Central nervous system infections — meningitis, encephalitis, and brain abscess — remain high-morbidity, high-mortality conditions, made harder by multidrug resistance and by the growing population of immunocompromised patients. The most meaningful recent progress has come as much from diagnostics as from new drugs.
Diagnostic advances
Metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid can, in a single unbiased assay, screen for viruses, bacteria, fungi, and parasites. In the landmark prospective PDAID study, mNGS of CSF identified a diagnosis in a meaningful subset of otherwise-undiagnosed neurological infections — roughly a quarter of cases where conventional testing had come up empty — and changed management for some patients. It is best used as an adjunct to, not a replacement for, standard testing, and yield is higher when samples are taken early and before prolonged antimicrobial exposure.
Multiplex PCR panels allow rapid, simultaneous detection of common meningitis and encephalitis pathogens directly from CSF, improving the speed and accuracy of viral diagnosis and helping shorten unnecessary empiric therapy.
Emerging and optimized therapies
Intrathecal / intraventricular antimicrobials deliver high drug concentrations directly to the CSF, which is particularly valuable against multidrug-resistant Gram-negative organisms such as carbapenem-resistant Acinetobacter baumannii and Pseudomonas, and in device- or surgery-related infections where systemic antibiotics penetrate poorly. This approach can improve local efficacy while limiting systemic toxicity.
Newer β-lactam/β-lactamase-inhibitor combinations — ceftazidime-avibactam, ceftolozane-tazobactam, and meropenem-vaborbactam — have been used successfully against resistant CNS pathogens, usually in combination regimens for device- or post-surgical infections. CNS-relevant adverse effects deserve attention: encephalopathy and myoclonus with ceftazidime-avibactam, rare encephalopathy with ceftolozane-tazobactam, and seizures with meropenem-vaborbactam in predisposed patients; dosing should account for renal function.
Antifungal innovation is focused on improving blood-brain-barrier penetration — targeting fungal cell-wall components and efflux pathways — to raise efficacy while limiting host toxicity in cryptococcal and mold infections.
Clinical pearls
For post-surgical and nosocomial CNS infections, prompt source control (debridement, device removal) paired with susceptibility-guided combination therapy is central, with infectious-diseases and microbiology input. High rates of inappropriate empiric treatment in MDR settings make early, accurate diagnostics essential. Immunocompromised patients often need extended diagnostics spanning mycobacterial, fungal, and viral panels. Updated international guidance — including recent ESCMID recommendations on brain abscess and subdural/epidural empyema, and the 2025 WHO meningitis guidelines — increasingly emphasizes early etiologic diagnosis and stewardship.
| Approach | Main indication | Value |
|---|---|---|
| mNGS | Unknown-etiology CNS infection | Detects otherwise-missed pathogens; changes management |
| Multiplex PCR | Viral/bacterial CNS infection | Rapid, accurate; reduces empiric therapy |
| Intrathecal/intraventricular antimicrobials | MDR Gram-negative CNS infection | High local levels, lower systemic toxicity |
| Newer β-lactam/β-lactamase combos | MDR / device infection | Effective; watch CNS adverse effects |
| Antifungal innovation | Fungal/cryptococcal infection | Improved CNS penetration (developmental) |
Further reading: mNGS of CSF (Wilson et al., NEJM 2019); ESCMID guideline on brain abscess, subdural empyema and epidural abscess (2024); WHO meningitis guidelines (2025).