730. Cefiderocol for the Treatment of Achromobacter xylosoxidans Infections in Two Lung Transplant Patients with Cystic Fibrosis

Abstract

Background Achromobacter xylosoxidansis a highly resistant Gram-negative bacterium that causes chronic infections in patients with cystic fibrosis (CF). Treatment options for A. xylosoxidans are limited. In the peri-lung transplant setting, the treatment of A. xylosoxidans infections is especially challenging. Cefiderocol is a novel siderophore cephalosporin antibiotic with broad anti-Gram-negative activity, including against A. xylosoxidans. We report here two cases of compassionate use of cefiderocol in CF lung transplant recipients with A. xylosoxidans infection.MethodsCefiderocol was obtained through compassionate use from its manufacturer, with approval from the local Institutional Review Board. In the first case, it was used as salvage treatment, and in the second case as a planned part of the peri-transplant regimen.ResultsA male in his 20s with CF and a trimethoprim-sulfamethoxazole (TMP-SMX) allergy was chronically colonized by A. xylosoxidans, which was sensitive only to piperacillin–tazobactam (PIP-TAZ), and TMP-SMX. After lung transplant, he developed A. xylosoxidansbacteremia, and extended-infusion PIP-TAZ was started. Repeat bronchoscopy grew A. xylosoxidans. Due to lack of improvement, cefiderocol was added to PIP-TAZ with rapid clinical improvement. However, after completing his course, he was readmitted with A. xylosoxidans pneumonia. He was treated with 6 weeks of cefiderocol and imipenem and has been well since with an 8-month follow-up. In the second case, cefiderocol was used as part of the planned peri-transplant regimen for a female with CF in her late teens, with chronic A. xylosoxidans colonization, which was intermediate to PIP-TAZ, and resistant to all other drugs tested. Her native lungs grew 4+ A. xylosoxidans at the time of explant. Post-transplant, she was treated with 5 weeks of meropenem and 6 weeks of cefiderocol. At four-month follow-up, she is doing well. However, she is asymptomatically colonized with A. xylosoxidanspost-transplant. Isolates from both cases were susceptible to cefiderocol (case #1 MIC = 0.12; case #2 pretreatment MIC = 1, post-treatment MIC.ConclusionCefiderocol may be a useful option for lung transplant recipients with A. xylosoxidans infections.DisclosuresAnne Lachiewicz, MD, MPH, MicroGenDx: Consultant; Shionogi: Consultant.