Treatment Of Esophageal Candidiasis Research Articles

SAT-LB88 Recurrent Dysphagia Due to an Esophageal Stricture in a Patient With Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED)

Background: Chronic Mucocutaneous Candidiasis is one of the hallmark features of Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED). Untreated esophageal candidiasis may lead to complications such as esophageal stricture, rupture and or fistula formation1,2. Case Presentation:A 31-year-old man with a past medical history significant for APECED with involvement including hypoparathyroidism, hypothyroidism and adrenal insufficiency presented to the Emergency Department with dysphagia and globus sensation after eating. This was the fourth time in the last 2 years that the patient had presented with this chief complaint. The patient underwent emergent esophagogastroduodenoscopy (EGD) where a large meat bolus was identified at approximately 20 cm and removed. A discrete esophageal tear at 19-20 cm was identified and clipped. The esophagus was noted to be diffusely narrowed with mild corrugation, and biopsies showed evidence of esophageal candidiasis. A chest CT scan demonstrated diffuse pneumomediastinum and soft tissue emphysema throughout the esophagus, suspicious for a tear. Fluoroscopic Esophagogram showed mild narrowing of the upper third of the esophagus without evidence of gross extravasation. The patient was placed on NPO (nothing by mouth) diet, started total parenteral nutrition, and treated with IV Fluconazole, administered for 10 days and then transitioned to oral Fluconazole for a total of 21 days, with improvement. A subsequent repeat fluoroscopic esophagogram showed absence of extravasation at the previously identified level of the esophagus. The patient is currently scheduled for a repeat EGD in 3 months. Conclusion:This case demonstrates a significant complication of APECED involving esophageal candidiasis. Timely diagnosis and treatment of esophageal candidiasis in APECED may prevent life-threatening esophageal pathology.

Diagnosis and Treatment of Esophageal Candidiasis: Current Updates.

Esophageal candidiasis (EC) is the most common type of infectious esophagitis. In the gastrointestinal tract, the esophagus is the second most susceptible to candida infection, only after the oropharynx. Immunocompromised patients are most at risk, including patients with HIV/AIDS, leukemia, diabetics, and those who are receiving corticosteroids, radiation, and chemotherapy. Another group includes those who used antibiotics frequently and those who have esophageal motility disorder (cardiac achalasia and scleroderma). Patients complained of pain on swallowing, difficulty swallowing, and pain behind the sternum. On physical examination, there is a plaque that often occurs together with oral thrush. Endoscopic examination is the best approach to diagnose this disease by directly observing the white mucosal plaque-like lesions and exudates adherent to the mucosa. These adherent lesions cannot be washed off with water from irrigation. This disease is confirmed histologically by taking the biopsy or brushings of yeast and pseudohyphae invading mucosal cells. The treatment is by systemic antifungal drugs given orally in a defined course. It is important to differentiate esophageal candidiasis from other forms of infectious esophagitis such as cytomegalovirus, herpes simplex virus, gastroesophageal reflux disease, medication-induced esophagitis, radiation-induced esophageal injury, and inflammatory conditions such as eosinophilic esophagitis. Except for a few complications such as necrotizing esophageal candidiasis, fistula, and sepsis, the prognosis of esophageal candidiasis has been good.

Population pharmacokinetics of micafungin and its metabolites M1 and M5 in children and adolescents.

The aim of this analysis was to identify therapeutic micafungin regimens for children that produce the same micafungin exposures known to be effective for the prevention and treatment of Candida infections in adults. Pediatric pharmacokinetic data from 229 patients between the ages of 4 months and <17 years were obtained from four phase I and two phase III clinical trials. Population pharmacokinetic models were used to simulate the proportion of children who had a steady-state area under the concentration-time curve at 24 hours (AUC24) of micafungin within the 10th to 90th percentile range observed in a population of adults receiving a dose of micafungin with established efficacy for invasive candidiasis (100 mg/day), i.e., 75 to 139 μg·h/ml. Simulated pediatric dosages of 0.5 to 5 mg/kg of body weight/day were explored. A two-compartment model was used that incorporated body weight as a predefined covariate for allometric scaling of the pharmacokinetic parameters. During construction of the model, aspartate aminotransferase and total bilirubin were also identified as covariates that had a significant effect on micafungin clearance. A dose of 2 mg/kg resulted in the highest proportion of children within the predefined micafungin AUC24 target range for invasive candidiasis. Cutoffs of 40 or 50 kg for weight-based dosing resulted in heavier children being appropriately dosed. Thus, dose regimens of 1, 2, and 3 mg/kg/day micafungin are appropriate for the prevention of invasive candidiasis, the treatment of invasive candidiasis, and the treatment of esophageal candidiasis, respectively, in children aged 4 months to <17 years.

