Feasibility of Continuous Infusion of Cefiderocol in Conjunction with the Establishment of Therapeutic Drug Monitoring in Patients with Extensively Drug-Resistant Gram-Negative Bacteria

Abstract

Background and Objective Resistance to antibacterial substances is a huge and still emerging issue, especially with regard to Gram-negative bacteria and in critically ill patients. We report a study in six patients infected with extensively drug-resistant Gram-negative bacteria in a limited outbreak who were successfully managed with a quasi-continuous infusion of cefiderocol. Methods Patients were initially treated with prolonged infusions of cefiderocol over 3 h every 8 h, and the application mode was then switched to a quasi-continuous infusion of 2 g over 8 h, i.e. 6 g in 24 h. Therapeutic drug monitoring (TDM) was established using an in-house liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Results Determined trough plasma concentrations were a median of 50.00 mg/L [95% confidence interval (CI) 27.20, 74.60] and steady-state plasma concentrations were a median of 90.96 mg/L [95% CI 37.80, 124]. No significant differences were detected with respect to acute kidney injury/continuous renal replacement therapy. Plasma concentrations determined from different modes of storage were almost equal when frozen or cooled, but markedly reduced when stored at room temperature. Conclusions (Quasi) continuous application of cefiderocol 6 g/24 h in conjunction with TDM is a feasible mode of application; the sample for TDM should either be immediately analyzed, cooled, or frozen prior to analysis.

Successful outpatient parenteral antibiotic therapy with cefiderocol for osteomyelitis caused by multi-drug resistant Gram-negative bacteria: a case report

“… 11 So far, only a few studies reported the results of cefiderocol therapeutic drug monitoring. 12 , 13 Prinz et al measured a median (interquartile range) trough concentration of 50.0 (27.2–74.6) mg/L in five critically ill patients. Gatti et al reported trough plasma concentrations of the free fraction ranging from 0.59 to 56.78 mg/L in 13 patients.…”

Continuous infusion of cefiderocol in a critically ill patient with continuous venovenous haemofiltration

“…In critically ill patients treated with continuous infusion of β‐lactams, an unbound concentration of >5 times the MIC is suggested 16 . However, limited information on cefiderocol as continuous infusion (CI) and its true therapeutic target has been assessed 17,18 …”