title: Fluconazole vs itraconazole-flucytosine association in the treatment of esophageal candidiasis in AIDS patients. A double-blind, multicenter placebo-controlled study. The Candida Esophagitis Multicenter Italian Study (CEMIS) Group.
abstract: OBJECTIVE
  To assess the role and the therapeutic efficacy of fluconazole and itraconazole-flucytosine association compared with placebo, in the treatment of endoscopically diagnosed esophageal candidiasis in a selected population of AIDS patients.
  
  
  METHODS
  Double-blind, placebo-controlled study.
  
  
  METHODS
  University Hospitals and AIDS Centers.
  
  
  METHODS
  Eighty-five HIV-positive patients (53 men and 32 women; mean age, 28 years) at first episode of esophageal candidiasis diagnosed by endoscopy (grades I to II of Kodsi's endoscopic classification and grades I to IIa of Barbaro's clinical classification). All the patients selected for the study provided informed consent.
  
  
  METHODS
  The patients have been double blindly randomized in 3 groups of patients in relation to pharmacologic therapy: (1) the patients of the first group (n = 30) received fluconazole (3 mg/kg daily orally) and placebo (100 mg/kg/daily orally); (2) the patients of the second group (n = 30) received itraconazole (3 mg/kg daily orally) and flucytosine (100 mg/kg daily orally); and (3) the patients of the third group (n = 25) received placebo (3 mg/kg daily orally) and placebo (100 mg/kg daily orally). After 2 weeks of treatment, the patients previously randomized to receive placebo only were double blindly randomized to receive fluconazole+placebo or itraconazole+flucytosine. To evaluate the efficacy of pharmacologic therapy, clinical and endoscopic examinations were performed at weeks 2 and 4 and at the end of follow-up (3 months).
  
  
  RESULTS
  At week 2, endoscopic cure (grade 0) was observed in 68.9% of the fluconazole+placebo group and in 72.4% of the itraconazole+flucytosine group (relative risk, 0.95; 95% confidence interval [CI], 0.68 to 1.33; p = 0.772); partial endoscopic response (grade I) was observed in 22.7% of the placebo group. Clinical cure (grade 0) was observed in 75.8% of fluconazole+placebo group and in 72.4% of itraconazole+flucytosine group (relative risk, 1.05; 95% CI, 0.77 to 1.42; p = 0.764), with a difference statistically significant for both treatments in comparison to placebo group (p < 0.001). Partial clinical response (grade I) was observed in 27.3% of the placebo group. At the end of follow-up, endoscopic cure was observed in 89.8% of the fluconazole+placebo group and in 94.8% of the itraconazole+flucytosine group (relative risk, 0.97; 95% CI, 0.83 to 1.08; p = 0.695). Clinical cure was observed in 94.8% of the fluconazole+placebo group and in 97.3% of the itraconazole+flucytosine group (relative risk, 0.97; 95% CI, 0.89 to 1.07; p = 0.981).
  
  
  CONCLUSIONS
  The results of this study have demonstrated that both fluconazole and itraconazole+flucytosine association are efficacious in short-term treatment of esophageal candidiasis in AIDS patients with a statistically significant difference in comparison to placebo. Both therapeutic regimens demonstrated a good therapeutic efficacy, without statistically significant difference, between them, in the rate of endoscopic and clinical cure. Itraconazole+flucytosine association may represent an alternative therapeutic regimen for patients with fluconazole-resistant Candida esophagitis.
authors.affiliation: Department of Emergency Medicine, University La Sapienza, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Barbaro
authors.forename: G
authors.initials: G
authors.lastname: Barbarini
authors.forename: G
authors.initials: G
authors.lastname: Di Lorenzo
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy*; D000284:Administration, Oral; D000328:Adult; D000935:Antifungal Agents / Q000627:therapeutic use*; D002177:Candidiasis / Q000175:diagnosis / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004941:Esophagitis / Q000175:diagnosis / Q000188:drug therapy*; D004945:Esophagoscopy; D005260:Female; D015725:Fluconazole / Q000627:therapeutic use*; D005437:Flucytosine / Q000008:administration & dosage*; D006801:Humans; D017964:Itraconazole / Q000008:administration & dosage*; D008297:Male; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D017964:Itraconazole; D015725:Fluconazole; D005437:Flucytosine