Probable ceftriaxone-resistant neurosyphilis in an HIV-positive patient: A case report of clinical failure and response to doxycycline

Neurosyphilis remains a severe manifestation of syphilis, particularly in individuals living with HIV, where atypical presentations and treatment challenges are more common. Although ceftriaxone is considered an alternative to penicillin G, emerging reports suggest possible therapeutic failure in immunocompromised hosts. We describe a 63-year-old man with well-controlled HIV infection who developed seizures and altered mental status. Cerebrospinal fluid analysis confirmed neurosyphilis, and he was treated with high-dose intravenous ceftriaxone (2 g twice daily) for ten days. Despite therapy, neurological symptoms persisted, and repeat investigations showed ongoing inflammation. Ceftriaxone was replaced with intravenous doxycycline (100 mg twice daily), resulting in rapid clinical improvement within 72 hours. Follow-up cerebrospinal fluid studies and imaging demonstrated complete resolution of inflammatory changes. The patient completed a 28-day doxycycline course with sustained recovery. This case underscores the potential for ceftriaxone failure in HIV-associated neurosyphilis and supports considering doxycycline as an effective alternative in refractory cases.