OBJECTIVES: High mortality rates and prolonged hospital stay are directly associated with invasive candidiasis, a leading fungal infection in hospitalised patients or in those undergoing solid organ transplants. We aimed compare the efficacy and safety of all available antifungal agents for treating invasive fungal infections caused by Candida spp.

METHODS: A systematic review with Bayesian network meta-analysis (NMA), surface under the cumulative ranking analysis (SUCRA) and stochastic multicriteria acceptability analyses (SMAA) were performed (PROSPERO-CRD42020149264). Searches were conducted in PubMed and Scopus (May-2021) and complemented by manual search. We included randomized controlled trials evaluating the effect of any dose or regimen of oral antifungals on the outcomes: mycological cure, discontinuation rates and adverse events. Networks meta-analysis were built for each outcome of interest. Results were reported as odds ratios (OR) with 95% credibility intervals (CrI) (Addis-v.1.17.6).

RESULTS: Thirteen trials (n=3,632) were included. No significant differences among therapies were found for the efficacy outcomes; however, the echinocandins caspofungin (50-150 mg), rezafungin (200-400mg) and micafungin (100-150 mg) led to higher rates of both clinical and mycological responses (SUCRA probabilities over 60%). Fluconazole (400 mg) was rated as the last option for overall response (17%). Regarding treatment discontinuation and abnormal liver function, caspofungin 150 mg was considered the safest therapy. Rezafungin (200-400mg) and micafungin (100 mg) were associated with lower discontinuation rates (<40%) while conventional amphotericin B (0.6-0.7mg/kg) was more likely led to this outcome (OR 0.08 [95% CrI 0.00-0.95] vs. caspofungin 150 mg) and to liver function impairment. Caspofungin had the highest benefit-risk ratio (SMAA).

CONCLUSIONS: Echinocandins should be used as first-line treatments for invasive candidiasis following a priority order of caspofungin and micafungin. Rezafungin, an under development echinocandin, represents an additional option that should be further investigated. Azoles and liposomal amphotericin B can be used as second-line treatments in cases of fungal resistance or hypersensitivity.