus nystatin oral suspensions. Once-weekly fluconazole to prevent recurrence of oropharyngeal candidiasis in patients with AIDS and AIDS-related complex: a double-blind placebo-controlled study. Trial of glucose versus fat emulsion in preparation of amphotericin for use in HIV infected patients with candidiasis. Gentian violet, ketoconazole and nystatin in oropharyngeal and esophageal candidiasis in Zairian AIDS patients.
The primary aim of this study was to compare the efficacy and safety of single-dose fluconazole and a 7-day regimen of itraconazole for the treatment of oropharyngeal candidiasis in human immunodeficiency virus (HIV)-positive patients. In this open-label trial, 40 HIV-positive patients with oropharyngeal candidiasis were randomized to receive either one dose of fluconazole 150 mg or seven daily doses of itraconazole 100 mg. Clinical condition was assessed at baseline, day 8, and day 30 (follow-up). In the fluconazole group, 15 of 20 (75%) patients were clinically cured on day 8, three (15%) were clinically improved, and two (10%) were treatment failures. At follow-up, six (30%) patients experienced relapse. In the itraconazole group, four of 17 (24%) patients were clinically cured at 8 days, and two (12%) were clinically improved; two patients relapsed by day 30. Ten (50%) patients in the itraconazole group were taking concomitant medications that could potentially affect the bioavailability of itraconazole. After excluding the results from these patients, clinical response rates remained significantly higher in the fluconazole treatment arm. These results suggest that a single 150-mg dose of fluconazole may be a safe, effective, and convenient therapy for acquired immune deficiency syndrome-related oropharyngeal candidiasis. The lower response rate in the patients who received itraconazole 100 mg daily for 7 days could be explained by drug interactions and the unpredictable absorption of itraconazole. 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. nan This multicentre study evaluated the clinical efficacy and tolerability of D0870 in treating oropharyngeal candidiasis in HIV-positive patients who had no history of clinical resistance to fluconazole.
                Three regimens were evaluated in two phases. In phase I a 50 mg initial dose was followed by 10 mg for 4 days (Group 1). In phase II a 100 mg initial dose was followed by 25 mg for 4 days (Group 2), or 10 mg for 5 days (Group 3).
                Clinical cure was obtained in 27 patients of a total of 35 (77%) and six other patients improved (17%). Two patients at the lowest dose failed and both had very low plasma concentration of D0870. No association was found between clinical outcome; minimum inhibitory concentration of D0870 pre-therapy for Candida albicans, maximum recorded plasma D0870 concentration, cfu of culture or CD4 cell count at entry. Overall, 37% of the patients experienced relapse during the 2 weeks post therapy. Tolerance was excellent. Mild adverse events possibly related to the study drug were recorded in five patients.
                D0870 demonstrates excellent efficacy at low doses in the treatment of HIV-related OPC and exhibits a favourable safety profile. Caspofungin is an antifungal agent of the novel echinocandin class. We investigated its efficacy, safety, and tolerability as therapy for oropharyngeal and/or esophageal candidiasis in a phase II dose-ranging study. Patients were randomized in a double-blind manner to receive either caspofungin acetate (35, 50, or 70 mg) or amphotericin B (0.5 mg/kg of body weight) intravenously once daily for 7 to 14 days. A favorable response required both complete resolution of symptoms and quantifiable improvement of mucosal lesions 3 to 4 days after discontinuation of study drug. Efficacy was assessed using a modified intent-to-treat analysis. No hypothesis testing of efficacy was planned or performed. Of 140 enrolled patients, 63% had esophageal involvement and 98% were infected with the human immunodeficiency virus (HIV) (median CD4 count, 30/mm(3)). A modestly higher proportion of patients in each of the caspofungin groups (74 to 91%) achieved favorable responses compared to amphotericin B recipients (63%), but there was considerable overlap in the 95% confidence intervals surrounding these point estimates. Similar trends were found in the subgroups with esophageal involvement, a history of fluconazole failure, and CD4 counts of < or =50/mm(3). A smaller proportion of patients receiving any dose of caspofungin experienced drug-related adverse events compared to patients given standard doses of conventional amphotericin B (P < 0.01). Caspofungin provided a generally well-tolerated parenteral therapeutic option for HIV-infected patients with oropharyngeal and/or esophageal candidiasis in this study. In a prospective, randomized, double-blind trial, 149 patients with advanced human immunodeficiency virus (HIV) infection were randomized to receive itraconazole capsules (200 mg daily) and 146 to receive a matched placebo. Both groups were monitored for evidence of fungal infections. Baseline characteristics of the two groups were similar. Failure of prophylaxis occurred in 29 (19%) of the itraconazole recipients and 42 (29%) of the placebo recipients (P = .004; log-rank test). There were 6 invasive fungal infections in the itraconazole group (4, histoplasmosis; 1, cryptococcosis; 1, aspergillosis) and 19 in the placebo group (10, histoplasmosis; 8, cryptococcosis; 1, aspergillosis) (P = .0007; log-rank test). Itraconazole significantly