Nosocomial meningitis is a severe complication with high mortality, particularly among patients with predisposing factors such as neurosurgical intervention or chronic kidney disease. Limited penetration of intravenous antibiotics into the cerebrospinal fluid (CSF) often leads to subtherapeutic concentrations. Meropenem, a broad-spectrum carbapenem effective against Gram-negative and multidrug-resistant organisms, demonstrates a low CSF to-serum penetration ratio (approximately 6–9%). In such cases, intrathecal administration offers a rational approach to achieve adequate local antibiotic levels. We report a 52-year-old man presenting with generalized seizures, high-grade fever, depressed consciousness (GCS 6), and positive meningeal signs. The working diagnosis was bacterial meningitis or meningoencephalitis with comorbid chronic kidney disease post hemodialysis. Empirical intravenous ceftriaxone was initiated before culture results were available, which later identified Methicillin-Resistant Staphylococcus aureus (MRSA). Despite standard therapy, the clinical response was suboptimal, prompting intrathecal administration of meropenem via an epidural catheter at a dose of 10 mg twice daily for ten days. Seizures resolved by day 2, and neurological improvement was observed by day 4, with no adverse effects or complications. This case demonstrates that low-dose intrathecal meropenem is a safe and effective adjunctive therapy for severe or refractory meningitis unresponsive to intravenous treatment. The intrathecal route achieves therapeutic CSF antibiotic levels while minimizing systemic toxicity, representing a practical and potentially life-saving option in critical central nervous system infections.