Norvancomycin for the treatment of central nervous system MRSA infections: A randomized controlled trial

Combined intravenous and intrathecal administration of norvancomycin (NVCM) is routinely employed in treating methicillin-resistant Staphylococcus aureus (MRSA) ventriculitis in patients following craniotomy. However, the optimal dosing regimen, the pharmacokinetics (PK) of NVCM in cerebrospinal fluid (CSF), and the clinical outcome are yet to be elucidated. Herein, a single-center randomized controlled trial was conducted in the Neurosurgery Department of the Second Hospital of Hebei Medical University (Shijiazhuang, China). Patients with MRSA ventriculitis after craniotomy were randomly assigned to two groups. The control group received 800 mg NVCM intravenously every 12 h, and the experimental group received 800 mg NVCM intravenously every 12 h and 16 mg NVCM intrathecal administration every 24 h. The primary outcome was the length of therapy, while the secondary outcomes included the area under the concentration-time curve in 0-24 h/minimum inhibitory concentration ratio (AUC_0-24h/MIC) of NVCM in CSF. A total of 29 patients (14 in the experimental group and 15 in the control group) were included in this study. Of these, 24 constituted the final analysis population, with 12 in each group. The average length of therapy in the experimental group was markedly shorter than that of the control group (11.2 ± 2.6 days vs. 16.6 ± 5.2 days, P = 0.005), while the AUC_0-24h/MIC in the experimental group was significantly higher than that in the control group (2306.57 ± 928.58 vs. 46.83 ± 27.48, P < 0.001) with no increase in adverse reactions. Combined intravenous and intrathecal administration can shorten the treatment time of intracranial infection without higher adverse reaction risks in our research. Further studies with larger sample size are warranted to verify its safety and efficacy.