delayed time to onset of histoplasmosis (P = .03; log-rank test) and cryptococcosis (P = .0005; log-rank test). Prophylaxis failure due to recurrent or refractory mucosal candidiasis occurred with similar frequency in the two groups (itraconazole, 15%; placebo, 16%). A survival benefit was not demonstrated. Itraconazole generally was well tolerated. Primary prophylaxis with itraconazole capsules prevents histoplasmosis and cryptococcosis in patients with HIV infection. This multicenter, open-label, third-party-masked trial compared the efficacy and safety of itraconazole oral solution (200 mg once daily) and clotrimazole troches (10 mg five times daily) in a population of immunocompromised subjects composed primarily of patients with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). Patients were treated for 14 days; patients who exhibited a clinical response were followed up for an additional month to document the occurrence of relapse. Efficacy was judged by changes from baseline in symptoms of oropharyngeal candidiasis (erythema, soreness/burning), extent of oral lesions, and the presence/absence of Candida species on fungal culture. A total of 162 patients were randomized, and 149 were evaluated for efficacy. The percentage of patients with negative cultures at the end of treatment was significantly greater in the itraconazole group than in the clotrimazole group (60% vs 32%, respectively). Negative culture plus clinical response was achieved in significantly more itraconazole-treated patients (53%) than clotrimazole-treated patients (30%); results were similar in the subgroup of patients with HIV/AIDS. Both drugs were well tolerated, with the most frequently reported adverse events for both agents involving the gastrointestinal system. In conclusion, systemic therapy with intraconazole oral solution is efficacious and well tolerated in immunocompromised patients, including those with HIV/AIDS, when administered once daily for 14 days for the treatment of oral candidiasis. This prospective study was designed to compare the efficacy and safety of itraconazole oral solution with those of clotrimazole troche in the treatment of oropharyngeal candidosis in acquired immunodeficiency syndrome (AIDS) patients. Patients were excluded if they had been treated with any antifungal agents 2 weeks prior to the study entry, were pregnant or nursing, or had significant liver disease. Twenty-nine patients (20 men and nine women), with a mean age of 32 years (15-62 years), were randomly, observer-blind treated with clotrimazole troche (10 mg, five times daily) or itraconazole oral solution (100 mg/10 mL, twice daily) for 1 week. Clinical and mycologic assessment were carried out on four consecutive days, in week 1, week 2, and week 4 after the start of treatment. Clinical evaluation was assessed by a scoring method (0-3, absent to severe) as follows: soreness, change in taste, erythema, removable white plaque, and extent of lesions. Mycologic assessment was performed by KOH preparation and fungal culture. Global evaluation, which is a summary of clinical and mycologic assessment at the end of treatment, was classified as cure (all signs and symptoms resolved with no evidence of infection), improvement (decrease in clinical score without complete resolution), or failure (lack of improvement or further deterioration). (Pons V, Greenspan D, Debruin M. Therapy for oropharyngeal candidiasis in HIV-infected patients: a randomized, prospective multicenter study of oral fluconazole versus clotrimazole troches. J Acquir Immune Defic Syndr 1993; 6: 1311-1316. ) Global evaluation at week 2 and week 4 was made in terms of no relapse or relapse. Any intercurrent medical events, whether human immunodeficiency virus (HIV)-related or not, were recorded. An intention-to-treat analysis was employed. Data were analyzed using the chi-squared test, Mann-Whitney U-test, and Student's t-test. Oropharyngeal candidiasis is the most common opportunistic infection among persons infected with human immunodeficiency virus (HIV). Use of some agents is hampered by lack of efficacy, emergence of resistance, adverse events, and need for intravenous administration. Posaconazole is an extended-spectrum triazole with potent in vitro activity against Candida species, including Candida albicans, Candida glabrata, and Candida krusei (including fluconazole-resistant strains).
                This multicenter, randomized, evaluator-blinded study of subjects with HIV infection and oropharyngeal candidiasis compared efficacy of posaconazole with that of fluconazole. Subjects received either 200 mg of posaconazole or fluconazole oral suspension on day 1, followed by 100 mg/day for 13 days. The primary study end point--clinical success (cure or improvement) on day 14--was evaluated for 329 subjects. Durability of clinical success was evaluated on day 42.
                Three hundred fifty subjects received posaconazole (n = 178) or fluconazole (n = 172). Clinical success occurred in 155 (91.7%) of 169 posaconazole recipients and in 148 (92.5%) of 160 fluconazole recipients (95% confidence interval, -6.61% to 5.04%), indicating that posaconazole was not inferior to fluconazole. On day 14, mycological success was 68% in both arms, but by day 42, significantly more posaconazole recipients than fluconazole recipients continued to have mycological success (40.6% vs. 26.4%; P=.038). Fewer posaconazole recipients than fluconazole recipients experienced clinical relapse (31.5% vs. 38.2%). Adverse events were similar between treatment arms.
