Penetration of cefoxitin into cerebrospinal fluid and treatment of meningitis caused by gram-negative bacteria

Two patients with meningitis caused by antibiotic-resistant Escherichia coli and Klebsiella pneumoniae were treated successfully with intravenous cefoxitin plus oral probenecid. A total of 25 patients with central nervous system disorders that required a diagnostic spinal tap were also given cefoxitin, with or without probenecid, for determination of the degree of penetration into cerebrospinal fluid. In patients with uninflamed meninges, little or no cefoxitin entered after a single dose of 4-6 g. After three doses of 4 g each over a 6-8-hr period, penetration was considerable (average, 7% of the simultaneous serum level). In patients with inflamed meninges, a similar concentration was achieved rapidly after a single 2-g dose. After a day of therapy, cerebrospinal fluid levels equivalent to 30%-70% of the simultaneous serum levels were found; as the inflammation subsided, cerebrospinal fluid levels fell to around 15% of those in serum. Probenecid did not appear to influence greatly the degree of penetration.