CRE RESPOND continues to demonstrate international leadership in antimicrobial optimisation through the DALI‑2 study (Defining Antibiotic Levels in Intensive care patients)—a major academic achievement and the first mulit-continent pharmacokinetic (PK) study to systematically evaluate antibiotic exposure in critically ill adults and children across a global ICU network.
Critically ill patients experience profound and unpredictable changes in drug handling, meaning standard antibiotic dosing often fails to achieve therapeutic exposures or may increase the risk of toxicity. DALI‑2 was designed to address this challenge by describing real‑world antibiotic concentrations and linking exposure to meaningful patient outcomes at scale.
The study aims to recruit approximately 1,000 adults and 250 children, with each participating ICU enrolling between 10 and 30 patients, including a maximum of 20 patients receiving beta‑lactam antibiotics per site. Importantly, DALI‑2 will include a wide range of more than 30 commonly used antibiotics, allowing for a comprehensive assessment of pharmacokinetic variability across different drug classes and patient populations.
DALI‑2 evaluates achievement of clinically relevant exposure targets, including multiple free time‑above‑MIC (fT>MIC) thresholds for beta‑lactam antibiotics and therapeutic vancomycin trough concentrations for adults and children. The study also examines how target attainment relates to clinical outcomes, including treatment success, mortality at Days 14 and 30, ICU‑free days, and the emergence of antibiotic resistance.
In addition, DALI‑2 assesses suspected adverse drug events, exploring relationships between antibiotic concentrations and neurotoxicity, nephrotoxicity, hepatotoxicity, and haematological toxicity, while characterising the pharmacokinetic variability of individual antibiotics in ICU patients.
A further strength of DALI‑2 is its focus on feasibility and readiness for global implementation, ensuring findings can translate into practice. As the first intercontinental PK study of its kind, DALI‑2 provides essential evidence to support safer, more effective antibiotic dosing for critically ill patients worldwide.
