Pharmacotherapy · 2024
Pharmacokinetics of cefiderocol in a patient with carbapenem-resistant Acinetobacter baumannii ventriculitis: A case report.
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Finch Natalie A, Granillo Alejandro, Pouya Nazanin, Bhimraj Adarsh, Miller William R, Tam Vincent H
Аннотация
OBJECTIVE: Cefiderocol is a novel antibiotic used to treat multidrug-resistant bacterial infections. However, there is limited data on its effectiveness for ventriculitis. The objective of this study was to evaluate cefiderocol concentrations in both serum and cerebrospinal fluid (CSF) during the treatment of ventriculitis.
METHOD: A 54-year-old patient with carbapenem-resistant Acinetobacter baumannii ventriculitis was given cefiderocol intravenously 2 g every 6 h (each dose administered over 3 h). Serial samples were obtained over a dosing interval at steady state, and cefiderocol concentrations in serum and CSF were assayed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Cefiderocol serum concentration-time profile was characterized by a one-compartment model with zero-order input. Penetration into CSF was estimated as the CSF AUC/unbound serum AUC ratio.
RESULTS: Observed total serum concentrations ranged between 24.6 and 76.7 mg/L, while CSF concentrations were approximately 10.0 mg/L. The AUC0-6 of the free drug in serum and CSF were 181.6 and 60.2 mg h/L, respectively.
CONCLUSION: We observed minimal fluctuation of cefiderocol concentrations in CSF, questioning the conventional reliance on CSF/serum area under the curve (AUC) ratio as a measure of CNS penetration. Our experience suggests that a single CSF concentration (random or trough) could be directly compared to the minimum inhibitory concentration, offering a potentially simpler approach to evaluate dosing adequacy.
METHOD: A 54-year-old patient with carbapenem-resistant Acinetobacter baumannii ventriculitis was given cefiderocol intravenously 2 g every 6 h (each dose administered over 3 h). Serial samples were obtained over a dosing interval at steady state, and cefiderocol concentrations in serum and CSF were assayed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Cefiderocol serum concentration-time profile was characterized by a one-compartment model with zero-order input. Penetration into CSF was estimated as the CSF AUC/unbound serum AUC ratio.
RESULTS: Observed total serum concentrations ranged between 24.6 and 76.7 mg/L, while CSF concentrations were approximately 10.0 mg/L. The AUC0-6 of the free drug in serum and CSF were 181.6 and 60.2 mg h/L, respectively.
CONCLUSION: We observed minimal fluctuation of cefiderocol concentrations in CSF, questioning the conventional reliance on CSF/serum area under the curve (AUC) ratio as a measure of CNS penetration. Our experience suggests that a single CSF concentration (random or trough) could be directly compared to the minimum inhibitory concentration, offering a potentially simpler approach to evaluate dosing adequacy.