New Antibiotics for the Treatment of Nosocomial Central Nervous System Infections

Nosocomial central nervous system (CNS) infections caused by carbapenem- and colistin-resistant Gram-negative bacteria, as well as vancomycin-resistant Gram-positive bacteria, present significant therapeutic challenges. This review explores the pharmacokinetics, pharmacodynamics, and clinical applications of new intravenous antibiotics aimed at treating these multi-resistant infections. A focus is placed on understanding how these antibiotics penetrate the cerebrospinal fluid (CSF) and their effectiveness in eradicating the pathogens.

Cefiderocol, a novel cephalosporin, shows promise due to its ability to achieve high-dose effectiveness similar to established cephalosporins. However, new glycopeptides such as dalbavancin, telavancin, and oritavancin, despite their efficacy in animal meningitis models, struggle to reach effective CSF concentrations through intravenous administration alone due to high plasma protein binding. β-lactam/β-lactamase inhibitor combinations also face challenges in achieving adequate CSF levels, with the β-lactamase inhibitor component often being insufficient. While Tedizolid offers a broader spectrum compared to linezolid, it presents less favorable pharmacokinetics, and Eravacycline fails to reach therapeutic CSF concentrations at standard intravenous doses.

Intraventricular therapy (IVT) should be considered for patients not responding adequately to systemic therapy alone, as it can enhance CSF penetration of many antibiotics. Cefiderocol is notable for its pharmacokinetics in CSF, comparable to other β-lactam antibiotics, requiring high doses (≥6 g/day) to treat carbapenem-resistant bacteria effectively. β-lactam/β-lactamase inhibitor combinations, despite their limitations, remain last-resort options for Cefiderocol-resistant infections. Overall, intravenous treatment is generally preferred to avoid adverse effects associated with intraventricular therapy, but combined intravenous and intraventricular approaches may be necessary for poorly responding CNS infections.

To read more, click here