(608) Cefiderocol for Difficult-to-Treat Resistance in Pseudomonas aeruginosa Ventriculitis

Introduction: Cefiderocol is often utilized as salvage therapy for difficult-to-treat resistance in Pseudomonas aeruginosa (DTR-PA). In vitro pharmacokinetic data supporting sufficient cerebrospinal fluid (CSF) concentrations of cefiderocol is limited. There is also a lack of clinical data describing consistent outcomes of cefiderocol for complex central nervous system (CNS) infections, such as ventriculitis that are often associated with extremely poor outcomes.

Description: A 56 yr-old female was admitted for large intraparenchymal hemorrhage, right to left midline shift with extensive intraventricular and subarachnoid hemorrhage. An external ventricular drain (EVD) was inserted and eventually replaced by a ventriculoperitoneal shunt (VP). She then developed ventilator-associated pneumonia (VAP) secondary to pan-susceptible Pseudomonas aeruginosa. Despite appropriate utilization of antimicrobial therapy and VAP-bundle protocol, she continued to clinically worsen with pneumonia secondary to DTR-PA. In-vitro antimicrobial susceptibility testing for cefiderocol was performed via Kirby-Bauer disk diffusion. Cefiderocol zone diameter was 23 mm which was interpreted as susceptible in the 34th Edition of Clinical and Laboratory Standards Institute M100™. She continued to decline and became unresponsive. CSF cultures were obtained and resulted with growth of DTR-PA with the same susceptibility pattern. The VP shunt was then removed and EVD was placed for worsening hydrocephalus. Patient was started on cefiderocol 2 g IV every 6-hr over 3-hr infusion (CrCl >120 mL/min) for 21-day. Neurologic examination showed no improvement and repeat CSF cultures resulted as no growth. Patient developed worsening hydrocephalus after 3-wk post-antimicrobial therapy and repeat CSF culture grew DTR-PA. Patient was restarted on cefiderocol for 9-wk. After completion of cefiderocol, repeat CSF cultures showed microbiological eradication of DTR-PA.

Discussion: We present a real-world example of a case utilizing cefiderocol for the treatment of DTR-PA ventriculitis. Cefiderocol has shown microbiological clearance of DTR-PA from CSF cultures during her admissions, however infection recurrence with the same organism has transpired multiple times raising potential questions about its clinical efficacy for ventriculitis.