Drug concentrations in the serum and cerebrospinal fluid of patients treated with cefoperazone/sulbactam after craniotomy

BACKGROUND: To identify changes in cefoperazone/sulbactam penetration into cerebrospinal fluid (CSF) after craniotomy and to investigate preliminarily whether cefoperazone/sulbactam CSF concentration can reach therapeutic level when administered intravenously after neurosurgical operation. METHODS: Neurosurgical patients with an indwelling ventricular drainage pipe who received prophylactic cefoperazone/sulbactam for the treatment of intracranial infection were received a cefoperazone/sulbactam 2:1, 3.0-g infusion for 3 hours every 6 hours for 24 h. Venous blood and CSF specimens were collected to determine cefoperazone/sulbactam concentrations. RESULTS: The cefoperazone and sulbactam concentrations in serum were highest at the second hour (237.54±336.72 mg/L and 66.52±80.38 mg/L, respectively) and then decreased. The cefoperazone and sulbactam concentrations in CSF were highest at the 4th hour (39.22±75.55 mg/L and 6.24±8.35 mg/L, respectively) and then decreased. CSF penetration measured by the ratio of peak concentrations (CSF/serum) was 8.6%±7.2% for cefoperazone and 13.5%±11.9% for sulbactam, CSF penetration measured by the ratio of trough concentrations (CSF/serum) was 13.4%±5.3% for cefoperazone and 106.5%±87.5% for sulbactam. CSF penetration represented by the ratio of area under the curve (AUC) of CSF and serum was 14.5% for cefoperazone and 22.6% for sulbactam. Neurosurgical impairment of the blood–brain barrier may improve the CSF penetration of these drugs, but it is difficult to reach the MIC(90) of resistant bacteria. If single intravenous administration time was extended to 3 hours, the serum concentrations of drugs were able to meet the PK/PD standard (T> MIC%> 50%) for treating common, highly resistant bacteria. CONCLUSIONS: The CSF penetration of cefoperazone/sulbactam may be enhanced after neurosurgical impairment of the blood–brain barrier. This study is a pilot research of cefoperazone/sulbactam using in neurosurgical individuals, However, it needs to be confirmed by further large-scale studies.