Coagulase-negative staphylococci (CoNS) are the main pathogens causing hospital-acquired external-ventricular-drain- (EVD-) and lumbar-drain- (LD-) associated meningitis and ventriculitis. The treatment of these infections can be challenging and may require combination of intraventricular and intravenous administration of antibiotics. Limited animal data demonstrate rapid daptomycin bactericidal activity, adequate penetration in the setting of inflamed meninges, and extended half-life in the ventricles Steenbergen et al. (2009). There are limited clinical data using daptomycin intravenously and/or intraventricularly for the treatment of central nervous system infections (CNS) Elvy et al. (2008), Stucki et al. (2007), Lee et al. (2008) and Wallace et al. (2009). We report here our experience in the treatment of an EVD-related infection.