7 Candidiasis

7 Candidiasis

Micafungin for the prophylaxis and treatment of Candida infections

Invasive fungal infection is a significant cause of morbidity and mortality worldwide. The incidence of these infections is steadily increasing. In addition, strains resistant to many commonly used antifungal agents are becoming more prevalent. Many new antifungals have become commercially available in recent years, which have vastly improved the ability to treat these infections effectively. Micafungin is one of three commercially available echinocandins available for use in the USA. This class of agents possess a unique mechanism of action that helps to reduce toxicity while maintaining potent antifungal activity. Micafungin is currently approved for the treatment of esophageal candidiasis in adults and is the only in its class approved for the prophylaxis of Candida infection in patients who have undergone hematopoietic stem cell transplantation. It was also recently approved in the USA for the treatment of candidemia and other forms of invasive candiaisis (acute disseminated candiaisis, Candida peritonitis and abscess). In general, micafungin is well tolerated and has favorable safety and drug-interaction profiles.

A comparative evaluation of properties and clinical efficacy of the echinocandins

With the increase in prevalence of fungal infections, newer antifungal agents are needed to effectively treat invasive disease, and at the same time minimize adverse effects from therapy. The echinocandins comprise a novel class of antifungals; their mechanism of action involves inhibiting 1,3-β-D-glucan synthase, which is essential in cell wall synthesis for certain fungi. All three echinocandins are US FDA-approved for the treatment of esophageal candidiasis. Caspofungin and anidulafungin are licensed for the treatment of candidemia, and other select forms of invasive candidiasis. Micafungin is at present the only echinocandin approved for prophylaxis of fungal infections in hematopoietic stem cell transplants; whereas caspofungin is approved for empiric therapy of febrile neutropenia. Although all three echinocandins are active against Aspergillus, only caspofungin is presently approved for salvage therapy in invasive aspergillosis. Combination therapy with echinocandins plus other licensed antifungal therapy shows promise in treating invasive aspergillosis. This article will explore the similarities and differences among the echinocandins.

Anidulafungin: a new echinocandin for candidal infections

Anidulafungin, a new echinocandin, has recently been approved for the treatment of esophageal candidiasis, candidemia and other forms of invasive candidiasis, such as peritonitis and intra-abdominal abscesses in non-neutropenic patients. It is fungicidal against Candida spp. including those that are azole- and polyene-resistant and fungistatic against Aspergillus spp. Owing to its poor oral bioavailability it can only be administered intravenously. Its pharmacokinetics allow for once-daily dosing and a steady state concentration is easily achieved on day 2 following a loading dose of double the maintenance dose on day 1. It does not need adjustment for hepatic or renal insufficiency; there are no known drug interactions and it has a favorable tolerability profile. Its mechanism of action, which differs from other classes of antifungals, should prevent cross-resistance with azoles and polyenes.

Micafungin: A New Echinocandin Antifungal

The echinocandins represent the newest class of antifungals to combat infections caused by Candida sp. Micafungin is an echinocandin recently approved by the United States Food and Drug Administration. It is indicated in adults for esophageal candidiasis and prophylaxis against candidal infections in hematopoietic stem cell transplant recipients. Micafungin exhibits in vitro fungicidal activity against Candida sp, including fluconazole-resistant isolates. Its in vivo efficacy is comparable to that of fluconazole in the treatment of esophageal candidiasis and superior to that of fluconazole for prophylaxis of invasive candidal infections. Because it is not significantly metabolized by the cytochrome P450 3A system, micafungin is associated with few drug interactions. Micafungin does not require adjustment in patients with renal and/or hepatic impairment, and it has been shown to be well tolerated in both adult and pediatric patients. Its efficacy against Candida sp, coupled with its overall safety and drug interaction profiles, makes it an attractive option in the treatment against esophageal candidiasis and prophylaxis against invasive candidal infections.

