Penetration of daptomycin in cerebrospinal fluid during pneumococcal meningitis

There are few data on the penetration of daptomycin into the cerebrospinal fluid (CSF) of patients with bacterial meningitis. This ancillary study of the AddaMap trial aimed to assess the CSF penetration of intravenous daptomycin in 13 patients with pneumococcal meningitis.

Daptomycin was administered at 10 mg/kg/day to 13 patients with pneumococcal meningitis admitted to the Dijon University Hospital. Blood and CSF samples were collected on days 3 and 8. The population pharmacokinetics of daptomycin in plasma and CSF were studied using a two-compartment model.

A large inter-individual variability in plasma areas under the curve (median, 25-75-percentile), 7843 h.mg/L (6606-9264), plasma peak, 107.5 mg/L (81.4-126.3) and trough 14 mg/L (7.6-19.3) concentrations and elimination half-lives, 8.8 hours (7.9-10.8), was observed. In CSF, the maximum concentration was 0.88 mg/L (0.57-2.82), and the elimination half-life was 23.8 hours (18.7-39.3). The AUC CSF/plasma ratio was 2.20% (1.7-2.3). Daptomycin CSF penetration was significantly correlated with CSF levels of proteins and lactate. CSF concentrations, 0.67 mg/L (0.39-0.86), were above the MIC90 of pneumococci resistant to beta-lactam. Simulations showed that a loading dose could reduce the time required to reach a biologically active concentration in CSF.

We conclude that daptomycin administered at a dose of 10 mg/kg/day achieves CSF concentrations that may exert non-lytic anti-pneumococcal effects and demonstrate significant activity against highly resistant pneumococcal strains. These findings suggest that daptomycin could be considered as a valuable adjunctive therapy in the treatment of pneumococcal meningitis.