Plasma and cerebrospinal fluid concentrations of cefiderocol during successful treatment of carbapenem-resistant Acinetobacter baumannii meningitis. (23rd July 2022)

• Record Type: Journal Article
• Authors: Kufel, Wesley D; Abouelhassan, Yasmeen; Steele, Jeffrey M; Gutierrez, Ramiro L; Perwez, Talha; Bourdages, George; Nicolau, David P
• Is Part Of: Journal of antimicrobial chemotherapy. Volume 77:Number 10(2022)
• Page Start: 2737
• Page End: 2741
• Publication Date: 2022-07-23
• Subjects: Anti-infective agents -- Periodicals; Chemotherapy -- Periodicals; 615.58
• DOI: 10.1093/jac/dkac248
• Languages: English
• ISSNs: 0305-7453

Abstract

Abstract: Background: To date, no real-world data are available to describe cefiderocol use in carbapenem-resistant Acinetobacter baumannii (CRAB) meningitis. Furthermore, cefiderocol pharmacokinetic (PK) data to support CNS penetration in human subjects are limited. These gaps pose a significant concern for clinicians who are faced with treating such infections when considering cefiderocol use. Objectives: To describe cefiderocol CSF and plasma PK and pharmacodynamic (PD) data from two different dosing regimens [2 g IV q6h (regimen 1) and 2 g IV q8h (regimen 2)] during treatment of CRAB meningitis. Patients and methods: A 61-year-old woman with CRAB meningitis was treated with cefiderocol and intraventricular gentamicin. Steady-state plasma and CSF cefiderocol concentrations were evaluated on Day 19 (regimen 1) and Day 24 (regimen 2) during the cefiderocol treatment course. Results: CSF AUC was 146.49 and 118.28 mg·h/L, as determined by the linear-log trapezoidal method for regimens 1 and 2, respectively. Penetration into CSF estimated as the AUCCSF /AUCfree plasma ratio was 68% and 60% for regimens 1 and 2, respectively. Estimated free plasma and CSF concentrations exceeded the MIC of the isolate for 100% of the dosing interval. Microbiological and clinical cure were achieved, and no cefiderocol-associated adverse effects were observed. Conclusions: Cefiderocol, when given as 2 g q8h and 2 g q6h, attained CSF concentrations that exceeded the organism-specific MIC and the CLSI susceptible breakpoint (≤4 mg/L) for 100% of the dosing interval.