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By use of an experimental lapin model, the effect of ceftriaxone therapy on inflammation during Hemophilus inf/uenzae type b (Hib) meningitis was evaluated. Meningitis was induced by intracisternal inoculation of 2 × 10⁴ to 2 × lO⁵ colony-forming units of Hib. Administration of ceftriaxone 6 h after infection provoked rapid bacterial lysis associated with greatly increased concentrations of bacteria-free endotoxin (lipooligosaccharide) and tumor necrosis factor a (TNF) in the cerebrospinal fluid (CSF). CSF TNF activity peaked 2 h after initiation of antibiotic therapy (24.4 ± 2 ng/ml), was significantly higher than that in untreated controls (1.4 ± 1.1 ng/ml; P <.05), and was associated with a substantially increased inflammatory response as reflected by higher CSF white blood cell count (24,500 ± 8,151 vs. 1,920 ± 644 in untreated controls; P < .05), lower glucose, and higher protein and lactate concentrations …