Corynebacterium striatum, a common component of the skin and mucosal microbiota of both immunocompetent and immunocompromised individuals, has become an emerging pathogen, colonizing indwelling medical devices and causing infections at multiple sites. A 3-year-old boy with an Ommaya reservoir in the right ventricle and a medical history of grade 3 intraventricular hemorrhage, Hirschsprung disease, catheter-related methicillin-resistant Staphylococcus aureus bacteremia, and congenital central hypoventilation syndrome was hospitalized for Ommaya reservoir infection with C. striatum. He was treated with ampicillin, to which the initial isolate was susceptible. C. striatum may have acquired multiple-drug resistance during the antibiotic treatment due to biofilm production. The Ommaya reservoir was replaced by external ventricular drainage. Cultures of the removed Ommaya reservoir, and cerebrospinal fluid samples grew C. striatum, which was susceptible to meropenem and vancomycin and resistant to other antibiotics. The antibiotic was switched to vancomycin to treat this new multidrug-resistant strain. After 8 days of vancomycin treatment, the cerebrospinal fluid culture obtained by a lumbar puncture was negative for C. striatum. In cases of device-associated infections caused by biofilm-producing bacteria, it is desirable to remove the device as soon as possible.