                Results demonstrate that posaconazole was as effective as fluconazole in producing a successful clinical outcome. However, posaconazole was more effective in sustaining clinical success after treatment was stopped. The purpose of the study was to investigate the safety and efficacy of lemon juice and lemon grass (Cymbopogon citratus) in the treatment of oral thrush in HIV/AIDS patients when compared with the control group using gentian violet aqueous solution 0.5%. Oral thrush is a frequent complication of HIV infection. In the Moretele Hospice, due to financial constraints, the treatment routinely given to patients with oral thrush is either lemon juice directly into the mouth or a lemon grass infusion made from lemon grass (Cymbopogon citratus) grown and dried at the hospice. These two remedies have been found to be very efficacious therefore are used extensively. Gentian violet, the first line medication for oral thrush in South Africa, is not preferred by the primary health clinic patients due to the visible purple stain which leads them to being stigmatized as HIV-positive. Cymbopogon citratus and Citrus limon have known antifungal properties.
                The study design was a randomised controlled trial. Ninety patients were randomly assigned to one of three groups: gentian violet, lemon juice or lemon grass. Inclusion criteria included being HIV-positive with a diagnosis of oral thrush. The study period was 11 days and patients were followed up every second day. International ethical principles were adhered to during the study.
                Of the 90 patients, 83 completed the study. In the intention-to-treat analysis, none of the p-values were significant therefore the null hypothesis could not be rejected. In the analysis of the participants who actually completed the trial, the lemon juice showed better results than the gentian violet aqueous solution 0.5% in the treatment of oral thrush in an HIV-positive population (p<0.02). The null hypothesis in terms of the lemon grass and gentian violet could also be rejected on the basis of the Chi-square test and the likelihood ratio test (p<0.05).
                Though the patient population was small, the use of lemon juice and lemon grass for the treatment of oral candidiasis in an HIV population was validated by the randomised controlled trial. This randomized comparative study assessed the efficacy and safety of a 10-mg once-daily topical regimen of miconazole nitrate mucoadhesive buccal tablet (n = 178) versus a 400-mg once-daily systemic regimen of ketoconazole (n = 179) in HIV-positive patients with oropharyngeal candidiasis. A total of 357 patients were treated for 7 or 14 days depending on response after 7 days of treatment. Clinical response was the primary outcome variable, and secondary outcomes included microscopy, time to cure, symptom scores, and safety outcomes. A per-protocol analysis of 332 patients demonstrated that miconazole nitrate was not statistically significantly inferior to ketoconazole treatment. At day 7, the clinical response rate was 135 of 156 (87%) for miconazole nitrate and 137 of 153 (90%) for ketoconazole (90% confidence interval of the treatment difference: [-9%; 3%]). At the end of treatment, dysphagia was 1% in both groups. Microscopic findings paralleled the clinical results. The mucoadhesive tablet was generally well tolerated. A higher incidence of gastrointestinal disorders and drug-related adverse events was seen during ketoconazole treatment. The low-dose 10-mg miconazole mucoadhesive tablet is not inferior to systemic antifungal treatment with ketoconazole in the treatment of AIDS-related oropharyngeal candidiasis with and without dysphagia. It provides the first and only once-daily topical treatment option and should therefore be considered in first-line therapy for this condition, particularly in resource-poor settings, where ease of use can help to guarantee the success of therapy. Candidiasis is a frequent complication of infection with the human immunodeficiency virus (HIV); however, few data exist about the natural history, prevention, and treatment of mucosal candidiasis in women.
                To evaluate the safety and effectiveness of weekly fluconazole prophylaxis for mucosal candidiasis in women infected with HIV.
                Randomized, double-blind, placebo-controlled trial.
                14 sites participating in the Community Programs for Clinical Research on AIDS (CPCRA).
                323 women with HIV infection and CD4+ cell counts of 300 cells/mm3 or less.
                200 mg of fluconazole per week or placebo. Open-label fluconazole for candidiasis prophylaxis was permitted after two oropharyngeal or vaginal episodes or one esophageal episode.
                Development of mucosal candidiasis, clinical and in vitro resistance of Candida species to fluconazole, survival, and adverse events.
