Optimal antibiotic therapy for bacterial central nervous system infections in adults

Central nervous system (CNS) infections are a health concern, leading to high morbidity and mortality. Community-acquired and nosocomial meningitis are distinct entities with potentially different pathogens involved. Prompt antibiotic therapy is crucial. However, challenges arise due to the emergence of multidrug-resistant bacteria and the poor CNS penetration of most antibiotics.

This review summarizes the pathogenesis of bacterial CNS infections, the pharmacokinetics, and pharmacodynamics of several classes of antibiotics within the cerebrospinal fluid (CSF) and the optimal treatment of these infections in adults. A literature search was performed in PubMed and Embase including all available articles up to February 2025.

The selection of antibiotics with proven CNS penetration and activity against the suspected or confirmed pathogens is essential, particularly in the context of emerging resistance. Higher daily doses and continuous or extended infusions (CI/EI) help maintain therapeutic concentrations in critically ill patients, while intrathecal (IT) administration of antibiotics should be considered when systemic therapy alone is insufficient. Therapeutic drug monitoring (TDM) is crucial for optimizing dosing, especially for drugs with narrow therapeutic indices. Although CSF TDM remains uncommon and challenging, it should be performed in specialized centers with experience in antibiotic pharmacokinetics.