The Effectiveness of Newer Beta-Lactams for the Treatment of Antimicrobial-Resistant Gram-Negative Meningitis.

The treatment of gram-negative bacterial infections exhibiting resistance to all traditional β-lactam and fluoroquinolone agents (ie, difficult-to-treat resistance [DTR]) poses challenges due to the limited number of active antibiotic agents. Managing DTR gram-negative infections becomes even more complex when present in the central nervous system due to concerns for insufficient concentrations of agents in the cerebrospinal fluid and brain parenchyma. Several newer β-lactam agents with activity against DTR gram-negatives are available, including cefiderocol, ceftazidime-avibactam, ceftolozane-tazobactam, imipenem-cilastatin-relebactam, meropenem-vaborbactam, and sulbactam-durlobactam. This article examines host and drug factors that influence an antibiotic's effectiveness for the treatment of bacterial meningitis. The preclinical and clinical data in support of or against each of the aforementioned agents for the treatment of bacterial meningitis are also reviewed.