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

Abstract

BackgroundTo 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.MethodsNeurosurgical 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.ResultsThe 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 MIC90 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.ConclusionsThe 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.

Tracking Cefoperazone/Sulbactam Resistance Development In vivo in A. baumannii Isolated from a Patient with Hospital-Acquired Pneumonia by Whole-Genome Sequencing

“…This combination has recently been applied to treat critically ill patients receiving continuous venovenous hemofiltration, and 11 of 14 patients survived ( Gao et al, 2016 ). This combination was also administrated to treat neurosurgical patients in a pilot study, with the results showing that cerebrospinal fluid penetration of cefoperazone/sulbactam could be enhanced after neurosurgical impairment of the blood-brain barrier ( Wang et al, 2015 ). In a retrospective review of the outcomes for patients with cefoperazone/sulbactam treated A. baumannii bacteremia, 77% of the patients (27/35) presented successful clinical efficacy ( Choi et al, 2006 ).…”

Tissue Penetration of Antimicrobials in Intensive Care Unit Patients: A Systematic Review—Part I

“…Cefazolin, ceftriaxone and cefixime display a reduced CSF distribution (lower than 0.1X) [ 14 ]. A similar penetration rate was measured for ceftarolin (with daily doses of 0.3–0.6 g q12h) in five patients admitted to a neurosurgical ICU [ 51 ], while the CSF/serum AUC ratio for cefoperazone was 0.15X [ 52 ]. On the contrary, in a French study, which enrolled 16 patients treated with high doses of ceftriaxone (77–131 mg/kg), the CSF/plasma ratio was highly variable (0.01–1.03 X) when CSF samples were collected 1.6–24 h after dosing both by lumbar puncture (LPD) and external ventricular drainage (EVD) [ 53 ].…”

Successful Treatment of Postneurosurgical Ventriculitis Caused by Extensively Drug-resistant Acinetobacter baumannii in a Child: Case Report

“…Sulbactam offers direct antimicrobial activity against Acinetobacter species, including XDRAB and PDRAB (17). Cefoperazone and sulbactam can penetrate the CSF in bacterial meningitis, and the CSF penetration of cefoperazone/sulbactam may enhance after neurosurgical impairment of the blood-brain barrier (18). Tigecycline combined with cefoperazone/sulbactam is more effective than cefoperazone/sulbactam alone against pulmonary MDRAB and XDRAB infections (19).…”