Cerebrospinal Fluid Pharmacokinetics of Tigecycline in Lumbar and Ventricular Compartments After Lumbar Intrathecal Administration: A Three-Patient Case Series.

Abstract

Background: Lumbar intrathecal administration of tigecycline has been increasingly used as a salvage treatment for multidrug-resistant (MDR) intracranial infections. However, whether lumbar administration can generate adequate tigecycline exposure in ventricular cerebrospinal fluid (CSF), remains insufficiently characterized.

Case presentation: We retrospectively analyzed three patients with intracranial infections who received 5mg tigecycline through a lumbar drainage catheter and had concurrent lumbar and ventricular CSF access. The underlying conditions were postoperative primary meningioma, brain abscess, and traumatic cerebral contusions, respectively. The identified pathogens included Acinetobacter johnsonii (tigecycline MIC, 0.5 mg/L), Aspergillus fumigatus, and Klebsiella pneumoniae (tigecycline MIC, 2.0 mg/L). Paired lumbar and ventricular CSF samples were collected at scheduled time points after dosing, and tigecycline concentrations were quantified by liquid chromatography-tandem mass spectrometry (LC‑MS/MS). Following a 5 mg lumbar intrathecal dose, the lumbar CSF peak concentration (C_max) was reached within 1 hour across all patients (933.89, 269.07, and 256.71 mg/L). In contrast, the ventricular C_max values were substantially lower (0.67, 7.05, and 2.64 mg/L), with ventricular time to peak concentration (T_max) delayed to 4-6 hours. The ventricular‑to‑lumbar area‑under‑the‑curve ratio (V/L AUC_1-24h ratio), ranged from 0.33% to 7.13%, indicating markedly attenuated and variable ventricular exposure relative to lumbar exposure. In the two patients with bacterial infections and available tigecycline MICs, ventricular CSF concentrations exceeded the corresponding MIC for at least part of the dosing interval. No neurotoxic adverse events were observed.

Conclusion: In this three-patient case series, 5 mg lumbar intrathecal tigecycline achieved measurable but markedly attenuated ventricular CSF exposure, with substantial interpatient variability, and no predefined neurotoxic adverse events were documented in this small series. Lumbar intrathecal administration may be considered when ventricular administration is unavailable or undesirable, with individualized assessment and therapeutic drug monitoring where feasible.