Systemic antifungal therapy for oesophageal candidiasis – systematic review and meta-analysis of randomized controlled trials

Introduction: Oesophageal candidiasis is a common infection among individuals with immunosuppression, associated with significant morbidity. Available guidelines recommend fluconazole as the preferred treatment; however, data regarding its effectiveness in an era of increased fluconazole resistance has not been systematically compiled. Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) addressing systemic antifungal therapy for oesophageal candidiasis was undertaken. The primary outcome was clinical response. Subgroup analysis was planned based on immune status and Candida spp. Results: Twelve RCTs were included, of which six compared fluconazole with other azoles, four compared fluconazole with echinocandins, and two compared amphotericin deoxycholate with echinocandins. Most RCTs mainly included human-immunodeficiency-virus-positive individuals. No significant differences were found between fluconazole and comparators for the outcomes of clinical response or combined clinical and endoscopic response [relative risk (RR) 1.02, 95% confidence interval (CI) 0.97–1.07 and RR 1.06, 95% CI 0.98–1.15, respectively]. No differences were found between fluconazole and other azoles for other outcomes; however, compared with echinocandins, fluconazole had significantly higher mycological response rates and lower early relapse rates (RR 1.09, 95% CI 1.02–1.17 and RR 0.42, 95% CI 0.26–0.68, respectively). No significant differences were demonstrated between fluconazole and comparators for overall or severe adverse events. Information required for the planned subgroup analyses was not available. Conclusions: No differences in efficacy or safety were found between fluconazole and other azoles for the treatment of candida oesophagitis. The use of echinocandins resulted in lower mycological cure rates and higher relapse rates. Additional RCTs should evaluate these interventions among broader patient populations and a wider spectrum of Candida spp.