Echinocandins in the management of invasive fungal infections, part 2

The chemistry, pharmacology, spectrum of activity, resistance, pharmacokinetics, pharmacodynamics, clinical efficacy, adverse effects, drug interactions, dosage and administration, cost, and place in therapy of echinocandins are reviewed. Three echinocandins are currently available: caspofungin, micafungin, and anidulafungin. The principal mechanism of action of the echinocandins is the noncompetitive inhibition of beta-(1,3)-D-glucan synthase, an essential component of the cell wall of many fungi that is not present in mammalian cells. Echinocandins exhibit fungicidal activity against Candida species, including triazole-resistant isolates, and fungistatic activity against Aspergillus species. While fungistatic against mold, echinocandins may hold promise for the treatment of these pathogens when given in combination with amphotericin B or broad-spectrum triazoles, such as voriconazole. To date, resistance to echinocandins has been reported in only two patients. Echinocandins exhibit concentration-dependent activity against Candida species. In clinical trials, caspofungin has demonstrated efficacy in treating candidemia, esophageal candidiasis, and febrile neutropenia. Micafungin has demonstrated efficacy as antifungal prophylaxis in hematopoietic stem cell transplant recipients and in the treatment of esophageal candidiasis. Anidulafungin received approved labeling from the Food and Drug Administration in February 2006. Clinical efficacy data will be forthcoming. Echinocandins are fungicidal against yeast and fungistatic against mold. Their limited toxicity profile and minimal drug-drug interactions make them an attractive new option for the treatment of invasive fungal infections. Their cost may limit their use as initial therapy for patients with fungemia in medical centers or intensive care units with a high rate of triazoleresistant Candida infections.

Global Surveillance of In Vitro Activity of Micafungin against Candida : a Comparison with Caspofungin by CLSI-Recommended Methods

Micafungin is an echinocandin antifungal agent that has recently been approved for the prevention of invasive fungal infection and the treatment of esophageal candidiasis. Prospective sentinel surveillance for the emergence of in vitro resistance to micafungin among invasive Candida sp. isolates is indicated. We determined the in vitro activity of micafungin against 2,656 invasive (bloodstream or sterile site) unique patient isolates of Candida spp. collected from 60 medical centers worldwide in 2004 and 2005. We performed antifungal susceptibility testing according to the Clinical and Laboratory Standards Institute (CLSI) M27-A2 method and used a 24-hour prominent inhibition endpoint for determination of the MIC. Caspofungin was tested in parallel against all isolates. Of 2,656 invasive Candida sp. isolates, species distribution was 55.6% Candida albicans, 14.4% Candida parapsilosis, 13.4% Candida glabrata, 10.1% Candida tropicalis, 2.4% Candida krusei, 1.7% Candida guilliermondii, 0.9% Candida lusitaniae, 0.6% Candida kefyr, and 0.9% other Candida species. Overall, micafungin was very active against Candida (MIC50/MIC at which 90% of the isolates tested are inhibited [MIC90], 0.015/1 microg/ml; 96% inhibited at a MIC of < or =1 microg/ml, 100% inhibited at a MIC of < or =2 microg/ml) and comparable to caspofungin (MIC50/MIC90, 0.03/0.25 mug/ml; 99% inhibited at a MIC of < or =2 microg/ml). Results by species, expressed as MIC50/MIC90 (micrograms per milliliter), were as follows: C. albicans, 0.015/0.03; C. glabrata, 0.015/0.015; C. tropicalis, 0.03/0.06; C. krusei, 0.06/0.12; C. kefyr, 0.06/0.06; C. parapsilosis, 1/2; C. guilliermondii, 0.5/1; C. lusitaniae, 0.12/0.25; other Candida spp., 0.25/1. Although the species distribution varied considerably among the different geographic regions, there was no difference in micafungin activity across the regions. Micafungin has excellent in vitro activity against invasive clinical isolates of Candida from centers worldwide.

