Cerebrospinal Fluid Concentrations of Meropenem and Vancomycin in Ventriculitis Patients Obtained by TDM-Guided Continuous Infusion

Abstract

Effective antibiotic therapy of cerebral infections such as meningitis or ventriculitis is hindered by low penetration into the cerebrospinal fluid (CSF). Because continuous infusion of meropenem and vancomycin and routine therapeutic drug monitoring (TDM) have been proposed to optimize antimicrobial exposure in ventriculitis patients, an individualized dosing strategy was implemented in our department. We present a retrospective analysis of meropenem and vancomycin concentrations in serum and CSF in the first nine ventriculitis patients treated with continuous infusion and TDM-guided dose optimization aiming at 20–30 mg/L. Median initial dosing was 8.8 g/24 h meropenem and 4.25 g/24 h vancomycin, respectively, resulting in median serum concentrations of 21.3 mg/L for meropenem and 24.5 mg/L for vancomycin and CSF concentrations of 3.4 mg/L for meropenem and 1.7 mg/L for vancomycin. Median CSF penetration was 15% for meropenem and 7% for vancomycin. With initial dosing, all but one patient achieved CSF concentrations above 1 mg/L. Dose adjustment according to TDM ensured sufficient CSF concentrations in all patients within 48 h of treatment. Given the limited penetration, continuous infusion of meropenem and vancomycin based on renal function and TDM-guided dose optimization appears a reasonable approach to attain sufficient CSF concentrations in ventriculitis patients.

Application of therapeutic drug monitoring to the treatment of bacterial central nervous system infection: a scoping review

“…Most studies described the management of individuals with CNS infections using CSF and/or blood TDM of vancomycin, 16 , 18–29 often alongside TDM of other co-administered antibiotics including meropenem, 16 , 18 , 27 , 29 piperacillin/tazobactam, 26 gentamicin, 21 levofloxacin 26 and ciprofloxacin. 26 Other studies described CSF and/or blood TDM of linezolid, 17 , 30 flucloxacillin, 31 colistin 32 and ceftazidime/avibactam.…”

The CSF Vancomycin Concentration in Patients With Post-operative Intracranial Infection Can Be Predicted by the WBCs to Total Cells Ratio and the Serum Trough Concentration

“…They compared the ratio of CSF concentration to serum trough concentration on the day 3 or 4 with 500 mg intravenously every 6 h, and they showed that CSF/serum ratio was 0.291 ± 0.118. Tiede et al (16) reported the vancomycin CSF/serum ratio was only 7% in nine patients with ventriculitis secondary to subarachnoid hemorrhage. They compared the drug concentration in blood and CSF at 24 and 72 h after the start of continuous intravenously infusion.…”

Plasma and Cerebrospinal Fluid Population Pharmacokinetics of Meropenem in Neurocritical Care Patients: a Prospective Two-Center Study

“…However, the ongoing large multicenter BLING trial program has demonstrated the feasibility of continuous meropenem infusion (29)(30)(31). Tiede et al used continuous meropenem and vancomycin infusion with therapeutic drug monitoring-guided dose optimization for successful treatment of ventriculitis in a retrospective cohort study (32). Continuous infusion may have varying impacts upon CSF penetration.…”