                After a median follow-up of 29 months, 72 of 162 patients receiving fluconazole and 93 of 161 patients receiving placebo had at least one episode of candidiasis (relative risk [RR], 0.56 [95% Cl, 0.41 to 0.77); P < 0.001). Weekly fluconazole was effective in preventing oropharyngeal candidiasis (RR, 0.50 [Cl, 0.33 to 0.74]; P < 0.001) and vaginal candidiasis (RR, 0.64 [Cl, 0.40 to 1.00]; P = 0.05) but not esophageal candidiasis (RR, 0.91 [Cl, 0.48 to 1.72]; P > 0.2). Relative risks were similar for women who had a history of mucosal candidiasis (RR, 0.5 [Cl, 0.35 to 0.75]) and those who did not (RR, 0.69 [Cl, 0.35 to 1.34]). Absolute risk reduction for patients with a history of infection was 25.6 per 100 person-years, which is more than twice the reduction of 11.2 per 100 person-years seen in patients with no history of infection. This difference reflects the higher risk of patients who previously had an infection. Candida albicans was not usually resistant to fluconazole in vaginal specimens in clinical or in vitro settings; such resistance occurred in less than 5% of patients in each group.
                Weekly fluconazole (200 mg) seems to be safe and effective in preventing oropharyngeal and vaginal candidiasis. This regimen has a useful role in the management of HIV-infected women who are at risk for recurrent mucosal candidiasis. 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. Oropharyngeal candidasis (thrush) is the most common opportunistic infection in individuals who are positive for the human immunodeficiency virus (HIV) and those who have progressed to AIDS. Itraconazole has a broad in vitro spectrum of activity, including a wide variety of Candida species. Our study determined the relative efficacy of a new oral solution formulation of itraconazole and fluconazole tablets in the treatment of oropharyngeal candidiasis.
                This was a prospective randomized, third-party-blind, multicenter trial conducted at 12 centers in the United States. One hundred seventy-nine HIV-positive patients with mycologically documented oropharyngeal candidiasis were treated with itraconazole oral solution 200 mg/ day for 7 or 14 days, or fluconazole tablets 100 mg/day for 14 days. Severity of disease was scored clinically before treatment and at clinical evaluations on days 3, 7, 14, 21, 35, and 42. Semi-quantitative cultures of mouth washings were also obtained on these days.
                Both 14-day and 7-day regimens of itraconazole oral solution were equivalent to fluconazole for most efficacy parameters. The clinical response rate was 97% after 14 days of itraconazole and 87% after 14 days of fluconazole. Itraconazole oral solution given for 7 days was also equivalent to fluconazole treatment for 14 days. Approximately one half of patients in all three groups relapsed by 1 month after completion of treatment. There were few adverse reactions to either drug.
                Itraconazole oral solution is well tolerated and offers an alternative at least as effective as fluconazole in the treatment of oropharyngeal candidiasis. To evaluate the efficacy of alcohol-based and alcohol-free melaleuca oral solution in patients with AIDS and fluconazole-refractory oropharyngeal candidiasis.
                We performed a prospective, single-center, open-label study in a university-based inner city HIV/AIDS clinic. The study included 27 patients with AIDS and oral candidiasis clinically refractory to fluconazole. Patients were randomized 1:1 to receive either alcohol-based or alcohol-free melaleuca oral solution four times daily for 2-4 weeks. Thirteen patients were enrolled into cohort 1, and 14 patients were enrolled into cohort 2. The main outcome measure was resolution of clinical lesions of oral candidiasis. Evaluations were performed at 2 and 4 weeks for clinical signs and symptoms of oral candidiasis and quantitative yeast cultures.
                All C. albicans isolates showed some degree of in vitro resistance to fluconazole. Overall, using a modified intent-to-treat analysis, 60% of patients demonstrated a clinical response to the melaleuca oral solution (7 patients cured and 8 patients clinically improved) at the 4-week evaluation.
