Dose optimisation of antibiotics used for meningitis

Purpose of review Central nervous system (CNS) infections such as ventriculitis and meningitis are associated with significant morbidity and mortality. In part, this may be due to increased difficulties in achieving a therapeutic antibiotic concentration at the site of infection due to both the pharmacokinetic (PK) changes observed during critical illness and the reduced antibiotic penetration through the blood brain barrier. This paper reviews the pharmacodynamics (PD) and CNS PKs of antibiotics used for Gram-negative bacterial CNS infections to provide clinicians with practical dosing advice. Recent findings Recent PK studies have shown that currently used intravenous antibiotic dosing regimens may not achieve a therapeutic exposure within the CNS, even for reportedly `susceptible' bacteria per the current clinical meningitis breakpoints. Limited data exist for new beta-lactam antibiotic/beta-lactamase inhibitor combinations, which may be required for multidrug resistant infections. Intraventricular antibiotic administration, although not a new concept, has further evidence demonstrating improved patient outcomes compared with intravenous therapy alone, despite the ongoing paucity of PK studies guiding dosing recommendations. Summary Clinicians should obtain the bacterial minimum inhibitory concentration when treating patients with CNS Gram-negative bacterial infections and consider the underlying PK/PD principles when prescribing antibiotics. Therapeutic drug monitoring, where available, should be considered to guide dosing. Intraventricular therapy should also be considered for patients with ventricular drains to optimise clinical outcomes.

Automated summary

Infections in the central nervous system (CNS) such as ventriculitis and meningitis lead to significant morbidity and mortality. Achieving therapeutic antibiotic concentration in the site of infection is challenging due to pharmacokinetic changes during critical illness and limited antibiotic penetration through the blood-brain barrier. Clinicians should consider bacterial minimum inhibitory concentration and PK/PD principles when prescribing antibiotics for CNS gram-negative bacterial infections, and therapeutic drug monitoring may be necessary. Intraventricular therapy may be beneficial for patients with ventricular drains to improve clinical outcomes.