1083 DIFFUSION OF MOXALACTAM INTO CSF OF CHILDREN WITH BACTERIAL MENINGITIS

Moxalactam (MOX), a new oxa-β-lactam antibiotic,is active against an expanded spectrum of gram negative organisms including Haemophilus influenzae. It has also been reported to diffuse into cerebrospinal fluid. We administered IV MOX to children (6 wks-4½ yrs) receiving conventional antimicrobial therapy for bacterial meningitis. Plasma and CSF specimens were collected 2 to 3 hours after a dose and assayed for MOX concentration by HPLC (capable of detecting 1 μg/ml of MOX). Eight patients received single doses of 15 or 25 mg/kg. In 11 determinations the plasma levels ranged between 4.7 and 29.4 μg/ml but MOX was detected in the CSF in only one instance. Eight patients received 50 mg/kg of MOX every 8 hours for 3 doses, and in 5 patients the drug diffused into CSF. MOX was detectable in 3/5 of CSF specimens early in the course of illness (2nd or 3rd day) and averaged 20% (range 2.5 to 30%) of plasma concentration. It was detectable in 5/11 of CSF specimens obtained later in the illness (13th to 22nd day) and averaged 15.7% (6 to 36%) of plasma concentration. There was no correlation between the diffusion of MOX into CSF and the CSF white cell count, however MOX diffused to a greater extent in patients with higher CSF protein content. In summary, MOX diffuses into CSF but such diffusion is unpredictable. Caution must be exercised in using MOX alone in the treatment of meningitis.