Drug concentrations in the serum and cerebrospinal fluid of patients treated with norvancomycin after craniotomy

Abstract

Intracranial infection by gram-positive cocci is commonly found after craniotomy. Norvancomycin was independently developed in China, and had demonstrated therapeutic capability against gram-positive infection. This study investigated the serum and cerebrospinal fluid (CSF) concentrations in patients that received intravenous injection of norvancomycin after craniotomy. Patients with an indwelling catheter in the operational area/ventricle after craniotomy were administered norvancomycin by two approaches: (1) The conventional group consisted of 14 cases that were infused with 0.8 g norvancomycin for 1 h, every 12 h; (2) The continuous administration group consisted of 14 cases that were infused with 0.8 g norvancomycin for 1 h, and then another 0.4 g for 11 h with extended infusion, followed by continuous infusion of 0.4 g norvancomycin for 12 h. Samples of serum and CSF were collected at different time-points to measure norvancomycin levels after administration. In the conventional and continuous administration groups, the peak serum concentrations of norvancomycin were 55.52 ± 26.04 and 59.22 ± 41.88 mg/L, respectively, while those at 24 h were 8.21 ± 6.04 and 8.01 ± 4.17 mg/L, respectively. Meanwhile, peak CSF concentrations were 16.31 ± 11.15 and 8.82 ± 8.91 mg/L, respectively, while those at 24 h were 6.12 ± 2.34 and 6.24 ± 4.38 mg/L, respectively. This preliminary study showed that for the early administration of standard doses of norvancomycin post-neurosurgery, the CSF concentration in both the conventional and continuous administration groups reached or exceeded the 90 % minimum inhibitory concentration (MIC90, 2 mg/L) of target bacteria such as methicillin-resistant Staphylococcus aureus (MRSA).