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Objective: To describe cerebral spinal fluid (CSF) penetration of tigecycline., Case Summary: A 38-year-old woman experienced a right internal carotid artery dissection and right anterior and middle cerebral artery strokes due to unknown causes and subsequently developed vasogenic edema requiring right hemi-craniectomy. Her postoperative course was complicated by multiple infections, and she developed multidrug, carbapenem-resistant Acinetobacter baumannii cerebritis. She was treated with a prolonged course of multiple antibiotics, including 18 days of therapy with tigecycline. Time-paired serum and CSF samples were obtained, and tigecycline concentrations were analyzed by high-performance liquid chromatography. We report serial, steady-state, serum, and CSF concentrations of tigecycline when administered in the Food and Drug Administration-approved dose of 50 mg every 12 hours. CSF concentrations remained relatively stable, suggesting that tigecycline did not accumulate in the CSF, at least in our patient. Tigecycline concentrations in the CSF were between 0.035 and 0.048 mg/L, while corresponding serum concentrations were 0.097-0.566 mg/L. The calculated tigecycline penetration ratio in this patient ranged from 0% to 52%, depending on the calculation methodology utilized., Discussion: Concentrations, regardless of sample timing relative to dose, remained relatively stable in the CSF of our patient. The pharmacodynamic profile of tigecycline is not completely elucidated; however, it is presumed that the drug must be at the site of infection for efficacy. Our patient never obtained tigecycline concentrations in excess of the minimum inhibitory concentration for A. baumannii in either the serum or the CSF., Conclusions: Our patient experienced low CSF tigecycline concentrations and failed to achieve a clinical response while on therapy. CSF drug disposition of tigecycline requires further systematic study to fully elucidate the pharmacokinetic profile. Reduced CSF concentrations urge caution in the treatment of cerebritis with standard dosing of tigecycline.