Introduction Real-life data about cefiderocol use to treat extensively drug-resistant bacteria are scarce. We aim to report our early experience in patients with difficult-to-treat infections and limited therapeutic options. Methods Patients treated with cefiderocol from March 2018 to April 2022 in a tertiary-care hospital in Spain were included. Demographic, clinical, and microbiological data were collected up to 90 days after the end of treatment or until death. Survival status was recorded at 30 and 90 days. Results Ten patients were included, seven of them critically ill. Ventilator-associated pneumonia (40%) and bacteremia (40%) were the main infections. Multidrug-resistant or extensively drug-resistant P. aeruginosa was the most frequently isolated pathogen (70%, of which six patients were infected with bacteria with difficult-to-treat resistance), followed by A. baumannii , E. coli , and A. xylosoxidans (10% each). Seven patients received combination therapy. Clinical and microbiological cures were achieved in 90% and 80% of patients, respectively. Two previously susceptible strains (20%) developed resistance to cefiderocol. Overall, 30-day and 90-day mortality rates were 10% and 50%, respectively, although two out of five patients died due to the infection. No serious adverse events were reported, except for one patient who developed thrombocytopenia. Conclusion Cefiderocol seems to be an effective and safe rescue therapy for patients infected with difficult-to-treat pathogens, although there is a definite risk of the emergence of resistance.

Objective24-hour urine creatinine clearance (ClCr 24 hours) remains the gold standard for estimating glomerular filtration rate (GFR) in critically ill patients; however, simpler methods are commonly used in clinical practice. Serum creatinine (SCr) is the most frequently used biomarker to estimate GFR; and cystatin C, another biomarker, has been shown to reflect GFR changes earlier than SCr. We assess the performance of equations based on SCr, cystatin C and their combination (SCr-Cyst C) for estimating GFR in critically ill patients.MethodsObservational unicentric study in a tertiary care hospital. Patients with cystatin C, SCr and ClCr 24 hours measurements in ±2 days admitted to an intensive care unit were included. ClCr 24 hours was considered the reference method. GFR was estimated using SCr-based equations: Chronic Kidney Disease Epidemiology Collaboration based on creatinine (CKD-EPI-Cr) and Cockcroft-Gault (CG); cystatin C-based equations: CKD-EPI-CystC and CAPA; and Cr-CystC-based equations: CKD-EPI-Cr-CystC. Performance of each equation was assessed by calculating bias and precision, and Bland-Altman plots were built. Further analysis was performed with stratified data into CrCl 24 hours <60, 60–130 and ≥130 mL/min/1.73 m2.ResultsWe included 275 measurements, corresponding to 186 patients. In the overall population, the CKD-EPI-Cr equation showed the lowest bias (2.6) and best precision (33.1). In patients with CrCl 24 hours <60 mL/min/1.73 m2, cystatin-C-based equations showed the lowest bias (<3.0) and CKD-EPI-Cr-CystC was the most accurate (13.6). In the subgroup of 60≤ CrCl 24 hours <130mL/min/1.73 m2, CKD-EPI-Cr-CystC was the most precise (20.9). However, in patients with CrCl 24 hours ≥130mL/min/1.73 m2, cystatin C-based equations underestimated GFR, while CG overestimated it (22.7).ConclusionsOur study showed no evidence of superiority of any equation over the others for all evaluated parameters: bias, precision and Lin’s concordance correlation coefficient. Cystatin C-based equations were less biased in individuals with impaired renal function (GFR <60 mL/min/1.73 m2). CKD-EPI-Cr-CystC performed properly in patients with GFR from 60–130 mL/min/1.73 m2 and none of them were accurate enough in patients ≥130 mL/min/1.73 m2.