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Tuberculous meningitis (TBM) presents a critical neurologic emergency characterized by high mortality and morbidity rates, necessitating immediate therapeutic intervention, often ahead of definitive microbiological and molecular diagnoses. The primary hurdle in effective TBM treatment is the blood–brain barrier (BBB), which significantly restricts the delivery of anti-tuberculous medications to the central nervous system (CNS), leading to subtherapeutic drug levels and poor treatment outcomes. The standard regimen for initial TBM treatment frequently falls short, followed by adverse side effects, vasculitis, and hydrocephalus, driving the condition toward a refractory state. To overcome this obstacle, intrathecal (IT) sustained release of anti-TB medication emerges as a promising approach. This method enables a steady, uninterrupted, and prolonged release of medication directly into the cerebrospinal fluid (CSF), thus preventing systemic side effects by limiting drug exposure to the rest of the body. Our review diligently investigates the existing literature and treatment methodologies, aiming to highlight their shortcomings. As part of our enhanced strategy for sustained IT anti-TB delivery, we particularly seek to explore the utilization of nanoparticle-infused hydrogels containing isoniazid (INH) and rifampicin (RIF), alongside osmotic pump usage, as innovative treatments for TBM. This comprehensive review delineates an optimized framework for the management of TBM, including an integrated approach that combines pharmacokinetic insights, concomitant drug administration strategies, and the latest advancements in IT and intraventricular (IVT) therapy for CNS infections. By proposing a multifaceted treatment strategy, this analysis aims to enhance the clinical outcomes for TBM patients, highlighting the critical role of targeted drug delivery in overcoming the formidable challenges presented by the blood–brain barrier and the complex pathophysiology of TBM.

Surgical site infections (SSIs) after spinal surgery present significant challenges, including poor antibiotic penetration and biofilm formation on implants, leading to frequent treatment failures. Polymethylmethacrylate (PMMA) is widely used for localized drug delivery in bone infections, yet quantifying individual drug release kinetics is often impractical. This retrospective study analyzed 23 cases of deep SSIs (DSSIs) following spinal surgery treated with antibiotic-loaded PMMA. A mathematical model estimated personalized drug release kinetics from PMMA, considering disease types, pathogens, and various antibiotics. The study found that vancomycin (VAN), ceftriaxone (CRO), and ceftazidime (CAZ) reached peak concentrations of 15.43%, 15.42%, and 15.41%, respectively, within the first two days, which was followed by a lag phase (4.91–4.92%) on days 2–3. On days 5–7, concentrations stabilized, with CRO at 3.22% and CAZ/VAN between 3.63% and 3.65%, averaging 75.4 µg/cm2. Key factors influencing release kinetics include solubility, diffusivity, porosity, tortuosity, and bead diameter. Notably, a patient with a low glomerular filtration rate (ASA IV) was successfully treated with a shortened 9-day intravenous VAN regimen, avoiding systemic complications. This study affirms the effectiveness of local drug delivery systems (DDS) in treating DSSIs and underscores the value of mathematical modeling in determining drug release kinetics. Further research is essential to optimize release rates and durations and to mitigate risks of burst release and tissue toxicity.