Echinocandins in the management of invasive fungal infections, part 1

The chemistry, pharmacology, spectrum of activity, resistance, pharmacokinetics, pharmacodynamics, clinical efficacy, adverse effiects, drug interactions, dosage and administration, cost, and place in therapy of echinocandins are reviewed. Three echinocandins are currently available: caspofungin, micafungin, and anidulafungin. The principal mechanism of action of the echinocandins is the noncompetitive inhibition of beta-(1,3)-dglucan synthase, an essential component of the cell wall of many fungi that is not present in mammalian cells. Echinocandins exhibit fungicidal activity against Candida species, including triazole-resistant isolates, and fungistatic activity against Aspergillus species. While fungistatic against mold, echinocandins may hold promise for the treatment of these pathogens when given in combination with amphotericin B or broad-spectrum triazoles, such as voriconazole. To date, resistance to echinocandins has been reported in only two patients. Echinocandins exhibit concentration- dependent activity against Candida species. In clinical trials, caspofungin has demonstrated efficacy in treating candidemia, esophageal candidiasis, and febrile neutropenia. Micafungin has demonstrated efficacy as antifungal prophylaxis in hematopoietic stem cell transplant recipients and in the treatment of esophageal candidiasis. Anidulafungin received approved labeling from the Food and Drug Administration in February 2006. Clinical efficacy data will be forthcoming. Echinocandins are fungicidal against yeast and fungistatic against mold. Their limited toxicity profile and minimal drug-drug interactions make them an attractive new option for the treatment of invasive fungal infections. Their cost may limit their use as initial therapy for patients with fungemia in medical centers or intensive care units with a high rate of triazoleresistant Candida infections.

Emerging echinocandins for treatment of invasive fungal infections

The echinocandins are a new class of antifungals, developed in response to the need for safe and effective antifungals for the treatment of invasive fungal infections. These agents work by inhibiting 1,3-β-d-glucan synthase, an enzyme essential for production of cell walls in select fungi. Echinocandins appear to demonstrate favourable activity in vitro against a variety of yeasts (including both Candida albicans and non-albicans Candida) as well as select moulds (including Aspergillus spp.) In general, all echninocandins demonstrate a favourable safety profile and require once-daily parenteral administration. Caspofungin is the first of these agents to be available in the US, and is approved for empirical antifungal therapy in febrile neutropenic patients, candidaemia and select forms of invasive candidiasis, and for management of invasive aspergillosis in patients refractory to or intolerant of other therapies. Micafungin was recently approved by the FDA for treatment of oesophageal candidiasis, and for the prophylaxis of fungal infections in haematopoietic stem cell transplant recipients. Emerging data indicate micafungin may have an important role in the treatment of invasive forms of candidiasis. Anidulafungin is an echinocandin approved in the US for treatment of candidaemia and oesophageal candidiasis. Aminocandin (HMR-3702, IP-960) is an investigational agent, with published experience limited to in vitro studies and animal models of infection.

Severe Esophageal Candidiasis In An Immunocompetent Patient

We report a rare case of a healthy immunocompetent adult woman admitted with worsening odynophagia secondary to severe esophageal candidiasis and then summarize the state-of-the-art knowledge on epidemiology, diagnosis, pathogenesis, clinical picture and treatment of esophageal candidiasis in immunocompetent patients. The patient was a 70-year-old healthy lady who presented to the hospital with worsening symptoms. An upper GI endoscopy with biopsy revealed histopathologic changes consistent with esophageal candidiasis. Patient's symptoms were improved after treatment was initiated with oral fluconazole. Physicians need to remain alert to the varied presentations of esophageal candidiasis also in immunocompetent patient.

Caspofungin

Caspofungin (Cancidas) is the first of a new class of antifungal agents, the echinocandins, that inhibit the synthesis of the fungal cell wall component beta-(1,3)-D-glucan. Caspofungin is administered once daily by slow intravenous infusion and is used to treat infections caused by Candida spp. and Aspergillus spp. Caspofungin is a valuable new antifungal agent with a novel mechanism of action. In comparative clinical trials, caspofungin was no less effective than liposomal amphotericin B in the empirical treatment of neutropenic patients with persistent fever, amphotericin B deoxycholate in the treatment of invasive candidiasis or fluconazole in the treatment of oesophageal candidiasis. Caspofungin also displayed broadly similar efficacy to amphotericin B deoxycholate in oesophageal or oropharyngeal candidiasis and was effective as salvage therapy in patients with invasive aspergillosis who were refractory to or intolerant of standard therapy. The tolerability profile of caspofungin was similar to that of fluconazole and superior to that of amphotericin B deoxycholate and liposomal amphotericin B. Therefore, in the appropriate indications, caspofungin is a viable alternative to amphotericin B deoxycholate, liposomal amphotericin B or fluconazole.

Micafungin.