                Both formulations of the melaleuca oral solution appear to be effective alternative regimens for patients with AIDS suffering from oropharyngeal candidiasis refractory to fluconazole. Over 37 months, we conducted a prospective double-blind, randomized study in a cohort of 138 HIV-infected patients to compare the effect of two different strategies on the prevention and treatment of oropharyngeal candidiasis relapses and on the development of clinical and microbiological resistance to fluconazole. Each episode was treated with a 7 day course of fluconazole 200 mg/day, followed by secondary prophylaxis with fluconazole 150 mg once weekly matched to placebo. The duration of the double-blind phase of the study, from the day of randomization to the first primary end-point, was 347 +/- 186 days for the fluconazole group and 196 +/- 128 days for the placebo group (P < 0.001). A total of 33 patients remained relapse-free during the course of the study. Clinical failure was observed in a total of five patients (four in the fluconazole group, one in the placebo group; P = 0.15). Microbiological resistance was recorded in 12 patients (eight in the fluconazole group, four in the placebo group; P = 0.20). There were no significant treatment group differences in microbiological resistance whether comparisons were made for all cases or for cases up to 1 month post-study. In the few patients who developed clinical and/or microbiological resistance, the cumulative dose of fluconazole before entry into the study was a mean value of 8.6 g (compared with 2.9 g in patients without clinical and/or microbiological resistance). In summary, patients treated with secondary prophylaxis suffered fewer relapses of oropharyngeal candidiasis. Development of resistant candidiasis (clinical and/or microbiological) was rarely seen in either group and its incidence was not significantly different. This double-blind trial compared the clinical and mycological efficacy and safety of itraconazole oral solution with those of fluconazole capsules in the treatment of oropharyngeal candidiasis in patients with AIDS. A total of 244 patients were enrolled and randomized to one of three groups for treatment with itraconazole oral solution (100 mg twice daily for 7 days or 100 mg once daily for 14 days) or fluconazole capsules (100 mg once daily for 14 days). Among 194 evaluable cases, complete response (clearance of all symptoms and signs) or marked improvement was noted in 54 of 60 patients (90%) receiving once-daily itraconazole and in 65 of 72 fluconazole-treated patients (90%) at the end of treatment; these results were statistically equivalent (P = .0024). Twice-daily itraconazole produced a clinical response in 51 of 62 patients (82%). The groups were equivalent in terms of early relapse (within the 18-day period studied); 37% of patients in the twice-daily itraconazole group, 35% in the once-daily itraconazole group, and 34% in the fluconazole group relapsed. Drug tolerability was comparable between the three groups. These results show that, in the treatment of oropharyngeal candidiasis, itraconazole oral solution and fluconazole capsules at a 100-mg single daily dose for 14 days are equally effective. Fluconazole, a newly available triazole, has been evaluated extensively as a treatment for thrush. It has been effective in the treatment of this condition in patients with HIV infection. Clotrimazole troches have been a common treatment for thrush in patients with HIV infection for several years. This study compared the efficacy and safety of fluconazole 100 mg tablets once per day versus clotrimazole 10 mg troches five times per day in the treatment of thrush in patients with HIV infection. Patients were evaluated at baseline, day 7, 14, 28, and 42. The following parameters were evaluated: clinical cure, colonization at the end of treatment, relapse at day 28, and relapse at day 42. Side effects including liver enzyme values were also monitored. Clinical cure was superior with fluconazole tablets than with clotrimazole troches. Also, rates of colonization at the end of therapy and relapse at days 28 and 42 were less with fluconazole tablets than with clotrimazole troches. However, these differences were not statistically significant. Patient compliance with fluconazole was superior to that of clotrimazole. This difference was statistically significant. Both fluconazole tablets and clotrimazole troches are effective in treating thrush in patients with HIV infection. The avoidance of multiple-per-day dosing would appear to favor fluconazole. In a randomized, open study, the efficacy of fluconazole as a prophylaxis of recurrent oral candidiasis in patients with advanced stages of HIV-infection (CD4 cell count less than 100/mm3) was studied. For this purpose, the frequency of episodes of oral candidiasis during two different prophylaxis regimens (50 mg/day vs. 100 mg/day) were compared to an untreated control group. Sixty-five HIV-positive patients were included in the study from May, 1989 to January, 1990. Of these, 58 were evaluated over an observation time of 137-215 days. Prophylaxis with fluconazole clearly reduced the occurrence of oral candidiasis. In 20 out of 21 patients in the untreated control group, a total of 60 relapses occurred. In the prophylaxis group receiving 50 mg/day (group 2), two out of 18 patients had four relapses. In the group receiving 100 mg/day (group 3), four out of 19 patients had nine relapses in total. Of 3575 observation days in the control group, treatment due to oral candidiasis was necessary on 393 days (28%). In group 2, on 57 of 3316 days (2%), fluconazole in a higher dosage was administered for treatment. In group 3, relapse treatment with fluconazole 200 mg/day, or treatment with ketoconazole, became necessary in 116 out of 3314 observation days (3%). In all relapses, Candida albicans cfu greater than 10(3)/ml were isolated in the oral wash-outs. As compared to the untreated control group, fluconazole prophylaxis in a daily dosage of 50 as well as 100 mg led to significantly less frequent relapses of oral candidiasis (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) To determine the efficacy and toxicity of two systemically active antifungal agents in the treatment of buccal and oesophageal candidiasis 111 HIV-infected patients with microscopically-confirmed candidiasis were randomized to receive either 200 mg itraconazole once a day or 200 mg ketoconazole twice a day for 28 days in a double blind study. After 1 week of treatment, 75 