Fluconazole vs Other Antifungals for Esophageal Candidiasis in Patients With HIV

Results of a systematic review and meta-analysis found no difference between the safety and efficacy of fluconazole vs other antifungal agents, including azoles and echinocandins, for the treatment of esophageal candidiasis. These findings were published in the International Journal of Antimicrobial Agents.

Investigators at Tel Aviv University in Israel searched publication databases through August 2021 for studies that assessed systemic antifungal therapy in adults with esophageal candidiasis. A total of 12 randomized controlled trials (RCTs) were included in this analysis. In 11 of the RCTs, the majority of the patient population (75%) was positive for HIV infection. The primary outcome was clinical response.

Among the 12 RCTs included, 6 compared treatment with fluconazole vs other azoles, 4 compared fluconazole with echinocandins, and 2 compared amphotericin deoxycholate with echinocandins. Most studies used an oral route of administration for fluconazole, at a dose of 200 mg daily for a duration of at least 2 weeks to 6 to 8 weeks.

In regard to clinical response at the end of treatment (n=3936), no differences between fluconazole and other antifungal interventions were observed (relative risk [RR], 1.02; 95% CI, 0.97-1.07; I² =79%). Findings were similar after the 1 RCT with significant heterogeneity was excluded from the analysis (RR, 1.01; 95% CI, 0.99-1.02).

After stratification of studies by oral (n=5) and intravenous (n=3) routes of administration, the findings remained the same. Findings also were unchanged after stratification of studies by fluconazole doses of 200 (n=9) and 100 mg (n=2).

Compared with other azoles, no differences were reported for endoscopic cure rate and endoscopic response (RR, 1.03; 95% CI, 0.97-1.10), mycologic response (RR, 0.92; 95% CI, 0.84-1.00), and late relapse (RR, 1.15; 95% CI, 0.78-1.69).

Compared with echinocandins, no differences were reported for endoscopic cure rate (RR, 1.02; 95% CI, 1.0-1.04), endoscopic response (RR, 1.04; 95% CI, 0.86-1.26), and late relapse (RR, 0.70; 95% CI, 0.44-1.10). However, the investigators observed a significantly increased mycologic response (RR, 1.09; 95% CI, 1.02-1.17) and a decreased rate of early relapse (RR, 0.42; 95% CI, 0.26-0.68; I² =21%).

Of note, results of 1 RCT showed that the clinical response to fluconazole was significantly increased compared with anidulafungin (RR, 1.39; 95% CI, 1.25-1.54).

In the safety analysis, no significant differences were observed between fluconazole and comparators for 28-day mortality (RR, 1.10; 95% CI, 0.75-1.6) and adverse event occurrence, including any event (RR, 0.94; 95% CI, 0.83-1.05), severe events (RR, 1.66; 95% CI, 0.60-4.60), or events requiring treatment discontinuation (RR, 0.72; 95% CI, 0.42-1.25).

This study was limited by poor external validity as the majority of included patients were HIV-positive.

According to the investigators, “additional [RCTs]…should be conducted to guide optimal treatment in the current clinical setting.”

Reference

Mwassi HA, Yahav D, Ayada G, et al. Systemic anti-fungal therapy for esophageal candidiasis – systematic review and meta-analysis of randomized controlled trials. Int J Antimicrob Agents. 2022;106590. doi:10.1016/j.ijantimicag.2022.106590