Clinical evaluation of antifungal de-escalation in Candida infections: a systematic review and meta-analysis

Objective De-escalation (DES) from echinocandins to azoles is recommended by several medical societies in Candida infections. We summarize the evidence of DES on clinical and microbiological cure and 30-day survival and compare it with continuing the treatment with echinocandins (Non-DES). Methods We searched MEDLINE, Embase, Web of Science, Scopus. Studies describing DES in inpatients and reporting any of the outcomes evaluated were included. Pooled estimates of the tree outcomes were calculated with a fixed or random-effects model. Heterogeneity was explored stratifying by subgroups and via meta-regression. This systematic review is registered with PROSPERO (CRD42023475486). Results Of 1853 records identified, 9 studies were included, totaling 1575 patients. Five studies stepped-down to fluconazole; one to voriconazole and three to any of azoles. The mean day of DES was 5.2 (4.6–6.5) days. The clinical cure OR was 1.29 (95%CI: 0.88–1.88); the microbiological cure 1.62 (95%CI: 0.71–3.71); and 30-day survival 2.17 (95%CI: 1.09–4.32). The 30-day survival data into subgroups showed higher effect on critically ill patients and serious-risk bias studies. Meta-regression did not identify significant effect modifiers. Conclusions DES is a safe strategy; it showed no higher 30-day mortality and a trend toward greater clinical and microbiological cure.