To review the pharmacology, mycology, chemistry, in vitro susceptibility, pharmacokinetics, clinical efficacy, safety, tolerability, dosage, and administration of micafungin, an echinocandin antifungal agent. A MEDLINE search, restricted to English language, was conducted from 1978 to November 2003. Supplementary sources included program abstracts from the Interscience Conference on Antimicrobial Agents and Chemotherapy and the Infectious Diseases Society of America from 1996 to 2003 and information available through the manufacturer's Web site. In vitro and preclinical studies, as well as Phase II and III clinical trials, were evaluated to summarize the clinical efficacy and safety of micafungin. All published and unpublished trials and abstracts citing micafungin were selected. Micafungin has shown in vitro activity against many yeasts and a variety of molds. Micafungin can be administered only parenterally. Efficacy has been illustrated in open noncomparative studies of esophageal candidiasis in HIV-infected patients and in comparative trials as antifungal prophylaxis in patients undergoing hematopoietic stem-cell transplantation. Adverse events appear mild and limited; the most commonly reported adverse events include hyperbilirubinemia, nausea, and diarrhea. Micafungin has activity against Aspergillus spp. and a variety of Candida spp., including azole-resistant strains. Micafungin demonstrates efficacy in the treatment of esophageal candidiasis in HIV-infected patients and appears superior to fluconazole as antifungal prophylaxis in patients undergoing hematopoietic stem-cell transplantation. Based on case reports and in vitro efficacy, micafungin may prove to be a clinically useful agent in the treatment of other fungal diseases; however, these indications await the results of clinical trials.

Anidulafungin: an echinocandin antifungal

Anidulafungin (LY-303366, V-echinocandin™, Vicuron Pharmaceuticals, Inc.) is a new echinocandin antifungal agent with broad spectrum activity against Candida and Aspergillus spp. Anidulafungin exhibits low toxicity, concentration-dependent fungicidal activity for Candida, and a prolonged post antifungal effect (> 12h). In vitro activity demonstrates excellent potency and spectrum versus azole-susceptible and -resistant Candida spp. and a low minimum effective concentration for Aspergillus spp. In vivo anidulafungin is fungicidal against Candida in neutropenic animal models of disseminated candidiasis. Against Candida anidulafungin exhibits concentration-dependent killing and clearance of residual fungal burden in target organs (liver, lung, spleen, kidney) and plasma/tissue concentrations exceed the minimum inhibitory and minimum fungicidal concentrations of the infecting organism throughout the dosing interval. Although the activity of anidulafungin in animal models of pulmonary or disseminated aspergillosis shows increased survival and improvement in the pulmonary infarct score, the effect on residual fungal burden and Aspergillus antigenemia determination does not indicate in vivo fungicidal activity. It seems that the major effect of anidulafungin and other echinocandins in vivo against Aspergillus spp. is the decrease in the angioinvasive potential of the organisms. Clinically, anidulafungin has been shown to be safe and effective in the treatment of oesophageal candidiasis and candidemia. Further clinical application of this new antifungal agent is warranted.

Anidulafungin: review of a new echinocandin antifungal agent

Anidulafungin (Vicuron Pharmaceuticals) is a new echinocandin antifungal with potent activity against Aspergillus and Candida spp. Anidulafungin is a noncompetitive inhibitor of (1,3)-β-d-glucan synthase within fungal cells. The drug is rapidly distributed and steady-state concentrations are achieved after the first dose, when a loading dose of twice the daily maintenance dose is given on day 1. Drug biotransformation occurs via chemical degradation, with no hepatic metabolism or renal elimination. A favorable pharmacokinetic profile and lack of significant drug interactions suggest that patients can receive anidulafungin without dosage adjustments. These characteristics, in addition to comparable efficacy to fluconazole (Diflucan®, Pfizer Ltd) in the treatment of esophageal candidiasis, support further investigation of its use in the treatment of systemic fungal infections caused by Candida and Aspergillus spp.

