Acinetobacter baumannii (AB) nosocomial infections, especially those due to multi-drug resistant (MDR) strains, are increasingly detected. We report a case of a 42-year-old male patient affected by low-grade ependymoma who developed AB-MDR post-neurosurgical ventriculitis. Initially, because of in vitro susceptibility, we used a combination of intravenous colistin and tigecycline. This treatment resulted in the improvement of the patient's initial condition. However, soon after, the infection relapsed; tigecycline was stopped and treatment with intrathecal colistin was initiated. Cure was achieved by continuing this treatment for approximately three weeks, without adverse effects.