Real-World Evidence: Cefiderocol Therapeutic Drug Monitoring in Critically Ill, Obese Patients with Klebsiella pneumoniae Infections

: Background/Objectives: Cefiderocol (FDC) is a siderophore-containing cephalosporin that retains activity against many β-lactamase-producing bacteria, such as New Delhi metallo-β-latamase-producing (NDM) K. pneumoniae. Its use in critically ill patients is still limited, since the recommended dosing regimens are mainly derived from studies on healthy subjects, while critical illness is often associated with critical alterations in drug pharmacokinetics. Therefore, the aim of this study was to investigate FDC pharmacokinetic/pharmacodynamic (PK/PD) parameters in real-life patients based on their body weight and renal function. Methods: Patients with K. pneumoniae infections and indications for FDC were enrolled. Drug quantification in plasma was performed at the steady state at different timings. PK/PD targets of fCmin > 4 mg/L (most common) and more stringent targets of fCmin > 8 and 12 mg/L (4× and 6× the EUCAST breakpoint MIC) were considered in relation to patients' characteristics, 14 days of microbiological eradication and 30-day mortality. Results: Ten patients were enrolled in this study. Mortality, as well as the failure to achieve microbiological eradication, increased with BMI. In a PK/PD point of view, all patients reached the PK/PD targets of fCmin > 4 mg/L and > 8 mg/L, while only 20% reached a fCmin > 12 mg/L, with a key influence of renal function. However, no significant association was found between PK/PD target attainment and treatment outcomes. Conclusions: Our study may be useful for the real-world use of FDC, highlighting the impact of renal function on the achievement of ideal PK/PD thresholds. Nevertheless, the lack of a significant association between PK/PD and outcomes, partially due to the small sample size, highlights the complex impact of patients' clinical conditions other than drug PK.