and 82% of the patients on itraconazole and ketoconazole, respectively, had responded clinically. After 4 weeks of treatment, this had risen to 93% in each group. One patient discontinued itraconozole because of toxicity (rash), five patients discontinued ketaconazole (two nausea, two hepatotoxicity and one rash). Despite successful clinical and mycological clearance, 80% patients had a further episode of candidosis within the next 3 months. Recurrent oropharyngeal candidiasis is common in patients with acquired immunodeficiency syndrome and the acquired immunodeficiency syndrome-related complex. It causes local pain and discomfort, loss of taste, and aversion to food and may lead to secondary complications. We examined, in a double-blind study, whether recurrent thrush could be prevented by prophylaxis. Twenty-five patients with one to four previous thrush episodes who had no thrush at the outset of the study were randomized to receive 100 mg of fluconazole or placebo daily for 12 weeks. If thrush occurred, prophylaxis was stopped and patients were treated conventionally, after which prophylaxis was resumed. After the randomized study, some patients were given continuous fluconazole (open phase). In the randomized study, thrush occurred in eight of 13 placebo-treated patients and none of 12 fluconazole-treated patients. Possible side effects were not different between the groups. Dermatophytosis and onychomycosis and cryptococcuria also improved in the fluconazole-treated patients, and fungal colonization was significantly decreased. One episode of thrush occurred in the open phase in an intermittently compliant patient (group total, 71.5 patient-months of fluconazole treatment); in contrast, the 25 patients also had had two episodes of Candida esophagitis, three of cryptococcosis, and 13 of dermatophytosis before entry. Subsequent to entry in the randomized trial, in 92.3 patient-months without fluconazole, there were 35 episodes of thrush, one of esophagitis, one of cryptococcemia, and one of dermatophytosis, and preexisting dermatophytosis and onychomycosis were unchanged or worsened. Individual patients observed with and without fluconazole treatment also showed its efficacy. In conclusion, thrush can be prevented in patients with acquired immunodeficiency syndrome and the acquired immunodeficiency syndrome-related complex with negligible toxic effects. Larger trials to confirm prevention of all mycoses with prophylaxis should be considered. In a randomised, double-blind study the efficacy and toxicity of oral fluconazole 50 mg daily and ketoconazole 200 mg daily were compared for the treatment of oropharyngeal candidiasis in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC). 20 episodes (18 patients) were treated with fluconazole and 20 episodes (19 patients) with ketoconazole. Pretreatment clinical features and laboratory test results were similar in both groups. 17 episodes (85%) in the fluconazole group and 16 (80%) in the ketoconazole group could be evaluated. There was clinical cure at the end of therapy in all fluconazole-treated and 12 of 16 (75%) ketoconazole-treated episodes. Cultures were negative at the end of therapy in 87% of the fluconazole group and 69% of the ketoconazole group. 1 patients stopped taking fluconazole because of severe nausea. 1 of 18 fluconazole-treated and 4 of 19 ketoconazole-treated patients had transient rises in alanine or aspartate aminotransferase. Fluconazole seemed more effective than ketoconazole in the treatment of oral thrush among AIDS and ARC patients. 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. In an open multicentre study the efficacy and safety of fluconazole versus ketoconazole were evaluated in the treatment of 46 pediatric patients with oropharyngeal candidiasis and AIDS or HIV infection. Twenty-four subjects received oral fluconazole in a dosage of 3 mg/kg/day and 22 subjects received oral ketoconazole in a dosage of 7 mg/kg/day. The treatment duration ranged from 5 to 49 days. Results showed that fluconazole and ketoconazole have comparable efficacy and safety in the treatment of oropharyngeal candidiasis in HIV-infected children. Patients treated with fluconazole had higher clinical and mycological cure rates at the end of therapy (88% and 71% respectively) than those treated with ketoconazole (81% and 57% respectively). One case of drug-related side effects (diarrhea and abdominal pain) in a patient receiving ketoconazole resulted in discontinuation of treatment. Follow-up examinations 2 and 4 weeks post-treatment showed a comparably high rate of relapse in both patient groups. The efficacy of oral itraconazole and ketoconazole in the treatment of oropharyngeal and/or esophageal candidiasis, and the rate of post-treatment relapse, were compared in a multicenter, prospective, double-blind, double-dummy, randomized, parallel-group trial. A total of 143 adult HIV-positive patients with oropharyngeal and/or esophageal candidiasis were assigned to receive either itraconazole or ketoconazole (200 mg/day). Patients with oropharyngeal and esophageal candidiasis were treated for 2 and 4 weeks, respectively. Patients were evaluated clinically and mycologically after 1, 2 and 4 (for esophageal patients) weeks of therapy, and relapses were compared in a 6-week post-treatment follow-up period. Of 129 evaluable patients, 98 had oropharyngeal candidiasis and 31 esophageal infection. CDC classification, CD4+ cell counts, and number of previous episodes of oropharyngeal or esophageal candidiasis were comparable in both groups. Oropharyngeal infection was cleared clinically at 21 days in 71% of patients receiving itraconazole and 60% receiving ketoconazole, and esophageal candidiasis was cleared at 41 days in 100% of patients receiving itraconazole and 91% receiving ketoconazole. Marginally significant differences were found between itraconazole and ketoconazole in rates of clearing of infection clinically in patients with oropharyngeal and esophageal candidiasis (p = 0.0614 and 0.0781, respectively). Mean rates of infection relapse were not statistically different in the two treatment groups. Adverse events were generally mild and not considered drug related. Itraconazole is marginally more efficacious than ketoconazole in the treatment of oropharyngeal and esophageal candidiasis in HIV-positive patients and both drugs appear safe and well tolerated. The effects of continuous or intermittent therapy with fluconazole on the recurrence of and the development of fluconazole resistance are not known.
