Cerebrospinal fluid pharmacokinetics of ceftaroline in neurosurgical patients with an external ventricular drain.
J Antimicrob Chemother
; 74(3): 675-681, 2019 03 01.
Article
en En
| MEDLINE
| ID: mdl-30535190
ABSTRACT
BACKGROUND:
Owing to its antibacterial properties, ceftaroline could be attractive for prevention or treatment of bacterial post-neurosurgical meningitis/ventriculitis. However, few data are available concerning its meningeal concentrations.OBJECTIVES:
To investigate ceftaroline CSF pharmacokinetics in ICU patients with an external ventricular drain (EVD).METHODS:
Patients received a single 600 mg dose of ceftaroline as a 1 h intravenous infusion. Blood and CSF samples were collected before and 0.5, 1, 3, 6, 12 and 24 h after the end of the infusion. Concentrations were assayed in plasma and CSF by LC-MS/MS. A two-step compartmental pharmacokinetic analysis was conducted. Ceftaroline plasma data were first analysed, and thereafter plasma parameters estimated and corrected for protein binding of 20% were fixed to fit unbound CSF concentrations. In the final model, parameters for both plasma and CSF data were simultaneously estimated.RESULTS:
Nine patients with an EVD were included. The Cmax was 18.29 ± 3.33 mg/L in plasma (total concentrations) and at 0.22 ± 0.17 mg/L in CSF (unbound concentration). The model-estimated CSF input/CSF output clearance ratio was 9.4%, attesting to extensive efflux transport at the blood-CSF barrier.CONCLUSIONS:
Ceftaroline CSF concentrations are too low to ensure prophylactic protection against most pathogens with MICs between 1 and 2 mg/L, owing to its limited central distribution.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Cefalosporinas
/
Ventrículos Cerebrales
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Líquido Cefalorraquídeo
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Drenaje
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Procedimientos Neuroquirúrgicos
/
Antibacterianos
Tipo de estudio:
Etiology_studies
Límite:
Adolescent
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Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Año:
2019
Tipo del documento:
Article