# Cefiderocol for Treatment of Ventriculitis (4MRGN A. baumannii)—Results of Therapeutic Drug Monitoring in Blood and Cerebrospinal Fluid

## TL;DR

This paper reports on the use of cefiderocol to treat a brain infection in a critically ill patient, showing it reaches effective levels in cerebrospinal fluid.

## Contribution

Demonstrates that standard cefiderocol dosing achieves therapeutic concentrations in cerebrospinal fluid during severe central nervous system infections.

## Key findings

- Cefiderocol achieved median CSF concentrations of 6.98 μg/mL, sufficient to eradicate A. baumannii.
- The drug's CSF/serum concentration ratio ranged from 0.38 to 0.76, indicating adequate CNS penetration.
- The patient later developed a K. pneumoniae infection, successfully treated with alternative antibiotics.

## Abstract

Background: Cefiderocol, a siderophore cephalosporin, is approved for the treatment of infections caused by multi-drug-resistant Gram-negative bacteria (MRGN). At present, few data are available on the pharmacokinetics of this substance in critically ill patients, particularly for the treatment of central nervous system infections. Patients and Methods: Here, we reported on a 22-year-old male patient after severe open head trauma. Initial screening revealed colonization with 4MRGN A. baumannii (OXA-23) (perianal) and 4MRGN K. pneumoniae (KPC) (tracheal). Unfortunately, he developed ventriculitis (4MRGN A. baumannii). According to microbiological testing, the patient with normal renal function received 3 × 2 g/d i.v. cefiderocol as a prolonged infusion (3 h) and colistin 3 × 3 Mio. IU/d i.v. for 2 weeks. In addition to serum trough levels, drug monitoring was performed in the cerebrospinal fluid (CSF) via external ventricular drainage (24 h aliquots). Results: Serum and CSF specimens analyzed by liquid chromatography–mass spectroscopy (LC-MS) in the presence of severe meningeal inflammation yielded average CSF concentrations of cefiderocol from 5.48 to 8.40 (median 6.98) μg/mL and a concentration ratio CCSF mean/Cserum trough from 0.38 to 0.76 (median 0.48). The cefiderocol levels in the CSF were sufficient for eradication of A. baumannii. A subsequent CSF infection with K. pneumoniae (found initially in screening and resistant to cefiderocol) after completed treatment with cefiderocol was successfully treated with gentamicin (intrathecally) and ceftazidime/avibactam (i.v.). However, the patient died due to a Candida tropicalis infection detected in the CSF on day 71. Conclusions: Our results indicate that standard dosages of cefiderocol are sufficient for treatment of CNS infections in the presence of a severe disruption of the blood–CSF barrier.