Diffusion of a New Beta-lactam (LY 127935) into Cerebrospinal Fluid. Implications for Therapy of Gram-negative Bacillary Meningitis

LY 127935, a new oxa beta-lactam with an expanded gram-negative spectrum, was administered intravenously to seven patients, including two patients with documented gram-negative bacillary meningitis. In the patients receiving continuous therapy (2 g intravenously every 8 hours) cerebrospinal fluid trough levels of LY were never less than 6 micrograms/ml. Peak cerebrospinal fluid levels of LY ranged from 25 to 39 micrograms/ml and occurred approximately 2.5 hours after the intravenous administration of the drug. Cerebrospinal fluid levels of LY were 19 per cent to greater than 100 per cent of simultaneous serum levels. Cerebrospinal fluid bactericidal activity was 1:4 to 1:256. Intravenous LY, because of its expanded gram-negative spectrum and excellent cerebrospinal fluid penetration, is a potentially useful antibiotic in the treatment of gram-negative bacillary meningitis.