Stereotactic aspiration by neuroendoscopy for treatment of deep-seated intracranial hematomas is widely accepted because this procedure is minimally invasive and thereby reduces the probability of iatrogenic brain damage. Herein, we describe an outbreak of trimethoprim/sulfamethoxazole (TMP/SXT)-resistant Stenotrophomonas maltophilia meningitis, possibly from a contaminated neuroendoscopy, and review the previous use of antimicrobial therapies for this condition without TMP/SXT. This is the first reported outbreak of TMP/SXT-resistant S. maltophilia meningitis. The discussion emphasizes the importance of adequate disinfection processes before and after endoscopic neurosurgery and the use of therapeutic options other than TMP/ SXT when encountering S. maltophilia meningitis.