Empirical versus pre-emptive antifungal therapies for invasive fungal infections in critically ill patients.

Abstract

Background: The initiation strategy of antifungal therapy (AT) is among the most discussed practices for patients vulnerable to invasive fungal infections (IFI). In low-resource countries, there are also no appropriate consensus or guidelines for this issue. Given this clinical gap, we aimed to investigate the use of empirical and pre-emptive therapy in an Asian intensive care setting.

Methods: We conducted a retrospective cohort study (timeframe 2019-2020) on critically ill adults receiving systemic antifungals for ≥ 3 days. The exposure was empirical or pre-emptive therapy of systemic antifungals. The primary outcome was IFI-related mortality (in percentage, including in-hospital death or discharge/transfer with death prognosis). The secondary outcomes included overall rationale of AT (in percentage) and length of AT (LoAT, in days). We used logistic and linear regression to investigate the outcomes and reported the estimates with the 95% confidence interval (95% CI).

Results: During a median follow-up of 27 days, among 157 included patients (median age 68, 48.4% being female), we recorded 77 deaths (49.0% [95% CI 41.0-57.1%]) that were related to IFI (60 [51.7%] in the empirical group; 17 [41.5%] in the pre-emptive group; adjusted odds ratio of IFI-related mortality 1.86 [95% CI 0.74 to 4.63; p = 0.184]). The overall rationale of AT was at 45.2% (95% CI 37.2-53.4%; 41.4% [95% CI 32.3-50.9%] in the empirical group; 56.1% [95% CI 40.0-71.5%] in the pre-emptive group; adjusted odds ratio of receiving rational AT: 0.75 [95% CI 0.31 to 1.87]). The median LoAT was 8 days (IQR 6-14; 8 days [IQR 6-13.3] in the empirical group; 9 days [IQR 6-14] in the pre-emptive group; adjusted mean difference - 1.1 days [95% CI -3.2 to 1.0]).

Conclusion: Among critically ill patients on systemic antifungals for ≥ 3 days, the proportion of IFI-related mortality was high. The overall rationale of AT was at a low level, with the median LoAT lower than the generally recommended duration of at least 14 days. There were no significant differences in IFI-related mortality, overall rationale of AT, and LoAT between those receiving empirical and pre-emptive therapy.

Clinical trial number: Not applicable.