Penetration of spectinomycin into cerebrospinal fluid duirng experimental meningitis

Abstract

The concentration of spectinomycin in serum and cerebrospinal fluid was compared in rabbits with and without experimental pneumococcal meningitis. When injected intravenously, spectinomycin could not be detected in the cerebrospinal fluid of normal rabbits. In rabbits with meningeal inflammation, however, spectinomycin penetrated the blood-brain barrier and produced significant cerebrospinal fluid concentrations, equal to or well above spectinomycin minimal inhibitory concentrations for many bacterial species.Although spectinomycin is currently used primarily for treating infections with strains of Neisseriagonorrhoeae resistant to penicillin (5), this aminocyclitol is active in vitro against a variety of gram-positive and gram-negative bacteria (4, 8) at concentrations that persist in serum for 8 h or longer after intramuscular delivery of 2-to 4-g doses (2, 7). The broad-spectrum activity of spectinomycin might be exploitable in the treatment of meningitis, provided that the compound crossed the blood-brain barrier. The present study in rabbits with pneumococcal meningitis was designed to examine this possibility.A strain of type HI pneumococcus, isolated from a child with meningitis, was grown overnight in brain heart infusion broth (BBL, Microbiology Systems), and the suspension was adjusted to 108 colony-forming units per ml by using a 0.5 McFarland standard.New Zealand white rabbits weighing 2.5 to 3.5 kg were anesthesized with ketamine (30 mg/kg), acepromazine (3 mg/kg), and scopalamine (0.15 mg/kg), given together as a single intramuscular injection. With a 25-gauge needle, 0.5 to 1.0 ml of cerebrospinal fluid (CSF) was removed from the cisterna magna, and 0.5 ml of a pneumococcal suspension (5 x 107 colorny-forming units per ml) in brain heart infusion broth was injected intracistemally.Rabbits were studied when they developed signs of meningitis with lethargy and fever 12 to 24 h after intracisternal inoculation. A total of 21 rabbits with evidence ofmeningitis were given spectinomycin (60 mg/kg) intravenously over 1 min. CSF (0.5 to 1.0 ml) via cisternal puncture and heart blood were obtained at 15, 30, 60, 120, and 480 min after the intravenous injection of spectinomycin. Cell counts were performed on all CSF samples; those samples containing more than 30,000 erythrocytes per mm3 were considered to be significantly contaminated by blood and were not included in the study.Serum and CSF samples were assayed by a cup-plate method described by Bennett et al.(1). The assay organism was Escherichia coli (UC 527), and the medium was sterile streptomycin assay agar with yeast extract (antibiotic medium no. 5; BBL). On the day of each study, spectinomycin hydrochloride standards of 320, 160, 80, 40, 20, 10, 5, and 2.5 ,ug/ml were made up in sterile saline and pooled rabbit serum for use in the CSF and serum samples, respectively. The 5-ytg/ml standard produced the minimum readable zone. Each assay was run in duplicate, and the CSF and serum concentrations were calculated from a standard curve.Spectinomycin c...

In vitro antibacterial activity of trospectomycin (U-63366F), a novel spectinomycin analog

“…However, because of its broad spectrum, numerous investigators have touted the use of spectinomycin for other infectious diseases despite its low potency. These include meningitis (6), pelvic inflammatory disease (21), chancroid (L. Fransen, H. Nsanze, J. 0.…”