                We studied human immunodeficiency virus (HIV)-positive patients with CD4 cell count <350 x 10(6)/L and oropharyngeal candidiasis in a prospective, randomized study. After initial treatment, 20 patients (16 of whom completed 3 months of follow-up) received continuous fluconazole at 200 mg/day, and 48 patients (28 of whom completed follow-up) received intermittent therapy at the time of symptomatic relapses. Oral samples were obtained weekly during episodes of infection and quarterly as surveillance cultures. Development of resistance was defined as a fourfold rise in minimum inhibitory concentration (MIC) to at least 16 microg/mL from the initial culture in the same species, the emergence of new, resistant (MIC > or =16 microg/mL) species, or a significant increase in the proportion of resistant isolates.
                During a mean follow-up of 11 months, median annual relapse rates were lower in patients on continuous therapy (0 episodes/year) than in patients on intermittent therapy (4.1 episodes/year; P <0.001). Sterile cultures were seen in 6 of 16 (38%) patients on continuous therapy compared with 3 of 28 (11%) on intermittent therapy (P = 0.04). Microbiological resistance developed in 9 of 16 (56%) patients on continuous treatment, compared with 13 of 28 (46%) on intermittent treatment (P = 0.75). However, despite isolates with increased MICs, 42 of 44 patients responded to fluconazole in doses up to 800 mg/day.
                In patients with frequent recurrences, continuous suppressive therapy significantly reduced relapses and colonization. Resistance occurred with both continuous and intermittent therapy; however, therapeutic responses were excellent. To assess the efficacy and tolerance of fluconazole (150 mg oral dose, once a week) in the prevention of recurrent oropharyngeal candidiasis in patients with moderate to severe human immunodeficiency virus (HIV) infection.
                A randomised, double-blind, placebo-controlled trial.
                Eighty-four patients with moderate to severe HIV infection who had successfully completed two to four weeks treatment with fluconazole for oropharyngeal candidiasis were randomly allocated to receive either placebo or fluconazole. Pre-treatment clinical and laboratory characteristics were similar in the two groups.
                Success was classified as absence throughout the course of treatment of clinical evidence of oropharyngeal candidiasis, and failure as recurrence or relapse of symptomatic oropharyngeal candidiasis.
                Of 73 evaluable patients the median time to relapse was > or = 168 days in the fluconazole group and 37 days in the placebo group (P < 0.0001). One patient in the placebo group and 18 patients in the fluconazole group completed six months' treatment without clinical relapse (P < 0.001).
                Fluconazole was well tolerated and prevented clinical relapse of oropharyngeal candidiasis in 71% of patients who completed three months of treatment (95% confidence interval [CI], 55-86) and 58% (95% CI, 41-75) who completed six months of treatment. In human immunodeficiency virus (HIV)-infected patients, fluconazole prophylaxis is associated with reductions in the rate of fungal infection. However, concerns exist with regard to the use of fluconazole prophylaxis and the risk of development of fluconazole treatment-refractory infections.
                We performed a randomized, open-label trial that compared oral fluconazole given continuously (200 mg 3 times weekly; the "continuous fluconazole arm") with fluconazole that was provided only for episodes of orophayngeal candidiasis (OPC) or esophageal candidiasis (EC) (the "episodic fluconazole arm") in HIV-infected persons with CD4+ T cell counts of <150 cells/mm3 and a history of OPC. The primary study end point was the time to development of fluconazole-refractory OPC or EC, which was defined as lack of response to 200 mg fluconazole given daily for 14 or 21 days, respectively.
                A total of 413 subjects were randomized to receive continuous fluconazole, and 416 were randomized to receive episodic fluconazole. After 42 months, 17 subjects (4.1%) in the continuous fluconazole arm developed fluconazole-refractory OPC or EC infections, compared with 18 subjects (4.3%) in the episodic fluconazole arm, with no difference between treatment arms with regard to the time to development of a fluconazole-refractory infection within 24 months (P=.88, by log-rank test) or before the end of the study (P=.97, by the log-rank test). Continuous fluconazole therapy was associated with fewer cases of OPC or EC (0.29 vs. 1.08 episodes per patient-year; P<.0001) and fewer invasive fungal infections (15 vs. 28 episodes; P=.04, by chi2 test), but not with improved survival, compared with episodic fluconazole therapy.