Anidulafungin* is as effective as fluconazole in the treatment of oesophageal candidiasis,

Anidulafungin* is as effective as fluconazole in the treatment of oesophageal candidiasis,

Voriconazole: A New Triazole Antifungal Agent

To review the pharmacology, in vitro susceptibility, pharmacokinetics, clinical efficacy, and adverse effects of voriconazole, a triazole antifungal agent. A MEDLINE search, restricted to English language, was conducted from 1990 to June 2002. Supplementary sources included program abstracts from the Interscience Conference on Antimicrobial Agents and Chemotherapy and the Infectious Diseases Society of America from 1996 to 2001 and manufacturer information available through the Food and Drug Administration's Web site. All published and unpublished trials and abstracts citing voriconazole were selected. Voriconazole has shown in vitro activity against many yeasts and a variety of mold and dermatophyte isolates. Voriconazole can be administered either orally or parenterally. It exhibits good oral bioavailability, wide tissue distribution including distribution into the central nervous system, and hepatic metabolism. Drug interactions occur through inhibition of the CYP2C9, CYP2C19, and CYP3A4 isoenzymes, resulting in alterations in kinetic parameters of either voriconazole or the interacting agent. Efficacy has been illustrated in open, noncomparative studies of aspergillosis in immunocompromised patients. Human case reports describe successful treatment of rare fungal pathogens. The most commonly reported adverse events include visual disturbances and elevations in liver function tests. Voriconazole is at least as effective as amphotericin B in the treatment of acute invasive aspergillosis in immunocompromised patients. It has similar efficacy as fluconazole in treatment of esophageal candidiasis. Voriconazole did not achieve statistical non-inferiority to liposomal amphotericin B for empirical therapy in patients with neutropenia and persistent fever, diminishing enthusiasm for use in this indication until additional trials are completed. Based on case reports and in vitro efficacy, voriconazole may prove to be a clinically useful agent in the treatment of other fungal disease.

Fluconazole vs. Flucytosine in the Treatment of Esophageal Candidiasis in AIDS Patients: A Double-Blind, Placebo-Controlled Study

Contrasting opinions exist as to the pharmacological treatment of esophageal candidiasis in human immunodeficiency virus (HIV)-positive patients. The aim of this study has been to evaluate the role, therapeutic efficacy, and the cost-benefit ratio of two antifungal drugs, fluconazole and flucytosine, compared with a placebo, in the treatment of endoscopically-diagnosed esophageal candidiasis in patients with acquired immune deficiency syndrome (AIDS). The study included 60 HIV-positive patients (38 males and 22 females, mean age 27 +/- 2) with a first episode of esophageal candidiasis diagnosed by endoscopy (grades I-II of Kodsi's endoscopic classification, and grades I-IIa of Barbaro's clinical classification). No other opportunistic infection of the esophagus was detected. In a double-blind procedure, patients were randomized into three groups of 20 patients each, receiving either fluconazole (3 mg/kg/daily per os), flucytosine (100 mg/kg/daily per os) or placebo. After two weeks of treatment, the patients previously assigned to receive the placebo were double-blindly randomized to receive fluconazole (eight patients) or flucytosine (nine patients). In order to evaluate the efficacy of pharmacological therapy, clinical examination was performed at weeks 2 and 5, and then every week up to the end of follow-up (three months); endoscopic examination was performed at weeks 2 and 5, and at the end of follow-up. At week 2, endoscopic cure (grade 0) was observed in 13 patients (65%) of the fluconazole group and in three patients (15%) in the flucytosine group (relative risk ratio: 0.23; 95% C.I.: 0.10-0.48; p < 0.05), and a partial endoscopic response (grade I) was observed in two patients (10%) in the placebo group. Complete clinical remission (grade 0) was observed in 16 patients (80%) in the fluconazole group and 12 patients (60%) in the flucytosine group (relative risk ratio: 0.75; 95% C.I.: 0.42-0.89; p = n.s.), while six patients (30%) in the placebo group presented partial clinical remission (grade I). At the end of follow-up, endoscopic cure was observed in 19 patients (70%) in the fluconazole group and in nine patients (33%) in the flucytosine group (relative risk ratio: 0.47; 95% C.I.: 0.19-0.65; p < 0.05). Complete clinical remission was observed in 21 patients (77.7%) in the fluconazole group and in 17 patients (63%) in the flucytosine group (relative risk ratio: 0.81; 95% C.I.: 0.53-0.92; p = n.s.). No noticeable side-effects were observed in the patients in either treatment group, without a statistically significant difference in comparison with the placebo. The results of this study have demonstrated that both fluconazole and flucytosine are safe and well tolerated in the treatment of esophageal candidiasis in AIDS patients. Fluconazole showed greater therapeutic efficacy than flucytosine, with a difference that was statistically significant in terms of the rate of endoscopic cure.