Title : Vancomycin levels in CSF versus brain ECF: Which compartment reflects the target site in postoperative meningoencephalitis?
Abstract:
Introduction: A fundamental principle of rational antimicrobial therapy is the ability of a drug to achieve concentrations at or above the minimum inhibitory concentration (MIC) at the site of infection. In central nervous system (CNS) infections, cerebrospinal fluid (CSF) drug concentrations have traditionally been considered a surrogate for target-site exposure. However, accumulating evidence over the past decades suggests that drug concentrations in brain extracellular fluid (ECF), measured using cerebral microdialysis, may more accurately reflect antimicrobial exposure at the site of parenchymal infection.
Whether CSF and brain ECF represent interchangeable compartments—or fundamentally distinct pharmacokinetic spaces—remains clinically relevant, particularly in postoperative meningoencephalitis. In this report, we present comparative data on vancomycin concentrations in CSF and brain ECF in four patients with suspected or confirmed postoperative meningoencephalitis.
Methods: Four patients undergoing multimodal neuromonitoring, including cerebral microdialysis and external ventricular drainage (EVD), were included. Vancomycin concentrations were measured under predicted steady-state conditions in CSF obtained from the EVD and in brain microdialysate collected over the dosing interval. Sampling was performed on two consecutive days to account for interday variability.
Microdialysis was conducted using a 70 Microdialysis Bolt Catheter with a 10 mm semipermeable membrane (20 kDa molecular weight cut-off) and a perfusion flow rate of 0.3 µL/min. Vancomycin concentrations were determined using a homogeneous enzyme immunoassay (EMIT® 2000). Brain ECF concentrations were corrected for in vitro probe recovery, as previously described.
Results: Two of the four patients received systemic vancomycin only, while two received additional intraventricular vancomycin (10–20 mg/day). In patients treated systemically only, vancomycin concentrations in CSF were extremely low or undetectable, whereas measurable concentrations were observed in brain ECF. Conversely, in patients receiving intraventricular vancomycin, CSF concentrations were markedly higher than those measured in brain ECF.
Conclusions: CSF and brain ECF represent distinct pharmacokinetic compartments for vancomycin in postoperative meningoencephalitis. Drug concentrations in one compartment cannot be reliably used to predict exposure in the other. Clinicians and researchers should carefully consider the relevant target site when interpreting vancomycin concentrations to assess therapeutic adequacy and optimize dosing strategies.
