Are contemporary antifungal doses sufficient for critically ill patients? Outcomes from an international, multicenter pharmacokinetics study for Screening Antifungal Exposure in Intensive Care Units-the SAFE-ICU study.

Summary

In an international prospective PK study across 30 ICUs (n=339), antifungal target attainment during treatment was suboptimal for several agents (e.g., voriconazole 57.1%, amphotericin B 41.7%) with wide variability, whereas prophylaxis generally achieved >80% targets. The findings support therapeutic drug monitoring and dose optimization in critically ill patients.

Key Findings

• Prospective multicenter PK study in 339 ICU patients across 12 countries and 30 ICUs
• During treatment, target attainment was low for voriconazole (57.1%), posaconazole (63.2%), micafungin (64.1%), and amphotericin B (41.7%)
• Prophylaxis achieved >80% target attainment for most antifungals
• Only 26% of pathogen-positive cases had MIC data available, limiting individualized PK/PD targeting

Clinical Implications

Implement routine or selective TDM for azoles and consider PK-guided dose adjustments, ensure MIC testing when feasible, and differentiate dosing strategies for prophylaxis versus treatment in critically ill patients.

Limitations

• Observational PK study without standardized dosing or direct clinical outcome endpoints
• MIC data were available in only 26% of pathogen-positive cases

Future Directions

Randomized or adaptive dosing trials comparing PK-guided versus standard dosing, integration of real-time MIC data, and population PK modeling to refine dosing in diverse ICU phenotypes.