                Continuous fluconazole therapy is not associated with significant risk of fluconazole-refractory OPC or EC, compared with episodic fluconazole therapy, in HIV-infected patients with access to active antiretroviral therapy. A total of 167 human immunodeficiency virus (HIV)-infected patients with oropharyngeal candidiasis were randomly assigned to receive 14 days of therapy with liquid suspension fluconazole (100 mg once daily) or liquid nystatin (500,000 U four times daily). At day 14, 87% of the fluconazole-treated patients were clinically cured, as opposed to 52% in the nystatin-treated group (P < .001). Fluconazole eradicated Candida organisms from the oral flora in 60%, vs. a 6% eradication rate with nystatin (P < .001). The fluconazole group had fewer relapses noted on day 28 (18%, vs. 44% in the nystatin group; P < .001). This relapse difference no longer existed by day 42. Fluconazole oral suspension as a systemic therapy was more effective than liquid nystatin as a topical therapy in the treatment of oral candidiasis in HIV-infected patients and provided a longer disease-free interval before relapse. Fluconazole 50 mg daily for 14-28 days was effective in the treatment of patients with AIDS and AIDS-related complex with severe oropharyngeal and oesophageal candidiasis. Of 24 patients entered, 17 (81%), including seven with oesophageal candidiasis, were clinically cured and two (9.5%) improved at the end of treatment. Following clinical cure, 14 patients were entered into the double-blind phase of the study, where fluconazole (150 mg) or placebo capsules were given once weekly. Treatment was double blind. Fluconazole 150 mg once weekly was found to be effective in maintaining patients both clinically and mycologically free of oropharyngeal candidiasis. To compare the tolerance, efficacy, and pharmacokinetics of amphotericin deoxycholate (Fungizone) prepared in a parenteral fat emulsion (Intralipid 20%) or glucose in HIV patients with candidiasis.
                Non-blind randomised controlled trial.
                University hospital; tertiary clinical care.
                22 HIV positive patients with oral candidiasis.
                Amphotericin 1 mg/kg/day given on four consecutive days as a one hour infusion dissolved in either 5% glucose (amphotericin-glucose) or parenteral fat emulsion at a final concentration of 2 g/l fat emulsion (amphotericin-fat emulsion).
                Clinical tolerance (fever, chills, sweats, nausea, arterial pressure, and pulse rate); biological tolerance (serum creatinine, electrolyte, and magnesium values); clinical score of candidiasis; and serum concentrations of amphotericin.
                11 patients were enrolled in each group. All the amphotericin-fat emulsion infusions were given without serious problem whereas four amphotericin-glucose infusions were stopped because of renal impairment (n = 3) or severe chills (n = 2), or both. For patients completing the amphotericin-glucose treatment creatine concentration increased by 42 mumol/l; four of seven patients had at least one creatinine value > or = 133 mumol/l versus one of 11 receiving amphotericin-fat emulsion. Magnesium concentration fell significantly with amphotericin-glucose but not with amphotericin-fat emulsion. Clinical side effects were noted in 36/38 infusions with amphotericin-glucose but 10/44 with amphotericin-fat emulsion. Oral candidiasis score was reduced similarly in both groups. Serum amphotericin concentrations were significantly lower and the volume of distribution of the drug higher after infusion of amphotericin-fat emulsion than after amphotericin-glucose.
                Clinical and renal toxicity of amphotericin are reduced when the drug is prepared in fat emulsion. Preparation is simple and cost effective. Its efficacy is similar to that of conventional amphotericin. A randomized un-blinded study on the treatment of oropharyngeal and esophageal candidiasis was conducted in Kinshasa (Zaire), among 141 inpatients with AIDS and oropharyngeal candidiasis, of whom 136 also had esophageal candidiasis. The study compared the efficacy of gentian violet mouth washes (1.5 ml 0.5% aqueous solution b.i.d.), oral ketoconazole (200 mg/day, after a meal) and nystatin mouth washes (200.000 U oral suspension q.i.d.). Patients treated with mouth washes swallowed their medication after mouth washing. Patients enrolled in this study had a very high mortality (probability of death: 41.6% after 14 days). After 14 days, 72 patients could be evaluated. At that time, oropharyngeal lesions had disappeared in similar proportions of patients treated with gentian violet (11/26, 42%) and ketoconazole (10/23, 43%), and in a lower proportion of patients treated with nystatin (2/23, 9%; p less than 0.05). In esophageal candidiasis, ketoconazole seemed more efficient than both other treatments: esophageal lesions had disappeared in 5 (24%) of the 21 patients on ketoconazole, compared to less than 10% of patients on both other treatments (p = 0.07). The suboptimal results observed with all 3 treatments could be explained by the profound immunosuppression of patients enrolled in the study. This study suggests that gentian violet is effective treatment for oropharyngeal candidiasis. As it is very cheap (0.5 US$/treatment course in Kinshasa), we suggest that its use should be assessed in larger studies.